Low-dose histidine-tryptophan-ketoglutarate solution for myocardial protection.
The effect of histidine-tryptophan-ketoglutarate (HTK) solution for myocardial protection has been shown in experimental and clinical studies using long ischemic times and high dosages. In our study we compared myocardial protection in isolated coronary bypass with a short period of ischemia using low dosage HTK and cold crystalloid cardioplegia. Each group contained 21 coronary artery disease patients. Cardioplegic solutions were administered antegrade in 10 to 15 mL/kg in one shot. This dosage of HTK was lower than that mentioned in the literature. We measured malondialdehyde, lactate, creatine kinase, creatine kinase-MB, and troponin-I levels. Aortic clamping time in the HTK group 33.9 +/- 8.2 minutes, versus 36.2 +/- 11.3 minutes in the crystalloid cardioplegia group (P > .05). Levels of creatine kinase and malondialdehyde were lower in HTK group at 24 hours and 2 minutes, respectively. Lactate levels were lower in the crystalloid cardioplegia group at 2 minutes in the coronary sinus serum sample, but there were no statistically differences among ischemic serum markers in both groups. Only intervals between aortic clamping and cardiac arrest were statistically meaningful (HTK 63.3 +/- 14.7 seconds versus crystalloid cardioplegia 53.6 +/- 15.6 seconds, P = .044). Our study shows that use of low-dose HTK for short clamping time operations is as successful for myocardial protection as crystalloid cardioplegia. Longer times for fibrillation can be explained with the low levels of potassium in HTK solution, but this length did not cause a biochemical or clinical difference.


Application of a protein-blotting procedure to the study of human glucocorticoid receptor interactions with DNA.
To exert their effects, glucocorticoid receptor complexes interact selectively with DNA sequences known as glucocorticoid regulatory elements. We have studied the interaction between human glucocorticoid receptors and mouse mammary tumor virus (MMTV) DNA by means of a procedure that permits analysis after immobilization of the receptor on nitrocellulose. Proteins from crude cytosolic or nuclear extracts were electrophoresed on NaDodSO4/PAGE gels, soaked in a urea buffer to remove NaDodSO4, transferred to nitrocellulose, and probed with nick-translated MMTV [32P]DNA in a 5% nonfat dry milk buffer, which minimizes nonselective DNA-protein interactions. We present evidence that MMTV [32P]DNA interacts selectively with the glucocorticoid receptor. These data include comigration of [3H]dexamethasone mesylate-labeled band and bound MMTV [32P]DNA on gel electrophoresis systems; localization of DNA-binding activity in the cytosol of cells incubated with steroid at 0 degrees C and in the nucleus and cytosol of cells incubated at 37 degrees C; binding of the MMTV DNA to highly purified receptor; and absence of MMTV DNA binding activity in extracts from cells whose receptor has been down-regulated. Furthermore, glucocorticoid receptors analyzed under these conditions exhibit selective binding to DNA fragments that contain glucocorticoid regulatory elements.


Survey of Motion Tracking Methods Based on Inertial Sensors: A Focus on Upper Limb Human Motion.
Motion tracking based on commercial inertial measurements units (IMUs) has been widely studied in the latter years as it is a cost-effective enabling technology for those applications in which motion tracking based on optical technologies is unsuitable. This measurement method has a high impact in human performance assessment and human-robot interaction. IMU motion tracking systems are indeed self-contained and wearable, allowing for long-lasting tracking of the user motion in situated environments. After a survey on IMU-based human tracking, five techniques for motion reconstruction were selected and compared to reconstruct a human arm motion. IMU based estimation was matched against motion tracking based on the Vicon marker-based motion tracking system considered as ground truth. Results show that all but one of the selected models perform similarly (about 35 mm average position estimation error).


Risk among Combat Veterans with Post-traumatic Stress Disorder: The Impact of Psychosocial Factors on the Escalation of Suicidal Risk.
The purpose of this study was to (a) evaluate the influence of post-traumatic stress disorder (PTSD) and other comorbid disorders on suicidal risk among combat veterans and (b) evaluate the impact of psychosocial factors on the escalation of suicidal risk. Data were gathered from a random and representative sample of 215 Kosovo War veterans. Subjects were assessed for the presence of lifetime and current psychiatric disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Revision (DSM-IV TR) using the following questionnaires: Harvard Trauma Questionnaire (HTQ), Beck's Depression Inventory (BDI) and Beck's Suicide Intent Scale (BSIS). Suicidal ideations were observed in 44 (20.5%) of the 215 subjects. High suicide risk was found in 31.8% veterans diagnosed with PTSD and comorbid major depressive disorder. In addition, high suicide risk was also observed in the group of unemployed veterans, veterans dissatisfied with social/economic attainment and veterans dissatisfied with living conditions. Our study showed that socioeconomic factors contributes to the deterioration of symptoms of major depression, PTSD and other comorbid disorders, with a direct impact of worsening suicidal ideations and suicidal behavior among war veterans.


The Characteristics and Distribution of Nerve Plexuses in the Dartos Fascia From Concealed Penis Children.
The purpose of this study is to analyze the nerve plexus distribution in dartos fascia of concealed penis (CP). A total of 28 CP patients met ASA categories I and II were included, with median age of 3.5 years (8 months-5 years). During the surgery, tissue samples of dartos fascia at points 3, 6, 9, and 12 o'clock of the penile shaft were collected. Standard hematoxylin and eosin (H&E) staining and S-100 immunohistochemical staining were used to analyze the nerve plexus distribution among different positions. The number of nerve plexuses in superficial fascia collected at the 6 o'clock position of the penile shaft was the most abundant among four positions (median 7.25, range 1-24). The abundant nerve plexuses in the dartos fascia of CP patients, especially at the 6 o'clock position, indicate that the surgery on the preputial frenulum should avoid damage to the dartos fascia, as it might be related to maintain the erection and sexual function in adolescence.


Dual-dermal-barrier fashion flaps for the treatment of sacral pressure sores.
The sacral region is one of the most vulnerable sites for the development of pressure sores. Even when surgical reconstruction is performed, there is a high chance of recurrence. Therefore, the concept of dual-dermal-barrier fashion flaps for sacral pressure sore reconstruction was proposed. From September 2007 to June 2010, nine patients with grade IV sacral pressures were enrolled. Four patients received bilateral myocutaneous V-Y flaps, four patients received bilateral fasciocutaneous V-Y flaps, and one patient received bilateral rotation-advanced flaps for sacral pressure reconstruction. The flaps were designed based on the perforators of the superior gluteal artery in one patient's reconstructive procedure. All flaps' designs were based on dual-dermal-barrier fashion. The mean follow-up time was 16 months (range = 12-25). No recurrence was noted. Only one patient had a complication of mild dehiscence at the middle suture line, occurring 2 weeks after the reconstructive surgery. The dual-dermal fashion flaps are easily duplicated and versatile. The study has shown minimal morbidity and a reasonable outcome.


Interleukin-10 protects nitric oxide-dependent relaxation during diabetes: role of superoxide.
Interleukin (IL)-10, an anti-inflammatory cytokine, preserves endothelial function during acute inflammation. We tested the hypotheses that IL-10 plays a protective role in blood vessels during diabetes by suppressing impairment of endothelium-dependent relaxation and that protection by IL-10 is mediated by effects on superoxide (O(2-)). Streptozotocin (150 mg/kg i.p.) or citrate buffer was injected into IL-10-deficient (IL-10(-/-)) mice and wild-type controls (IL-10(+/+)). In IL-10(+/+) and IL-10(-/-) mice, blood glucose levels were approximately 120 mg/dl after citrate administration and approximately 400 mg/dl after streptozotocin administration. Vasorelaxation was examined in arteries in vitro 12-16 weeks later. Maximum relaxation to acetylcholine (30 micromol/l) was 88 +/- 3% (means +/- SE) in nondiabetic mice and 84 +/- 3% in diabetic IL-10(+ /+) mice (P > 0.05). Thus, at this time point, diabetes did not impair endothelium-dependent relaxation in vessels in wild-type mice. In contrast, maximum relaxation in vessels from diabetic IL-10(-/-) mice was significantly decreased (74 +/- 5%) compared with nondiabetic IL-10(-/-) mice (93 +/- 2%, P < 0.05). Superoxide dismutase with polyethylene glycol (PEG-SOD) restored impaired responses to acetylcholine to levels seen in controls. Responses to acetylcholine also were improved by allopurinol (an inhibitor of xanthine oxidase) in vessels from diabetic IL-10(- /-) mice. Thus, diabetes produces greater impairment of relaxation to acetylcholine in IL-10(-/-) mice than in IL-10(+/ +) mice. These findings provide direct evidence that IL-10 impedes mechanisms of endothelial dysfunction during diabetes. Restoration of vasorelaxation with PEG-SOD or allopurinol suggests that the mechanism(s) by which IL-10 preserves endothelium-dependent vasorelaxation involves O(2-), perhaps by reducing production of O(2-) by xanthine oxidase.


An A-ELISA to detect hepatitis A virus in estuarine samples.
An amplified enzyme-linked immunosorbent assay (A-ELISA) for detecting and quantifying hepatitis A virus in estuarine water samples is described. The test was five times more sensitive than a standard ELISA and at least two times more sensitive than radioimmunoassay. Test sensitivity was unaffected by the procedures used to concentrate the virus in estuarine samples or by the presence of humic and tannic acids in test samples. Nonspecific reactions were not encountered with a number of enteroviruses or with a rotavirus. A high sensitivity and specificity combined with speed, low cost, and freedom from radiolabels made the A-ELISA useful for detecting hepatitis A virus in environmental samples. The virus was detected in 3 of 20 estuarine water samples examined by A-ELISA.


Five days of postoperative antimicrobial therapy decreases infectious complications following pancreaticoduodenectomy in patients at risk for bile contamination.
Pancreaticoduodenectomy (PD) is associated with high morbidity, in part as a result of infectious complications increased by preoperative bile contamination. The aim of the present study was to assess the effect on the incidence of infectious complications of short-term antimicrobial therapy (AMT) in high-risk patients. Patients with a high risk for positive intraoperative bile culture (i.e. those with ampulloma or pancreatic adenocarcinoma with preoperative endoscopic procedures) (high-risk group, n = 99) were compared with low-risk patients (i.e. those with pancreatic adenocarcinoma without preoperative endoscopic procedures) (low-risk group, n = 76). The high-risk group received a 5-day course of perioperative AMT secondarily adapted to the bile antibiogram. The low-risk group received only the usual antimicrobial prophylaxis. Positive bile cultures were significantly more frequent in high-risk patients (81% versus 12%; P < 0.001). The overall rate of infectious complications was lower in the high-risk group (29% versus 46%; P = 0.018). The statistically significant decrease in the rate of infectious complications reflected reduced rates of urinary tract infections, pulmonary infections and septicaemia. Rates of wound infection (3% versus 5%; P = 0.639) and intra-abdominal abscess (7% versus 7%; P = 0.886) were similar in the high- and low-risk groups, as was the need for curative AMT. This exploratory study suggests that a postoperative short course of AMT in patients at high risk for biliary contamination reduces the overall rate of infectious complications after PD. The adaptation of perioperative antimicrobial policy to the patient's risk for bile contamination seems promising and should be further evaluated.


