The Driving Force for the Acylation of β-Lactam Antibiotics by L,D-Transpeptidase 2: Quantum Mechanics/Molecular Mechanics (QM/MM) Study.
β-lactam antibiotics, which are used to treat infectious diseases, are currently the most widely used class of antibiotics. This study focused on the chemical reactivity of five- and six-membered ring systems attached to the β-lactam ring. The ring strain energy (RSE), force constant (FC) of amide (C-N), acylation transition states and second-order perturbation stabilization energies of 13 basic structural units of β-lactam derivatives were computed using the M06-2X and G3/B3LYP multistep method. In the ring strain calculations, an isodesmic reaction scheme was used to obtain the total energies. RSE is relatively greater in the five-(1a-2c) compared to the six-membered ring systems except for 4b, which gives a RSE that is comparable to five-membered ring lactams. These variations were also observed in the calculated inter-atomic amide bond distances (C-N), which is why the six-membered ring lactams C-N bond are more rigid than those with five-membered ring lactams. The calculated ΔG# values from the acylation reaction of the lactams (involving the S-H group of the cysteine active residue from L,D transpeptidase 2) revealed a faster rate of C-N cleavage in the five-membered ring lactams especially in the 1-2 derivatives (17.58 kcal mol-1 ). This observation is also reflected in the calculated amide bond force constant (1.26 mDyn/A) indicating a weaker bond strength, suggesting that electronic factors (electron delocalization) play more of a role on reactivity of the β-lactam ring, than ring strain.


Mid- to long-term results of single-stage surgery for patients with chronic osteomyelitis using a bioabsorbable gentamicin-loaded ceramic carrier.
Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier. A prospective series of 100 patients with Cierny-Mader Types III and IV chronic ostemyelitis, affecting 105 bones, were treated with a single-stage procedure including debridement, deep tissue sampling, local and systemic antibiotics, stabilization, and immediate skin closure. Chronic osteomyelitis was confirmed using strict diagnostic criteria. The mean follow-up was 6.05 years (4.2 to 8.4). At final follow-up, six patients (six bones) had recurrent infection; thus 94% were infection-free. Three infections recurred in the first year, two in the second year, and one 4.5 years postoperatively. Recurrence was not significantly related to the physiological class of the patient (1/20 Class A (5%) vs 5/80 Class B (6.25%); p = 0.833), nor was it significantly related to the aetiology of the infection, the organisms which were cultured or the presence of nonunion before surgery (1/10 with nonunion (10%) vs 5/90 without nonunion (5.6%); p = 0.570). Organisms with intermediate or high-grade resistance to gentamicin were significantly more likely in polymicrobial infections (9/21; 42.8%) compared with monobacterial osteomyelitis (7/79 (8.9%); p < 0.001). However, recurrence was not significantly more frequent when a resistant organism was present (1/16 for resistant cases (6.25%) vs 5/84 in those with a microbiologically sensitive infection (5.95%); p = 0.958). We found that a single-stage protocol, including the use of a high-delivery local antibiotic ceramic carrier, was effective over a period of several years. The method can be used in a wide range of patients, including those with significant comorbidities and an infected nonunion.Cite this article: Bone Joint J 2022;104-B(9):1095-1100.


Nicotinic acetylcholine receptors of muscle and neuronal (alpha7) types coexpressed in a small cell lung carcinoma.
SCC-37 is a small cell lung carcinoma line that aberrantly expresses muscle-type nicotinic acetylcholine receptors (nAChRs). It was established from a patient with a paraneoplastic autoimmune neuromuscular disorder, myasthenia gravis. When grown as a xenograft tumor, SCC-37 cells express plasma membrane receptors that bind 1251-labeled alpha-bungarotoxin (125I-alpha-BTx), cosediment with 9S nAChR pentamers, and bind to a monoclonal antibody (MAb 35) specific for muscle-type (alpha1 subunit) alpha-BTx receptors. The agonist carbamylcholine (carbachol) stimulates influx of 22Na+ in SCC-37 cells; this is inhibited by alpha-BTx and by d-tubocurarine. Long-term cultured SCC-37 cells have functional and ligand-binding evidence for surface coexpression of both alpha1 and neuronal-type (alpha7 subunit) alpha-BTx receptors. A subclone of SCC-37, designated SCC-A9, expresses only the neuronal-type (alpha7 subunit) alpha-BTx receptors on its surface. Carbachol does not stimulate 22Na+ influx in SCC-A9 cells, but cytisine initiates a sustained influx of Ca2+. Activation of this response is inhibited by alpha-BTx and by the alpha7-selective antagonist methyllycaconitine. Addition of Co2+ abrogates the sustained elevation of intracellular free Ca2+ concentration, implying that the cytisine-stimulated influx of Ca2+ is sustained by secondary opening of voltage-sensitive channels in the plasma membrane. Surface receptors for 125I-alpha-BTx are blocked by methyllycaconitine and d-tubocurarine. Solubilized alpha-BTx receptors from plasma membranes of SCC-A9 cells cosediment with 10S neuronal nAChR pentamers and bind to an alpha7-specific monoclonal antibody (MAb P27) but not to the muscle nAChR-reactive MAb 35. However, MAb P27 and MAb 35 both bind to alpha-BTx receptors solubilized from the cytoplasmic compartments of SCC-A9 and the parental SCC-37 line. Reverse transcription-PCR analysis revealed RNA transcripts for alpha7 and alpha1 subunits in both SCC-A9 and SCC-37 cells. The nAChRs that are expressed in these novel human cell lines can regulate cation fluxes directly as well as indirectly by synergizing with the activity of voltage-sensitive Ca2+ channels. These activities may influence the secretion of autocrine growth factors and the transcription of growth regulatory genes and thus be pertinent to the growth and metastasis of malignant neuroendocrine neoplasms.


[The results of the dynamic observation of patients with reactive Yersinia arthritis].
As many as 50 patients with reactive Yersinia arthritis were followed up. There were 4 men and 46 women. The mean age of the patients was 31.1 yr. The mean follow-up period was 30.8 months. In 72% of the cases, the disease was preceded by diarrhea. During the first examination, mono-oligoarthritis was detected in 78% of the patients. Extra-articular alterations (damage of muscles, ligaments, heart, skin changes, etc) were also recorded. The results of bacteriological analyses were positive in 22 out of the 50 patients. In 16 persons, Yersinia might be cultivated from the different biological media: blood, feces, urine, fauces, and synovial fluid. In 47 persons, arthritis took a chronic course. Persistence of antibodies of the types 03 and 09 seen for many years merits attention. Monoclonal anti-Yersinia antibodies were also detectable repeatedly. In 8 patients, in whom Yersinia were cultivated from a lot of the biological media, the disease ran an especially grave course. The role of circulating specific antibodies in patients with Yersinia arthritis and the trigger role they may play in the development of RA and ankylosing spondylarthritis requires further discussion.


Effect of volatile compounds on excimer laser power delivery.
To determine whether vapors from perfume, hairspray, oil-based paint, or water-based paint affect excimer laser beam power delivery at the corneal surface. We measured the power delivery of an Apex Plus laser before, during, and after exposure to vapors from the following volatile compounds: three types of perfume, hair spray, an oil-based paint, and a water-based paint. A digital calorimeter was used to measure the steady-state beam power of the laser during laser discharge at the corneal plane. Multiple trials were run with each compound, and the change in laser energy over time was examined to determine if any of the compounds caused degradation of the laser optics. The presence of a volatile compound in the room caused no change in mean laser energy in comparison to before and after the compound was present. However, perfumes caused a progressive decline in laser beam power throughout the trials. Controlling for this progressive decline, there was no significant difference from perfume to perfume. None of the compounds tested caused a decline in laser beam power while present in the room. However, the presence of any perfume caused a deterioration in beam power over time, suggesting a degradation of the laser optics for all perfumes. Laser centers should consider advising their patients and staff to not wear perfumes in the laser suite.


Analysis of single hair by XRF discloses mercury intake.
Utilizing information obtained from the X-ray fluorescence linear scanning along a single strand of hair in a recent fatal exposure to dimethylmercury, it was possible to determine the circumstances leading to the fatal result. When the Dartmouth chemistry professor displayed symptoms of mercury toxicity, samples of her urine and blood were found to have considerable amounts of mercury by a commercial laboratory. The Dartmouth medical people immediately started treatment with a chelator on January 29, 1997 to remove the mercury, and sent the first samples of blood, urine and hair taken on January 31, 1997 to our laboratory. Our X-ray fluorescence analysis of a single strand of hair shown in Figure 1 shows a single large peak of intake of mercury confirming the information revealed by examination of her laboratory notebook that she had spilled some dimethylmercury about 5 months previous to the date the hair sample was taken. Figure 2 shows two peaks, the peak closest to the scalp end of the hair shows the effect of the large amount of mercury released by the chelator, part of which appeared in the blood. Utilizing the start of the first increase in the blood level as August 14, 1996, and the second as caused by the chelator on January 29, 1997, a count of the number of 2-mm points measured between the two dates gives an accurate growth of the hair during that time. A close examination of Figure 1 indicates that it required five points, each of 2 mm, along the hair to reach the maximum. This indicates a time period of 10 mm of growth equal to 23 days during which a large concentration of methylmercury was entering the blood as evidenced by the hair concentration. The professor died on June 11, 1997.


UVB-mediated activation of p38 mitogen-activated protein kinase enhances resistance of normal human keratinocytes to apoptosis by stabilizing cytoplasmic p53.
Human keratinocytes respond to UV rays by developing a fast adaptive response that contributes to maintaining their functions and survival. We investigated the role of the mitogen-activated protein kinase pathways in transducing the UV signals in normal human keratinocytes. We found that UVA, UVB or UVC induced a marked and persistent activation of p38, whereas c-Jun N-terminal kinase or extracellular signal-regulated kinase were less or not activated respectively. Inhibition of p38 activity by expression of a dominant-negative mutant of p38 or with SB203580 impaired cell viability and led to an increase in UVB-induced apoptosis. This sensitization to apoptosis was independent of caspase activities. Inhibition of p38 did not sensitize transformed HaCaT keratinocytes to UVB-induced apoptosis. In normal keratinocytes, expression of a dominant-negative mutant of p53 increased UVB-induced cell death, pointing to a role for p53. In these cells, UVB triggered a p38-dependent phosphorylation of p53 on Ser-15. This phosphorylation was associated with an SB203580-sensitive accumulation of p53, even in the presence of a serine phosphatase inhibitor. Accumulated p53 was localized mainly in the cytoplasm, independently of CRM1 nuclear export. In HaCaT cells, p53 was localized exclusively in the nucleus and its distribution and level were not affected by UVB or p38 inhibition. However, UVB induced an SB203580-insensitive phosphorylation on Ser-15 of mutated p53. Overall, our results suggest that, in normal human keratinocytes, protection against UVB depends on p38-mediated phosphorylation and stabilization of p53 and is tightly associated with the cytoplasmic sequestration of wild-type p53. We conclude that the p38/p53 pathway plays a key role in the adaptive response of normal human keratinocytes against UV stress.


