Biosensors: frontiers in rapid detection of COVID-19.
The rapid community-spread of novel human coronavirus 2019 (nCOVID19 or SARS-Cov2) and morbidity statistics has put forth an unprecedented urge for rapid diagnostics for quick and sensitive detection followed by contact tracing and containment strategies, especially when no vaccine or therapeutics are known. Currently, quantitative real-time polymerase chain reaction (qRT-PCR) is being used widely to detect COVID-19 from various types of biological specimens, which is time-consuming, labor-intensive and may not be rapidly deployable in remote or resource-limited settings. This might lead to hindrance in acquiring realistic data of infectivity and community spread of SARS-CoV-2 in the population. This review summarizes the existing status of current diagnostic methods, their possible limitations, and the advantages of biosensor-based diagnostics over the conventional ones for the detection of SARS-Cov-2. Novel biosensors used to detect RNA-viruses include CRISPR-Cas9 based paper strip, nucleic-acid based, aptamer-based, antigen-Au/Ag nanoparticles-based electrochemical biosensor, optical biosensor, and Surface Plasmon Resonance. These could be effective tools for rapid, authentic, portable, and more promising diagnosis in the current pandemic that has affected the world economies and humanity. Present challenges and future perspectives of developing robust biosensors devices for rapid, scalable, and sensitive detection and management of COVID-19 are presented in light of the test-test-test theme of the World Health Organization (WHO).


Domperidone in the treatment of dyspepsia: a double-blind placebo-controlled study.
Domperidone, at a dosage of 20 mg t.d.s before meals, in a double-blind, crossover, placebo-controlled trial reduced the level of the symptoms of dyspepsia by 76% compared to a 16% reduction with placebo. This difference was statistically significant (p less than 0.001). Thirteen of the fourteen patients in the study preferred domperidone to placebo. Four patients in the active treatment period and one in the placebo complained of mild side-effects.


The value of repetitive sequences in chloroplast DNA for phylogeographic inference: a comment on Vachon & Freeland 2011.
In a recent Technical Advance article, Vachon and Freeland (2011, Molecular Ecology Resources, 11, 279-285.) evaluate the utility of repetitive and non-repetitive variation in the chloroplast genome for phylogeographic inference, using variation in Phragmites australis as an example. While we agree that repetitive and nonrepetitive regions evolve at different rates and homoplasy can impact results, we disagree with the conclusion that repetitive regions are inappropriate for large-scale phylogeographic studies. Here we describe limitations to the study dataset and analysis, and provide an alternative viewpoint on the utility of repetitive regions for phylogeographic studies.


Clinical outcomes and complications of laparoscopic sacrocolpopexy with versus without concomitant hysterectomy for pelvic organ prolapse in Hong Kong Chinese patients after median follow-up of 7 years.
This retrospective cohort study is aimed at comparing outcomes and complications of laparoscopic sacrocolpopexy (LSC) with or without concomitant hysterectomy in the Hong Kong Chinese population. Women with stage II or above uterine or apical vault prolapse who underwent LSC with or without concomitant hysterectomy in a regional referral unit from 2007 to 2019 were included. The primary objectives were to compare the anatomical outcomes by pelvic organ prolapse quantification system (POP-Q) and recurrence of apical vault prolapse (≥stage II). The secondary objective was to compare the functional outcomes and complications. Anatomical recurrence and incidence of mesh exposure were analyzed using the Kaplan-Meier method. Cox proportional hazard regression was performed to identify risk factors of anatomical recurrence. Seventy-six women were included for analysis. The recurrence rate of apical vault prolapse was 3.9% after a median follow-up time of 83 months (20-190 months). A significant reduction of POP-Q scores of three compartments in both groups of women were demonstrated (p<0.001). There was no difference between the two groups in terms of functional outcomes and complications. 6.6% of women developed mesh exposure. The time to recurrence of apical vault prolapse was shorter in women who had LSC with prior hysterectomy (p =0.019). No risk factors were identified for recurrence of apical vault prolapse. Laparoscopic sacrocolpopexy with concomitant hysterectomy is comparable with LSC alone. The recurrence and complication rates are low. We suggest that LSC with concomitant hysterectomy might be offered to women with pelvic organ prolapse, with women's preference taken into account.


In-hospital, 30- and 90-day mortality in elderly trauma patients with operative feeding tubes.
Nutrition is essential in the treatment of elderly trauma patients (ETP). ETP experience dysphagia at rates six times higher than the non-trauma elderly population (NTEP) and are at increased risk for malnutrition. Operative feeding tube (OFT) placement is often used to aid with the nutritional management of ETP. Elderly patients experience higher rates of morbidity and mortality when compared to the general population, especially in the traumatic setting, with some data suggesting in-hospital mortality as high as 10%. However, the mortality rates and associated comorbidities associated with OFT in ETP are unknown. The purposes of this study were to establish the mortality rate in hospital as well as 30- and 90-days following discharge among elderly trauma patients (ETP) receiving OFT, and to assess factors associated with mortality within this population. A retrospective review of all trauma patients from a single Level I Trauma Center from 01/2010-09/2020 was conducted. Exclusion criteria were patients under 65 years of age or those with previously placed OFT. Demographics, comorbidities, injury mechanisms, injury severity scores (ISS), and OFT data were collected from the institutional trauma registry. Mortality data were obtained using the Social Security Death Index. Mortality at discharge, 30 days, and 90 days following discharge were the primary outcomes. Bivariate analysis was conducted to compare characteristics and comorbidities of patients alive and dead at the time points of interest. There were 151 ETP who received OFT. Patients were largely male (67.5%), severely injured via a blunt mechanism (95%), and had a median age of 76 years. 11 (7.3%) experienced in-hospital mortality following feeding tube placement, 21 (13.9%) died within 30 days, and 31 (20.5%) within 90 days. Bivariate analysis demonstrated that ETP who died were more likely to have a history of dementia (p = 0.004), congestive heart failure (p = 0.014), and end-stage liver disease (p = 0.034). No other patient or injury factors were associated with mortality after OFT placement. Mortality rates for ETP with OFT were higher than anticipated, yet favorable compared to recently reported data. Patients who died were more likely to have dementia, CHF, or ESLD than those who survived. The few comorbidities associated with mortality suggest that nearly all ETP who undergo OFT placement are at risk for mortality. Additionally, the data highlights the importance of early goals of care discussions for ETP and their loved ones when operative feeding tubes are being considered. Level III. Prognostic/Therapeutic/Diagnostic Test/Economic/Decision.


Zwitterionic heterogemini surfactants containing ammonium and carboxylate headgroups 2: aggregation behavior studied by SANS, DLS, and cryo-TEM.
The aggregation behavior in aqueous solution of zwitterionic heterogemini surfactants, N,N-dimethyl-N-[2-(N'-alkyl-N'-β-carboxypropanoylamino)ethyl]-1-alkylammonium bromides (2C(n)AmCa, in which n represents hydrocarbon chain lengths of 8, 10, 12, and 14), with nonidentical headgroups containing ammonium and carboxylate was investigated through small-angle neutron scattering (SANS), dynamic light scattering (DLS), and cryogenic transmission electron microscopy (cryo-TEM) techniques. We found that the aggregation behavior of 2C(n)AmCa strongly depended on the hydrocarbon chain length and the surfactant concentration. 2C(8)AmCa forms spherical micelles with radius of approximately 2 nm in solution. 2C(10)AmCa forms rod-like micelles at low concentration in the solution, and the structure changes to vesicles with increasing concentration. The membrane thickness of the vesicle is independent of the surfactant concentration. Aggregation shape transitions were also observed for 2C(12)AmCa. In addition, it appears that the vesicles of 2C(12)AmCa coexist with the rod-like micelles at a wide range of surfactant concentrations. Interestingly, 2C(14)AmCa forms vesicles with averaged membrane thickness of 2.32 nm in solution, even at the extremely low concentration of 10 times the cmc. Thus, it was concluded that 2C(n)AmCa exhibits unique aggregation behavior, such as the formation of spherical micelle→rod-like micelle→rod-like micelle+vesicle (coexistence)→vesicle with increasing hydrocarbon chain length and surfactant concentration. We also found that the membrane structure is an interdigitated bilayer when the vesicles are formed. This formation of interdigitated structures is related to the origins of the effective properties of 2C(n)AmCa in solution.


Autoimmune chronic urticaria: transferability of autologous serum skin test.
At least 30 % of children with chronic urticaria have an autoimmune aetiology with a positive autologous serum skin test (ASST). ASST is cheap, easy to perform and has good sensibility and specificity in detecting autoantibodies. In case of concern about reliability of ASST because of antihistamine medications, test transferability seems to be feasible.


Interface strain in vertically stacked two-dimensional heterostructured carbon-MoS2 nanosheets controls electrochemical reactivity.
Two-dimensional (2D) materials offer numerous advantages for electrochemical energy storage and conversion due to fast charge transfer kinetics, highly accessible surface area, and tunable electronic and optical properties. Stacking of 2D materials generates heterogeneous interfaces that can modify native chemical and physical material properties. Here, we demonstrate that local strain at a carbon-MoS2 interface in a vertically stacked 2D material directs the pathway for chemical storage in MoS2 on lithium metal insertion. With average measured MoS2 strain of ∼0.1% due to lattice mismatch between the carbon and MoS2 layers, lithium insertion is facilitated by an energy-efficient cation-exchange transformation. This is compared with low-voltage lithium intercalation for unstrained MoS2. This observation implies that mechanical properties of interfaces in heterogeneous 2D materials can be leveraged to direct energetics of chemical processes relevant to a wide range of applications such as electrochemical energy storage and conversion, catalysis and sensing.