Soluble thiabendazolium salts with anthelminthic properties.
Thiabendazole is an anthelmintic drug used to treat strongyloidiasis (threadworm), cutaneous and visceral larva migrans, trichinosis, and other parasites. The active pharmaceutical ingredient is typically administered orally as tablets that should be chewed before swallowing. Current formulations combine the active ingredient with excipients, including sodium saccharinate as a sweetener. Thiabendazole's low aqueous solubility hinders fast dissolution and absorption through the mucous membranes. We sought to reformulate this medicine to improve both solubility and palatability. We utilized the possibility of protonation of the azole nitrogen atom and selected four different hydrogen donors: saccharin, fumaric, maleic, and oxalic acids. Solvothermal synthesis resulted in salts with each co-former, whereas neat and liquid-assisted grinding enabled the synthesis of additional formulations. Product formation was observed by powder X-ray diffraction. To better understand the structural basis of the proton transfer, we solved the crystal structures of the salts with saccharin, maleic acid, and oxalic acid using single-crystal X-ray diffraction. The structure of the salt with fumaric acid was solved by powder X-ray diffraction. We further characterized the salts with vibrational spectroscopic and thermoanalytical methods. We report a broad tunability of the aqueous solubility of thiabendazole by salt formation. Reformulation with maleic acid provided a 60-fold increase in solubility, while saccharin and oxalic acid gave a modest improvement. Fumaric acid resulted in a solid with only slightly higher solubility. Furthermore, saccharin is a sweetener, while the acids taste sour. Therefore, the salts formed also result in an intrinsic improvement of palatability. These results can inform new strategies for oral and chewable tablet formulations for treating helminthic infections.


Competitive advantages of Caedibacter-infected Paramecia.
Intracellular bacteria of the genus Caedibacter limit the reproduction of their host, the freshwater ciliate Paramecium. Reproduction rates of infected strains of paramecia were significantly lower than those of genetically identical strains that had lost their parasites after treatment with an antibiotic. Interference competition occurs when infected paramecia release a toxic form of the parasitic bacterium that kills uninfected paramecia. In mixed cultures of infected and uninfected strains of either P tetraurelia or of P novaurelia, the infected strains outcompeted the uninfected strains. Infection of new host paramecia seems to be rare. Infection of new hosts was not observed in either mixtures of infected with uninfected strains, or after incubation of paramecia with isolated parasites. The competitive advantages of the host paramecia, in combination with their vegetative reproduction, makes infection of new hosts by the bacterial parasites unnecessary, and could be responsible for the continued existence of "killer paramecia" in nature. Caedibacter parasites are not a defensive adaptation. Feeding rates and reproduction of the predators Didinium nasutum (Ciliophora) and Amoeba proteus (Amoebozoa, Gymnamoebia) were not influenced by whether or not their paramecia prey were infected. Infection of the predators frequently occurred when they preyed on infected paramecia. Caedibacter-infected predators may influence competition between Paramecium strains by release of toxic parasites into the environment that are harmful to uninfected strains.


Smartphones and mobile applications (apps) in clinical nursing education: A student perspective.
Nurse educators are exploring how mobile technology can support students in clinical practice. However, the view of nursing students on the use of smartphones and mobile applications (apps) to enhance clinical education has not been explored. Their opinions are vital to capture if the right technology is to be designed, evaluated, implemented and used. A self-reported questionnaire, based on a review of the literature, was used to understand the opinions of undergraduate nursing students towards the use of smartphones and mobile apps to support learning in clinical environments. Descriptive statistics were utilised to describe participants and the mobile devices and apps they currently use. Thematic analysis was employed to code open-ended questions and explore students' perspective on how mobile apps can support learning and how best to implement and use them in practice. Two hundred nursing students across a four-year Bachelor of Nursing programme responded to the questionnaire. Most reported owning a smartphone but just under half used mobile apps to help them learn in clinical practice. A range of educational apps such as calculators, drug reference guides and medical dictionaries were used with varying frequency. Nursing students reported numerous benefits of mobile technology such as better access to educational material, improvements in knowledge and confidence, and reduced levels of anxiety around learning in practice. Barriers such as negative attitudes of nursing staff, poor Wi-Fi connectivity, and the quality of educational content available on mobile apps were identified as some of the issues preventing the adoption of mobile learning in clinical nursing education. Nursing students have a unique perspective on how smartphones and mobile apps can support learning in clinical practice. Nursing faculty need to undertake more rigorous research to determine if mobile technology can improve learning outcomes, how best to personalise mobile apps to students needs and ensure both hardware devices and educational software can be integrated in practice to support clinical training.


Recent hotspot volcanism on Venus from VIRTIS emissivity data.
The questions of whether Venus is geologically active and how the planet has resurfaced over the past billion years have major implications for interior dynamics and climate change. Nine "hotspots"--areas analogous to Hawaii, with volcanism, broad topographic rises, and large positive gravity anomalies suggesting mantle plumes at depth--have been identified as possibly active. This study used variations in the thermal emissivity of the surface observed by the Visible and Infrared Thermal Imaging Spectrometer on the European Space Agency's Venus Express spacecraft to identify compositional differences in lava flows at three hotspots. The anomalies are interpreted as a lack of surface weathering. We estimate the flows to be younger than 2.5 million years and probably much younger, about 250,000 years or less, indicating that Venus is actively resurfacing.


Depression and sarcopenia: a Mendelian randomization analysis.
The association between depression and sarcopenia has been reported in observational studies but the causality of depression on sarcopenia remained unknown. We aimed to assess the causal effect between major depressive disorder (MDD) and sarcopenia using the two-sample Mendelian randomization (MR) method. A set of genetics instruments were used for analysis, derived from publicly available genetic summary data. Clinically, appendicular lean mass (ALM) and low hand grip strength (LHGS) have been widely used for the diagnosis of sarcopenia. Inverse-variance weighted method, weighted median method, MR-Egger, MR Pleiotropy RESidual Sum and Outlier test were used for the bidirectional MR analyses. No evidence for an effect of MDD on sarcopenia risk was found. MDD was not associated with ALM [effect = -0.17 (-0.60 to 0.27), P = 0.449] and LHGS [effect = 0.24 (-0.46 to 0.93), P = 0.506]. Sarcopenia was not associated with MDD [ALM: odds ratio (OR) = 0.999 (0.996-1.001), P = 0.374; LHGS: OR = 0.999 (0.996-1.002), P = 0.556]. MDD and Sarcopenia might mutually have no causal effect on each other.


Shape and director-field transformation of tactoids.
Tactoids are droplets of a nematic phase that under suitable conditions form in dispersions of elongated colloidal particles. We theoretically study the shape and the director-field configuration of such droplets for the case where a planar anchoring of the director field to the interface is favored. A minimum of four regimes can be identified in which the droplets have a different structure. Large droplets tend to be nearly spherical with a director field that is bipolar if the surface tension is strongly anisotropic and homogeneous if this is not so. Small droplets can become very elongated and spindlelike if the surface tension is sufficiently anisotropic. Depending on the anchoring strength, the director field is then either homogeneous or bipolar. We find that the more elongated the tactoid, the more strongly it resists the crossing over from a homogeneous to a bipolar structure. This should have implications for the nucleation rate of the nematic phase. Our calculations qualitatively describe the size dependence of the aspect ratio of tactoids found in recent experiments.


[Pain symptoms of osteoarthritis-aspects of etiology and therapy].
Due to demographic changes and associated socioeconomic problems osteoarthritis is of increasing value. Simultaneously there are more and more older people who want to practice sports. Pain symptoms of osteoarthritis can be positively influenced by paracetamol and NSAR, in combination with orthopedic aids and physical therapy in early stages. Apart from these established pain-therapeutic procedures as well as first evident results of osteoarthritis modifying drugs, gene-therapy offers promising approaches that will have to be confirmed in further studies. In case of failure of conservative treatment there are several surgical options. Arthroscopic surgery mostly offers pain reduction only for a short period of time. A slower progression of osteoarthritis in the long run can only be achieved by osteotomy provided the right indication. Ultimately joint replacement exists as a reliable and successful treatment option in hip, knee and shoulder surgery.


Cerebral circulation estimated by laser speckle flowgraphy in retrograde femoral arterial perfusion during minimally invasive cardiac surgery.
Laser speckle flowgraphy (LSFG) is a novel modality to assess blood flow of the optic nerve head (ONH), which is reported to be a surrogate marker of cerebral microcirculation. We conducted LSFG measurements during minimally invasive cardiac surgery with retrograde femoral arterial perfusion and evaluated its feasibility and usability as a neuromonitor. We prospectively enrolled 7 patients who underwent mitral valve repair through a right minithoracotomy with retrograde femoral arterial perfusion. LSFG was used to analyse the ONH blood flow based on examinations of the mean blur rate (MBR). The MBR was measured after the induction of anaesthesia (time 1); after the initiation of cardiopulmonary bypass (time 2); during cardiac arrest (time 3) and after the termination of cardiopulmonary bypass (time 4). All procedures were performed successfully, and there were no neurovascular complications or deaths. LSFG measurements were easily and uneventfully conducted without any related complications. The MBR was 11.2 ± 2.3 at time 1, 11.1 ± 1.8 at time 2, 11.3 ± 1.7 at time 3 and 13.6 ± 3.5 at time 4. Statistically, the MBR at time 4 was significantly higher than those at all other times ( P < 0.05). LSFG measurements were safely conducted during minimally invasive cardiac surgery and assessed ONH blood flow quantitatively. We consider this modality to be easy to manipulate and less operator dependent, resulting in good reproducibility. The results are well visualized and compared quantitatively. Our result suggests that LSFG might be an accurate neuromonitor. clinicaltrials.gov : 15102-2.