A comparison of medical therapy and ablation for atrial fibrillation in patients with heart failure.
Atrial fibrillation and heart failure frequently co-exist and the combination is associated with a worse prognosis than either condition alone. A number of pharmacological agents and invasive procedures have been shown to benefit this complex patient group. In this review, we compare different therapeutic approaches to atrial fibrillation and heart failure, including pharmacotherapy, left atrial catheter ablation and pace-and-ablate. Left atrial catheter ablation is an efficacious option for restoring sinus rhythm and is most likely to provide benefit to those in whom durable sinus rhythm can be expected, and whose life expectancy is not significantly reduced by other pathologies or advanced age. A pace-and-ablate approach, particularly with physiological pacing, may provide more benefit to those with low chance of maintaining sinus rhythm. Both invasive options generally outperform pharmacotherapy, although it is important to individualize the approach for each patient through shared decision-making.


Optimization and stabilization of gold nanoparticles by using herbal plant extract with microwave heating.
In this study, we have synthesized the gold nanoparticles by using Hibiscus rosa-sinensis, a medicinal plant. The gold nanoparticles were synthesized rapidly by the involvement of microwave heating. By changing of plant extract concentration, gold solution concentration, microwave heating time and power of microwave heating the optimized condition was identified. The surface Plasmon resonance found at 520 nm confirmed the gold nanoparticles synthesis. The spherical sized nanoparticles in the size range of 16-30 nm were confirmed by Transmission Electron Microscope (TEM). The stability of the nanoparticles is very well proved in the invitro stability tests. The biochemical like alkaloids and flavonoids play a vital role in the nanoparticles synthesis was identified using the Fourier Transform Infrared Spectroscopy (FTIR). Combining the phytochemical and microwave heating, the rapid synthesis of gold nanoparticles is the novel process for the medically applicable gold nanoparticles production.


Clinicopathological Analysis and Multipronged Quantitative Proteomics Reveal Oxidative Stress and Cytoskeletal Proteins as Possible Markers for Severe Vivax Malaria.
In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure. In this multi-disciplinary study we have performed a comprehensive analysis of clinicopathological parameters and serum proteome profiles of vivax malaria patients with different severity levels of infection to investigate pathogenesis of severe malaria and identify surrogate markers of severity. Clinicopathological analysis and proteomics profiling has provided evidences for the modulation of diverse physiological pathways including oxidative stress, cytoskeletal regulation, lipid metabolism and complement cascades in severe malaria. Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection. To the best of our knowledge, this is the first comprehensive proteomics study, which identified some possible cues for severe P. vivax infection. Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity.


Glucose withdrawal induces oxidative stress followed by apoptosis in glioblastoma cells but not in normal human astrocytes.
Tumor cells rely preferentially on anaerobic glycolysis rather than on respiration for ATP generation, a phenomenon known as the Warburg effect. We explored the effects of glucose withdrawal on glioblastoma multiforme-derived cell lines and their nontransformed counterparts, normal human astrocytes. We found that glucose withdrawal induces extensive apoptosis in glioblastoma multiforme cells but not in normal astrocytes. In all cells examined, ATP levels are sustained on glucose withdrawal due to elevation of fatty acid oxidation and ensuing respiration; however, we show that oxidative stress generated in the mitochondrial respiratory chain is the direct cause of cell death in glioblastoma multiforme cells. Oxidative stress that only occurs in glioblastoma multiforme cells underlies the selective susceptibility to glucose withdrawal-induced apoptosis documented in the malignant cells. This study implicates glycolysis as a potentially efficient and selective target for glioblastoma multiforme treatment.


Prompting Depression Treatment Seeking among Smokers: A Comparison of Participants from Six Countries in an Internet Stop Smoking RCT.
Websites containing information and advice about health are increasingly common and popular. It is important to understand whether the material these sites contain can positively influence individual behavior, and whether populations differ in their response to that material. Participants in an international web-based stop smoking randomized controlled trial (RCT) were screened for major depression; participants whose history and/or depression symptoms were deemed of concern were offered one of two prompts (Strong and Mild) to seek treatment, depending on depression history. Participants from 3 predominantly English-speaking and 3 predominantly Spanish-speaking countries were analyzed. Individuals given a Strong prompt were more likely to seek treatment for depression than those given a weak prompt (16.6% vs. 10.2% of previously untreated individuals reported seeking treatment), controlling for symptom level and other variables. Country-specific differences were observed, with participants from South Africa and Spain departing from the common pattern of Strong prompt leading to higher likelihood of treatment seeking. Older age and female gender, but not symptom level predicted higher likelihood of seeking treatment following a prompt. The results suggest that information provided by the health websites can promote help seeking in affected individuals.


Sleep deprivation and its consequences on house officers and postgraduate trainees.
To determine sleep deprivation and its consequences on doctors in tertiary care hospitals. The cross-sectional study was conducted from February to May 2012 and comprised house officers and postgraduate trainees at 4 public and 1 private tertiary care hospitals in Karachi. The subjects were posted in wards, out-patient departments and emergencies. A proforma was designed with questions about duration of duty hours, sleep deprivation and its effects on quality of performance, and presence of anxiety, depression, medical errors, frequent cold and infections, accidents, weight changes, and insomnia. Duration of 1 hour was given to fill the proforma. SPSS 20 was used for data analysis. The study comprised 364 subjects: 187 (51.37%) house officers and 177 (48.62%) postgraduate trainees. There were 274 (75.27%) females and 90 (24.72%) males. Of those who admitted to being sleep deprived (287; 78.84%), also complained of generalised weakness and poor performance (n = 115; 40%), anxiety (n = 110; 38%), frequent cold and infections (n = 107; 37%), personality changes (n = 93; 32%), depression (n = 86; 30%), risk of accidents (n = 68; 23.7%), medical errors (n = 58; 20%) and insomnia (n = 52; 18%). Having to spend 80-90 hours per week in hospitals causes sleep deprivation and negative work performance among doctors. Also, there is anxiety, depression and risk of accidents in their personal lives.


Identification of risk loci for primary aldosteronism in genome-wide association studies.
Primary aldosteronism affects up to 10% of hypertensive patients and is responsible for treatment resistance and increased cardiovascular risk. Here we perform a genome-wide association study in a discovery cohort of 562 cases and 950 controls and identify three main loci on chromosomes 1, 13 and X; associations on chromosome 1 and 13 are replicated in a second cohort and confirmed by a meta-analysis involving 1162 cases and 3296 controls. The association on chromosome 13 is specific to men and stronger in bilateral adrenal hyperplasia than aldosterone producing adenoma. Candidate genes located within the two loci, CASZ1 and RXFP2, are expressed in human and mouse adrenals in different cell clusters. Their overexpression in adrenocortical cells suppresses mineralocorticoid output under basal and stimulated conditions, without affecting cortisol biosynthesis. Our study identifies the first risk loci for primary aldosteronism and highlights new mechanisms for the development of aldosterone excess.


The role of community engagement in addressing bystander risks in research: The case of a Zika virus controlled human infection study.
There is limited guidance on how to assess the ethical acceptability of research risks that extend beyond research participants to third parties (or "research bystanders"). Community or stakeholder engagement has been proposed as one way to address potential harms to community members, including bystanders. Despite widespread agreement on the importance of community engagement in biomedical research, this umbrella term includes many different goals and approaches, agreement on which is ethically required or recommended for a particular context. We analyse the case of a potential Zika virus human challenge trial to assess whether and how community engagement can help promote the ethical acceptability of research posing risks to bystanders. We conclude that, in addition to having intrinsic value, community engagement can improve the identification of bystander risks, effective approaches to minimizing them, and transparency about bystander risks for host communities.


Elemental: An Open-Source Wireless Hardware and Software Platform for Building Energy and Indoor Environmental Monitoring and Control.
This work demonstrates an open-source hardware and software platform for monitoring the performance of buildings, called Elemental, that is designed to provide data on indoor environmental quality, energy usage, HVAC operation, and other factors to its users. It combines: (i) custom printed circuit boards (PCBs) with RFM69 frequency shift keying (FSK) radio frequency (RF) transceivers for wireless sensors, control nodes, and USB gateway, (ii) a Raspberry Pi 3B with custom firmware acting as either a centralized or distributed backhaul, and (iii) a custom dockerized application for the backend called Brood that serves as the director software managing message brokering via Message Queuing Telemetry Transport (MQTT) protocol using VerneMQ, database storage using InfluxDB, and data visualization using Grafana. The platform is built around the idea of a private, secure, and open technology for the built environment. Among its many applications, the platform allows occupants to investigate anomalies in energy usage, environmental quality, and thermal performance via a comprehensive dashboard with rich querying capabilities. It also includes multiple frontends to view and analyze building activity data, which can be used directly in building controls or to provide recommendations on how to increase operational efficiency or improve operating conditions. Here, we demonstrate three distinct applications of the Elemental platform, including: (1) deployment in a research lab for long-term data collection and automated analysis, (2) use as a full-home energy and environmental monitoring solution, and (3) fault and anomaly detection and diagnostics of individual building systems at the zone-level. Through these applications we demonstrate that the platform allows easy and virtually unlimited datalogging, monitoring, and analysis of real-time sensor data with low setup costs. Low-power sensor nodes placed in abundance in a building can also provide precise and immediate fault-detection, allowing for tuning equipment for more efficient operation and faster maintenance during the lifetime of the building.