Characterization of a novel cellulose synthesis inhibitor.
The physiological effects of an experimental herbicide and cellulose synthesis inhibitor, N2-(1-ethyl-3-phenylpropyl)-6-(1-fluoro-1-methylethyl)-1,3,5-triazine-2,4-diamine, called AE F150944, are described. In the aminotriazine molecular class, AE F150944 is structurally distinct from other known cellulose synthesis inhibitors. It specifically inhibits crystalline cellulose synthesis in plants without affecting other processes that were tested. The effects of AE F150944 on dicotyledonous plants were tested on cultured mesophyll cells of Zinnia elegans L. cv. Envy, which can be selectively induced to expand via primary wall synthesis or to differentiate into tracheary elements via secondary wall synthesis. The IC50 values during primary and secondary wall synthesis in Z. elegans were 3.91 x 10(-8) M and 3.67 x 10(-9) M, respectively. The IC50 in suspension cultures of the monocot Sorghum halapense (L.) Pers., which were dividing and synthesizing primary walls, was 1.67 x 10(-10) M. At maximally inhibitory concentrations, 18-33% residual crystalline cellulose synthesis activity remained, with the most residual activity observed during primary wall synthesis in Z. elegans. Addition to Z. elegans cells of two other cellulose synthesis inhibitors, 1 microM 2,6-dichlorobenzonitrile and isoxaben, along with AE F150944 did not eliminate the residual cellulose synthesis, indicating little synergy between the three inhibitors. In differentiating tracheary elements, AE F150944 inhibited the deposition of detectable cellulose into patterned secondary wall thickenings, which was correlated with delocalization of lignin as described previously for 2, 6-dichlorobenzonitrile. Freeze-fracture electron microscopy showed that the plasma membrane below the patterned thickenings of AE F150944-treated tracheary elements was depleted of cellulose-synthase-containing rosettes, which appeared to be inserted intact into the plasma membrane followed by their rapid disaggregation. AE F150944 also inhibited cellulose-dependent growth in the rosette-containing alga, Spirogyra pratensis, but it did not inhibit cellulose synthesis in Acetobacter xylinum or Dictyostelium discoideum, both of which synthesize cellulose via linear terminal complexes. Therefore, AE F150944 may inhibit crystalline cellulose synthesis by destabilizing plasma membrane rosettes.


Temperature and solvent facilitated extrusion based 3D printing for pharmaceuticals.
On demand manufacturing of patient-specific oral doses provides significant advantages to patients and healthcare staff. Several 3D printing (3DP) technologies have been proposed as a potential digital alternative to conventional manufacturing of oral tablets. For an additive manufacturing approach to be successful for on-demand preparation, a facile process with minimal preparation steps and training requirements is needed. A novel hybrid approach to the 3D printing process is demonstrated here based on combining both a solvent and heating to facilitate extrusion. The system employed a moderate elevated temperature range (65-100 °C), a brief drying period, and a simple set-up. In this approach, a compact material cylinder is used as a pharmaceutical ink to be extruded in a temperature-controlled metal syringe. The process proved compatible with hygroscopic polymers [Poly(vinyl alcohol (PVA) and polyvinylpyrrolidone (PVP)] and a number of pharmaceutical fillers (lactose, sorbitol and D-mannitol). The fabricated tablets demonstrated acceptable compendial weight and content uniformity as well as mechanical resistance. In vitro drug release of theophylline from 3D printed tablets was dependent on the nature of the polymer and its molecular weight. This reported approach offers significant advantages compared to other 3DP technologies: simplification of pre-product, the use of a moderate temperature range, a minimal drying period, and avoiding the use of mechanically complicated machinery. In the future, we envisage the use of this low-cost and facile approach to fabricate small batches of bespoke tablets.


A global temperature control of silicate weathering intensity.
Silicate weathering as an important negative feedback can regulate the Earth's climate over time, but much debate concerns its response strength to each climatic factor and its evolution with land surface reorganisation. Such discrepancy arises from lacking weathering proxy validation and scarce quantitative paleo-constraints on individual forcing factors. Here we examine the catchment-scale link of silicate weathering intensity with various environmental parameters using a global compilation of modern sediment dataset (n = 3828). We show the primary control of temperature on silicate weathering given the monotonic increase of feldspar dissolution with it (0-30 °C), while controls of precipitation or topographic-lithological factors are regional and subordinate. We interpret the non-linear forcing of temperature on feldspar dissolution as depletion of more reactive plagioclase (relative to orthoclase) at higher temperature. Our results hint at stronger temperature-weathering feedback at lower surface temperature and support the hypothesis of increased land surface reactivity during the late Cenozoic cooling.


The ACE/DD genotype is associated with the extent of exercise-induced left ventricular growth in endurance athletes.
We studied the impact of the angiotensin-converting enzyme (ACE)/DD genotype on morphologic and functional cardiac changes in adult endurance athletes. Trained athletes usually develop adaptive left ventricular hypertrophy (LVH), and ACE gene polymorphisms may regulate myocardial growth. However, little is known about the impact of the ACE/DD genotype and D allele dose on the cardiac changes in adult endurance athletes. METHODS; Echocardiographic studies (including tissue Doppler) were performed in 61 male endurance athletes ranging in age from 25 to 40 years, with a similar period of training (15.6 +/- 4 h/week for 12.6 +/- 5.7 years). The ACE genotype (insertion [I] or deletion [D] alleles) was ascertained by polymerase chain reaction (DD = 27, ID = 31, and II = 3). Athletes with the DD genotype were compared with their ID counterparts. The DD genotype was associated with a higher left ventricular mass index (LVMI) than the ID genotype (162.6 +/- 36.5 g/m(2) vs. 141.6 +/- 34 g/m(2), p = 0.031), regardless of other confounder variables. As a result, 70.4% of DD athletes and only 42% of ID athletes met the criteria for LVH (p = 0.037). Although systolic and early diastolic myocardial velocities were similar in DD and ID subjects, a more prolonged E-wave deceleration time (DT) was observed in DD as compared with ID athletes, after adjusting for other biologic variables (210 +/- 48 ms vs. 174 +/- 36 ms, respectively; p = 0.008). Finally, a positive association between DT and myocardial systolic peak velocity (medial and lateral peak S(m)) was only observed in DD athletes (p = 0.013, r = 0.481). The ACE/DD genotype is associated with the extent of exercise-induced LVH in endurance athletes, regardless of other known biologic factors.


Chronic total occlusion in non-infarct-related artery is associated with increased short-and long-term mortality in patients with ST-segment elevation acute myocardial infarction complicated by cardiogenic shock (from the CREDO-Kyoto AMI registry).
We aimed to investigate the effect of chronic total occlusion (CTO) in non-infarct-related artery (IRA) on short- and long-term mortality in ST-segment elevation myocardial infarction (STEMI) patients complicated by cardiogenic shock (CS). Previous studies show contradictory results about the clinical effect of CTO in non-IRA on short-term mortality in STEMI patients with CS. From the CREDO-Kyoto AMI registry enrolling 5429 patients, the current study population consisted of 313 STEMI patients with multivessel disease complicated by CS who underwent primary PCI for the nonleft main coronary artery culprit lesion within 24 hr after onset. They were divided according to the presence of CTO (CTO group: N = 100 and non-CTO group: N = 213). Hemodynamic compromise was more profound in the CTO group as suggested by the more frequent use of intra-aortic balloon pumping and/or extracorporeal membrane oxygenation. Infarct size estimated by the peak creatine phosphokinase level was larger in the CTO group than in the non-CTO group. The cumulative 30-day and 5-year incidences of all-cause death were significantly higher in the CTO group than in the non-CTO group (34.0% vs 18.0%, P = 0.001, and 64.5% vs 46.0%, P = 0.0001). After adjusting for confounders, the excess risk of the CTO group relative to the non-CTO group for all-cause death remained significant both at 30 days and at 5 years (hazard ratio [HR]: 2.05, 95% confidence interval [CI]: 1.27-3.29, P = 0.003, and HR: 1.90, 95% CI: 1.34-2.69, P = 0.0004). In STEMI patients complicated by CS, CTO in non-IRA was associated with increased 30-day and 5-year mortality.


Binding of peptides in solution by the Escherichia coli chaperone PapD as revealed using an inhibition ELISA and NMR spectroscopy.
PapD is the prototype member of a family of periplasmic chaperones which are required for assembly of virulence associated pili in pathogenic, gram-negative bacteria. In the present investigation, an ELISA has been developed for evaluation of compounds as inhibitors of PapD. Synthetic peptides, including an octamer, derived from the C-terminus of the pilus adhesin PapG were able to inhibit PapD in the ELISA. Evaluation of a panel of octapeptides in the ELISA, in combination with NMR studies, showed that the peptides were bound as extended beta-strands by PapD in aqueous solution. The PapD-peptide complex was stabilized by backbone to backbone hydrogen bonds and interactions involving three hydrophobic peptide side chains. This structural information, together with previous crystal structure data, provides a starting point in efforts to design and synthesize compounds which bind to chaperones and interfere with pilus assembly in pathogenic bacteria.


Atomistic Insights into the Origin of High-Performance Thermoelectric Response in Hybrid Perovskites.
Due to their tantalizing prospect of heat-electricity interconversion, hybrid organic-inorganic perovskites have sparked considerable research interests recently. Nevertheless, understanding their complex interplay between the macroscopic properties, nonintuitive transport processes, and basic chemical structures still remains far from completion, although it plays a fundamental role in systematic materials development. On the basis of multiscale first-principles calculations, this understanding is herein advanced by establishing a comprehensive picture consisting of atomic and charge dynamics. It is unveiled that the ultralow room-temperature lattice thermal conductivity (≈0.20 W m-1 K-1 ) of hybrid perovskites is critical to their decent thermoelectric figure of merit (≈0.34), and such phonon-glass behavior stems from not only the inherent softness but also the strong anharmonicity. It is identified that the 3D electrostatic interaction and hydrogen-bonded networks between the PbI3- cage and embedded cations result in the strongly coupled motions of inorganic framework and cation, giving rise to their high degree of anharmonicity. Furthermore, such coupled motions bring about low-frequency optical vibrational modes, which leads to the dominant role of electron scattering with optical phonons in charge transport. It is expected that these new atomistic-level insights offer a standing point where the performance of thermoelectric perovskites can be further enhanced.


Lipases in bovine milk and the relationship between the lipoprotein lipase and tributyrate hydrolysing activities in cream and skim-milk.
The lipoprotein lipase and tributyrate hydrolysing activities were found to be similarly distributed in the fractions obtained when whole milk was separated into skim-milk and cream, and when the cream was washed and freed from lipid. These enzyme activities in skim-milks and in extracts of lipid-free cream could not be separated by affinity chromatography on heparin-Sepharose. The enzymes were inactivated to the same degree when incubated at 37 degrees C in the presence of 1-5 M-NaCl, pH 8-5, and both showed marked decrease in stability at 4 degrees C in UV-light caused the same decrease in both lipoprotein lipase and tributyrate hydrolysing activities. An antiserum against a highly purified skim-milk lipoprotein lipase caused total inhibition of the lipoprotein lipase and tributyrate hydrolysing activities in skim-milk and in extracts of lipid-free cream. It is suggested that in bovine milk there is only one major lipase and that it is identical to lipoprotein lipase.