Consciousness around the time of saccadic eye movements.
During saccadic eye movements, the job of the nervous system is not to perceive a change in stimulation from the receptors, but to prevent a change from reaching consciousness. These movements occupy an intermediate range between actions that are almost always conscious, such as finger movements, and those that are never conscious, such as the smooth-muscle actions of the digestive system. Consciousness in this context requires attention to the consequences of an action.


Periosteal chondroma of the proximal phalanx of the thumb.
A 52-year-old man presented with a periosteal chondroma in the base of the proximal phalanx of the right thumb. Magnetic resonance imaging (MRI) showed invasion of the bone marrow, which suggested malignancy. Although the clinical and MRI findings indicated a malignant tumour, the histopathological examination showed a benign periosteal chondroma.


Electronic nature of substituent X governs reaction mechanism in aminolysis of 4-pyridyl X-substituted-benzoates in acetonitrile.
A kinetic study is reported for aminolysis of 4-pyridyl X-substituted-benzoates 5a-i. Plots of pseudo-first-order rate constants (k(obsd)) vs [amine] curve upward for the reactions of substrates possessing a strong electron-withdrawing group in the benzoyl moiety (5a-d) but are linear for the reactions of those bearing an electron-donating group (5e-i), indicating that the electronic nature of substituent X governs the reaction mechanism. The k(1)k(2)/k(-1) and k(1)k(3)/k(-1) values were calculated from the intercept and slope of the linear plots of k(obsd)/[amine] vs [amine], respectively. The Hammett plot for k(1)k(2)/k(-1) consists of two intersecting straight lines, while the Yukawa-Tsuno plot exhibits an excellent linear correlation with ρ(X) = 0.41 and r = 1.58, implying that the nonlinear Hammett plot is not due to a change in rate-determining step but is caused by stabilization of substrates possessing an electron-donating group through resonance interactions. The small ρ(X) suggests that the k(2)/k(-1) ratio is little influenced by the nature of substituent X. The Brønsted-type plots for aminolysis of 4-pyridyl 3,5-dinitrobenzoate 5a are linear with β(nuc) = 0.98 and 0.79 for k(1)k(2)/k(-1) and k(1)k(3)/k(-1), respectively. The effect of amine basicity on the microscopic rate constants is also discussed.


Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib.
Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib.


Optimization Models for Scheduling of Jobs.
This work is motivated by a particular scheduling problem that is faced by logistics centers that perform aircraft maintenance and modification. Here we concentrate on a single facility (hangar) which is equipped with several work stations (bays). Specifically, a number of jobs have already been scheduled for processing at the facility; the starting times, durations, and work station assignments for these jobs are assumed to be known. We are interested in how best to schedule a number of new jobs that the facility will be processing in the near future. We first develop a mixed integer quadratic programming model (MIQP) for this problem. Since the exact solution of this MIQP formulation is time consuming, we develop a heuristic procedure, based on existing bin packing techniques. This heuristic is further enhanced by application of certain local optimality conditions.


Antiviral activities of type I interferons to SARS-CoV-2 infection.
There is an urgent need to identify antivirals to curtail the COVID-19 pandemic. Herein, we report the sensitivity of SARS-CoV-2 to recombinant human interferons α and β (IFNα/β). Treatment with IFN-α or IFN-β at a concentration of 50 international units (IU) per milliliter reduces viral titers by 3.4 log or over 4 log, respectively, in Vero cells. The EC50 of IFN-α and IFN-β treatment is 1.35 IU/ml and 0.76 IU/ml, respectively, in Vero cells. These results suggest that SARS-CoV-2 is more sensitive than many other human pathogenic viruses, including SARS-CoV. Overall, our results demonstrate the potential efficacy of human Type I IFN in suppressing SARS-CoV-2 infection, a finding which could inform future treatment options for COVID-19.


Evaluation of the Antibacterial Activity and Efflux Pump Reversal of Thymol and Carvacrol against Staphylococcus aureus and Their Toxicity in Drosophila melanogaster.
The antibacterial activity and efflux pump reversal of thymol and carvacrol were investigated against the Staphylococcus aureus IS-58 strain in this study, as well as their toxicity against Drosophila melanogaster. The minimum inhibitory concentration (MIC) was determined using the broth microdilution method, while efflux pump inhibition was assessed by reduction of the antibiotic and ethidium bromide (EtBr) MICs. D. melanogaster toxicity was tested using the fumigation method. Both thymol and carvacrol presented antibacterial activities with MICs of 72 and 256 µg/mL, respectively. The association between thymol and tetracycline demonstrated synergism, while the association between carvacrol and tetracycline presented antagonism. The compound and EtBr combinations did not differ from controls. Thymol and carvacrol toxicity against D. melanogaster were evidenced with EC50 values of 17.96 and 16.97 µg/mL, respectively, with 48 h of exposure. In conclusion, the compounds presented promising antibacterial activity against the tested strain, although no efficacy was observed in terms of efflux pump inhibition.


Outcomes of a total cavopulmonary connection in patients with impaired ventricular function.
Our aim was to evaluate outcomes following a total cavopulmonary connection (TCPC) in patients with preoperatively impaired ventricular function (VF). Of 483 consecutive TCPC patients, 44 (9.1%) had impaired VF (ejection fraction <50%, Group A), and 439 patients had normal VF (ejection fraction ≥50%, Group B). We compared the clinical outcomes between the groups. The median age at TCPC was 2.8 (interquartile range 1.9-8.3) years in Group A and 2.3 (1.8-3.5) years in Group B (P = 0.025). An atrioventricular valve (AVV) operation prior to (38.6 vs 27.1%, P < 0.001) and concomitant with (31.8 vs 12.1%, P < 0.001) the TCPC was performed more frequently in Group A. The median intensive care unit stay (7.0 vs 7.0 days, P = 0.737) and 30-day survival (97.7 vs 98.4%, P = 0.737) were not significantly different between groups. Freedom from death, transplantation (P = 0.115) and catheter intervention (P = 0.603) showed no difference between groups. However, freedom from cardiac reoperation was significantly lower in Group A (P < 0.001). VF was resolved in 22 of the 39 (56.4%) survivors in Group A. The recovered patients had a lower incidence of AVV reoperation (0 vs 6, P = 0.002) and pacemaker rhythm (0 vs 5, P = 0.006). In patients planned for TCPC, impaired VF is often associated with AVV regurgitation. TCPC can be performed with low risk and comparable clinical results except for cardiac reoperation in patients with impaired VF when compared to patients with normal VF. Following TCPC, VF recovers in half of the survivors. A competent AVV and sinus rhythm are prerequisites for recovery.


Family-based consent and motivation for familial organ donation in Bangladesh: An empirical exploration.
The government of Bangladesh approved the human organ transplantation law in 1999 and updated it in 2018. This legislation approved both living-related donor and posthumous organ transplantation. The law only allows family members to legally donate organs to their relatives. The main focus of this study was to explore how Bangladeshis make donation decisions on familial organs for transplantation. My ethnographic fieldwork with forty participants (physicians and nurses, a healthcare administrator, organ donors, recipients, and their relatives) disclosed that the organ donation decision was family-based. An assessment of the relationship between religion, culture, and biomedicine leads to the conclusion that deciding on donating organs to relatives is primarily family-based and is perceived to be steeped in Islamic ethical principles and religious cultural tradition. The family-based consent and motivation for donor-recipient pair organ transplantation strengthen an altruistic environment for the family and act as the moral and legal authority that ensures ethical healthcare outcomes for Bangladeshis.


Interleukin-1β downregulates RBP4 secretion in human adipocytes.
The excessive accumulation of adipose tissue in the obese state is linked to an altered secretion profile of adipocytes, chronic low-grade inflammation and metabolic complications. RBP4 has been implicated in these alterations, especially insulin resistance. The aim of the present study was to determine if a local inflammatory micro-environment in adipose tissue regulates RBP4 expression and secretion. Human SGBS and primary adipocytes cultured with conditioned media from human THP-1 macrophages were used as an in vitro model for adipose inflammation. Adipocytes were exposed to recombinant TNF-α, IL-1β, IL-6 or IL-8. In addition, coexpression of IL-1β and RBP4 was measured in adipose tissue samples from 18 healthy females. RBP4 expression was studied by quantitative PCR and ELISA. RBP4 mRNA expression and secretion was significantly reduced upon incubation with macrophage-conditioned media in SGBS adipocytes and human primary adipocytes. Out of several factors studied we identified IL-1β as a new factor regulating RBP4. IL-1β significantly downregulated RBP4 mRNA and secretion in a time- and dose-dependent manner. IL-1β mediated its inhibitory effects on RBP4 expression via IL-1 receptor and NF-κB, as incubation with the IL-1 receptor blocking antibody and the NF-κB inhibitors CAPE and SC-514 reversed its effect. Most interestingly, RBP4 mRNA was negatively correlated with IL-1β mRNA in subcutaneous adipose tissue. Adipose tissue inflammation as found in the obese state might lead to a downregulation in local RBP4 levels. IL-1β was identified as a major factor contributing to the decrease in RBP4. The increase in circulating RBP4 that often precedes the development of systemic insulin resistance is most likely unrelated to inflammatory processes in adipose tissue.


Expression of RNA and antigens of human immunodeficiency virus type-1 (HIV-1) in lymph nodes from HIV-1 infected individuals.
The presence of proteins (p17 and p24 core proteins, gp41 envelope protein) and mRNA (gag/pol and env gene segments) of human immunodeficiency virus type-1 (HIV-1) was analyzed on frozen tissue sections of lymph nodes from HIV-1 infected individuals. Thirty-one lymph nodes were categorized in the stages of follicle hyperplasia (n = 18), follicle degeneration (n = 5), and total depletion (n = 8). The follicle dendritic cells in germinal centers showed the presence of core proteins and, to a lesser extent, gp41. The staining patterns, being similar to those of immunoglobulins, suggested that they occur in the form of immune complexes. In addition there were solitary cells expressing viral protein, in particular gp41, and mRNA. The number of mRNA-positive cells was very low: about five positive cells were observed in a tissue section with about ten (hyperplastic) follicles. HIV-1-mRNA-positive cells were observed both in follicles and interfollicular areas and showed no differences between various stages. The extent and intensity of distinct HIV-1 proteins and HIV-1-mRNA gene segments in follicles were significantly correlated, as was their presence in interfollicular areas. No significant correlation was found between the presence of HIV-1 components in follicles and in interfollicular areas. This indicates that processes involving HIV-1 components occur in a segregated manner in both lymph node compartments. The presence of HIV-1 components did not correspond to any clinical classification (CDC criteria), nor to other histochemical characteristics. An exception was the correlation between gp41-positive cells and CD1-positive interdigitating cells in the interfollicular areas.