The Mammography Quality Standards Act of 1992. History and philosophy.
The Mammography Quality Standards Act (MQSA) of 1992 established a precedent in the practice of mammography by creating federal quality standards for all parts of the mammography system. Heralded by some as crucial so all US women can reap the full benefits of early detection of breast cancer, MQSA implementation was delegated to the Food and Drug Administration (FDA) on June 2, 1993. In this article the major historical forces that surrounded MQSA's enactment as well as the FDA's philosophy on regulation development, inspections, and compliance under MQSA is summarized.


The Role of Music Therapy in the Emotional Regulation and Psychological Stress Relief of Employees in the Workplace.
With the increasing global attention to the problem of staff stress, scholars in the fields of sociology, psychology, and medicine are seeking effective solutions. Music therapy has entered the field of vision of scholars with its unique advantages and is used to maintain the mental health of workers in various industries and improve work efficiency. To solve the problem of employees' psychological pressure, ordinary psychotherapy is mainly done through conversation. At present, the psychological pressure generated by employees in the workplace is obviously unable to be treated by ordinary psychological treatment methods. Music therapy can play its role in this situation. This article collects a large amount of data through surveys to obtain the job satisfaction data of medical care, education, and restaurant staff for the corresponding occupations, analyzes the data, and considers the role of music therapy in this type of industry to relieve the psychological pressure of relevant staff. In the end, it is concluded that music therapy can stimulate employees' creative inspiration, eliminate employee fatigue, and eliminate some potential unfavorable factors. It can also enhance the friendship between employees, improve employee work efficiency and employees' sense of corporate identity, and reduce employee pain sense. In general, music therapy can have a positive impact in many areas, especially in corporate applications, which can have a positive impact on employees in many aspects in the workplace.


Loss to follow-up occurs at all stages in the diagnostic and follow-up period among HIV-infected patients in Guinea-Bissau: a 7-year retrospective cohort study.
To describe loss to follow-up (LTFU) at all stages of the HIV programme. A retrospective cohort study. The HIV clinic at Hospital National Simão Mendes in Bissau, Guinea-Bissau. A total of 4080 HIV-infected patients. Baseline characteristics, percentages and incidence rates of LTFU as well as LTFU risk factors at four different stages: immediately after HIV diagnosis (stage 1), after the first CD4 cell count and before a follow-up consultation (stage 2), after a follow-up consultation for patients not eligible for antiretroviral treatment (ART; stage 3) and LTFU among patients on ART (stage 4). Almost one-third of the patients were lost to the programme before the first consultation where ART initiation is decided; during the 7-year observation period, more than half of the patients had been lost to follow-up (overall incidence rate=51.1 patients lost per 100 person-years). Age below 30 years at inclusion was a risk factor for LTFU at all stages of the HIV programme. The biggest risk factors were body mass index <18.5 kg/m(2) (stage 1), male gender (stage 2), HIV-2 infection (stage 3) and CD4 cell count <200 cells/μL (stage 4). In this study, LTFU constituted a major problem, and this may apply to other similar ART facilities. More than half of the patients were lost to follow-up shortly after enrolment, possibly implying a high mortality. Thus, retention should be given a high priority.


Amplitude-Modulated Cavity-Enhanced Absorption Spectroscopy with Phase-Sensitive Detection: A New Approach Applied to the Fast and Sensitive Detection of NO2.
Accurate and sensitive measurements of NO2 play an extremely important role in atmospheric studies. Increasingly, studies require NO2 measurements with parts per trillion by volume (pptv-level) detection limits. Other desirable instrument attributes include ease of use, long-term stability, and low maintenance. In this work, we report the development of an amplitude-modulated multimode-diode-laser-based cavity-enhanced absorption spectroscopy (AM-CEAS) system operating at 406 nm that uses phase-sensitive detection for extremely sensitive NO2 detection. The laser was TTL-modulated at 35 kHz. The mirror reflectivity was determined to be 99.985% based on the ring-down time measurement. The cavity base length was 47.5 cm, giving an effective absorption pathlength of ∼3.26 km. AM-CEAS achieved a 1σ detection precision of 35 pptv in a 1 s data acquisition time (4.98 × 10-10 cm-1), over 4 times lower than that attained using a ring-down approach and the same optical system. The AM-CEAS precision improved to 8 pptv over a data acquisition time of 30 s (1.14 × 10-10 cm-1). The AM-CEAS method with the multimode diode laser integrates the advantages of high light injection efficiency like on-axis alignment cavity ring-down spectroscopy, low cavity-mode noise like off-axis alignment CEAS, and narrow-bandwidth high-sensitivity weak signal detection of modulation spectroscopy, providing a powerful, straightforward, and general method for ultrasensitive absorption and extinction measurements.


The effect of NK cell activation by tumor cells on antigen-specific antibody responses.
In addition to mediating direct cytotoxicity, NK cells can exert regulatory effects on specific immune responses. For example, injection of poly (I:C) can alter specific Ab responses, which is attributable to the production of IFN-gamma by NK cells. To test whether direct activation of NK cells can exert the same effect, we have injected, at the same time as Ag challenge, BCL1-C11 tumor cells, which are highly effective inducers of IFN-gamma production by NK cells. The results show a specific enhancement of the IgG2a response, which does not occur with a tumor (70Z/3) that does not induce IFN-gamma production. This enhancement is NK cell and IL-12 dependent. However, BCL1-C11 cells cannot directly induce IL-12 production in peritoneal exudate cells (PECs). On the other hand, PECs from tumor-treated mice produce IL-12 in response to LPS, suggesting that they are primed in vivo. Furthermore, the IL-12 production is NK cell and IFN-gamma dependent. These results indicate that if tumor cells can directly activate NK cells to produce IFN-gamma, this cytokine initiates an amplification loop by activating macrophages to produce IL-12, which in turn activates NK cells further, resulting in the alteration of the isotype distribution of specific Ab responses. Production of the appropriate Ab isotype should enhance Ab-dependent cellular cytotoxicity against targets mediated by NK cells, implicating their role(s) in the specific immune response as well as the initial nonspecific phase.


Bioaugmentation of activated sludge with elemental sulfur producing strain Thiopseudomonas denitrificans X2 against nitrate shock load.
The sulfide and nitrogen compounds in wastewaters are toxic and cause a serious environmental problem. Thiopseudomonas denitrificans X2, which is the type species of a novel genus Thiopseudomonas was used for bioaugmentation. It oxidized sulfide and acetate with nitrate, and generated elemental sulfur that could be recovered as resource. The generation rate of elemental sulfur was enhanced significantly by the bioaugmentation under the condition of excessive nitrate feeding. The inoculums survived and worked actively in the activated sludge system as the dominant population. Thiopseudomonas denitrificans X2 could be applied to wastewater treatment and resource recovery simultaneously.


Behavior of Listeria monocytogenes During the Manufacture and Ripening of Cheddar Cheese.
The ability of Listeria monocytogenes to survive the Cheddar cheesemaking process and persist during ripening of cheese was examined. Pasteurized whole milk inoculated to contain 5 ×102 cells of L. monocytogenes [strain Scott A, V7 or California (CA)]/ml was made into stirred-curd Cheddar cheese in a pilot-plant-sized vat. Cheese was ripened at 6 or 13°C. Listeria counts were obtained by surface-plating samples diluted in Tryptose Broth (TB) on McBride Listeria Agar (MLA). Initial TB dilutions were stored at 3°C and plated on MLA after 2, 4, 6 and 8 weeks if the organism was not detected with the original plating on MLA. Selected Listeria colonies from each sample were confirmed biochemically. During Cheddar cheese manufacture, Listeria counts remained relatively constant at ca. 5 x 102/ml of milk. After pressing the curd overnight, numbers of L. monocytogenes increased to about 1 × 103/g. Generally, greatest numbers of Listeria , about 5 × 103 cells/g, were detected in cheese after 14 d of ripening. Listeria counts for all 3 strains decreased during further ripening and except for strain V7, no appreciable difference in survival occurred in cheese aged at 6 or 13°C. Strains Scott A, CA and V7 survived for as long as 224, 154 and at least 434 d, respectively, in Cheddar cheese of normal composition. Strains V7 and CA were uniformly distributed throughout another set of cheese blocks and numbers of Listeria decreased uniformly throughout blocks of cheese during 98 d of storage.


How language production shapes language form and comprehension.
Language production processes can provide insight into how language comprehension works and language typology-why languages tend to have certain characteristics more often than others. Drawing on work in memory retrieval, motor planning, and serial order in action planning, the Production-Distribution-Comprehension (PDC) account links work in the fields of language production, typology, and comprehension: (1) faced with substantial computational burdens of planning and producing utterances, language producers implicitly follow three biases in utterance planning that promote word order choices that reduce these burdens, thereby improving production fluency. (2) These choices, repeated over many utterances and individuals, shape the distributions of utterance forms in language. The claim that language form stems in large degree from producers' attempts to mitigate utterance planning difficulty is contrasted with alternative accounts in which form is driven by language use more broadly, language acquisition processes, or producers' attempts to create language forms that are easily understood by comprehenders. (3) Language perceivers implicitly learn the statistical regularities in their linguistic input, and they use this prior experience to guide comprehension of subsequent language. In particular, they learn to predict the sequential structure of linguistic signals, based on the statistics of previously-encountered input. Thus, key aspects of comprehension behavior are tied to lexico-syntactic statistics in the language, which in turn derive from utterance planning biases promoting production of comparatively easy utterance forms over more difficult ones. This approach contrasts with classic theories in which comprehension behaviors are attributed to innate design features of the language comprehension system and associated working memory. The PDC instead links basic features of comprehension to a different source: production processes that shape language form.