Barriers to the early integration of palliative care in pediatric oncology in 11 Eurasian countries.
The early integration of palliative care significantly improves quality of life for children with cancer. However, cultural, structural, and socioeconomic barriers can delay the integration of palliative care into cancer care, particularly in low-income and middle-income countries. To date, little is known regarding the timing of and barriers to palliative care integration in Eurasia. The Assessing Doctors' Attitudes on Palliative Treatment (ADAPT) survey evaluates physician perceptions regarding palliative care integration into pediatric oncology in Eurasia. This evidence-based survey was adapted to the regional context; iteratively reviewed by US and regional panelists; and piloted in English, Russian, and Mongolian. After distribution to physicians caring for children with cancer, statistical analysis was complemented by qualitative analysis of open-ended responses. A total of 424 physician responses were received from 11 countries in the Eurasian region. Study findings demonstrated wide variability in access to palliative care experts across countries (18%-96%), with the majority of providers (64%) reporting that the initial palliative care consultation typically occurs when curative options are no longer available. Providers desired an earlier initial palliative care consultation than what currently occurs in their setting (P < .001). Primary barriers to timely consultation included limited access to palliative care services and specialists, lack of physician education, and perceived family resistance. The current study is the first to identify physician perceptions of the delayed timing of palliative care integration into childhood cancer care and associated barriers in Eurasia. These findings will inform the development of targeted interventions to mitigate local structural and cultural barriers to access and facilitate earlier palliative care integration in the region.


Estrogen-induced proliferation of uterine epithelial cells is independent of estrogen receptor alpha binding to classical estrogen response elements.
Acting via the estrogen receptor (ER), estradiol exerts pleomorphic effects on the uterus, producing cyclical waves of cellular proliferation and differentiation in preparation for embryo implantation. In the classical pathway, the ER binds directly to an estrogen response element to activate or repress gene expression. However, emerging evidence supports the existence of nonclassical pathways in which the activated ER alters gene expression through protein-protein tethering with transcription factors such as c-Fos/c-Jun B (AP-1) and Sp1. In this report, we examined the relative roles of classical and nonclassical ER signaling in vivo by comparing the estrogen-dependent uterine response in mice that express wild-type ERalpha, a mutant ERalpha (E207A/G208A) that selectively lacks ERE binding, or ERalpha null. In the compound heterozygote (AA/-) female, the nonclassical allele (AA) was insufficient to mediate an acute uterotrophic response to 17beta-estradiol (E2). The uterine epithelial proliferative response to E2 and 4-hydroxytamoxifen was retained in the AA/-females, and uterine luminal epithelial height increased commensurate with the extent of ERalpha signaling. This proliferative response was confirmed by 5-bromo-2'-deoxyuridine incorporation. Microarray experiments identified cyclin-dependent kinase inhibitor 1A as a nonclassical pathway-responsive gene, and transient expression experiments using the cyclin-dependent kinase inhibitor 1A promoter confirmed transcriptional responses to the ERalpha (E207A/G208A) mutant. These results indicate that nonclassical ERalpha signaling is sufficient to restore luminal epithelial proliferation but not other estrogen-responsive events, such as fluid accumulation and hyperemia. We conclude that nonclassical pathway signaling via ERalpha plays a critical physiologic role in the uterine response to estrogen.


Transcranial magnetic motor evoked potentials (tcMMEP) for functional monitoring of motor pathways during scoliosis surgery.
Transcranial magnetic motor evoked potentials (tcMMEP) were used to assess the functional integrity of the descending motor pathways. The tcMMEP, recorded bilaterally from anterior tibialis muscles, were evoked by an electric current induced in the motor cortex by a high-intensity transient magnetic field applied to the scalp surface. Potentials were recorded from ten of 12 volunteer subjects and preoperatively in 11 of 11 scoliotic patients. Group mean latency in the volunteers (32.0 +/- 2.1 msec) did not differ from that of the scoliotics (28.6 +/- 5.0 msec), but values in the latter group were more variable. During nitrous oxide-narcotic anesthesia, tcMMEP with reproducible latencies were obtained in 9 of 11 (82%) cases. A small, but statistically significant, increase in latency occurred during anesthesia. Compared with preoperative values (523 +/- 490 microV), individual tcMMEP amplitudes were significantly decreased intraoperatively (163 +/- 153 microV). Although the absolute amplitudes varied widely, the minimum recorded value was over 20 microV. Thus, intraoperative tcMMEP waveforms were readily discriminable from background electrical noise. These results demonstrate the technical feasibility of intraoperative tcMMEP monitoring. Combined somatosensory evoked potential and tcMMEP monitoring may provide a more complete picture of spinal cord function, intraoperatively.


Structural characterization and stability study of green synthesized starch stabilized silver nanoparticles loaded with isoorientin.
Isoorientin (Iso) is a natural flavonoid, the effect of metal nanoparticles loaded with it was unknown. In this study, silver nanoparticles (AgNPs) were synthesized by corn starch and sodium citrate with the green synthesis method, and the structural characterization and stability of AgNPs loaded with Iso (AgNPs-Iso) were examined by UV-vis spectroscopy and zetasizer. Results showed that AgNPs (65 ± 0.87 nm, spheres) successfully loaded with Iso (117 ± 2.13 nm, loading efficiency: 76.60%). There are no significant changes of the stability of AgNPs and AgNPs-Iso in pH 5-9 and 0-0.30 M of NaCl solution. AgNPs-Iso was more stable than AgNPs in the simulated gastrointestinal digestion in vitro. Furthermore, AgNPs-Iso showed the lower erythrocytes hemolysis ratio and cytotoxicity, and exhibited a notably inhibitive effect on α-glucosidase and pancreatic lipase. Therefore, this study could provide the basic support for the further development of highly stable and lowly cytotoxic AgNPs-Iso on Type II diabetes and obesity.


Pulmonary Artery Development Over Time in Severe Ebstein Anomaly.
Recently, the outcome of severe Ebstein anomaly (EA) has improved with the prevalence of the Starnes procedure. However, time-dependent changes in the size of the central pulmonary artery (PA) have not been fully understood. A retrospective chart review of patients with EA who underwent the Starnes procedure during the neonatal period and those with pulmonary atresia with intact ventricular septum (PAIVS) was performed at Fukuoka Children's Hospital. There were 14 patients in the severe EA group and 36 in the PAIVS group, with mean observational periods of 3.8 and 4.2 years, respectively. No significant difference in survival was observed between the groups. However, the mean size of the central PA was smaller in the severe EA group at each surgical stage (after systemic-to-pulmonary shunt, after the bidirectional Glenn procedure, and after the Fontan procedure). A significantly larger ventricular volume was observed in the severe EA group after the Fontan procedure. The growth of the central PA was poor in patients with severe EA. Patients with severe EA should be carefully monitored in this regard both before and after undergoing the Fontan procedure. Further studies regarding long-term prognosis are expected.


Molecular and immunochemical characterization of profilin as major allergen from Platanus acerifolia pollen.
The Platanus acerifolia (P. acerifolia) pollen is one of the most common causes of allergic respiratory symptoms in China. However, the allergenic components in P. acerifolia are not fully studied yet. The study aimed to determine the molecular and immunochemical characterization of the profilin from P. acerifolia pollen. The coding sequence of profilin was amplified, cloned, and then expressed in Escherichia coli BL21 cells and purified by nickel affinity chromatography. Protein refolding was followed by structural characterization and homology 3D model building. The allergenicity and cross-reactivity were assessed by ELISA, immunoblotting, or basophil activation test (BAT) using the sera of P. acerifolia allergic patients. The cDNA sequence of profilin was cloned with a 396 bp open reading frame coding for 131 amino acids. The molecular weight of the profilin was approximately 14 kDa, and the predicted structure consisted of 3 α-helixes and 7 β-sheets. Physicochemical analysis indicated the profilin was a stable, relatively thermostable, and relatively conserved protein. The allergenicity determined by ELISA, western blot, and BAT suggested 76.9% (30/39) of the P. acerifolia pollen allergic patients displayed specific IgE recognition of the profilin. The profilin shared > 80% sequence identity with Pop n 2, the profilin from Populus nigra, and observed a significant cross-reactivity with Pop n 2 in IgE-inhibition assay. Profilin, as one of the major component allergens in P. acerifolia pollen, was identified and characterized at molecular and immunochemical levels in this study. These findings would contribute to developing diagnostic and therapeutic strategies for P. acerifolia pollen allergic patients.


Balance disorders as potential confounders associated with an increased risk of acute cerebrovascular accidents.
There is a higher risk of stroke after suffering from balance disorders (BDs) such as vertigo or dizziness. The causal relationship remains unclear due to the limited scope of the existing studies and the high prevalence of cardiovascular risk factors (CVRFs) in BD patients. The objective of this study is to clarify the role that BDs seem to have in the development of acute cerebrovascular accidents (ACAs). This is an observational prospective study. The CVRFs and demographic factors of a sample of our population were noted. Five clusters of patients were tracked over the course of 2 years to detect and diagnose BDs and ACAs. The causal relationships between the CVRFs, BDs and ACAs were analyzed in a univariate analysis. A logistic regression multivariant analysis was performed on those variables that reached statistical significance. The sample included 7886 participants and 31 ACAs were recorded. CVRFs that reached statistical significance included age ≥ 60, hypertension, diabetes mellitus, dyslipidemia, ischemic heart disease, atrial fibrillation and previous ACAs. The relationship between BDs and ACAs always reached statistical significance, regardless of how the BD variable was defined. Five different multivariate analyses were performed, but in none of them did the BD variables significantly reduce the deviance and thus, they were not taken into account when building the final model. This study shows that BDs are probably confounders that are closely linked to other CVRFs and they are also useful red flags to identify patients at a higher risk of suffering from ACAs.


A pantographic reproducibility index for use in diagnosing temporomandibular joint dysfunction: a report on research.
The pantographic reproducibility index (PRI) has been developed to quantitate incoordinated mandibular movements; one of the signs and symptoms of TMJ dysfunction. The PRI has been proven valid clinically in controlled research using more than 200 patients and scoring more than 2300 pantographic tracings during the past 10 years. The PRI can be used to determine (1) the presence or absence of TMJ dysfunction; (2) the success of treatment modalities such as occlusal splints, occlusal adjustments, and restorative treatments; (3) the prevalence of TMJ dysfunction; and (4) the level of TMJ dysfunction on experimental patients.


[Odontoiatric pathology and bacterial endocarditis: risk factors and prevention].
The risk of bacterial endocarditis in dentistry is examined and responsibilities for prevention clarified. A review of the principal chemotherapeutic protocols currently followed by International Cardiologist Associations is presented.