Is There Any Relationship between TSH Levels and Prognosis in Acute Coronary Syndrome?
Some small studies have related higher levels of thyrotropin (TSH) to potentially worse prognosis in acute coronary syndromes. However, this relationship remains uncertain. To analyze the outcomes of patients with acute coronary syndromes in relation to the value of TSH at admission. Observational and retrospective study with 505 patients (446 in group I [TSH ≤ 4 mIU/L] and 59 in group II [TSH > 4 mIU/L]) with acute coronary syndromes between May 2010 and May 2014. We obtained data about comorbidities and the medications used at the hospital. The primary endpoint was in-hospital all-cause death. The secondary endpoint included combined events (death, non-fatal unstable angina or myocardial infarction, cardiogenic shock, bleeding and stroke). Comparisons between groups were made by one-way ANOVA and chi-square test. Multivariate analysis was determined by logistic regression. Analyses were considered significant when p < 0.05. Significant differences between groups I and II were observed regarding the use of enoxaparin (75.2% vs. 57.63%, p = 0.02) and statins (84.08% vs. 71.19%, p < 0.0001), previous stroke (5.83% vs. 15.25%, p = 0.007), combined events (14.80% vs. 27.12%, OR = 3.05, p = 0.004), cardiogenic shock (4.77% vs. 6.05%, OR = 4.77, p = 0.02) and bleeding (12.09% vs. 15.25%, OR = 3.36, p = 0.012). In patients with acute coronary syndromes and TSH > 4 mIU/L at admission, worse prognosis was observed, with higher incidences of in-hospital combined events, cardiogenic shock and bleeding.


Bioinspired Oil-Infused Slippery Surfaces with Water and Ion Barrier Properties.
Encapsulation materials play an important role in many applications including wearable electronics, medical devices, underwater robotics, marine skin tagging system, food packaging, and energy conversation and storage devices. To date, all the encapsulation materials, including polymer layers and inorganic materials, are solid materials. These solid materials suffer from limited barrier lifetimes due to pinholes, cracks, and nanopores or from complicated fabrication processes and limited stretchability for interfacing with complex 3D surfaces. This paper reports a solution to this material challenge by demonstrating bioinspired oil-infused slippery surfaces with excellent waterproof property for the first time. A water vapor transmission test shows that locking a thin layer of oil on the silicone elastomer improves the water vapor barrier performance by three orders of magnitude. Accelerated lifetime tests suggest robust water barrier characteristics that approach 226 days at 37 °C even under severe mechanical damage. A combination of temperature- and thickness-dependent experimental measurements and reaction-diffusion modeling reveals the key waterproof property. In addition to serving as a barrier to water, the oil-infused surface demonstrates an attractive ion barrier property. All these exceptional properties suggest the potential applications of slippery surfaces as encapsulation materials for medical devices, underwater electronics, and many others.


Education and coronary heart disease risk: potential mechanisms such as literacy, perceived constraints, and depressive symptoms.
Education is inversely associated with coronary heart disease (CHD) risk; however the mechanisms are poorly understood. The study objectives were to evaluate the extent to which rarely measured factors (literacy, time preference, sense of control) and more commonly measured factors (income, depressive symptomatology, body mass index) in the education-CHD literature explain the associations between education and CHD risk. The study sample included 346 participants, aged 38 to 47 years (59.5% women), of the New England Family Study birth cohort. Ten-year CHD risk was calculated using the validated Framingham risk algorithm that utilizes diabetes, smoking, blood pressure, total cholesterol, high-density lipoprotein cholesterol, age, and gender. Multivariable regression and mediation analyses were performed. Regression analyses adjusting for age, race/ethnicity, and childhood confounders (e.g., parental socioeconomic status, intelligence) demonstrated that relative to those with greater than or equal to college education, men and women with less than high school had 73.7% (95% confidence interval [CI; 29.5, 133.0]) and 48.2% (95% CI [17.5, 86.8]) higher 10-year CHD risk, respectively. Mediation analyses demonstrated significant indirect effects for reading comprehension in women (7.2%; 95% CI [0.7, 19.4]) and men (7.2%; 95% CI [0.8, 19.1]), and depressive symptoms (11.8%; 95% CI [2.5, 26.6]) and perceived constraint (6.7%, 95% CI [0.7, 19.1]) in women. Evidence suggested that reading comprehension in women and men, and depressive symptoms and perceived constraint in women, may mediate some of the association between education and CHD risk. If these mediated effects are interpreted causally, interventions targeting reading, depressive symptoms, and perceived constraint could reduce educational inequalities in CHD.


[The protective effect of shenfu injection on myocardium against ischemia reperfusion injury in rats].
To observe the protective effect of Panax Ginseng (PG), Aconitum Carmichaeli (AC), and their combination (PG-AC) on myocardial ischemia/reperfusion injury in rats. Rat's ischemia reperfusion injury model was established by ligating left anterior descending coronary artery for 60 min followed by reperfusion for 240 min. Forty male rats were randomly divided into five groups, the sham operation group, the model group, the three treated groups. The three treated groups were treated with PG, AC and PG-AC respectively by given the drugs 10 min before ischemia reperfusion, and to the sham operation group and the model group, saline was given instead. The infarction area, pathologic changes of myocardial tissue (under light and electron microscopy), activity of creatine phosphokinase (CK) and lactate dehydrogenase (LDH) in serum, content of malondialdehyde (MDA) and superoxide dismutase (SOD) in myocardial tissue were observed to evaluate the protective effect of treatment. The area of acute myocardial infarction was lesser, activity of LDH and CK were lower in the three treated groups than those in the model group. Content of SOD was significantly higher and that of MDA was markedly lower in the former three than those in the model group. Light and electron microscopic examination showed that the necrotic degeneration and pathologic changes of myocardiocytes in the treated groups were significantly milder than that of the model group. As comparing the effect between the three treated groups, PG-AC showed the best, and insignificant difference was shown between PG and AC. Both PG and AC, and their combination have obviously protective effects on myocardium against ischemia reperfusion injury, which of PG-AC is superior to that of PG or AC used singly.


Covalent adduct formation between the antihypertensive drug hydralazine and abasic sites in double- and single-stranded DNA.
Hydralazine (4) is an antihypertensive agent that displays both mutagenic and epigenetic properties. Here, gel electrophoretic, mass spectroscopic, and chemical kinetics methods were used to provide evidence that medicinally relevant concentrations of 4 rapidly form covalent adducts with abasic sites in double- and single-stranded DNA under physiological conditions. These findings raise the intriguing possibility that the genotoxic properties of this clinically used drug arise via reactions with an endogenous DNA lesion rather than with the canonical structure of DNA.


Lower urinary tract symptoms (LUTS) and sexual function in both sexes.
It has been stated that lower urinary tract symptoms (LUTS) do not affect sexual function to any significant degree, but a recent study has suggested that there might be an association in men. The present study was conducted to investigate the relationship between LUTS and sexual problems in both men and women aged 40-65 years. The survey was conducted in Denmark between May and June 2003. Detailed questionnaires were mailed to a random sample of 15,000 men and women aged 40-65 years. LUTS and sexual function were assessed by validated symptom scales. Multivariate regression analysis was performed using logistic regression for dichotomous dependent variables of sexual function. The independent variables for both sexes were age, LUTS, partner status, body mass index (BMI), alcohol consumption and co-morbidities. A total of 15,000 questionnaires were mailed out, 8491 were completed and returned, and 7741 were deemed valuable and included in the analysis. LUTS and sexual dysfunction were common in both men and women. Logistic regression analysis of items related to erection problems and satisfaction with sex life in men and sexual function in women showed that LUTS are an independent risk factor for sexual dysfunction in both men and women aged 40-65 years. Significant effects on sexual function were also found for the independent variables of partner status and co-morbidities. The presence of LUTS is an independent risk factor for sexual dysfunction in men and women. These results highlight the clinical importance of evaluating LUTS in patients with sexual dysfunction, and the need to consider sexual issues in the management of patients with LUTS.


Myocardial bridges: A review.
Much has been written regarding the potential clinical significance of myocardial bridges. As such bridging is often seen in normal individuals, it is clear that not all arteries bridged by myocardial segments produce clinical symptoms thereby suggesting that this feature may simply be an anatomical variant. However, some authors who have considered these bridges as the cause of cardiac ischemia have suggested two potential mechanisms for their pathophysiology. The first is a phasic systolic compression of the bridged segment with persistent mid-to-late diastolic reduction in arterial diameter and the second proposes a reduction in arterial flow. Both mechanisms may contribute to a reduced reserve in coronary blood flow. In this review, we discuss the evidence that exists regarding myocardial bridging and the potential for bridging to cause myocardial ischemia.


Endothelium and disordered fibrin turnover in the injured lung: newly recognized pathways.
To review derangements of pathways of fibrin turnover that promote pathologic fibrin deposition in the acute respiratory distress syndrome and to review the contribution of the endothelium and parenchymal lung cells to the derangements. In addition, to review how these pathways can be exploited in specific clinical circumstances, including sepsis and acute lung injury. Lastly, to review newly recognized posttranscriptional and urokinase-dependent pathways by which the fibrinolytic system is regulated in the lung. Medical literature published in English from 1966 to present. Local abnormalities of fibrin turnover in the injured lung recapitulate the systemic changes observed in sepsis. In both circumstances, the procoagulant response is increased, whereas fibrinolytic activity is concurrently depressed. The increased procoagulant activity is related to tissue factor associated with factor VII/VIIa. Fibrinolytic activity in the vasculature is mainly attributable to tissue plasminogen activator, whereas extravascular fibrinolytic activity in the lung is mainly attributable to urokinase plasminogen activator (uPA). Depressed fibrinolytic activity is in large part attributable to plasminogen activator inhibitor-1. In sepsis, activated protein C is also deficient, potentiating the inflammatory response, coagulopathy, and depressed fibrinolysis. Recombinant human activated protein C (drotrecogin alfa [activated]) was successful as an intervention for sepsis in a recent phase 3 clinical trial (PROWESS). Recently, novel posttranscriptional pathways that regulate expression of uPA, its receptor (uPAR), and plasminogen activator inhibitor-1 have been identified. The responsible mechanisms involve cis-trans interactions between newly recognized messenger RNA (mRNA) binding sequences and mRNA binding proteins. A 51 nucleotide mRNA binding sequence within the coding region of uPAR mRNA interacts with a novel 50-kDa mRNA binding protein to destabilize the message. Sequences within the 3' untranslated region of uPA or plasminogen activator inhibitor-1 mRNA interact with 30- and 60-kDa proteins, respectively, to regulate message stability. All of these pathways operate in lung epithelial cells, and endothelial cells regulate uPA expression through a similar pathway. In addition, uPA itself is capable of inducing expression of other components of the fibrinolytic system, including uPAR. This observation defines another feedback loop that could amplify local fibrinolysis and other uPA- or uPAR-mediated cellular responses, including cellular proteolysis, proliferation, and directed cellular migration. Novel posttranscriptional pathways regulate expression of uPA, uPAR, and plasminogen activator inhibitor-1. uPA itself is capable of inducing other components of the fibrinolytic system. Some or all of these newly recognized pathways are operative in endothelial and parenchymal lung cells and may influence disordered fibrin turnover in the injured lung.