Reasons for refusing a donor heart for transplantation in Brazil.
Major advances have been made in heart transplantation, but there is a discrepancy between the number of patients potentially treatable by transplantation and the limited number of viable grafts. The aim of this study was to evaluate the reasons for refusal of donor hearts. This was a retrospective analysis of donor data from an organ procurement organization in the state of São Paulo (Brazil) between 2010 and 2012. Fisher's exact test, Student's t-test, and the Mann-Whitney U-test were used in the statistical analysis. Only 26 (7.9%) of 328 potential heart donors actually became donors. Most donors were men (18/26, 69.2%), Caucasians (14/26, 53.8%), and had a mean age of 23.5 yr. There were significant associations of use of donor hearts with the variables: brain death after trauma (p = 0.002), history of hypertension (p = 0.001), electrocardiographic changes (p = 0.007), and age (p = 0.001). Older age (n = 101, 33.4%) was the main reason for refusal of donor hearts, followed by poor medical history (n = 44, 14.6%), cardiac arrest of the donor during donor care (n = 25, 8.3%), use of vasopressor drugs (n = 23, 7.6%), and hemodynamic instability (n = 20, 6.6%). Age, poor medical history, cardiac arrest, use of vasopressors, and hemodynamic instability were the most prevalent reasons for refusal of donor hearts. Echocardiogram evaluation is a potential intervention to improve heart transplantation conversion in Brazil.


Restricted diffusion of tyrosine hydroxylase and phenylethanolamine N-methyltransferase from digitonin-permeabilized adrenal chromaffin cells.
Tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase; L-tyrosine,tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 188.8.131.52] and phenylethanolamine N-methyltransferase, EC 18.104.22.168) are involved in catecholamine biosynthesis and are considered soluble proteins. However, they may actually be localized on the surface of the chromaffin granule. We have used the detergent digitonin to permeabilize the plasma membrane of cultured adrenal chromaffin cells to investigate the subcellular localization of TyrOHase and PMTase. A digitonin titration of the release of proteins and catecholamines revealed the existence of at least three subcellular compartments that are distinguished by their digitonin sensitivity: (i) soluble proteins, which were released upon treatment of the cells with low digitonin concentrations (5 microM), (ii) a "digitonin-sensitive" cytoplasmic protein pool, which required higher concentrations of digitonin for release (10 microM) and included TyrOHase and PMTase, and (iii) the chromaffin granule, which was insensitive to digitonin. Analysis of the rates of release of all of these proteins revealed that the rate of TyrOHase and PMTase release was slower at 10 microM than at 40 microM digitonin, while the rates of release of the other proteins were similar at both concentrations and varied in proportion to their respective sizes. Treatment with cytoskeletal disrupting agents had no effect on TyrOHase or PMTase efflux. These data suggest that TyrOHase and PMTase are in a detergent-labile association in the cell. This is consistent with the concept that TyrOHase and PMTase may be localized on the surface of the chromaffin granule.


Urinary tract infections and asymptomatic bacteriuria in renal transplant recipients.
Asymptomatic bacteriuria and urinary tract infection are common complications after kidney transplantation. In this population, if urinary tract infection occurred in the first six months post procedure, it carries a grave impact on both graft and patient survival. Renal transplant recipients with urinary tract infection are often clinically asymptomatic as a consequence of immunosuppression. Urinary tract infection, however, may progress to acute pyelonephritis, bacteremia and the full blown picture of urosepsis. PubMed and Cochrane databases were searched. The purpose of this review is to discuss the screening and treatment of urinary tract infection and asymptomatic bacteriuria in renal transplant recipients and to evaluate the guidelines on the basis of a review of published evidence.


Strategies against methicillin-resistant Staphylococcus aureus persisters.
Chronic Staphylococcus aureus infections are complicated by frequent relapses not only from the development of drug resistance to conventional antibiotics, but also through the formation of persister bacterial cells. Bacterial persisters are in a transient, metabolically inactive state, making conventional antibiotics that target essential cellular growth processes ineffective, resulting in high clinical failure rates of antibiotic chemotherapy. The development of new antibiotics against persistent S. aureus is an urgent issue. Over the last decade, new strategies to identify S. aureus persister-active compounds have been proposed. This review summarizes the proposed targets, antipersister compounds and innovative methods that may augment conventional antibiotics against S. aureus persisters. The reviewed antipersister strategies can be summarized as two broad categories; directly targeting growth-independent targets and potentiating existing, ineffective antibiotics by aiding uptake or accessibility.


[A case of recurrent gastric cancer successfully treated with radiation therapy].
We report a case of recurrent gastric cancer that was effectively controlled with radiation therapy. A 63-year-old man underwent total gastrectomy, cholecystectomy and D2 dissection in February 2006 for early gastric cancer in the upper third area that was diagnosed with papillary adenocarcinoma and Stage IA (T1 (SM), N0, H0, P0, CY0, M0). He underwent lateral segmentectomy of the liver for liver metastasis of S2/3. He suffered from No. 12 lymph node(LN)metastasis in February 2009, so CPT-11, next to S-1, was administered. Portal tumor thrombosis (PTT) and liver S8 metastasis were observed in September 2009. First, chemoradiotherapy (CRT) ( S-1 80 mg/body+total of 65 Gy per 26 Fr) for #12 LN and PTT was performed and, in turn, stereotactic radiation therapy (SRT: total of 52.8 Gy per 4 Fr) was performed. A complete response in all of tumors was noted and he was presently alive with no sign of recurrence after 19 months after CRT and SRT. Grade 3 or 4 adverse events were not recognized. It is thought that radiation therapy is one of effective treatments for localized metastasis from gastric cancer.


Muscle activation patterns and postural control following stroke.
Many stroke survivors have residual sensorimotor deficits that impact negatively on balance and quality of life. The purpose of this review is to provide an overview of the impairments in motor control following stroke and the impact of those impairments on muscle activation patterns during postural control in stroke. Motor control impairments following stroke result in force production that is slow, weak and lacking in precision making it difficult to produce a fast rate of force development with sufficient magnitude to be effective for postural responses. Whether postural perturbations require feedback or feedforward responses, there is impairment to the timing, magnitude and sequencing of muscle activation following stroke. The impairment in muscle activation is dependent on the extent of the motor control impairments and strategies used by the individuals following stroke to compensate for the impairments. The central nervous system uses a variety of mechanisms to improve the muscle activation patterns needed for the recovery of postural responses following stroke.


Role of aminophylline in atropine resistant atrioventricular block.
Atrioventricular (AV) block may be induced by ischaemia as a result of production of adenosine, a metabolite that accumulates during hypoxia and ischaemia. Adenosine antagonism has been shown to reverse experimental AV node block in dogs. Recently, theophylline has been shown to be highly effective in diminishing the frequency and severity of bradycardia in newborn infants with apnoea-bradycardia spells. We report here a case of acute inferior wall myocardial infarction who developed atropine resistant AV block which was reversed by aminophylline, a competitive, antagonist of adenosine.


National Survey on the importance of sleep in the quality of academic life and mental health of college students in Portugal.
The academic years are a period of vulnerability when considering sleep problems and mental health. Growing evidence suggests poor sleep patterns are related to impaired academic life and lower psychological well-being. The aim of this study was to explore the importance of sleep habits and report the associations of sleep problems with quality of academic life and different dimensions of mental health (e.g. worries, anxiety, self-regulation and resilience) in a large sample of college students. The HBSC/JUnP data base comprises a representative sample of 2991 college students (n=2203; 73.7% women), aged from 18 to 35 years old (22.43±3.83). Participants socio-demographic characteristics included sex and age. Besides, participants were inquired about sleep duration, characteristics of their sleep habits, questions about quality academic life, namely feeling bored in university, pressure from academic work and academic performance perception and mental health, namely worries, anxiety, self-regulation and resilience. Results showed most young people report an average value for sleep habits (M=4.41; SD=1.46) and that they sleep an average of 7 hours a night. More than half of the young people report either being affected by difficulty falling asleep, showing signs of sleep onset insomnia (67.7%). The conducted analyses indicated that the difficulty falling asleep (having insomnia) was associated with poor/reasonable academic performance perception, higher levels of concerns and anxiety, and lower levels of self-regulation and resilience, thus jeopardizing the mental health of college students. In turn, that characteristics of sleep was also associated with poor sleep habits. In conclusion, this study showed that poor sleep habits were associated with a worse level of academic performance perception and low levels of mental health among college students in Portugal. Universities offer enormous potential as settings to promote sleep-health programs since they can reach many young people who are future-oriented and willing to learn. There is then the need for academic researchers, teaching staff and health professionals working for college students health, to develop and test a wide array of sleep-promoting interventions (e.g., education classes, online programs, adjustment of class time), thus preventing negative secondary outcomes.


Recreational physical activity and the risk of preeclampsia: a prospective cohort of Norwegian women.
Previous case-control studies suggest that recreational physical activity protects against preeclampsia. Using a prospective design, the authors estimated the risk of preeclampsia for pregnant women according to level of physical activity, taking other variables that influence risk into consideration. The data set comprised 59,573 pregnancies from the Norwegian Mother and Child Cohort Study (1999-2006). Information on physical activity and other exposures was extracted from questionnaire responses given in pregnancy weeks 14-22, whereas diagnosis of preeclampsia was retrieved from the Medical Birth Registry of Norway. Estimation and confounder control was performed with multiple logistic regression. About 24% of pregnant women reported no physical activity, and 7% reported more than 25 such activities per month. The adjusted odds ratio was 0.79 (95% confidence interval: 0.65, 0.96) for preeclampsia when comparing women who exercised 25 times or more per month with inactive women. The association appeared strongest among women whose body mass index was less than 25 kg/m(2) and was absent among women whose body mass index was higher than 30 kg/m(2). These results suggest that the preventive effect of recreational physical activity during pregnancy may be more limited than has been shown in case-control studies and may apply to nonobese women only.


Factors influencing waiting time in hypospadias repair surgery.
Hypospadias is a common congenital anomaly of the urethra and phallus, which is not life threatening. It is thus less prioritised in a resource-limited setting. The aim of this study was to evaluate the management of hypospadias by our paediatric surgery unit and determine the factors affecting the delay between presentation and surgical repair while proffering possible solutions to such delay in hypospadias repair surgery. This was a retrospective review of all hypospadias repair surgeries carried out by our paediatric surgery unit over a 38-month period, evaluating the period between presentation and first surgery for each patient. Data were analysed using IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Released 2011, Armonk, NY, USA). Chi-square test was used to compare categorical variables and P ≤ 0.05 was considered significant. In 38 months, 47 operations for hypospadias were carried out on 42 boys. Thirty-seven patients (88.1%) had >3 months delay to surgery. The most frequent contributory factor to delay was unavailable theatre space (13 patients, 31%). Surgical outcome was good in only 16 patients (44%). Of the 16 patients with good outcome, 10 (63%) were operated between the ages of 2-4 years (P > 0.05). Multiple factors are responsible for delays in carrying out hypospadias surgery in resource-limited environments, notably securing a functional operating theatre suite in the light of more urgent conditions. To combat these delays, we recommend having dedicated hypospadias repair sessions and surgeons dedicated to hypospadias repair. Hypospadias outreach camps are also proposed.