Leg preference associated with protective stepping responses in older adults.
Asymmetries in dynamic balance stability have been previously observed. The goal of this study was to determine whether leg preference influenced the stepping response to a waist-pull perturbation in older adult fallers and non-fallers. 39 healthy, community-dwelling, older adult (>65 years) volunteers participated. Participants were grouped into non-faller and faller cohorts based on fall history in the 12 months prior to the study. Participants received 60 lateral waist-pull perturbations of varying magnitude towards their preferred and non-preferred sides during quiet standing. Outcome measures included balance tolerance limit, number of recovery steps taken and type of recovery step taken for perturbations to each side. No significant differences in balance tolerance limit (P ≥ 0.102) or number of recovery steps taken (η(2)partial ≤ 0.027; P ≥ 0.442) were observed between perturbations towards the preferred and non-preferred legs. However, non-faller participants more frequently responded with a medial step when pulled towards their non-preferred side and cross-over steps when pulled towards their preferred side (P=0.015). Leg preference may influence the protective stepping response to standing balance perturbations in older adults at risk for falls, particularly with the type of recovery responses used. Such asymmetries in balance stability recovery may represent a contributing factor for falls among older individuals and should be considered for rehabilitation interventions aimed at improving balance stability and reducing fall risk.


Animacy and competition in relative clause production: a cross-linguistic investigation.
This work investigates production preferences in different languages. Specifically, it examines how animacy, competition processes, and language-specific constraints shape speakers' choices of structure. English, Spanish and Serbian speakers were presented with depicted events in which either an animate or inanimate entity was acted upon by an agent. Questions about the affected participant in these events prompted the production of relative clauses identifying these entities (e.g., the bag the woman is punching). Results indicated that in English, animacy plays a strong role in determining the choice of passive structures. In contrast, it plays a less prominent role in Spanish and Serbian structure choices, where more active structures were produced to varying degrees. Critically, the semantic similarity between the agent and the patient of the event correlated with the omission of the agent in all languages, indicating that competition resulted in the agent's inhibition. Similarity also correlated with different functional choices in Spanish. The results suggest that similarity-based competition may influence various stages of production planning but its manifestations are constrained by language-specific grammatical options. Implications for models of sentence production and the relationship between production and comprehension are discussed.


Model-Based Risk Prediction of Rivaroxaban with Amiodarone for Moderate Renal Impaired Elderly Population.
Increased bleeding risk was found associated with concurrent prescription of rivaroxaban and amiodarone. We previously recommended dose adjustment for rivaroxaban utilizing a physiologically based pharmacokinetic (PBPK) modeling approach. Our subsequent in vitro studies discovered the pivotal involvement of human renal organic anion transporter 3 (hOAT3) in the renal secretion of rivaroxaban and the inhibitory potency of amiodarone. This study aimed to redefine the disease-drug-drug interactions (DDDI) between rivaroxaban and amiodarone and update the potential risks. Prospective simulations were conducted with updated PBPK models of rivaroxaban and amiodarone incorporating hOAT3-related parameters. Simulations to recapitulate previously explored DDDI in renal impairment showed a higher bleeding tendency in all simulation scenarios after integrating hOAT3-mediated clearance into PBPK models. Further sensitivity analysis revealed that both hOAT3 dysfunction and age could affect the extent of DDDI, and age was shown to have a more pivotal role on rivaroxaban in vivo exposure. When amiodarone was prescribed along with our recommended dose reduction of rivaroxaban to 10 mg in moderate renal impaired elderly people, it could result in persistently higher rivaroxaban peak concentrations at a steady state. To better manage the increased bleeding risk among such a vulnerable population, a dose reduction of rivaroxaban to 2.5 mg twice daily resulted in its acceptable in vivo exposure. Close monitoring of bleeding tendency is essential for elderly patients with moderate renal impairment receiving co-prescribed rivaroxaban and amiodarone. Further dose reduction is recommended for rivaroxaban to mitigate this specific DDDI risk.


A segmentation and classification scheme for single tooth in MicroCT images based on 3D level set and k-means+.
Accurate classification of different anatomical structures of teeth from medical images provides crucial information for the stress analysis in dentistry. Usually, the anatomical structures of teeth are manually labeled by experienced clinical doctors, which is time consuming. However, automatic segmentation and classification is a challenging task because the anatomical structures and surroundings of the tooth in medical images are rather complex. Therefore, in this paper, we propose an effective framework which is designed to segment the tooth with a Selective Binary and Gaussian Filtering Regularized Level Set (GFRLS) method improved by fully utilizing 3 dimensional (3D) information, and classify the tooth by employing unsupervised learning i.e., k-means++ method. In order to evaluate the proposed method, the experiments are conducted on the sufficient and extensive datasets of mandibular molars. The experimental results show that our method can achieve higher accuracy and robustness compared to other three clustering methods.


An amphipathic peptide with antibiotic activity against multidrug-resistant Gram-negative bacteria.
Peptide antibiotics are an abundant and synthetically tractable source of molecular diversity, but they are often cationic and can be cytotoxic, nephrotoxic and/or ototoxic, which has limited their clinical development. Here we report structure-guided optimization of an amphipathic peptide, arenicin-3, originally isolated from the marine lugworm Arenicola marina. The peptide induces bacterial membrane permeability and ATP release, with serial passaging resulting in a mutation in mlaC, a phospholipid transport gene. Structure-based design led to AA139, an antibiotic with broad-spectrum in vitro activity against multidrug-resistant and extensively drug-resistant bacteria, including ESBL, carbapenem- and colistin-resistant clinical isolates. The antibiotic induces a 3-4 log reduction in bacterial burden in mouse models of peritonitis, pneumonia and urinary tract infection. Cytotoxicity and haemolysis of the progenitor peptide is ameliorated with AA139, and the 'no observable adverse effect level' (NOAEL) dose in mice is ~10-fold greater than the dose generally required for efficacy in the infection models.


Extreme expansion of NBS-encoding genes in Rosaceae.
Nucleotide binding site leucine-rich repeats (NBS-LRR) genes encode a large class of disease resistance (R) proteins in plants. Extensive studies have been carried out to identify and investigate NBS-encoding gene families in many important plant species. However, no comprehensive research into NBS-encoding genes in the Rosaceae has been performed. In this study, five whole-genome sequenced Rosaceae species, including apple, pear, peach, mei, and strawberry, were analyzed to investigate the evolutionary pattern of NBS-encoding genes and to compare them to those of three Cucurbitaceae species, cucumber, melon, and watermelon. Considerable differences in the copy number of NBS-encoding genes were observed between Cucurbitaceae and Rosaceae species. In Rosaceae species, a large number and a high proportion of NBS-encoding genes were observed in peach (437, 1.52%), mei (475, 1.51%), strawberry (346, 1.05%) and pear (617, 1.44%), and apple contained a whopping 1303 (2.05%) NBS-encoding genes, which might be the highest number of R-genes in all of these reported diploid plant. However, no more than 100 NBS-encoding genes were identified in Cucurbitaceae. Many more species-specific gene families were classified and detected with the signature of positive selection in Rosaceae species, especially in the apple genome. Taken together, our findings indicate that NBS-encoding genes in Rosaceae, especially in apple, have undergone extreme expansion and rapid adaptive evolution. Useful information was provided for further research on the evolutionary mode of disease resistance genes in Rosaceae crops.


Cancerostatics. III. Synthesis and some chemical transformations of 3-cyano-5(pyridyl-4.)pyrid-2-one.
In reaction of 3-dimethylamino-2-(pyridyl-4')acrolein with cyanoacetic acid and malononitrile new derivatives of 3,4'-dipyridyl were obtained. The synthesis of pyridyl-4-cyanoacetaldehyde 2 is also described. One of these compounds (8) showed significant cytostatic activity against transplanted Ehrlich ascites carcinoma and Nemeth-Kellner lymphoma.


The development of soma size changes in the C-laminae of the cat lateral geniculate nucleus following monocular deprivation.
This study examined the pattern of soma size changes in the cat dorsal lateral geniculate nucleus (dLGN) from 4 weeks of age to adulthood following monocular lid suture at two weeks of age. Different patterns of soma size changes were found between the A-laminae and C-laminae. In layers A, A1, and C significant soma size differences were found between the deprived and non-deprived laminae by 4 weeks of age. However, the magnocellular portion of layer C was affected more by deprivation than the parvocellular portion. Layer C1 did not reveal significant soma size changes until 20 weeks of age. Layer C2 did not exhibit any soma size changes at any age. These differential responses to monocular deprivation suggest different time courses of development among the dLGN laminae.


Derivatization and high-performance liquid chromatographic determination of urinary glycolic acid.
A high-performance liquid chromatographic method for the determination of urinary glycolic acid is proposed, based on pre-column derivatization with phenylhydrazine coupled with the enzymatic oxidation of glycolate to glyoxylate. The phenylhydrazone formed is separated by liquid chromatography and detected at 324 nm. The minimum detectable concentration of glycolate was 10.0 mumol/l. The recovery of glycolate added to urine averaged 96.1%. The day-to-day coefficients of variation calculated by analysis of two urine samples with normal and high glycolate contents were 4.6 and 7.5%, respectively. Results of analyses of urine samples from healthy persons, idiopathic calcium stone formers and Type I primary hyperoxaluria patients are reported.


Maternal-Fetal Hepatitis E Transmission: Is It Underestimated?
Hepatitis E virus (HEV) is an enterically transmitted virus; and several modes of transmission have been proposed, including blood transfusion, person to person transmission, and transplacental transmission. HEV during pregnancy is associated with an unfavorable prognosis for mothers and in severe cases can cause acute fulminate hepatitis and death. Transplacental transmission of HEV usually results in unfavorable outcomes of pregnancy, mainly fetal loss, preterm labor, and hepatic dysfunction in neonates. In this review, we will summarize the effects of HEV on maternal-fetal health in various clinical situations.


Physical properties of the nucleus studied by micropipette aspiration.
Understanding the physical properties of the cell nucleus is critical for developing a deeper understanding of nuclear structure and organization as well as how mechanical forces induce changes in gene expression. We use micropipette aspiration to induce large, local deformations in the nucleus, and microscopy to image nuclear shape as well as the response of fluorescently labeled components in the inner nucleus (chromatin and nucleoli) and the nuclear envelope (lamins and membranes). By monitoring the response of nuclear structures to these deformations, we gain insights into the material properties of the nucleus. Here we describe the experimental protocols for micropipette aspiration of nuclei in living cells as well as isolated nuclei. In addition to confocal imaging, deformed nuclei can be imaged by brightfield or epifluorescence microscopy.


On helicases and other motor proteins.
Helicases are molecular machines that utilize energy derived from ATP hydrolysis to move along nucleic acids and to separate base-paired nucleotides. The movement of the helicase can also be described as a stationary helicase that pumps nucleic acid. Recent structural data for the hexameric E1 helicase of papillomavirus in complex with single-stranded DNA and MgADP has provided a detailed atomic and mechanistic picture of its ATP-driven DNA translocation. The structural and mechanistic features of this helicase are compared with the hexameric helicase prototypes T7gp4 and SV40 T-antigen. The ATP-binding site architectures of these proteins are structurally similar to the sites of other prototypical ATP-driven motors such as F1-ATPase, suggesting related roles for the individual site residues in the ATPase activity.