Three-Dimensional Topography of the Emerging Point of the Ophthalmic Artery.
During periorbital noninvasive and surgical procedures, there is the risk of iatrogenic injury to the emerging point of the ophthalmic artery. This study aimed to determine the three-dimensional location of the emerging point of the ophthalmic artery and to provide clinicians with anatomical information that would help them to avoid associated complications. Seventeen hemifaces of the emerging point of the ophthalmic artery from 10 Korean and seven Thai cadavers were dissected and scanned by a three-dimensional scanner. The emerging points of the ophthalmic artery of 30 healthy Korean volunteers were also detected using an ultrasound imaging system. The transverse distance from the medial canthus to the emerging of the ophthalmic artery was 3.8 ± 1.0 mm medially, and the vertical distance was 14.0 ± 2.9 mm superiorly. The transverse distance from the midline was 16.5 ± 1.7 mm to the emerging point of the ophthalmic artery and 20.0 ± 2.0 mm to the medial canthus. The measured depth from the skin surface to the emerging point of the ophthalmic artery was 4.8 ± 1.7 mm by means of three-dimensional scanning and 4.5 ± 1.1 mm using ultrasound detection. The vertical distance from the inferior margin of the superior orbital rim to the emerging point of the ophthalmic artery was 5.3 ± 1.4 mm. These data inform clinicians about the anatomical three-dimensional location of the emerging point of the ophthalmic artery, which will help them to avoid iatrogenic injury when they are performing periorbital clinical procedures.


Antimuscarinic therapy for the treatment of mixed incontinence.
Mixed urinary incontinence, the combination of stress incontinence and urge incontinence, affects millions of Americans, significantly impacting their quality of life. Treatment of mixed incontinence is a therapeutic challenge, and the debate over whether patients are best managed initially with medication or surgery is ongoing. The literature supports the efficacy of both antimuscarinic therapy and surgery for the treatment of mixed incontinence, but patient selection likely influences treatment outcome. Following is a literature review that critically evaluates the efficacy of antimuscarinic agents for the treatment of mixed incontinence and addresses some of the controversial issues regarding surgical and pharmacologic therapy. Clinical parameters that might influence therapeutic outcomes and recommendations regarding treatment are also presented.


A pressure-gradient mechanism for vortex shedding in constricted channels.
Numerical simulations of the unsteady, two-dimensional, incompressible Navier-Stokes equations are performed for a Newtonian fluid in a channel having a symmetric constriction modeled by a two-parameter Gaussian distribution on both channel walls. The Reynolds number based on inlet half-channel height and mean inlet velocity ranges from 1 to 3000. Constriction ratios based on the half-channel height of 0.25, 0.5, and 0.75 are considered. The results show that both the Reynolds number and constriction geometry have a significant effect on the behavior of the post-constriction flow field. The Navier-Stokes solutions are observed to experience a number of bifurcations: steady attached flow, steady separated flow (symmetric and asymmetric), and unsteady vortex shedding downstream of the constriction depending on the Reynolds number and constriction ratio. A sequence of events is described showing how a sustained spatially growing flow instability, reminiscent of a convective instability, leads to the vortex shedding phenomenon via a proposed streamwise pressure-gradient mechanism.


Determinants of Awareness and Practice of Breast Self Examination Among Rural Women in Trichy, Tamil Nadu.
Breast cancer is the most common cancer among women worldwide, and it can be detected at an early stage through self-examination which increases the chance of survival. This study aimed to assess knowledge and practice of breast self-examination (BSE) among females in a rural area of Trichy district. This community-based, cross-sectional study was carried out among a total sample of 200 women in rural area of Trichy. The participants were interviewed using a structured interviewer-administered questionnaire to obtain information on their sociodemographic characteristics, awareness on breast cancer, and knowledge, attitude, practice of BSE. Data were entered into MS Excel and analyzed using SPSS version 20.0. Spearman correlation and Chi-square test were used to analyze the association between the variables. The mean age of the study group was 36.9 ± 8.8 years. Eighty percent were literates. Most of the women 178 (89%) were aware of breast cancer. Only 26% of the women were aware of BSE. Only 18% of the females had ever checked their breast and 5% practiced it regularly. Awareness of BSE was found to be significantly associated with age and educational attainment. The level of knowledge and practice of BSE among females are unacceptably low. Efforts should be made to increase level of knowledge and practice of BSE through health education programs.


Cryoablation of localized prostate cancer: neoadjuvant downsizing of prostate cancer with LH-RH analogue depot before cryosurgery.
Radical prostatovesiculectomy, radiation therapy, and complete androgen deprivation are acknowledged therapeutic concepts in the treatment of organ-confined prostate cancer. With cryoablation of the prostate, minimal invasive therapy has become available since 1991. Improvements in cryotechnique and progress in transrectal high-resolution ultrasound permit thermo-induced damage to the whole gland to be curative. Downstaging of prostate cancer by hormone ablative therapy remains a controversial issue at this time, but the use of androgen ablation decreases the size of the prostate gland which facilitates cryosurgery and improves the results. The freezing equipment has a limited capacity, and in certain instances large gland volumes prevent adequate freezing of the prostate. Since percutaneous prostate cryosurgery leaves dead tissue in situ to be resorbed over time, downsizing reduces the amount of necrotic tissue to be resorbed, reducing the potential for complications, particularly abscesses. The use of androgen ablation also increases the deposition of fat in the area of the Denonvillier's fascia, making freezing of the rectum less likely during the procedure. In our study androgen ablative therapy was completed before performing cryosurgery in 26 of 43 patients (58%). The 17 patients not given androgen ablation therapy had gland volumes < 40 ml, tumor volumes < 3 ml, and no evidence of extracapsular tumor. The neoadjuvant therapy consisted of a 3- to 10-month course of leuprolide acetate combined with an antiandrogen.


Transparent Glass-Ceramics Produced by Sol-Gel: A Suitable Alternative for Photonic Materials.
Transparent glass-ceramics have shown interesting optical properties for several photonic applications. In particular, compositions based on oxide glass matrices with fluoride crystals embedded inside, known as oxyfluoride glass-ceramics, have gained increasing interest in the last few decades. Melt-quenching is still the most used method to prepare these materials but sol-gel has been indicated as a suitable alternative. Many papers have been published since the end of the 1990s, when these materials were prepared by sol-gel for the first time, thus a review of the achievements obtained so far is necessary. In the first part of this paper, a review of transparent sol-gel glass-ceramics is made focusing mainly on oxyfluoride compositions. Many interesting optical results have been obtained but very little innovation of synthesis and processing is found with respect to pioneering papers published 20 years ago. In the second part we describe the improvements in synthesis and processing obtained by the authors during the last five years. The main achievements are the preparation of oxyfluoride glass-ceramics with a much higher fluoride crystal fraction, at least double that reported up to now, and the first synthesis of NaGdF₄ glass-ceramics. Moreover, a new SiO₂ precursor was introduced in the synthesis, allowing for a reduction in the treatment temperature and favoring hydroxyl group removal. Interesting optical properties demonstrated the incorporation of dopant ions in the fluoride crystals, thus obtaining crystal-like spectra along with higher efficiencies with respect to xerogels, and hence demonstrating that these materials are a suitable alternative for photonic applications.


Elevated Midtrimester Triglycerides as a Biomarker for Postpartum Hyperglycemia in Gestational Diabetes.
Whether elevated triglyceride (TG) levels during pregnancy were a biomarker for postpartum abnormal glucose metabolism (AGM) in women with previous gestational diabetes mellitus (GDM) remained unknown. The aim of this study was to investigate the association between TG levels during the second trimester and postpartum AGM in GDM women. This was a retrospective cohort study including 513 GDM women. A 75 g oral glucose tolerance test (OGTT) was performed, and lipid levels were determined during pregnancy and the postpartum period. GDM patients were categorized into tertiles according to their TG levels at 24-28 weeks of gestation (TG < 2.14 mmol/L, TG: 2.14-2.89 mmol/L, and TG > 2.89 mmol/L). A logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). During pregnancy, women in the high TG tertile showed higher HbA1c levels (5.47 ± 0.58% versus 5.28 ± 0.49%, p = 0.006), higher total cholesterol (TC) levels (5.85 ± 1.23 mmol/L versus 5.15 ± 0.97 mmol/L, p = 0.026), and higher HOMA-IR (2.36 (1.62-3.45) versus 1.49 (0.97-2.33), p < 0.001) than the participants in the low TG tertile. After delivery, the prevalence rates of AGM based on above tertiles of TG levels during pregnancy were 26.90%, 33.33%, and 43.27%, respectively (p = 0.006). High TG tertile during the second trimester was associated with the presence of postpartum AGM (adjusted OR: 2.001, 95% CI: 1.054-3.800, p = 0.034). The elevated midtrimester TG levels were not only accompanied by higher glucose and lipid levels and more severe insulin resistance at the time of the measurement but were a biomarker for postpartum AGM as well.


Is there correlation between cognition and functionality in severe dementia? the value of a performance-based ecological assessment for Alzheimer's disease.
Besides significant cognitive decline, patients in later stages of Alzheimer's disease (AD) also present global functional impairment, usually reported by their caregivers. This study searched for preserved activities of daily living by investigating correlations among specific instruments for severe dementia with a performance-based functional scale. A sample of 95 moderate to severe AD patients and their caregivers underwent a neuropsychological battery consisting of screening tools, the Functional Assessment Staging Test (FAST), the Severe Mini-Mental State Examination (MMSEsev) and a performance-based ecological scale, the Performance Test of Activities of Daily Living (PADL). Consistent findings emerged from the comparisons among tests. PADL showed significant statistical correlation with MMSEsev (ρ<0.001), according to FAST subdivisions. Upon suspicion of unreliable caregiver reports, ecological scales may be useful for disease staging. Variable degrees of functionality and cognition may be present even in later stages of AD, requiring proper assessment.