Turning the Tide for Academic Women in STEM: A Postpandemic Vision for Supporting Female Scientists.
The "leaky pipeline" of women in science, technology, engineering, and mathematics (STEM), which is especially acute for academic mothers, continues to be problematic as women face continuous cycles of barriers and obstacles to advancing further in their fields. The severity and prevalence of the COVID-19 pandemic both highlighted and exacerbated the unique challenges faced by female graduate students, postdocs, research staff, and principal investigators because of lockdowns, quarantines, school closures, lack of external childcare, and heightened family responsibilities, on top of professional responsibilities. This perspective provides recommendations of specific policies and practices that combat stigmas faced by women in STEM and can help them retain their careers. We discuss actions that can be taken to support women within academic institutions, journals, government/federal centers, university-level departments, and individual research groups. These recommendations are based on prior initiatives that have been successful in having a positive impact on gender equity─a central tenet of our postpandemic vision for the STEM workforce.


Caudal epidural injections with sarapin or steroids in chronic low back pain.
Epidural steroid injections are the most commonly used procedures to manage chronic low back pain in interventional pain management settings. Approaches available to access the epidural space in the lumbosacral spine include the interlaminar, transforaminal, and caudal. The overall effectiveness of epidural steroid injections has been highly variable. This study included 65 patients who underwent diagnostic facet joint nerve blocks utilizing comparative local anesthetic blocks and were shown to be negative for facet joint pain and other problems such as sacroiliac joint pain before enrollment into the study. They were randomly selected from 105 patients negative for facet joint pain allocated into three groups, with Group I consisting of 15 patients comprising a convenience control sample treated conservatively; Group II, consisting of 22 patients treated with caudal epidural with local anesthetic and Sarapin(R); and Group III, consisting of 33 patients treated with caudal epidural with a mixture of local anesthetic, and betamethasone. The study period lasted for 3 years. Results showed that there was significant improvement in patients receiving caudal epidural injections, with a decrease in pain associated with improved physical, functional and mental status; and decreased narcotic intake combined with return to work. The study showed that at 1 month 96% of the patients evaluated showed significant improvement, which declined to 56% at 3 months and 16% at 6 months, with administration of 1 to 3 injections. Cumulative relief with 1 to 12 injections was noted in 96% of the patients at 1 month, 95% at 3 months, 85% at 6 months, and 67% at 1 year. The study also showed cost effectiveness of this treatment, with a cost of $ 2550 for 1-year improvement of quality of life . In conclusion, caudal epidural injections with steroids or Sarapin are an effective modality of treatment in managing chronic, persistent low back pain that fails to respond to conservative modalities of treatments and is also negative for facet joint pain. The treatment is not only effective clinically but also is cost effective.


The interstitial compartment as a therapeutic target in heart failure.
Congestion is the single most important contributor to heart failure (HF) decompensation. Most of the excess volume in patients with HF resides in the interstitial compartment. Inadequate decongestion implies persistent interstitial congestion and is associated with worse outcomes. Therefore, effective interstitial decongestion represents an unmet need to improve quality of life and reduce clinical events. The key processes that underlie incomplete interstitial decongestion are often ignored. In this review, we provide a summary of the pathophysiology of the interstitial compartment in HF and the factors governing the movement of fluids between the interstitial and vascular compartments. Disruption of the extracellular matrix compaction occurs with edema, such that the interstitium becomes highly compliant, and large changes in volume marginally increase interstitial pressure and allow progressive capillary filtration into the interstitium. Augmentation of lymph flow is required to prevent interstitial edema, and the lymphatic system can increase fluid removal by at least 10-fold. In HF, lymphatic remodeling can become insufficient or maladaptive such that the capacity of the lymphatic system to remove fluid from the interstitium is exceeded. Increased central venous pressure at the site of the thoracic duct outlet also impairs lymphatic drainage. Owing to the kinetics of extracellular fluid, microvascular absorption tends to be transient (as determined by the revised Starling equation). Therefore, effective interstitial decongestion with adequate transcapillary plasma refill requires a substantial reduction in plasma volume and capillary pressure that are prolonged and sustained, which is not always achieved in clinical practice. The critical importance of the interstitium in the congestive state underscores the need to directly decongest the interstitial compartment without relying on the lowering of intracapillary pressure with diuretics. This unmet need may be addressed by novel device therapies in the near future.


Harmful molecular mechanisms in sepsis.
Sepsis and sepsis-associated multi-organ failure are major challenges for scientists and clinicians and are a tremendous burden for health-care systems. Despite extensive basic research and clinical studies, the pathophysiology of sepsis is still poorly understood. We are now beginning to understand that sepsis is a heterogeneous, dynamic syndrome caused by imbalances in the 'inflammatory network'. In this Review, we highlight recent insights into the molecular interactions that occur during sepsis and attempt to unravel the nature of the dysregulated immune response during sepsis.


Cd and Zn interactions and toxicity in ectomycorrhizal basidiomycetes in axenic culture.
Metal contamination in soils affects both above- and belowground communities, including soil microorganisms. Ectomycorrhizal (ECM) fungi are an important component in belowground community and tolerant strains have great potential in enhancing plant-based remediation techniques. We assessed cadmium and zinc toxicity in five ECM species in liquid media (Hebeloma subsaponaceum; H. cylindrosporum; H. crustuliniforme; Scleroderma sp.; Austroboletus occidentalis) and investigated the potential of Zn to alleviate Cd toxicity. Due to highly divergent results reported in the literature, liquid and solid media were compared experimentally for the first time in terms of differential toxicity thresholds in Cd and Zn interactions. A wide range of Cd and Zn concentrations were applied to ectomycorrhizal fungi in axenic cultures (in mg L-1): 0; 1; 3; 9; 27; 81; 243 for the Cd treatments, and 0; 1; 30; 90; 270; 810; 2,430 for Zn. Combined Zn and Cd treatments were also applied to H. subsaponaceum and Scleroderma sp. Dry weight was recorded after 30 days, and in case of solid medium treatments, radial growth was also measured. All species were adversely affected by high levels of Cd and Zn, and A. occidentalis was the most sensitive, with considerable biomass decrease at 1 mg L-1 Cd, while Scleroderma sp. and H. subsaponaceum were the most tolerant, which are species commonly found in highly contaminated sites. Cd was generally 10 times more toxic than Zn, which may explain why Zn had little impact in alleviating Cd effects. In some cases, Cd and Zn interactions led to a synergistic toxicity, depending on the concentrations applied and type of media used. Increased tolerance patterns were detected in fungi grown in solid medium and may be the cause of divergent toxicity thresholds found in the literature. Furthermore, solid medium allows measuring radial growth/mycelial density as endpoints which are informative and in this case appeared be related to the high tolerance indices found in H. subsaponaceum.


Morphology-based assessment of Cd2+ cytotoxicity using microfluidic image cytometry (microFIC).
Microfluidic systems have significant implications in the field of in vitro cell-based assays since they may allow conventional cell-based assays to be conducted in an automated and high-throughput fashion. In this study, we combined a simple microfluidic cells-on-chip system with a morphology-based image cytometric analysis approach for the assessment of Cd(2+) induced apoptosis of Chang liver cell line. A simple and efficient in situ monitoring method for quantifying the progress of a cell death event was developed and is presented here. Reasonable agreement of the estimated EC(50) value from this study with those from the literature and a close correlation between the observed changes in cell morphology (i.e., circularity) and the amount of reactive oxygen species (ROS) generation confirmed the validity of this morphology-based microfluidic image cytometric (microFIC) assessment method. We propose this morphology-based microFIC approach as an easy and efficient way to assess cytotoxicity which can be adapted to high-throughput screening platforms for in vitro cytotoxicity assays as well as drug screening.


Salmeterol/fluticasone treatment reduces circulating C-reactive protein level in patients with stable chronic obstructive pulmonary disease.
Evidence suggests that systemic inflammation may play an important role in the progression and morbidity of chronic obstructive pulmonary disease. It remains controversial whether inhaled corticosteroid in combination with a long-acting beta(2)-adrenoceptor agonist can attenuate systemic inflammation. We evaluated the effect of salmeterol/fluticasone propionate on circulating C-reactive protein level in stable chronic obstructive pulmonary disease patients. An open-label clinical trial was conducted to recruit 122 outpatients with stable moderate-to-severe chronic obstructive pulmonary disease from department of respiratory medicine in two teaching hospitals between June 2007 and March 2008. Patients were randomized into two groups (1:1) to receive either the combination of 50 microg salmeterol and 500 microg fluticasone twice daily (n = 61), or the combination of 206 microg albuterol and 36 microg ipratropium q.i.d (n = 61) over 6 months. Circulating C-reactive protein concentrations were measured before randomization and during the follow-up. The efficacy of treatment was also assessed by spirometry, as well as health status and dyspnea score at baseline and after 6-month treatment. Baseline characteristics of two groups were similar. Compared with ipratropium/albuterol, the combination of salmeterol/fluticasone significantly reduced circulating level of C-reactive protein (-1.73 vs. 0.08 mg/L, respectively, P < 0.05) after 6-month treatment. Forced expiratory volume in one second (FEV(1)) and health status also improved significantly in salmeterol/fluticasone group compared with ipratropium/albuterol. Salmeterol/fluticasone treatment subjects who had a decrease of circulating C-reactive protein level had a significant improvement in FEV(1) and St George's Respiratory Questionnaire total scores compared with those who did not (185 vs. 83 ml and -5.71 vs. -1.79 units, respectively, both P < 0.01). Salmeterol/fluticasone treatment reduced circulating C-reactive protein concentration in clinically stable moderate-to-severe chronic obstructive pulmonary disease patients after 6-month treatment.