Clinical comparability between the CFC and HFA budesonide pressurised metered-dose inhalers in paediatric patients with asthma: a randomised controlled trial.
To evaluate the efficacy and tolerability of a novel hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) formulation of budesonide (Pulmicort) versus the conventional chlorofluorocarbon (CFC) pMDI formulation in paediatric patients with asthma. This was a Phase III, multicentre, 12-week, double-blind, randomised, parallel-group study involving children (6-12 years of age) with mild to moderate asthma. Patients received either budesonide HFA pMDI or budesonide CFC pMDI 200 mug twice daily, with or without a spacer (NebuChamber/Nebunette). Primary efficacy endpoint: mean percentage change in forced expiratory volume in 1 second (FEV(1)) from baseline to week 12. Secondary efficacy endpoints included changes in FEV(1) per cent of predicted normal, forced vital capacity, morning and evening peak expiratory flow rate, asthma symptoms and use of rescue medication. A total of 159 patients received treatment (HFA 77, CFC 82). For mean percentage change in FEV(1) from baseline to week 12, the difference between the treatments (CFC pMDI - HFA pMDI) was -3.1% (95% confidence interval [CI] -8.0% to 1.8%) for the full analysis set and was not affected by spacer use. The upper CI was < 10% (the predefined non-inferiority margin), so non-inferiority was demonstrated. Improvements in the secondary efficacy endpoints with both budesonide formulations were not significantly different. In both groups there were similar numbers of adverse events and no evidence of oral candidiasis at week 12. Treatment with budesonide HFA pMDI is effective and well tolerated in children with asthma and is clinically comparable to budesonide CFC pMDI.


Sub-brow skin excision Combined with retro-orbicularis fat resection: A Technique for upper eyelid bulkiness and laxity correction.
Many people are characterized by a swollen appearance and loose skin of upper eyelids, especially Asians. Retro-orbicularis oculus fat (ROOF) lying in the lateral canthus area is a critical factor of the bulkiness formation. Although several approaches have been reported, most of them intend to remove orbicularis muscle and preaponeurotic fat through a double-eyelid incision, leaving ROOF untreated. Consequently, an unnatural eyelid fold is formed and the lateral supraorbital region remains bloated . Sixty-seven patients underwent sub-brow skin excision combined with ROOF resection. The key point was to excise the loose skin and thick ROOF through an incision along with the lower 1/3 of the eyebrow. Surgical outcomes were evaluated 6 months postoperatively by the heights of the designed line from the palpebral margin to the pupil center (HPPC), medial cornea (HPMC), and lateral canthus (HPLC). The pinch test, photographs, and complications were also recorded. The preoperative average HPPC, HPMC, and HPLC were 9.68 ± 1.73, 7.68 ± 1.24, and 6.82 ± 1.12 mm, while the postoperative average measurements were 7.25 ± 0.51, 5.99 ± 0.54, and 5.54 ± 0.61 mm, respectively. The result of the pinch test was improved and postoperative scarring was inconspicuous. Two patients had transient numbness in the eyebrow region that subsided within seven days. Two patients had slight asymmetry of eyebrow position but did not need a second operation. Sub-brow skin excision combined with ROOF resection is an effective technique for improving upper eyelid bulkiness and skin excess with low revision rates.


Morphological assessment of neurite outgrowth in hippocampal neuron-astrocyte co-cultures.
Neurite outgrowth is a fundamental event in brain development, as well as in regeneration of damaged neurons. Astrocytes play a major role in neuritogenesis, by expressing and releasing factors that facilitate neurite outgrowth, such as extracellular matrix proteins, and factors that can inhibit neuritogenesis, such as the chondroitin sulfate proteoglycan neurocan. In this unit we describe a noncontact co-culture system of hippocampal neurons and cortical (or hippocampal) astrocytes for measurement of neurite outgrowth. Hippocampal pyramidal neurons are plated on glass coverslips, which are inverted onto an astrocyte feeder layer, allowing exposure of neurons to astrocyte-derived factors without direct contact between these two cell types. After co-culture, neurons are stained and photographed, and processes are assessed morphologically using Metamorph software. This method allows exposing astrocytes to various agents before co-culture in order to assess how these exposures may influence the ability of astrocytes to foster neurite outgrowth.


The clinical features of spasms in patients with a cervical cord injury.
A study concerning subjective symptoms of spasms which occur during 24 hours was carried out in 13 quadriplegic patients. All had spasms. Tonic and clonic spasms occurred involving their limbs and trunk. Extensor spasms occurred more often in the lower limbs than in the upper limbs. The duration of spasms was 8 seconds on average and the frequency was 15 times on average per day. The spasms which were severe tended to last longer in duration and were more frequent in occurrence. No spasms occurred without a trigger. The activities in daily living were interfered with by spasms in most patients. Most of these activities also triggered spasms.


Absent pulmonary valve syndrome with aortic regurgitation in a 50-year-old man.
A 50-year-old man was diagnosed as having absent pulmonary valve syndrome with aneurysmal dilatation of the pulmonary arteries. He also had a large subaortic ventricular septal defect and severe aortic regurgitation. He underwent successful intracardiac repair and aortic valve replacement. This case is presented in view of its rarity and controversies in the surgical management.


Antigenicity of subregions of recombinant bovine leukemia virus (BLV) glycoprotein gp51 for antibody detection.
Bovine leukemia virus (BLV) is an enveloped virus, found worldwide that can infect cattle and induce many subclinical symptoms and malignant tumors. BLV infection causes severe economic losses in the cattle industry. The identification of BLV-infected cattle for segregation or elimination would be the most effective way to halt the spread of BLV infection on farms, owing to the lack of effective treatments and vaccines. Therefore, antibody detection against the viral glycoprotein gp51 is an effective method for diagnosing BLV-infected animals. In this study, ten different subregions of gp51 containing a common B cell epitope are vital for developing antigens as epitope-driven vaccine design and immunological assays. Such antigens were produced in Escherichia coli expression system to react with antibodies in the serum from BLV-infected cattle and compete for antigenicity. Recombinant His-gp5156-110 and gp5133-301(full) had the same sensitivity in BLV-positive sera, indicating that antibodies responded to the limited subregion of viral gp51, a common B cell epitope. This finding provides significant information for antigen selection in BLV to use in antibody detection assays. Further studies are needed to evaluate the antigenicity of His-gp5156-110 and gp5133-301(full) as antigens for antibody detection assays using a larger number of bovine serum samples.


Zinc hydroxide stimulates superoxide production by rat alveolar macrophages.
The effect of zinc hydroxide on superoxide (O2-) production by rat alveolar macrophages was determined by chemiluminescence and by cytochrome c reduction. Zinc ions had no effect on the chemiluminescence of unstimulated alveolar macrophages. By contrast, zinc hydroxide (ZnOH2), a neutralized form of zinc ions, increased the chemiluminescence level and O2- release. Increased O2- release was inhibited by pertussis toxin, isoquinoline sulfonamide and pretreatment with EGTA. These findings indicate that zinc hydroxide formation from zinc compounds can stimulate the O2- production by alveolar macrophages by receptor-mediated and Ca(2+)-dependent process.


Synthetic dibenzylideneketones as promising anti-herpes simplex virus type 1 agents.
New antiviral agents for the treatment of herpes simplex virus type 1 (HSV-1) infection, which causes a highly prevalent and incurable disease, are needed. Here, we report for the first time the in vitro anti-HSV-1 activity of two dibenzylideneketone compounds: DBK1 and DBK2. DBK1 demonstrated virucidal activity, and high-resolution scanning electron microscopy showed that it caused morphological changes in the HSV-1 envelope. DBK2 was able to reduce HSV-1 plaque size in vitro. The DBKs are promising anti-HSV-1 candidates, as they exhibit low toxicity and exert an antiviral effect by acting at the early stages of HSV-1-host cell interaction.


Association of Dysfunctional Eating Patterns and Metabolic Risk Factors for Cardiovascular Disease among Latinos.
Latinos are at high risk for cardiovascular disease (CVD). Identifying behavioral factors associated with CVD risk in this population may provide novel targets for further research to reduce chronic disease disparities. Dysfunctional eating patterns (emotional eating [EE], uncontrolled eating [UE], and cognitive restraint of eating [CR]) may be associated with CVD risk but little is known about this relationship in Latinos. The aim of this study was to examine associations between dysfunctional eating patterns and metabolic risk factors for CVD in Latinos. The study used a cross-sectional design. Latino individuals (n=602), aged 21 to 84 years, were enrolled in the study from September 2011 to May 2013 from a community health center that serves 80% to 85% of the Latino population in Lawrence, MA. Individuals with complete data were included in this analysis (n=578). Dysfunctional eating patterns were measured with the Three Factor Eating Questionnaire-R18V2. CVD risk factors examined included obesity assessed by body mass index and waist circumference and diagnoses of type 2 diabetes, hypertension, and hyperlipidemia abstracted from electronic health records. Multivariable logistic and Poisson regressions adjusting for age, sex, perceived income, employment, education, physical activity, and perceived stress were performed. The no dysfunctional eating category (ie, no EE, no UE, or no CR) was used as the reference category in all analyses. High EE was associated with greater odds of obesity (odds ratio [OR] 2.19, 95% CI 1.38 to 3.45) and central obesity (OR 2.97, 95% CI 1.81 to 4.87), and diagnosis of type 2 diabetes (OR 1.99, 95% CI 1.13 to 3.48) and hypertension (OR 2.01, 95% CI 1.16 to 3.48). High UE was associated with obesity (OR 1.96, 95% CI 1.20 to 3.21) and central obesity (OR 2.33, 95% CI 1.38 to 3.94). Low and high CR were associated with obesity (OR 2.26, 95% CI 1.43 to 3.56 and OR 2.77, 95% CI 1.75 to 4.37, respectively) and central obesity (OR 2.04, 95% CI 1.25 to 3.32 and 2.51, 95% CI 1.54 to 4.08, respectively) and diagnosis of type 2 diabetes (OR 1.83, 95% CI 1.05 to 3.16 and OR 2.73, 95% CI 1.58 to 4.70, respectively) and hyperlipidemia (OR 1.94, 95% CI 1.16 to 3.24 and OR 2.14, 95% CI 1.28 to 3.55, respectively). Lastly, high EE and low and high CR were associated with increased odds of having a greater number of metabolic CVD risk factors (incidence-rate ratio [IRR] 1.33, 95% CI 1.13 to 1.58; IRR 1.34, 95% CI 1.13 to 1.58; and IRR 1.44, 95% CI 1.22 to 1.71, respectively). Dysfunctional eating patterns were positively associated with metabolic CVD risk factors in this Latino sample, with dose-response relationships for some associations. Future studies are needed to determine whether dysfunctional eating patterns influence CVD risk factors among Latinos.