Structure of eIF3b RNA recognition motif and its interaction with eIF3j: structural insights into the recruitment of eIF3b to the 40 S ribosomal subunit.
Mammalian eIF3 is a 700-kDa multiprotein complex essential for initiation of protein synthesis in eukaryotic cells. It consists of 13 subunits (eIF3a to -m), among which eIF3b serves as a major scaffolding protein. Here we report the solution structure of the N-terminal RNA recognition motif of human eIF3b (eIF3b-RRM) determined by NMR spectroscopy. The structure reveals a noncanonical RRM with a negatively charged surface in the beta-sheet area contradictory with potential RNA binding activity. Instead, eIF3j, which is required for stable 40 S ribosome binding of the eIF3 complex, specifically binds to the rear alpha-helices of the eIF3b-RRM, opposite to its beta-sheet surface. Moreover, we identify that an N-terminal 69-amino acid peptide of eIF3j is sufficient for binding to eIF3b-RRM and that this interaction is essential for eIF3b-RRM recruitment to the 40 S ribosomal subunit. Our results provide the first structure of an important subdomain of a core eIF3 subunit and detailed insights into protein-protein interactions between two eIF3 subunits required for stable eIF3 recruitment to the 40 S subunit.


Modifications in low-density lipoprotein receptor expression affects Cyclosporin A cellular uptake and cytotoxicity.
The purpose of this study was to test the effect of modulating the expression of the human low-density lipoprotein receptor (LDLr) in human embryonic kidney (293T) cells on Cyclosporin A (CsA) cellular uptake and CsA-mediated cytotoxicity. LDLr expression was modulated using RNA interference (RNAi) and an LDLr overexpression plasmid. One of the small-interfering RNA (siRNA) constructs, LDLr-792, showed a 60% decrease in LDLr protein expression. The downregulation effect was specific as transfection with an annexin V (AxV) siRNA construct did not decrease LDLr expression levels. AxV and ABCA1 expression levels were not affected in the cells transfected with LDLr-792 (LDLr(LOW) cells) compared to the controls. At a functional level, fluorescent low-density lipoprotein (LDL) (DiI-LDL) internalization in the LDLr(LOW) cells was decreased (30%) compared to control cells. We tested the dose-dependent cytotoxicity induced by CsA using a respiration assay. We found a decrease in CsA-mediated cytotoxicity in the range of CsA doses studied (1-10 microg/mL) in the LDLr(LOW) cells compared to the pSHAG-transfected cells, reaching a statistical significance at 10 microg/mL CsA. At higher CsA doses we found a significant decrease in LDLr expression. When the control and LDLr(LOW) cells were treated with another cytotoxic drug, gentamycin, there was no difference in the cell viability, suggesting that this effect is specific for CsA. We confirmed the association of LDLr expression levels with CsA uptake by overexpressing the LDLr. The LDLr overexpressing cells showed an enhanced uptake of radiolabelled CsA. Taken together these results suggest that CsA internalization and cytotoxicity are affected by the LDL receptor expression levels.


MAXILLOFACIAL TRAUMA, ETIOLOGY AND PROFILE OF PATIENTS: AN EXPLORATORY STUDY.
To describe the profile of patients with facial trauma admitted in a hospital located in a metropolitan area of Northeast Brazil. A cross-sectional and exploratory study was performed. A total of 244 cases were in agreement with the eligibility criteria. The variables include the sociodemographic characteristics of patients, etiology, type of trauma, treatment modalities, length of stay in a hospital and quarter of care. Descriptive statistics and Cluster Analysis were performed. The average age of patients was 31.16 years (SD = 15.17 years) and average hospitalization was 6.32 days (SD = 7.75 days). It was verified the automatic formation of four clusters with different profiles of patients. The variables which most contributed to the external differentiation between clusters were: length of stay in a hospital (p <0.001), etiology (p <0.001), type of facial trauma (p <0.001), presence of associated trauma (p <0.001), treatment modalities (p <0.001) and quarter of care (p <0.001). The most of patients were men, victims of traffic accidents, which suffered fracture of zygomatic complex and underwent surgery. Level of Evidence III, Retrospective Study.


Reaction sampling and reactivity prediction using the stochastic surface walking method.
The prediction of chemical reactivity and thus the design of new reaction systems are the key challenges in chemistry. Here, we develop an unbiased general-purpose reaction sampling method, the stochastic surface walking based reaction sampling (SSW-RS) method, and show that the new method is a promising solution for reactivity prediction of complex reaction systems. The SSW-RS method is capable of sampling both the configuration space of the reactant and the reaction space of pathways, owing to the combination of two recently developed theoretical methods, namely, the stochastic surface walking (SSW) method for potential energy surface (PES) exploration and the double-ended surface walking (DESW) method for building pathways. By integrating with first principles calculations, we show that the SSW-RS method can be applied to investigate the kinetics of complex organic reactions featuring many possible reaction channels and complex hydrogen-bonding networks, as demonstrated here using two examples, epoxypropane hydrolysis in aqueous solution and β-d-glucopyranose decomposition. Our results show that simultaneous sampling of the soft hydrogen-bonding conformations and the chemical reactions involving hard bond making/breaking can be achieved in the SSW-RS simulation, and the mechanism and kinetics can be predicted without a priori information on the system. Unexpected new chemistry for these reactions is revealed and discussed. In particular, despite many possible pathways for β-d-glucopyranose decomposition, the SSW-RS shows that only β-d-glucose and levoglucosan are kinetically preferred direct products and the 5- or 7-member ring products should be secondary products derived from β-d-glucose or levoglucosan. As a general tool for reactivity prediction, the SSW-RS opens a new route for the design of rational reactions.


Ulk1/Rab9-mediated alternative mitophagy confers cardioprotection during energy stress.
The heart relies on mitochondria-derived energy production for continuous contraction and relaxation; therefore, the maintenance of a pool of healthy mitochondria is essential for sustaining normal cardiac performance. Mitophagy serves as a critical process for maintaining mitochondrial quality control and involves the PTEN-induced kinase 1/Parkin (Pink1/Parkin) pathway and autophagosomes labeled with the autophagy proteins autophagy-related 7 (ATG) and light chain 3 (LC3). In this issue of the JCI, Saito and colleagues identify an alternative pathway for mitophagy that utilizes the serine/threonine protein kinase Unc-51-like kinase 1 (Ulk1) and the small GTPase Rab9 to clear damaged mitochondria independently of conventional autophagy proteins. Together, the results of this study reveal that Ulk1 phosphorylation of Rab9 at serine 179 is critical for alternative mitophagy and cardioprotection under energy stress conditions.


Multimodal Enzyme Delivery and Therapy Enabled by Cell Membrane-Coated Metal-Organic Framework Nanoparticles.
Therapeutic enzymes used for genetic disorders or metabolic diseases oftentimes suffer from suboptimal pharmacokinetics and stability. Nanodelivery systems have shown considerable promise for improving the performance of enzyme therapies. Here, we develop a cell membrane-camouflaged metal-organic framework (MOF) system with enhanced biocompatibility and functionality. The MOF core can efficiently encapsulate enzymes while maintaining their bioactivity. After the introduction of natural cell membrane coatings, the resulting nanoformulations can be safely administered in vivo. The surface receptors on the membrane can also provide additional functionalities that synergize with the encapsulated enzyme to target disease pathology from multiple dimensions. Employing uricase as a model enzyme, we demonstrate the utility of this approach in multiple animal disease models. The results support the use of cell membrane-coated MOFs for enzyme delivery, and this strategy could be leveraged to improve the usefulness of enzyme-based therapies for managing a wide range of important human health conditions.


Expression of NKp46 Splice Variants in Nasal Lavage Following Respiratory Viral Infection: Domain 1-Negative Isoforms Predominate and Manifest Higher Activity.
The natural killer (NK) cell activating receptor NKp46/NCR1 plays a critical role in elimination of virus-infected and tumor cells. The NCR1 gene can be transcribed into five different splice variants, but the functional importance and physiological distribution of NKp46 isoforms are not yet fully understood. Here, we shed light on differential expression of NKp46 splice variants in viral respiratory tract infections and their functional difference at the cellular level. NKp46 was the most predominantly expressed natural cytotoxicity receptor in the nasal lavage of patients infected with four respiratory viruses: respiratory syncytia virus, adenovirus, human metapneumovirus, or influenza A. Expression of NKp30 was far lower and NKp44 was absent in all patients. Domain 1-negative NKp46 splice variants (i.e., NKp46 isoform d) were the predominantly expressed isoform in nasal lavage following viral infections. Using our unique anti-NKp46 mAb, D2-9A5, which recognizes the D2 extracellular domain, and a commercial anti-NKp46 mAb, 9E2, which recognizes D1 domain, allowed us to identify a small subset of NKp46 D1-negative splice variant-expressing cells within cultured human primary NK cells. This NKp46 D1-negative subset also showed higher degranulation efficiency in term of CD107a surface expression. NK-92 cell lines expressing NKp46 D1-negative and NKp46 D1-positive splice variants also showed functional differences when interacting with targets. A NKp46 D1-negative isoform-expressing NK-92 cell line showed enhanced degranulation activity. To our knowledge, we provide the first evidence showing the physiological distribution and functional importance of human NKp46 splice variants under pathological conditions.


Increased nutritional value in food crops.
Modern agriculture and horticulture must combine two objectives that seem to be almost mutually exclusive: to satisfy the nutritional needs of an increasing human population and to minimize the negative impact on the environment. These two objectives are included in the Goal 2 of the 2030 Agenda for Sustainable Development of the United Nations: 'End hunger, achieve food security and improved nutrition and promote sustainable agriculture'. Enhancing the nutritional levels of vegetables would improve nutrient intake without requiring an increase in consumption. In this context, the use of beneficial rhizospheric microorganisms for improving, not only growth and yield, but also the nutrient quality of crops represents a promising tool that may respond to the challenges for modern agriculture and horticulture and represents an alternative to the genetic engineering of crops. This paper summarizes the state of the art, the current difficulties associated to the use of rhizospheric microorganisms as enhancers of the nutritional quality of food crops as well as the future prospects.