Pharmacological hypotheses: Is acetaminophen selective in its cyclooxygenase inhibition?
The precise mechanistic action of acetaminophen (ACT; paracetamol) remains debated. ACT's analgesic and antipyretic actions are attributed to cyclooxygenase (COX) inhibition preventing prostaglandin (PG) synthesis. Two COX isoforms (COX1/2) share 60% sequence structure, yet their functions vary. COX variants have been sequenced among various mammalian species including humans. A COX1 splice variant (often termed COX3) is purported by some as the elusive target of ACT's mechanism of action. Yet a physiologically functional COX3 isoform has not been sequenced in humans, refuting these claims. ACT may selectively inhibit COX2, with evidence of a 4.4-fold greater COX2 inhibition than COX1. However, this is markedly lower than other available selective COX2 inhibitors (up to 433-fold) and tempered by proof of potent COX1 inhibition within intact cells when peroxide tone is low. COX isoform inhibition by ACT may depend on subtle in vivo physiological variations specific to ACT. In vivo ACT efficacy is reliant on intact cells and low peroxide tone while the arachidonic acid concentration state can dictate the COX isoform preferred for PG synthesis. ACT is an effective antipyretic (COX2 preference for PG synthesis) and can reduce afebrile core temperature (likely COX1 preference for PG synthesis). Thus, we suggest with specificity to human in vivo physiology that ACT: (i) does not act on a third COX isoform; (ii) is not selective in its COX inhibition; and (iii) inhibition of COX isoforms are determined by subtle and nuanced physiological variations. Robust research designs are required in humans to objectively confirm these hypotheses.


Scale-Dependent Viscosity in Polymer Fluids.
In this communication, we use simple physical arguments to construct a "phase diagram" of various frequency and wave vector-dependent regimes of effective viscosity for polymer fluids, including nonentangled and entangled melts, semidilute solutions without and with hydrodynamic interactions, as well as the more exotic case of a melt of unconcatenated ring polymers.


A technique for repairing massive ventral incisional hernias without the use of a mesh.
Incisional hernias are common. Those involving large fascial defects are usually repaired using a synthetic mesh. Complications of such repairs involving mesh pose particular problems in management. This paper describes a new technique for repairing large ventral incisional hernias which does not involve the use of a mesh. Our repair is anatomical in first reconstructing the posterior rectus sheath and then using a darn to approximate the recti. We have used this technique successfully in three cases of massive incisional hernias measuring 20 cm or more in diameter and have not experienced any complications. In particular, no recurrences of the hernias have occurred. The technique described can be used to repair primary incisional hernias as well as salvage cases when previous repairs have failed.


[The value of cytological grading of prostatic adenocarcinoma. Comparison of the clinical state, the Gleason score and grade in 69 cases].
During a two-year period, 69 positive prostatic fine-needle cyto-aspirates were selected for a comparison between the cytological grade and the clinical data, and also with the Gleason score and grade obtained with needle-biopsy. The cytological grade is independent of stage, except for grade III that indicates an advanced tumor (T3-T4). On the other hand, the cytological grade provides valuable indications on the histopathological differenciation according to Gleason, with no grade II inferior to Gleason score 5, and no grade III inferior to Gleason 7. 90% of cytological grades III are Gleason grade 4. According to recent studies, we believe that the cytological grade I is related to invasive or in-situ carcinoma, but also to high-grade intra-ductal dysplasia. Thus, it is not surprising to find no correlation between grade I and the clinical status, nor between grade I and the Gleason score and grade, though grade I (or DIC 3) has a good diagnostic value.


[Changes of exhaled nitric oxide and peripheral blood eosinophils in children with asthma].
This study examined the levels of exhaled nitric oxide (eNO) and peripheral blood eosinophils (EOS) as well as the correlation between the two markers in children with bronchial asthma (AS),AS complicated by allergic rhinitis (AS/AR) and chronic cough variant asthma (CVA), in order to explore the value of eNOS detection in children with AS. The eNO level was measured using light-emitting electrochemical photometry in 12 children with AS, 29 children with AS/AR and 10 children with CVA. Peripheral blood EOS was counted by blood cell counter (Coulter JT). Forced expiratory volume in one second (FEV1) was assessed by lung function measurement. Thirty children without atopic disease and acute respiratory infection as well as without a family history of atopic diseasea served as the control group. The levels of eNO and blood EOS in the AS, the AS/AR and the CVA groups were significantly higher than those in the control group (p<0.01). The AS/AR group showed increased levels of eNO (50.3 + or - 6.7 ppb) and EOS (5.9 + or -4.2 x 109 ) compared with the AS (30.5 + or - 8.8 ppb and 4.2 + or - 3.2 x 109 respectively) and the CVA groups (26.0 + or - 3.2 ppb and 3.7 + or - 6.9 x 109 respectively) (p<0.05). There were no significant differences in eNO and EOS levels between the AS and the CVA groups. The eNO level was positively correlated with the EOS level (r=0.51, p<0.05), but not with FEV1 (r=0.144, p>0.05) in the AS group. NO is highly expressed in children with symptoms of atopy and can reflect the levels of eosinophilic airway inflammation in children with AS.


Illumina-based analysis of the rhizosphere microbial communities associated with healthy and wilted Lanzhou lily (Lilium davidii var. unicolor) plants grown in the field.
Lanzhou lily (Liliumdavidii var. unicolor) is the best edible lily as well as a traditional medicinal plant in China. The microbes associated with plant roots play crucial roles in plant growth and health. However, little is known about the differences of rhizosphere microbes between healthy and wilted Lanzhou lily (Lilium davidii var. unicolor) plants. The objective of this study was to compare the rhizosphere microbial community and functional diversity of healthy and wilted plants, and to identify potential biocontrol agents with significant effect. Paired end Illumina Mi-Seq sequencing of 16S rRNA and ITS gene amplicons was employed to study the bacterial and fungal communities in the rhizosphere soil of Lanzhou lily plants. BIOLOG technology was adopted to investigate the microbial functional diversity. Our results indicated that there were major differences in the rhizosphere microbial composition and functional diversity of wilted samples compared with healthy samples. Healthy Lanzhou lily plants exhibited lower rhizosphere-associated bacterial diversity than diseased plants, whereas fungi exhibited the opposite trend. The dominant phyla in both the healthy and wilted samples were Proteobacteria and Ascomycota, i.e., 34.45 and 64.01 %, respectively. The microbial functional diversity was suppressed in wilted soil samples. Besides Fusarium, the higher relative abundances of Rhizoctonia, Verticillium, Penicillium, and Ilyonectria (Neonectria) in the wilted samples suggest they may pathogenetic root rot fungi. The high relative abundances of Bacillus in Firmicutes in healthy samples may have significant roles as biological control agents against soilborne pathogens. This is the first study to find evidence of major differences between the microbial communities in the rhizospheric soil of healthy and wilted Lanzhou lily, which may be linked to the health status of plants.


The health compliance model.
Another model for integrating a wide diversity of evidence related to compliance is proposed, termed the Health Compliance (HC) model. The HC model incorporates situational-antecedent, consequence, and organismic factors, including cognitive processes, as they relate functionally to compliance behaviors. A selective review of the compliance literature suggests the scope and organizational possibilities of the model.


Word frequencies in toddlers' lexicons.
Word frequencies in toddlers' lexicons were examined in two studies using the Language Development Survey (LDS), a vocabulary checklist completed by parents (Rescorla, 1989). In Study 1, a high degree of consistency in LDS word frequencies was found when six samples of 24-month-olds were compared (total N = 758). Word frequency correlations in the .90s were found between large, unselected samples of toddlers of roughly similar socioeconomic status (SES). Correlations were somewhat lower but still highly significant when groups varying widely in SES were compared. In Study 2, LDS word frequencies in a sample of 40 late talkers traced from age 2 to 3 were compared to those in a large community sample from Study 1. Both lexicon size and age of the late talker influenced the degree of consistency found with respect to the community sample. The most common words reported in the lexicons of a sample of 422 24-month-olds were consistent with those identified in diary studies as among the highest frequency words used by young children in their early vocabularies.


Death from differentiated thyroid carcinoma: retrospective study of a 40-year investigation.
Differentiated thyroid carcinoma (DTC) usually has a good prognosis, but sometimes the course of the disease results in death. The aim of the present study was to assess the effect of some variables in time to death on fatal cases in our series. A total of 83 patients with DTC who died between 1958 and 1998 from differentiated thyroid cancer were retrospectively analyzed with respect to gender, age at diagnosis, histology, percentage of (131)I uptake by postoperative thyroid remnant, site of tumor growth, and its (131)I uptake, metastases and time to death. Univariate analysis revealed a significantly shorter time to death in local recurrence when comparing local lymph node metastases and distant metastases even if neither show (131)I uptake. Multivariate analysis revealed that age at diagnosis was the most important factor in conditioning the time to death. In conclusion, in those patients who died from DTC an older age at diagnosis and presence of local recurrence influenced the time to death independently of (131)I uptake.


Telomerase biogenesis requires a novel Mex67 function and a cytoplasmic association with the Sm7 complex.
The templating RNA is the core of the telomerase reverse transcriptase. In Saccharomyces cerevisiae, the complex life cycle and maturation of telomerase includes a cytoplasmic stage. However, timing and reason for this cytoplasmic passage are poorly understood. Here, we use inducible RNA tagging experiments to show that immediately after transcription, newly synthesized telomerase RNAs undergo one round of nucleo-cytoplasmic shuttling. Their export depends entirely on Crm1/Xpo1, whereas re-import is mediated by Kap122 plus redundant, kinetically less efficient import pathways. Strikingly, Mex67 is essential to stabilize newly transcribed RNA before Xpo1-mediated nuclear export. The results further show that the Sm7 complex associates with and stabilizes the telomerase RNA in the cytoplasm and promotes its nuclear re-import. Remarkably, after this cytoplasmic passage, the nuclear stability of telomerase RNA no longer depends on Mex67. These results underscore the utility of inducible RNA tagging and challenge current models of telomerase maturation.


Everyday Politics and the Leadership of Health Policy Implementation.
This article aims to prompt reflection about the everyday politics of health systems, their importance to health policy implementation, and what sort of leadership, provided by whom, is required to address them. It is founded on insights drawn from empirical and theoretical literature, combined with practical experience developed through relevant research and teaching. Ultimately it argues that the everyday politics of the health system represent the multiple actors, interests, and choices that frontline leaders routinely address and that influence the collective action taken through the system in pursuit of public value. Leadership to address these everyday politics entails the practice of power and support for collective sense-making. Nurturing these political leadership skills through new forms of leadership development is therefore a vital component of health system development.