Quantification of pressure gradients across stenotic valves by Doppler ultrasound.
Two-dimensional echocardiography has proven very useful in assessing valvular heart disease, but the technique is limited in certain groups of patients and is unable to quantify a transvalvular pressure gradient. Advances in the Doppler ultrasound techniques have made it possible to noninvasively measure velocity of flow across a stenotic heart valve and to calculate the pressure gradient. A commercially available, continuous and pulse wave Doppler instrument was utilized to assess the transvalvular pressure gradient in patients with mitral and aortic stenosis and the transmitral pressure half-time to calculate mitra valve area. Thirty-five consecutive adult patients with suspected aortic stenosis and 30 adult patients with suspected mitral stenosis underwent Doppler ultrasound examination within 24 hours of cardiac catheterization. An adequate Doppler examination was obtained in 81% of the patients with aortic stenosis, with a correlation between the Doppler-derived transaortic gradient and the catheterization-derived gradient of 0.94. The Doppler-measured gradient accurately separated those patients with significant aortic stenosis (gradients of greater than 50 mm Hg) from those patients with noncritical aortic stenosis. Similarly, an adequate Doppler examination was obtained in 90% of the adult patients with mitral stenosis. There was also close correlation between the mitral valve area and mean pressure gradient measured by the Doppler technique and that obtained at the time of cardiac catheterization (r = 0.87 and 0.85, respectively). The Doppler technique proved to be useful in those patients who had also undergone prior mitral commissurotomy. This study confirms that the combined continuous pulse wave Doppler technique will serve as a valuable addition to the diagnostic capabilities offered by echocardiography.


Effects of nectar concentration on butterfly feeding: measured feeding rates for Thymelicus lineola (Lepidoptera: Hesperiidae) and a general feeding model for adult Lepidoptera.
Field observations of the adult European skipper, Thymelicus lineola (Ochs), feeding on concentrated nectars (40-65% sucrose) from a variety of flower species led us to question recent literature stating that butterflies feed primarily, and most effectively, on dilute nectars. Rate of sucrose solution intake, volume consumed and feeding duration were measured for males and females at 25 and 35°C under laboratory conditions. As sucrose concentration increased, the volume of solution ingested per meal first increased and then decreased gradually, while sucrose intake was highest at concentrations ≧40%. Females fed more than males at all concentrations >10% while temperature had no significant effect on meal size. Feeding duration increased with concentration, was shorter at 35 than at 25°C, and was longer for females than males.The rate of volume intake decreased as concentration incresed, but not nearly as rapidly as predicted by earlier models. Rates did not differ between the sexes but were faster at 35 than 25°C. This increase was contributed to equally by a reduction in viscosity and an increase in power output of the cibarial pump. The form of the relations was similar, with maximum rate of sucrose intake occurring at 40% sucrose.A new mathematical model was developed to describe the rate - concentration relation based on the Hagen-Poiseuille equation for laminar fluid flow through pipes. Our model differs from previous models principally in that the power output of the insect's cibarial pump remains relatively constant while the pressure drop created by the pump to induce suction is highly variable. This change results in a very different feeding rate - sucrose concentration function with the optimal rate of sucrose intake at a concentration of approximately 40%. The model indicates that the same relation should hold for a wide range of proboscis shape and size and type of suction pump, and should therefore be applicable to all other nectar feeders with sucking mouth parts. Independent verifications of the model were carried out by measuring the rate of uptake of sucrose solutions of the adult common armyworm, Pseudaletia unipuncta (Haw.), and of human subjects using a volumetric pipette, both of which gave an excellent fit.Nectar concentrations which correspond to optimal rates of sucrose intake should be highly preferred by insects with high feeding costs, those which are time-limited, or which are very vulnerable while feeding. High transport costs and severe water stress may shift preferences to higher and lower concentrations respectively.


The influence of salinity on the kinetics of NH inf4sup+ uptake in Spartina alterniflora.
The effects of short- and long-term exposure to a range in concentration of sea salts on the kinetics of NH inf4sup+ uptake by Spartina alterniflora were examined in a laboratory culture experiment. Long-term exposure to increasing salinity up to 50 g/L resulted in a progressive increase in the apparent Km but did not significantly affect Vmax (mean Vmax=4.23±1.97 μmole·g-1·h-1). The apparent Km increased in a nonlinear fashion from a mean of 2.66±1.10 μmole/L at a salinity of 5 g/L to a mean of 17.56±4.10 μmole/L at a salinity of 50 g/L. These results suggest that the long-term effect of exposure to total salt concentrations within the range 5-50 g/L was a competitive inhibition of NH inf4sup+ uptake in S. alterniflora. No significant NH inf4sup+ uptake was observed in S. alterniflora exposed to 65 g/L sea salts. Short-term exposure to rapid changes in salinity significantly affected both Vmax and Km. Reduction of solution salinity from 35 to 5 g/L did not change Vmax but reduced Km by 71%. However, exposing plants grown at 5 g/L salinity to 35 resulted in an decrease in Vmax of approximately 50%. Exposure of plants grown at 35 g/L to a total sea salt concentration of 50 g/L for 48h completely inhibited uptake of NH inf4sup+ . For both experiments, increasing salinity led to an increase in the apparent Km similar to that found in response to long-term exposure. Our data are consistent with a conceptual model of changes in the productivity of S. alterniflora in the salt marsh as a function of environmental modification of NH inf4sup+ uptake kinetics.


[Energy restriction reduces oxidative stress in the aorta and heart and corrects the atherogenic risk in obese rat].
The aim was to see if 40% of caloric restriction can improve in rats, the oxidative stress induced by a high fat diet on liver, heart and aorta, and have a positive impact on the lipoproteins-cholesterol contents. Male Wistar rats (n=12) consumed at weaning obesegenic diet. The obese rats were divided into two groups (n=6) each consumed for 4 weeks a normocaloric diet (1,60 MJ) or a calorie restricted diet (40% of energy of the standard diet [0.96 MJ]). A control group (n=6) was fed a standard diet during the experiment. Caloric restriction decreased cholesterol and low-density lipoproteins-cholesterol, whereas the high-density lipoproteins-cholesterol was elevated. Levels of cholesterol in the aorta and heart were lowered in the group that consumed caloric restriction compared to normocaloric diet. The values of thiobarbituric acid reactive substances and hydroperoxides were lowered in the aorta and the heart. The caloric restriction compared to normocaloric diet increased positively the superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities in the heart and those of catalase and superoxide dismutase in aorta. In obese rats, caloric restriction may play a role in the antioxidant defense of cardiovascular system by reducing proatherogenic cholesterol and lipid peroxidation and increasing the antioxidant activity of some enzymes, which was in favor of reduction of cardiometabolic risk associated with obesity.


Validation of Point-of-Care ultrasound in the diagnosis of a diaphragmatic hernia.
Point-of-care ultrasound (POCUS) is a sensitive, specific tool for early diagnosis of diaphragm pathology in critically ill patients. We report the case of a patient with a history of iatrogenic diaphragmatic hernia who was admitted to the Resuscitation Unit after an emergency exploratory laparotomy. As the diagnosis of diaphragmatic hernia had already been confirmed, we determined the POCUS features that establish the diagnosis of diaphragmatic hernia: (1) normal bilateral diaphragmatic shortening fraction; (2) decreased diaphragmatic excursion; and (3) cephalic position of the diaphragmatic dome (4) greater in supine than in sitting position. We also outline a systematic ultrasound examination of the diaphragm and a POCUS-based differential classification of diaphragmatic dysfunction based on the functional integrity of the peripheral muscle and central diaphragmatic tendon in critically ill patients.


A low-cost paper-based synthetic biology platform for analyzing gut microbiota and host biomarkers.
There is a need for large-scale, longitudinal studies to determine the mechanisms by which the gut microbiome and its interactions with the host affect human health and disease. Current methods for profiling the microbiome typically utilize next-generation sequencing applications that are expensive, slow, and complex. Here, we present a synthetic biology platform for affordable, on-demand, and simple analysis of microbiome samples using RNA toehold switch sensors in paper-based, cell-free reactions. We demonstrate species-specific detection of mRNAs from 10 different bacteria that affect human health and four clinically relevant host biomarkers. We develop a method to quantify mRNA using our toehold sensors and validate our platform on clinical stool samples by comparison to RT-qPCR. We further highlight the potential clinical utility of the platform by showing that it can be used to rapidly and inexpensively detect toxin mRNA in the diagnosis of Clostridium difficile infections.


Cardiac assessment by first-pass angioscintigraphy in conjoined thoracopagus twins.
Dynamic computerized heart studies using 99Tc-DTPA demonstrated a joined heart in conjoined thoracopagus twins. In the case presented, the electrocardiogram, dynamic radioactive study, and the cardiac catheterization all gave basically the same results and correlated well with the postmortem examination. The dynamic study is presented in detail, stressing its advantage as a noninvasive and reliable procedure in the primary cardiac assessment of conjoined twins.


Problems of caregiving spouses of patients with dementia.
Twenty-six caregiving spouses of patients with dementia in the Netherlands were interviewed to better understand their problems and needs. Special attention was paid to the information the caregivers received from their general practitioner. Nineteen caregivers indicated that they received little or no information about the disease and its possible consequences. Furthermore, they experienced many problems, because of the disease and the daily care they provided; eleven caregivers indicated a decrease in social contact, which resulted in further problems. Caregivers who sought professional help at an early stage experienced fewer problems in providing daily care. The results of this project suggest that in future health education policy special attention should be paid to the role of the general practitioner and to the importance of a caregiver's social network.


The relationship between the capacity to evolve oxygen and the variable fluorescence of chlorophyll after microsecond illumination in Chlorella, pea leaves and pea thylakoids.
The relationship between the capacity to evolve oxygen following a flash of a few microseconds duration and the variable fluorescence of chlorophyll was determined in Chlorella, leaf disks of peas, and thylakoids of pea leaves. It was found that this relationship is linear in intact plant material, while it is nonlinear in thylakoids. However, in thylakoids, the recovery of the capacity to evolve oxygen does not track the decay of the variable yield of Chl a fluorescence. This nonlinear relationship in thylakoids results from a reduced rate in the oxygen evolution reaction with no change in the decay of the variable yield of Chl a fluorescence. From a new application of the matrix analysis method to oxygen flash yields, the S1'-->S2, S2'-->S3 and S3'-->S4-->S0 transitions are found to be slowed or delayed in pea thylakoids and this underlies the slower rate of the recovery of the capacity to evolve oxygen in thylakoids. It is concluded that in intact cells the QA-QB(-)-->QA QB- reaction was rate-limiting for the recovery of the capacity to evolve oxygen, the equal energy-transfer hypothesis and the sequential double-hit model are valid in pea leaves and that the apparent invalidity in thylakoids is actually due to slowing of reaction steps in the oxygen evolution mechanism.