Does hot weather affect work-related injury? A case-crossover study in Guangzhou, China.
Despite increasing concerns about the health effects of climate change, the extent to which workers are affected by hot weather is not well documented. This study aims to investigate the association between high temperatures and work-related injuries using data from a large subtropical city in China. We used workers' compensation claims to identify work-related injuries in Guangzhou, China during 2011-2012. To feature the heat effect, the study period was restricted to the warm seasons in Guangzhou (1 May-31 October). We conducted a time-stratified case-crossover study to examine the association between ambient outdoor temperatures, including daily maximum and minimum temperatures, and cases of work-related injury. The relationships were assessed using conditional Poisson regression models. Overall, a total of 5418 workers' compensation claims were included over the study period. Both maximum and minimum temperatures were significantly associated with work-related injuries, but associations varied by subgroup. One °C increase in maximum temperature was associated with a 1.4% (RR = 1.014, 95%CIs 1.012-1.017) increase in daily injury claims. Significant associations were seen for male and middle-aged workers, workers in small and medium-sized enterprises, and those working in manufacturing sector. And 1 °C increase in minimum temperature was associated with 1.7% (RR = 1.017, 95%CIs 1.012-1.021) increase in daily injury claims. Significant associations were observed for female and middle-aged workers, workers in large-sized enterprises, and those working in transport and construction sectors. We found a higher risk of work-related injuries due to hot weather in Guangzhou, China. This study provides important epidemiological evidence for policy-makers and industry that may assist in the formulation of occupational safety and climate adaptation strategies.


Ultrafast excited-state dynamics in the green fluorescent protein variant S65T/H148D. 1. Mutagenesis and structural studies.
Wild type green fluorescent protein (wt-GFP) and the variant S65T/H148D each exhibit two absorption bands, A and B, which are associated with the protonated and deprotonated chromophores, respectively. Excitation of either band leads to green emission. In wt-GFP, excitation of band A ( approximately 395 nm) leads to green emission with a rise time of 10-15 ps, due to excited-state proton transfer (ESPT) from the chromophore hydroxyl group to an acceptor. This process produces an anionic excited-state intermediate I* that subsequently emits a green photon. In the variant S65T/H148D, the A band absorbance maximum is red-shifted to approximately 415 nm, and as detailed in the accompanying papers, when the A band is excited, green fluorescence appears with a rise time shorter than the instrument time resolution ( approximately 170 fs). On the basis of the steady-state spectroscopy and high-resolution crystal structures of several variants described herein, it is proposed that in S65T/H148D, the red shift of absorption band A and the ultrafast appearance of green fluorescence upon excitation of band A are due to a very short (<or=2.4 A), and possibly low-barrier, hydrogen bond between the chromophore hydroxyl and introduced Asp148.


Muir-Torre syndrome.
Muir-Torre syndrome (MTS) is a rare autosomal-dominant genodermatosis characterized by sebaceous neoplasms and one or more visceral malignancies. Sebaceous tumors include sebaceous adenoma and carcinoma, which may be solitary or multiple. Visceral malignancies most often arise in the colorectum and endometrium. Because a subset of patients with phenotypic MTS will have germline mutations in the DNA mismatch repair genes hMSH2 and hMLH1, MTS is considered a phenotypic subtype of Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome), in which inherited defects in DNA mismatch repair genes result in microsatellite instability. Pathologists have an important role in the early detection and initial diagnosis of MTS: identification of at-risk individuals allows appropriate screening and surveillance for visceral malignancies, thereby reducing morbidity and mortality. Herein, we describe the clinicopathologic features of MTS.


Asymptomatic Versus Symptomatic Idiopathic Intracranial Hypertension in Children.
Idiopathic intracranial hypertension is a rare neurologic condition characterized by elevated intracranial pressure with normal cerebrospinal fluid analysis and neuroimaging. A subset of pediatric idiopathic intracranial hypertension patients are coincidentally found to have papilledema and elevated intracranial pressure without symptoms (eg, headache, visual blurring, tinnitus). This study aims to investigate the features of asymptomatic pediatric idiopathic intracranial hypertension. Retrospective case-control study of patients aged 0 to 18 years who received idiopathic intracranial hypertension diagnosis from 2005 to 2016. Subjects were included if they met established diagnostic criteria for idiopathic intracranial hypertension diagnosis. Subjects were classified as symptomatic if they presented with 1 symptom related to elevated intracranial pressure, and asymptomatic if no symptoms were present. Statistical analysis was performed to compare the 2 groups. 12 (22.6%) of 53 pediatric idiopathic intracranial hypertension subjects were asymptomatic. Compared to symptomatic idiopathic intracranial hypertension, asymptomatic idiopathic intracranial hypertension had younger age of onset, lower initial opening pressure on lumbar puncture, lower optic nerve edema grades bilaterally, lower likelihood of globe flattening on magnetic resonance imaging (MRI), and smaller required dose of acetazolamide for resolution of papilledema (all P < .05). Asymptomatic idiopathic intracranial hypertension is common among pediatric patients with papilledema and is an important disease entity that requires special clinical management. It may exist as a milder version of idiopathic intracranial hypertension that occurs in younger children, or as a precursor state that later evolves into symptomatic disease.


Evaluation of cytotoxicity of some common ophthalmic drugs.
The article "Evaluation of cytotoxicity of some common ophthalmic drugs" by M. Li, X.-M. Chen, J.-J. Liu, D.-M. Wang, L. Gan, X. Lv, Y. Qiao, published in Eur Rev Med Pharmacol Sci 2015; 19 (11): 1945-1950 has been withdrawn.


The early response in fMRI: a modeling approach.
A mathematical model is presented to study the generation of the early response phenomenon in fMRI. Initially, we demonstrate that a simple combination of the changes taking place in cerebral blood volume and flow could create the transient early signal decrease, by analyzing their effects on total per voxel deoxyhemoglobin content. Also, we examine the traditional paradigm for the early response: that it may be caused by an early burst of oxidative metabolism and conclude that such changes also explain the early transient response. We suggest that the volume effect may play a role in the generation of the early response phenomenon along with an early upregulation of oxidative metabolism, and that this role may be important if the early response phenomenon is shown to occur at the level of the venous blood pool, and not just at the level of the capillary bed.


Job dynamics of veterinary professionals in an academic research institution. II. Veterinary technician attendance, absenteeism, and pay distribution.
To understand and better manage attendance and overtime for a team of veterinary technicians, a retrospective analysis of the attendance and time card records was done over a 2-y period. The findings show that veterinary technicians were in the workplace for a combination of straight time and overtime hours for approximately 89% of all compensated hours. The remainder of paid compensation was for vacation (4%), holidays (4%), and sick leave (3%). This team of veterinary technicians earned significantly more overtime hours, as much as 9% of total annual compensated hours, than the reported 3% standard for animal resources programs nationwide. The majority of overtime hours (61%) were for assigned weekend and holiday duty and after-hours veterinary medical emergencies. Veterinary technicians expended sick leave at 75% of the amount accrued and at a statistically significantly rate 65% higher than the national average for unscheduled absences for hourly personnel in animal resources programs. Because the direct cost of absenteeism may exceed 645 dollars per employee annually and because work inappropriately done at premium pay outside of business hours is a controllable expense, sound management of attendance and overtime is important in cost containment for animal resources programs.


Safety and reliability of the sealing cuff pressure of the Microcuff pediatric tracheal tube for prevention of post-extubation morbidity in children: A comparative study.
The objective of this study is to evaluate the efficacy and safety of sealing pressure as an inflation technique of the Microcuff pediatric tracheal cuffed tube. A total of 60 children were enrolled in this study. After induction of anesthesia and intubation with Microcuff pediatric tracheal tube, patients were randomly assigned, to one of the three groups. Control group (n = 20) the cuff was inflated to a cuff pressure of 20 cm H2O; sealing group (n = 20) the cuff was inflated to prevent the air leak at peak airway pressure of 20 cm H2O and the finger group (n = 20) the cuff was inflated to a suitable pressure using the finger estimation. Tracheal leak, incidence and severity of post-extubation cough, stridor, sore throat and hoarseness were recorded. The cuff pressure as well as the volume of air to fill the cuff was significantly low in the sealing group when compared with the control group (P < 0.001); however, their values were significantly high in the finger group compared with both the control and the sealing group (P < 0.001). The incidence and severity of sore throat were significantly high in the finger group compared with both the control and the sealing group (P = 0.0009 and P = 0.0026). Three patients in the control group developed air leak around the endotracheal tube cuff. The incidence and severity of other complications were similar in the three groups. In pediatric N2O, free general anesthesia using Microcuff pediatric tracheal tub, sealing cuff pressure is safer than finger palpation technique regarding post-extubation morbidities and more reliable than recommended safe pressure in prevention of the air leak.


Association of exhaled nitric oxide to asthma burden in asthmatics on inhaled corticosteroids.
Fractional exhaled nitric oxide (FENO) is a marker of airway inflammation. Its role in assessing asthma burden in clinical practice needs more study. To determine whether higher FENO levels are associated with greater asthma burden. This was a multicenter cross-sectional retrospective study of atopic 12- to 56-year-old persistent asthmatics on inhaled corticosteroids (ICS). Questionnaire and 1-year retrospective administrative data were used to analyze by unadjusted and adjusted robust Poisson regression (relative risks) and negative binomial regression [incidence rate ratios (IRRs)] the associations of masked FENO levels (NIOX MINO®) to short-acting beta-agonist (SABA) dispensings and oral corticosteroid (OCS) use in the past year independent of spirometry and an asthma control tool [Asthma Control Test (ACT)]. FENO levels ranged from 7-215 ppb (median 28 ppb) in 325 patients. Higher FENO levels significantly correlated with more SABA dispensings and OCS courses in the past year, lower FEV(1)% predicted levels, but not ACT score. FENO highest (≥48 ppb) versus lowest (≤19 ppb) quartile values were associated independently in the past year with ≥7 SABA canisters dispensed (relative risk=2.40, 95% CI=1.25-4.62) and total number of SABA canisters dispensed (IRR=1.46, 95% CI=1.12-1.99) and with ≥1 OCS course (relative risk=1.48, 95% CI=1.06-2.07) and total number of OCS courses (IRR=1.71, 95% CI=1.09-2.66). The significant independent relationship of higher FENO levels to increasing SABA dispensings and OCS courses was confirmed by linear trend analyses. Independent and clinically meaningful associations between higher FENO levels and greater asthma burden during a prior year in persistent asthmatics on ICS suggest that FENO measurement may be a complementary tool to help clinicians assess asthma burden.