CHILD syndrome with thrombocytosis and congenital dislocation of hip: A case report from India.
Congenital Hemidysplasia with Ichthyosiform Nevus and Limb Defects (CHILD) is a very rare entity inherited as an X-linked trait. The cutaneous lesions are characteristic and usually involve the right side of the body. We report a case of CHILD syndrome in an Indian child affecting the left side with various other associations not yet described in the literature, such as thrombocytosis and congenital dislocation of the hip. The rarity of the syndrome prompted us to report this case.


[The Chinese medicine nutrient diet intervention prevent against the neurologic damage induce by EMF irradiation in rat hippocampus].
To observe the neurologic damage in rat hippocampus after electromagnetic field (EMF) acute or chronic irradiation and research the protective effects of Chinese medicine diet (CMD) which comprised ferulic acid, ginsenoside, astragalus polysaccharide and rhodiola sachalinensis. Eighty rats were divided into ten groups (n = 8): normal diet with shame irradiation group (NS), normal diet with chronic irradiation group (NCI), three groups of normal diet with acute irradiation after 3 h, 24 h, 72 h (NAI), Chinese medicine diet with shame irradiation group (CS), Chinese medicine diet with chronic irradiation group (CCI), three groups of Chinese medicine diet with acute irradiation after 3 h, 24 h, 72 h (CAI). The chronic EMF irradiation were performed by electromagnetic wave at 15 W/cm2 for 20 min everyday for 8 weeks continuously. The acute EMF irradiation were performed by electromagnetic wave at 65 W/cm2 for 20 min after feeding with CMD for 8 weeks. The learning and memory were evaluated by Morris water maze before/after electromagnetic wave irradiation. The apoptotic cells in hippocampus was detected by Tunel staining. The peroxidation damage of EMF and the protective effect of CMD intervention were assayed by measuring superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and reactive oxygen species (ROS). The acute and chronic EMF irradiation disturbed the ability of learning and memory significantly (P < 0.05), CMD intervention markedly antagonized this effect. The apoptotic cells in hippocampus increased evidently after EMF irradiation (P < 0.05), but CMD intervention reduced the apoptotic cells. The acute and chronic EMF irradiation induced the oxidative stress by down-regulating SOD activity, GSH-Px activity, ROS inhibiting and up-regulating the content of MDA obviously (P < 0.05), and CMD intervention reduced peroxidation damage significantly (P < 0.05). The acute and chronic EMF irradiation could initiate neurologic damage in hippocampus. CMD intervention has protective effect on the impaired learning and memory, the neuron apoptosis, the peroxidation damage induced by EMF irradiation. CMD intervention plays a significant protective role in antagonizing neurologic damage in the later stage of acute irradiation and chronic irradiation.


Concurrent hormone resistance (pseudohypoparathyroidism type Ia) and hormone independence (testotoxicosis) caused by a unique mutation in the G alpha s gene.
Defects in the G (guanine nucleotide-binding)-protein subunit (G alpha s) which stimulates adenylyl cyclase may result in either loss or gain of endocrine function. Reduced G alpha s activity is found in the hormone resistance syndrome, pseudohypoparathyroidism type Ia (PHP-Ia), while constitutive activation of G alpha s is associated with endocrine organ overactivity, including the gonadotropin-independent sexual precocity seen in patients with McCune-Albright syndrome. We identified two unrelated boys presenting with concurrent PHP-Ia and gonadotropin-independent sexual precocity (testotoxicosis). Mutational screening by denaturing gradient gel electrophoresis and sequencing of PCR-amplified exons of the G alpha s gene revealed a point mutation which generates an alanine-to-serine substitution in codon 366 of one G alpha s allele (A366S), an alanine present at the homologous position in all G-proteins. We have previously shown in transfected testis cells that the A366S mutation activates G alpha s by decreasing affinity for GDP, thereby increasing the rate of nucleotide exchange in a receptor-independent fashion. In contrast to differential stability of the activated mutant G alpha s protein in Leydig cells, with stability at 32 degrees C but not at 37 degrees C, skin fibroblasts with the mutation had the same reduced G alpha s levels at both temperatures. Our findings explain the limitation of clinical manifestations of G alpha s overactivity to testis, without involvement of other body appendages which are generally at lower than core body temperature. This unique mutation at a critically conserved residue of G alpha s is the first mutant G-protein which affects guanine nucleotide affinity and is associated with human disease, producing widely divergent and tissue-specific effects.


The role of natural enemies in the expression and evolution of mixed mating in hermaphroditic plants and animals.
Although a large portion of plant and animal species exhibit intermediate levels of outcrossing, the factors that maintain this wealth of variation are not well understood. Natural enemies are one relatively understudied ecological factor that may influence the evolutionary stability of mixed mating. In this paper, we aim for a conceptual unification of the role of enemies in mating system expression and evolution in both hermaphroditic animals and plants. We review current theory and detail the potential effects of enemies on fundamental mating system parameters. In doing so, we identify situations in which consideration of enemies alters expectations about the stability of mixed mating. Generally, we find that inclusion of the enemy dimension may broaden conditions in which mixed mating systems are evolutionarily stable. Finally, we highlight avenues ripe for future theoretical and empirical work that will advance our understanding of enemies in the expression and evolution of mixed mating in their hosts/victims, including examination of feedback cycles between victims and enemies and quantification of mating system-related parameters in victim populations in the presence and absence of enemies.


Lymphoscintigraphy cannot diagnose breast cancer.
Axillary lymphoscintigraphy was performed by the technique of Agwunobi and Boak (1) in 68 patients with operable cancer of the breast and 11 patients with benign disease. Contrary to their previous report, scans were found to be indistinguishable from normal in the majority of breast cancer patients with interpretable scans, and no pattern of uptake was found which was typical of carcinoma in the corresponding breast.


Light-induced water splitting by titanium-tetrahydroxide: a computational study.
Water oxidation by Ti(OH)4 in the ground and excited states was investigated using density functional (ΔSCF, TDDFT) methods gauged by the coupled cluster (CCSD, CCSD(T)) calculations. O2 and H2 are generated in a reaction sequence that starts with Ti(OH)4 reacting with H2O. This reaction can proceed by either nucleophilic attack by H2O or by H-atom abstraction from H2O. The nucleophilic attack has high energy barriers (40-120 kcal mol(-1)) in both the ground and excited states. On the other hand, H abstraction is effected by Ti(OH)4 in the excited state with a low energy barrier (4-8 kcal mol(-1)), generating OH˙. This is the rate-limiting barrier in the chain of O2 formation reactions proposed in this work. The production of free OH˙ radicals is not energetically feasible in the ground state. By absorbing two photons, two hydroxyl radicals are produced, which then form H2O2. By a stepwise H-abstraction from H2O2 and OOH˙, O2 is generated by absorbing two more photons. In each H-abstraction reaction a Ti(OH)4 is consumed and a Ti(OH)3H2O is produced. H2 production can proceed thermally from the latter in a very exothermic (68-105 kcal mol(-1)) bimolecular reaction. The solvent effects, modelled by explicit water molecules, have a limited influence on the reactivity.


Crystallization and crystallographic analysis of Bacillus subtilis xylanase C.
The recent biochemical characterization of the xylanases of glycosyl hydrolase family 5 (GH 5) has identified a distinctive endo mode of action, hydrolyzing the beta-1,4 xylan chain at a specific site directed by the position of an alpha-1,2-linked glucuronate moiety. Xylanase C (XynC), the GH 5 xylanase from Bacillus subtilis 168, has been cloned, overexpressed and crystallized. Initial data collection was performed and a preliminary model has been built into a low-quality 2.7 A resolution density map. The crystals belonged to the primitive monoclinic space group P2(1). Further screening identified an additive that resulted in large reproducible crystals. This larger more robust crystal form belonged to space group P2(1)2(1)2 and a resulting data set has been processed to 1.64 A resolution. This will be the second structure to be solved from this unique xylanase family and the first from a Gram-positive bacterium. This work may help to identify the structural determinants that allow the exceptional specificity of this enzyme and the role it plays in the biological depolymerization and processing of glucuronoxylan.


Effect of Superabsorbent Polymer on the Properties of Concrete.
Incorporating superabsorbent polymer (SAP), which has the abilities of absorption and desorption in concrete can achieve the effect of internal curing. The influences of the volume, particle size and ways of entrained water of SAP on the workability, compressive strength, shrinkage, carbonation resistance and chloride penetration resistance of concrete were analyzed through the macroscopic and microscopic test. The results show that pre-absorbed SAP can increase the slump of the mixture, but SAP without water absorption and pre-absorbed SAP with the deduction of internal curing water from mixing water can reduce the slump. The improvement effects of SAP on compressive strength of concrete increase gradually with the increase of age. Especially from 28 days, the compressive strength of concrete increases obviously. At later age, the compressive strengths of SAP concrete under natural curing environment exceed the strength of reference concrete under natural curing environment and nearly reach the strengths of reference concrete under standard curing environment. SAP effectively reduces the shrinkage of concrete, improves the concrete's abilities of carbonation resistance and chloride penetration resistance. The microscopic test results show that SAP can effectively improve the micro structure and make the pore structure refined. When SAP is added into concrete, the gel pores and small capillary pores are increased, the size of big capillary pores and air pores are reduced.


HLA class II+ human keratinocytes present Mycobacterium leprae antigens to CD4+ Th1-like cells.
In a variety of inflammatory skin diseases like leprosy, keratinocytes (KC) are induced to express MHC class II molecules and may therefore serve as antigen-presenting cells (APC) for MHC class II restricted T cells infiltrating the lesions. However, KC have been thought to be improper APC for MHC class II restricted T cells and to drive T cells into an anergic rather than into an activation state. We evaluated this issue in relation to leprosy and tested whether HLA-DR+ KC could present M. leprae antigens to well-defined, CD4+, cytotoxic as well as proliferative, Th1-like cell clones. Using a recently developed sensitive assay system which employs intact layers of basal KC as APC we found that most T-cell clones (6/8) lysed HLA-DR+ KC pulsed with M. leprae antigens. KC were only recognized after induction of HLA-DR expression by IFN-gamma, in an antigen-specific and HLA class II restricted manner. All T-cell clones tested also showed significant proliferation and IFN-gamma production in response to M. leprae antigens presented by HLA-DR+ KC, arguing against a KC dependent anergizing effect on T cells. Thus, HLA class II+ KC can function as proper APC for HLA class II restricted CD4+ Th 1-like cells. It seems therefore possible that antigen presentation by KC contributes to the local cell-mediated immune responses in DTH lesions.