Apoptosis and proinflammatory cytokine responses of primary mouse microglia and astrocytes induced by human H1N1 and avian H5N1 influenza viruses.
Patients with an influenza virus infection can be complicated by acute encephalopathy and encephalitis. To investigate the immune reactions involved in the neurocomplication, mouse microglia and astrocytes were isolated, infected with human H1N1 and avian H5N1 influenza viruses, and examined for their immune responses. We observed homogeneously distributed viral receptors, sialic acid (SA)-alpha2,3-Galactose (Gal) and SA-alpha2,6-Gal, on microglia and astrocytes. Both viruses were replicative and productive in microglia and astrocytes. Virus-induced apoptosis and cytopathy in infected cells were observed at 24 h post-infection (p.i.). Expression of IL-1beta, IL-6 and TNF-alpha mRNA examined at 6 h and 24 h p.i. was up-regulated, and their expression levels were considerably higher in H5N1 infection. The amounts of secreted proinflammatory IL-1beta, IL-6 and TNF-alpha at 6 h and 24 h p.i. were also induced, with greater induction by H5N1 infection. This study is the first demonstration that both human H1N1 and avian H5N1 influenza viruses can infect mouse microglia and astrocytes and induce apoptosis, cytopathy, and proinflammatory cytokine production in them in vitro. Our results suggest that the direct cellular damage and the consequences of immunopathological injury in the CNS contribute to the influenza viral pathogenesis.


Outcomes of the management of post-chemotherapy retroperitoneal lymph node dissection-associated anejaculation.
What's known on the subject? and What does the study add? Modern surgical techniques have allowed preservation of fertility in most patients after post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND), but some patients still have infertility after surgery. We reviewed our experience treating infertility in 26 men after PC-RPLND. Using a structured clinical pathway we obtained sperm in 81% of men for use in assisted reproduction. To evaluate the effectiveness of a clinical pathway on sperm retrieval outcomes in patients presenting with infertility after post-chemotherapy (PC) retroperitoneal lymph node dissection (RPLND). We carried out a retrospective review of patients with advanced testicular cancer, presenting with infertility after PC-RPLND in a large reproductive urology practice. We implemented a clinical pathway where pseudoephedrine was first administered. If this medication failed, electroejaculation (EEJ) and/or testicular sperm extraction (TESE) was carried out. The primary outcome was retrieval of sperm for use in assisted reproduction. Four men had retrograde ejaculation, of whom two converted to antegrade ejaculation with medical therapy. In all, 22 patients had failure of emission (FOE) and, of these, no patient converted to antegrade ejaculation with medication. In patients with FOE, sperm was found in 15/20 of those experiencing a successful EEJ. Seven patients underwent TESE for azoospermia on EEJ or no ejaculate on EEJ, three of whom had sperm found on TESE. Sperm was found for assisted reproduction in 81% (21/26) patients. There appears to be no role for the use of pseudoephedrine therapy in patients with FOE after PC-RPLND. The use of a structured clinical pathway may optimize patient care.


Subclinical inflammation after laser in situ keratomileusis in corneal grafts.
To evaluate postoperative inflammatory reaction in the eye after laser in situ keratomileusis (LASIK) in corneal grafts. Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. Ten eyes of 9 patients with penetrating keratoplasty (PKP) and significant postoperative refractive errors and astigmatism had LASIK 22 months or more after the PKP. All patients were treated with the VISX Star excimer laser and the Bausch & Lomb Hansatome microkeratome. Preoperative and early postoperative inflammation was evaluated by quantifying the aqueous flare intensity with a laser flare photometer (Kowa FM-500). A full ophthalmic assessment was also performed before LASIK and up to 6 months postoperatively. The inflammatory response was mild and limited to the first postoperative hour. The mean anterior chamber flare increased from 6.0 photons/millisecond (ph/ms) preoperatively to 14.0 ph/ms at 1 hour and then decreased to 6.7 ph/ms (hour 3), 6.8 ph/ms (day 1), and 8.2 ph/ms (day 7). The mean spherical equivalent (SE) refraction decreased from -3.81 diopters (D) (range -9.63 to -0.25 D) to -0.46 D (range -1.13 to +0.38 D), and the mean preoperative astigmatism decreased from 3.0 D (range 6.5 to 0.5 D) to 0.7 D (range 0.0 to 2.0 D). At the last examination, 9 eyes were within +/-1.0 D (6 within +/-0.5 D) and all were within +/-1.5 D of the intended SE refraction. Three eyes achieved full cylinder correction, and 7 were within +/-1.0 D of the intended correction. Eight eyes had a best corrected visual acuity of 20/40 or better (unchanged or gain of 1 to 4 lines [6], loss of 1 line [1], and loss of 3 lines [1]), and 8 had an uncorrected visual acuity of 20/50 or better. Uneventful LASIK induced subtle, short-lasting anterior chamber flare when measured by the laser flare meter. In corneal grafts, LASIK appeared to be a safe and effective procedure for residual refractive errors.


A comparison of methods for collecting data on performance during discrete trial teaching.
Therapists of children with autism use a variety of methods for collecting data during discrete-trial teaching. Methods that provide greater precision (e.g., recording the prompt level needed on each instructional trial) are less practical than methods with less precision (e.g., recording the presence or absence of a correct response on the first trial only). However, few studies have compared these methods to determine if less labor-intensive systems would be adequate to make accurate decisions about child progress. In this study, precise data collected by therapists who taught skills to 11 children with autism were reanalyzed several different ways. For most of the children and targeted skills, data collected on just the first trial of each instructional session provided a rough estimate of performance across all instructional trials of the session. However, the first-trial data frequently led to premature indications of skill mastery and were relatively insensitive to initial changes in performance. The sensitivity of these data was improved when the therapist also recorded the prompt level needed to evoke a correct response. Data collected on a larger subset of trials during an instruction session corresponded fairly well with data collected on every trial and revealed similar changes in performance.


From 2 Gy to 1 Gy per fraction: sparing effect in rat spinal cord?
Recently published results, from this group, on rat cervical spinal cord, a late responding tissue, indicated no further sparing with lowering the fraction size from 2 to 1.8, 1.5, and 1.3 Gy. In the present experiments a small but probably significant rise in tolerance is suggested, when the dose per fraction was decreased from 2 Gy down to 1 Gy. This rise would however still be much less than what is predicted by the linear quadratic model, based on the experimental data obtained with fraction sizes larger than 2 Gy.


Modulation of the sarcolemmal L-type current by alteration in SR Ca2+ release.
Modulation of the L-type current by sarcoplasmic reticulum (SR) Ca2+ release has been examined in patch-clamped mouse myotubes. Inhibition of SR Ca2+ release by inclusion of ryanodine in the internal solution shifted the half-activating voltage (V0.5) of the L-type current from 1.1 +/- 2.1 to -7.7 +/- 1.7 mV. Ruthenium red in the internal solution shifted V0.5 from 5.4 +/- 1.9 to -3.2 +/- 4.1 mV. Chelation of myoplasmic Ca2+ with 1, 2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid perfusion shifted V0.5 from 4.4 +/- 1.7 to -3.5 +/- 3.3 mV and increased the peak current. Extracellular caffeine (1 mM), which should enhance SR Ca2+ release, significantly decreased the peak Ca2+ current. In low (0.1 mM) internal EGTA, myotube contraction was abolished by internal perfusion with ryanodine or ruthenium red, whereas addition of caffeine to the extracellular solution lowered the contractile threshold, indicating that these modulators of SR Ca2+ release had the expected effects on contraction. Therefore, SR Ca2+ release appears to modulate the sarcolemmal L-type current, suggesting a retrograde communication from the SR to the sarcolemmal L-type channels in excitation-contraction coupling.


Serine/alanine amino acid polymorphism of the L and M cone pigments: effects on Rayleigh matches among deuteranopes, protanopes and color normal observers.
In a first experiment, groups of deuteranopes and protanopes were characterized psychophysically by the slopes of regression lines fitted to yellow intensity settings from their Rayleigh matches. In a second experiment, color normal male subjects were characterized by their 2 and 8 deg Rayleigh match points. All subjects had been previously characterized genetically by the presence of the amino acid serine or alanine at position 180 on their L cone or L/M hybrid opsins. Dichromats and color normal subjects with serine had greater sensitivity to the red primary than did those with alanine. Calculations based on psychophysical results suggest that the substitution of serine by alanine in the L cone opsin or L/M hybrid opsin produces a shift in lambda max of the expressed pigment toward shorter wavelengths by an amount varying between 2.6 and 4.3 nm, with the shifts in lambda max for the dichromats being larger than those for the color normal subjects.


The A2B trial, antibiotic prophylaxis for excision-graft surgery in burn patients: a multicenter randomized double-blind study.
The indication for antibiotic prophylaxis in burn patients remains highly controversial, with no consensus having been reached. The objective of antibiotic prophylaxis is to reduce the risk of postoperative local and systemic infections. Burn surgery is associated with a high incidence of bacteremia, postoperative infections, and sepsis. However, antibiotic prophylaxis exposes patients to the risk of selecting drug-resistant pathogens as well as to the adverse effects of antibiotics (i.e., Clostridium difficile colitis). The lack of data precludes any strong international recommendations regarding perioperative prophylaxis using systemic antibiotics in this setting. The goal of this project is therefore to determine whether perioperative systemic antibiotic prophylaxis can reduce the incidence of postoperative infections in burn patients. The A2B trial is a multicenter (10 centers), prospective, randomized, double-blinded, placebo-controlled study. The trial will involve the recruitment of 506 adult burn patients with a total body surface area (TBSA) burn of between 5 and 40% and requiring at least one excision-graft surgery for deep burn injury. Participants will be randomized to receive antibiotic prophylaxis (antibiotic prophylaxis group) or a placebo (control group) 30 min before the incision of the first two surgeries. The primary outcome will be the occurrence of postoperative infections defined as postoperative sepsis and/or surgical site infection and/or graft lysis requiring a new graft within 7 days after surgery. Secondary outcomes will include mortality at day 90 postrandomization, skin graft lysis requiring a new graft procedure, postoperative bacteremia (within 48 h of surgery), postoperative sepsis, postoperative surgical site infection, number of hospitalizations until complete healing (> 95% TBSA), number of hospitalization days living without antibiotic therapy at day 28 and day 90, and multiresistant bacterial colonization or infection at day 28 and day 90. The trial aims to provide evidence on the efficacy and safety of antibiotic prophylaxis for excision-graft surgery in burn patients. ClinicalTrials.gov NCT04292054 . Registered on 2 March 2020.