Sensor Histidine Kinase NarQ Activates via Helical Rotation, Diagonal Scissoring, and Eventually Piston-Like Shifts.
Membrane-embedded sensor histidine kinases (HKs) and chemoreceptors are used ubiquitously by bacteria and archaea to percept the environment, and are often crucial for their survival and pathogenicity. The proteins can transmit the signal from the sensor domain to the catalytic kinase domain reliably over the span of several hundreds of angstroms, and regulate the activity of the cognate response regulator proteins, with which they form two-component signaling systems (TCSs). Several mechanisms of transmembrane signal transduction in TCS receptors have been proposed, dubbed (swinging) piston, helical rotation, and diagonal scissoring. Yet, despite decades of studies, there is no consensus on whether these mechanisms are common for all TCS receptors. Here, we extend our previous work on Escherichia coli nitrate/nitrite sensor kinase NarQ. We determined a crystallographic structure of the sensor-TM-HAMP fragment of the R50S mutant, which, unexpectedly, was found in a ligand-bound-like conformation, despite an inability to bind nitrate. Subsequently, we reanalyzed the structures of the ligand-free and ligand-bound NarQ and NarX sensor domains, and conducted extensive molecular dynamics simulations of ligand-free and ligand-bound wild type and mutated NarQ. Based on the data, we show that binding of nitrate to NarQ causes, first and foremost, helical rotation and diagonal scissoring of the α-helices at the core of the sensor domain. These conformational changes are accompanied by a subtle piston-like motion, which is amplified by a switch in the secondary structure of the linker between the sensor and TM domains. We conclude that helical rotation, diagonal scissoring, and piston are simply different degrees of freedom in coiled-coil proteins and are not mutually exclusive in NarQ, and likely in other nitrate sensors and TCS proteins as well.


The law and practice associated with advance directives in Canada and Australia: similarities, differences and debates.
This article is a summary of research that investigated the Canadian and Australian legislative framework associated with advance directives in health care. The research focused on the context in which older people are encouraged to use advance directives. These are directions about refusal of medical treatment given in advance of incompetence. An advance directive may be given in a written document (living will) expressing one's wishes, by appointing another person (proxy) to make the decisions, or as a combination of the two. A lack of consistency and clarity about the terminology was found in both countries. This could be a barrier for older people to express their wishes in advance. Several confusing issues were also identified with the legislation related to advance directives. There appears to be a move towards appointing a substitute decision-maker, but with significant differences across the Australian States and in Canadian Provinces. The "conversation" about future decisions emerged as an important theme, together with an emphasis on the process of "advance care planning" replacing the focus on advance directive forms.


Do Histopathologic Parameters Affect the Rate of Recurrence in Auricular Keloid Patients?
The purpose of this study was to describe pathologic features in patients with auricular keloids and estimate its influence on the recurrence of the keloid disease. This study was done in 38 patients reaching the pathologic diagnosis of auricular keloids from March 2012 to February 2014. All patients were female. The average age was 24.06 ± 5.03 (18-47) and patients 21 to 23 showed the highest prevalence (38.2%). The gross morphology of auricular keloids based on our previously introduced classification was pedunculated type (25 patients, 65.8%) and sessile type (13 patients, 34.2%). A detailed case history was taken for every patient with special reference to clinical parameters, such as patient age, gross morphology, and various pathologic parameters, such as margin involvement, keloidal collagen area, perivascular lymphocytic infiltration in upper dermis, perivascular lymphocytic infiltration in keloid, presence of epidermal cyst, presence of foamy histiocytes, foreign body reaction, and superficial dermal involvement. Patient demographics and pathologic characteristics were evaluated as possible risk factors for keloid recurrence. Recurrence was defined as any elevation of the scar or extension beyond the original surgical field.Of these patients, 86.8% had successful treatment of their auricular keloids, whereas 13.2% had recurrences. Based on a current study, there was no significant correlation between the clinicopathologic findings and keloid recurrence.


Correlation between efficacy of the EGFR tyrosine kinase inhibitor and serum tumor markers in lung adenocarcinoma patients.
The mutation at epidermal growth factor receptor (EGFR) is a clinical predictor of EGFR tyrosine kinase inhibitors (TKI) in patients with non-small cell lung cancer (NSCLC). The serum carcinoembryonic antigen (CEA) level was regarded as a predictive factor for the EGFR-TKI efficacy. Are there any other serum markers? This study analysed the correlation between the EGFR-TKI treatment effect and multiple serum tumor markers only in lung adenocarcinoma to find serum predictive markers for the EGFR-TKI efficacy. Clinical features, survival time, and serum tumor marker levels before EGFR-TKI treatment were analysed, retrospectively, in 48 advanced lung adenocarcinoma patients treated with EGFR-TKI. With EGFR-TKI treatment, the response rate was 58.3% and disease control rate was 65.6% in lung adenocarcinoma; median survival time was 13.2 months. The efficiency of EGFR-TKI significantly correlated with smoking history and the serum level of CEA and CA199 (p < 0.05). Patients with a higher level of serum CEA and CA199 had a higher disease control rate and longer survival time (p < 0.05). Serum CA199 and CEA levels can predict the response of EGFR-TKI in lung adenocarcinoma patients.


[Pathological patterns in neonatal EEG before 30 weeks of gestational age].
Pathological features on very premature EEG concern background abnormalities and abnormal patterns. Positive rolandic sharp waves keep an important place regarding diagnosis and prognosis. Background abnormalities give essential complementary informations. Unusual patterns (abnormal localisation or morphological aspect, high amplitude) remain early markers of cerebral lesions. Analysis of these pathological features must always take into account treatment given to the baby, which can by itself modify the EEG.


Selective adsorption of plant products.
The results from this study demonstrate that neutral resins can selectively concentrate specific indole alkaloids from dilute aqueous mixtures. Adsorption was observed to provide a one to two order of magnitude improvement in concentrating these alkaloids, as compared to an equivalent single-staged extraction. Since the sorption correlates with the concentration of the neutral form of the dissolved alkaloid, the adsorption is dependent on both the pH of the medium and the pKa of the alkaloids. Also, adsorption is dependent on specific sorbent-sorbate characteristics. In this study, by exploiting differences in the acid-base properties and the sorption characteristics of specific indole alkaloids, separation factors of 20-30 were observed. Although this behavior is valuable for analytical separations, the present study considers the application to the primary recovery of alkaloids from plant cell processes. Throughout this study it was also observed that the polycarboxylic ester resin (XAD-7) behaved quite differently from the styrene divinylbenzene resin (XAD-4). Despite a lower capacity, the XAD-7 resin was considerably more selective in adsorbing indole alkaloids than the XAD-4 resin. These alkaloids could also be desorbed from the XAD-7 resin by acidifying the liquid, while organic solvents were required to desorb these compounds from the XAD-4 resin.


Heritability of diabetes mellitus in Ethiopian diabetics.
A prospective case control study was conducted in 859 diabetic probands and 1059 nondiabetic controls. These were interviewed for history of diabetes mellitus among their first degree relatives. The protocol also included second and third degree relatives. The prevalence of diabetes mellitus in the first degree relatives of cases and controls showed a statistically significant difference (Z = 6.7564 and P = 0.00000). Similarly, the prevalence of diabetes among the second and third degree relatives of cases and controls differed significantly (Z = 2.74, P = 0.006). There were 445 non-insulin dependent diabetes mellitus (NIDDM) and 414 insulin dependent diabetes mellitus (IDDM) in the diabetic probands. There was more family history of diabetes mellitus among the first degree relatives of NIDDM than IDDM and the difference is statistically significant (Z = 4.076, P = 0000). The second and third degree relatives of NIDDM and IDDM also differed significantly (Z = 4.05, P = 00005). This study indicates that heredity plays an important role in the genesis of diabetes mellitus in Ethiopian diabetics.


Studies of the pathways open to copper water oxidation catalysts containing proximal hydroxy groups during basic electrocatalysis.
Water oxidation can lead to a sustainable source of energy, but for water oxidation catalysts to be economical they must use earth abundant metals. We report here 2:1 6,6'-dihydroxybipyridine (6,6'-dhbp)/copper complexes that are capable of electrocatalytic water oxidation in aqueous base (pH = 10-14). Two crystal structures of the complex that contains 6,6'-dhbp and copper(II) in a ratio of 2:1 (complex 1) are presented at different protonation states. The thermodynamic acid dissociation constants were measured for complex 1, and these show that the complex is fully deprotonated above pH = 8.3 (i.e., under water oxidation conditions). CW-EPR, ENDOR, and HYSCORE spectroscopy confirmed that the 6,6'-dhbp ligand is bound to the copper ion over a wide pH range which shows how pH influences precatalyst structure. Additional copper(II) complexes were synthesized from the ligands 4,4'-dhbp (complex 2) and 6,6'-dimethoxybipyridine (complexes 3 and 4). A zinc complex of 6,6'-dhbp was also synthesized (complex 5). Crystal structures are reported for 1 (in two protonation states), 3, 4, and 5. Water oxidation studies using several of the above compounds (1, 2, 4, and 5) at pH = 12.6 have illustrated that both copper and proximal OH groups are necessary for water oxidation at a low overpotential. Our most active catalyst 1 was found to have an overpotential of 477 mV for water oxidation at a moderate rate of kcat = 0.356 s(-1) with a competing irreversible oxidation event at a rate of 1.082 s(-1). Furthermore, our combined work supports previous observations in which OH/O(-) groups on the bipyridine rings can hydrogen bond with metal bound substrate, support unusual binding modes, and potentially facilitate proton coupled electron transfer.


The future of behavioral sleep medicine: a report on the presentations given at the Ponte Vedra Behavioral Sleep Medicine Consensus Conference, March 27-29, 2009.
A major goal of the Behavioral Sleep Medicine Consensus Conference held in Ponte Vedra, Florida on March 27 through 29, 2009 was to have 15 key opinion leaders provide the latest information on their areas of expertise. Those leaders represented the breadth of the behavioral sleep medicine field (pediatrics, adults, insomnia, PAP adherence, and circadian rhythm disorders) and included clinicians and researchers from a variety of settings (academia, private practice, the military, and primary care). The presentations highlighted the milestones already achieved by the field (critical mass, solid empirical base, 30+ training programs, certification, dedicated journal, and dedicated textbook), as well as important future directions (more clinical research, public relations campaigns, training, and reimbursement).