Comparison of Membrane Inlet and Capillary Introduction Miniature Mass Spectrometry for Liquid Analysis.
Membrane inlet mass spectrometry (MIMS) is commonly used for detecting the components in liquid samples. When a liquid sample flows through a membrane, certain analytes will permeate into the vacuum chamber of a mass spectrometer from the solution. The properties of the membrane directly determine the substances that can be detected by MIMS. A capillary introduction (CI) method we previously proposed can also be used to analyze gas and volatile organic compounds (VOCs) dissolved in liquids. When CI analysis is carried out, the sample is drawn into the mass spectrometer with no species discrimination. The performance of these two injection methods was compared in this study, and similar response time and limit of detection (LOD) can be acquired. Specifically, MIMS can provide better detection sensitivity for most inorganic gases and volatile organic compounds. In contrast, capillary introduction shows wider compatibility on analyte types and quantitative range, and it requires less sample consumption. As the two injection methods have comparable characteristics and can be coupled with a miniature mass spectrometer, factors such as cost, pollution, device size, and sample consumption should be comprehensively considered when choosing a satisfactory injection method in practical applications.


Measurement of the angular distribution of light scattered from a glass fiber optical waveguide.
This paper reports the measurement of the angular distribution of light scattered from a low-loss fiber at 1.06 microm and 0.633 microm. In addition to Rayleigh scattering, a previously undetected, near-forward scattering peak was observed. The new peak is shown to be consistent with scattering by narrow dielectric filaments aligned with the axis. The total scattering loss rate at 0.633 microm is ~10 dB/km, about (1/4) of which is due to the near-forward peak. The total scattering loss rate at 1.06 microm is ~1 dB/km.


Silent Hypoxia in COVID-19: A Case Series.
The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global crisis challenging the worldwide healthcare systems. Many patients present with a mismatch of profound hypoxemia and few signs of respiratory distress (i.e., silent hypoxemia). This particular clinical presentation is often cited, but data are limited. We describe dyspnea sensation as assessed by using the BORG scale in pulmonary patients admitted to the emergency room during a 4-week period and transferred to the respiratory department of Siloah Hospital, Hannover, Germany. From October 1 to November 1, 2020, 82 patients with hypoxemia defined as oxygen demand to achieve an oxygen saturation (SpO2) ≥92% were included. In 45/82 (55%) patients, SARS-CoV-2 was detected by PCR on admission. Among non-COVID patients, exacerbation of COPD was the main diagnosis (15/37, 41%). All subjects rated their perceived dyspnea using the modified Borg CR10 scale. Patients in the non-COVID group suffered from more dyspnea on the modified Borg CR10 scale (median 1, IQR: 0-2 vs. median 5, IQR: 3-6, p < 0.001). In multivariate analysis, "silent hypoxemia" as defined by the dyspnea Borg CR10 scale ≥5 was independently associated with COVID-19 and presence of severe hypocapnia with an odds ratio of 0.221 (95% confidence interval 0.054, 0.907, p 0.036). Among pulmonary patients with acute hypoxemia defined as oxygen demand, patients suffering from COVID-19 experience less dyspnea compared to non-COVID patients. "Silent" hypoxemia was more common in COVID-19 patients.


Perceived Training Load, Muscle Soreness, Stress, Fatigue, and Sleep Quality in Professional Basketball: A Full Season Study.
This study aimed to compare the perceived training load (session-RPE) and wellness status (muscle soreness, stress, fatigue, and sleep quality) within and between regular (one-match) and congested (two matches) weeks. Fifteen professional basketball players from a European First league club participated in this study. Wellness status (Hooper's questionnaire) and perceived training loads (session-RPE) were measured for each training session and matches over a full season. Regular weeks presented moderately greater session-RPE than congested weeks (p = 0.201; d = 2.15, moderate effect). Both regular and congested weeks presented a decrease in perceived training load before matches, which was accompanied by improved wellness status on a match day. Congested weeks presented moderately lower sleep quality (p = 0.421; d = 1.320, moderate effect) and moderately greater fatigue (p = 0.468; d = 1.401, moderate effect) than regular weeks. Regular and congested weeks presented minimum differences for DOMS and stress. Lower wellness in congested weeks may be associated to an accumulative effect of training and match loads. Tapering phases before matches seem to play an important role for improving athletes' wellness and preventing overtraining.


Internet-capable publication database system.
Scientific databases are generally accessible to the public via the Internet. Reports of most peer-reviewed (quotable) research is thus available to researchers and others. However, other reports and information of interest to researchers and teachers such as poster presentations at congresses, articles describing techniques and teaching material, and details of vocational and continuing education courses (nonquotable literature) generally do not appear in such databases. This nonquotable literature is often of great use to teachers. A project was therefore initiated at the Münster Dental Clinic which aimed to address the problem by developing a database of all publications and other printed material produced by the staff (faculty). After a systematic search, all such publications (quotable and nonquotable) were entered in the database which is partially accessible via the Internet and fully accessible via the Münster Dental Clinic's Intranet. The complete list can be found in the protected Intranet areas, which can be accessed by all the Dental Clinic's staff members. The database also permits Münster Clinic staff to access the Internet and locate those publications that are on the Internet by year of publication and topic.


Metal Complexation in Xylem Fluid : II. THEORETICAL EQUILIBRIUM MODEL AND COMPUTATIONAL COMPUTER PROGRAM.
Theoretical considerations of metal complex formation in aqueous solutions were used to develop a computer program (CHELATE) to calculate all equilibrium species (free metal ions, metal complexes, etc.) in any user-defined system, such as xylem fluid. Mass-balance equations were established to describe each free metal ion and each free ligand concentration as a function of solution pH, total metal or total ligand, hydrogen-association constants, and the stability constants of known metal complexes. A default data base can be altered by the user to define any desired system covered by the stored equilibrium data. The program can currently handle nine metal ions, 35 ligands, and 500 complex species. The validity of the program was confirmed by using experimental test systems in which free-metal ion activity measurements were made with ion-selective electrodes.Program CHELATE was used to calculate the distribution of six metals in 0- to 1-hour exudate from soybean (Glycine max L. Merr.) and tomato (Lycopersicon esculentum Mill.) plants grown in normal and Zn-phytotoxic nutrient solutions. The results indicated that Fe is bound by citric acid, and Cu is bound by several amino acids in the normal-Zn exudate. Most of the Cu in soybean exudate is bound to asparagine and histidine. In tomato, Cu is bound to histidine, glutamine, and asparagine. Zinc, Mn, Ca, and Mg are bound primarily by citric acid and malic acid in both species; the per cent bound for these metals is lower than that for Fe and Cu. Zinc phytotoxicity caused equilibrium concentration shifts and resulted in the formation of several additional metal complexes not found in the normal-Zn exudate.


Absolute 99Tcm-DMSA renal uptake in children: optimum time to scan.
Absolute renal uptake was measured at 2, 4 and 6 h in 27 patients in order to determine a more convenient time for uptake compared with the 6-h measurement proposed by other authors. Measurements made at 2 and 4 h would need to be increased by 20 and 6%, respectively, to convert to the value at 6 h. Measurements at 4 h are a reasonable compromise to achieve a high-count/low-background image in a reasonable time and to obtain a good estimate of the predicted 6 h uptake at a single scanning session. The percent renal uptake at 6 h, U(6), can be derived from the percent uptake measured at t hours after injection, U(t), using the following formula: U(6) = U(t) x CF(t), where CF(t) = 1.0 + 0.03 (6 - t) for 4 < or = t < or = 6.


Bullous pemphigoid in infancy--a case report including new immunoblotting observations.
A 1-year-old boy developed bullous pemphigoid. Immunoblotting, which has not been previously reported in childhood pemphigoid, showed the serum reacted to a 190 kDa band only. Bullous pemphigoid is rare in infancy and childhood with only 40 cases previously reported. A brief review of the literature is given and treatment of childhood bullous pemphigoid is discussed.


Topotactic Conversion of α-Fe2O3 Nanowires into FeP as a Superior Fluorosensor for Nucleic Acid Detection: Insights from Experiment and Theory.
Nanostructures possess distinct quenching ability toward fluorophores with different emission frequencies and have been intensively used as nanoquenchers for homogeneous nucleic acid detection. Complete understanding of such a sensing system will provide significant guidance for the design of superior sensing materials, which is still lacking. In this Letter, we demonstrate the development of FeP nanowires as a nanoquencher for high-performance fluorescent nucleic acid detection with much superior performance to α-Fe2O3 counterparts. The whole detection process is complete within 1 min, and this fluorosensor presents a detection limit as low as 4 pM with strong discrimination of single-point mutation. Electrochemical tests and density functional theory calculations reveal that FeP NWs are superior in both conductivity for facilitated electron diffusion and hydrogen-evolving catalytic activity for favorable electron depletion, providing further experimental and theoretical insights into the enhanced sensing performance of the FeP nanosensor. Both faster electron transfer kinetics and stronger electron-consuming ability via catalyzed proton reduction enable FeP nanowires to be a superb nucleic acid nanosensor for applications.


Processing and Characterization of Spark Plasma Sintered SiC-TiB2-TiC Powders.
SiC-TiB2-TiC composites with matrices consisting of semiconductor material (SiC), conductive materials (TiB2-TiC), or their combination were fabricated by spark plasma sintering (SPS) at 2000 °C in a vacuum under a pressure of 80 MPa for 3 min. The composition and microstructure of the obtained composites were studied by X-ray diffraction and a scanning electron microscope equipped with an energy-dispersive detector. The flexural strength, Vickers hardness, and fracture toughness of SPSed samples were determined. Based on the observations in this work, three variations of the sintering process were proposed with different matrix compositions. The dense (99.7%) 60SiC-25TiB2-15TiC vol.% sintered ceramic composites exhibited the highest strength and hardness values of the studied composites, as well as a fracture toughness of 6.2 MPa·m1/2.