Low energy availability reduces myofibrillar and sarcoplasmic muscle protein synthesis in trained females.
Low energy availability (LEA) describes a state where the energy intake is insufficient to cover the energy costs of both exercise energy expenditure and basal physiological body functions. LEA has been associated with various physiological consequences, such as reproductive dysfunction. However, the effect of LEA on skeletal muscle protein synthesis in females performing exercise training is still poorly understood. We conducted a randomized controlled trial to investigate the impact of LEA on daily integrated myofibrillar and sarcoplasmic muscle protein synthesis in trained females. Thirty eumenorrheic females were matched based on training history and randomized to undergo 10 days of LEA (25 kcal · kg fat-free mass (FFM)-1 · day-1 ) or optimal energy availability (OEA, 50 kcal · kg FFM-1 · day-1 ). Before the intervention, both groups underwent a 5-day 'run-in' period with OEA. All foods were provided throughout the experimental period with a protein content of 2.2 g kg lean mass-1 · day-1 . A standardized, supervised combined resistance and cardiovascular exercise training programme was performed over the experimental period. Daily integrated muscle protein synthesis was measured by deuterium oxide (D2 O) consumption along with changes in body composition, resting metabolic rate, blood biomarkers and 24 h nitrogen balance. We found that LEA reduced daily integrated myofibrillar and sarcoplasmic muscle protein synthesis compared with OEA. Concomitant reductions were observed in lean mass, urinary nitrogen balance, free androgen index, thyroid hormone concentrations and resting metabolic rate following LEA. These results highlight that LEA may negatively affect skeletal muscle adaptations in females performing exercise training. KEY POINTS: Low energy availability (LEA) with potential health and performance impairments is widespread among female athletes. We investigated the impact of 10 days of LEA on daily integrated myofibrillar and sarcoplasmic muscle protein synthesis in young, trained females. We show that LEA impairs myofibrillar and sarcoplasmic muscle protein synthesis in trained females performing exercise training. These findings suggest that LEA may have negative consequences for skeletal muscle adaptations and highlight the importance of ensuring adequate energy availability in female athletes.


Multiple gingival recession coverage with an allogeneic biostatic fascia lata graft using the tunnel technique--A histological assessment.
Autogenous connective tissue graft (CTG) that can be safely harvested from the palatal mucosa is limited. Often a multi-stage surgical procedure is needed to cover multiple gingival recessions (MGR). To address this problem, efforts are being made to explore substitutes suitable in size to ensure surgical treatment in a single visit.The objective of the present study was the histological evaluation of tissue in the recipient site after augmentation with a hydrated biostatic Fascia Lata Allograft (FLA) in conjunction with MGR coverage at different healing stages. Twelve patients needing bilateral multiple gingival recession coverage participated in this study. On the test side, the tunnel technique with FLA was used, while CTG, harvested from the palatal mucosa, was used to cover MGR on the control side. Histological assessment was performed 3, 6, 9 and 12 months after augmentation. FLA was well tolerated by the host tissue. During all investigation periods histological images of all patients in the test side revealed a slow process of incorporation of the material grafted in the host connective tissue, showing a colonization of the graft with host fibroblasts and formation of new blood vessels. After 12 months, the graft had fully remodeled into connective tissue of the host gingiva. Apart from the limitations of the present study, we conclude that the FLA may serve as a substitute for autogenous CTG harvested from the palatal mucosa and can be applied as a technique for covering MGR in a single visit.


Development of 4,4'-dibromobinaphthalene analogues with potent photo-inducible DNA cross-linking capability and cytotoxicity towards breast MDA-MB 468 cancer cells.
Photoinduced DNA cross-linking process showed advantages of high spatio-temporal resolution and control. We have designed, synthesized, and characterized several 4,4'-dibromo binaphthalene analogues (1a-f) that can be activated by 350 nm irradiation to induce various DNA damage, including DNA interstrand cross-links (ICL) formation, strand cleavages, and alkaline labile DNA lesions. The degree and types of DNA damage induced by these compounds depend on the leaving groups of the substrates, pH value of the buffer solution, and DNA sequences. The DNA ICL products were produced from the carbocations formed via the oxidation of free radicals photo-generated from 1a-f. Most of these compounds alone exhibited minimum cytotoxicity towards cancer cells while 350 nm irradiation greatly improved their anticancer effects (up to 40-fold enhancement) because of photo-induced cellular DNA damage. This work provides guidance for further design of photo-inducible DNA cross-linking agents as potent photo-activated anticancer prodrugs with good control over toxicity and selectivity.


Symptoms and sleep patterns during inpatient treatment of methamphetamine withdrawal: a comparison of mirtazapine and modafinil with treatment as usual.
The safety and tolerability of modafinil (400 mg/day, n = 14) and mirtazapine (60 mg/day, n = 13) in inpatient methamphetamine withdrawal treatment were compared to a historical comparison group receiving treatment as usual (pericyazine, 2.5-10 mg/day, n = 22). Modafinil and mirtazapine were well tolerated, producing minimal positive subjective effects and no discontinuation effects in this open-label study. Side effects were mild and transient. Aches and pains were most commonly reported by participants receiving mirtazapine, whereas headache was reported by modafinil-treated participants. Modafinil-treated participants had a milder withdrawal syndrome as measured by the Amphetamine Cessation Symptom Assessment and less sleep disturbance in comparison to mirtazapine. Pericyazine was associated with a more severe withdrawal syndrome in comparison to mirtazapine and modafinil. Both modafinil and mirtazapine were safe and well tolerated in methamphetamine withdrawal treatment. However, these early findings of efficacy in symptom amelioration should be replicated in an adequately powered, randomized, placebo-controlled double-blind design.


Effect of exogenous cAMP in the rabbit right auricle.
Isotonic solution of cAMP-Na was applied into spontaneously beating auricular fibres by a cut-end method. Cyclic AMP enhanced the spontaneous rate (mean 48%) and increased the contractile tension (mean 297%). These results provided direct evidence that cAMP is involved in the spontaneous activity and contraction in the heart muscle.


Fluorescent human lung macrophages analyzed by spectral confocal laser scanning microscopy and multispectral cytometry.
Numerous highly fluorescent macrophages (MPhi), designated "smoker cells," exist in the lungs of smokers and subjects who have quit smoking within 5 years. The brightly fluorescent MPhi, however, are not present in the lungs of never smokers. Some investigators have speculated that the intense fluorescence of the MPhi is due to smoke-induced changes in the autofluorescence of naturally occurring (i.e., endogenous) compounds (e.g., NADP). In contrast, other researchers have theorized that the fluorescence is due to the uptake of tobacco smoke particulates (i.e., "tar"). Studies reported herein were undertaken to test the hypothesis that the origin of the MPhi fluorescence could be profiled with the novel technologies afforded by spectral confocal laser scanning microscopy (sCLSM) and multispectral cytometry (MSC). To this end, spectral emissions were obtained by sCLSM of optical sections of live MPhi isolated from fresh surgically excised human lung tissue and in air-dried lung tissue imprints. Confirmation of spectral profiles of these single cell observations was obtained in population studies with the use of high-throughput MSC in which multispectral analyses were performed with three different lasers. Proof of concept experiments demonstrated that relatively nonfluorescent MPhi from the lungs of nonsmokers became fluorescent upon short-term ex vivo exposure to tobacco smoke tar. Summarily, the studies reported herein document that the fluorescence of human lung MPhi is due to tobacco tar.


Social network in long-term diseases: a comparative study in relatives of persons with schizophrenia and physical illnesses versus a sample from the general population.
This study compares the social network of a sample of 709 relatives of patients with schizophrenia, 646 relatives of patients with physical diseases, and 714 lay respondents, recruited in 30 randomly selected Italian areas, stratified for geographic location and population density. Each respondent was asked to fill in the Social Network Questionnaire. The social network was less extended and supportive in relatives of patients with schizophrenia than in those of patients with physical diseases and in the general population. Multivariate analyses revealed that social contacts were similarly reduced in relatives of patients with schizophrenia and physical diseases, while social support was significantly lower in relatives of patients with schizophrenia than in the other two groups. Social resources were higher in young respondents and in those living in rural areas. These results highlight the need to provide the families of those with long-term diseases with interventions aimed at increasing their social resources.


Decreased benzodiazepine receptor and increased GABA level in cortical tubers in tuberous sclerosis complex.
To elucidate the functional characteristics of cortical tubers that might be responsible for epilepsy in tuberous sclerosis complex (TSC), proton magnetic resonance spectroscopy ((1)H-MRS) and [123I] iomazenil (123I-IMZ) single photon emission computed tomography (SPECT) were performed. (1)H-MRS using a clinical 3-tesla magnetic resonance imager was performed in four children with TSC and 10 age-and sex-matched healthy control subjects. A single voxel was set on the right parietal lobe in control subjects. In patients with TSC, a single voxel was set on the epileptogenic tuber in the parietal or temporal lobe, and another voxel was set on the contralateral normal-appearing brain region. N-Acetylaspartate (NAA), myo-Inositol (mIns) and Glutamate (Glu) were analyzed using a conventional STEAM (Stimulated Echo Acquisition Mode) method. The concentration of gamma-aminobutyric acid (GABA) was quantified using MEGA-Point Resolved Spectroscopy (PRESS). Interictal 123I-IMZ SPECT was examined in all four patients with TSC. A significant decrease in the NAA concentration and significant increases in the mIns and GABA concentrations were detected in the cortical tubers of all 4 patients. No significant difference was observed in Glu concentrations. In all of the cortical tubers detected by magnetic resonance imaging, 123I-IMZ binding was significantly decreased. Epileptogenesis in TSC might be caused by decreased inhibition secondary to the decrease in GABA receptors in dysplastic neurons of cortical tubers. An increase in the GABA concentration may compensate for decreased inhibition.


The role of carbon fibre as a flexor tendon substitute.
Experiments have been carried out on Rhesus monkeys to determine the effectiveness of carbon fibre as a flexor tendon substitute. Though the strength, flexibility and capacity to induce a neotendon make carbon fibre an ideal flexor tendon substitute, induction of fibrosis and accompanying increase in bulk of the implant resulted in failure.