Mechanistic study of laser desorption/ionization of small molecules on graphene oxide multilayer films.
Graphene and graphene oxide (GO) films have been explored to develop an efficient laser desorption/ionization mass spectrometry (LDI-MS) platform for the analysis of chemically and biologically important small molecules. The GO films were prepared by layer-by-layer (LBL) assembly cycles (one to ten layers) with precisely controlled thickness and surface roughness which are important structural factors for laser energy absorption capacity and laser energy transfer for efficient LDI-MS analysis. Amino acids, saccharides, and pyrenylated molecules were analyzed by LDI-MS on the LBL assembled GO films to reveal their structural influence on LDI-MS analysis of small molecules. Then, the structural influence of LBL assembled GO films on synergistic effect was investigated to develop an efficient and widely applicable LDI-MS analysis platform with an additional multiwalled carbon nanotube (MWCNT) layer. We found that the optimum number of GO film layers for LDI-MS analysis was dependent on the chemical structures of small molecules, and the laser energy threshold needed for LDI of small molecules on GO/MWCNT films could be lowered as the number of LBL assembled GO films increased underneath the MWCNT layer.


Topography-guided neutralization technique for the management of flap complication in laser in situ keratomileusis.
A 29-year-old male was referred following a flap loss after the creation of a thin, irregular flap with a visual acuity of logMAR 0.1 with -2.0 DS-2.75 DC × 175°. Corneal topography and anterior segment optical coherence tomography revealed an irregular corneal curvature and epithelial profile. Phototherapeutic keratectomy (PTK) followed by Topography - Guided Custom Ablation Treatment (TCAT), as a modification of the topographic neutralization technique protocol, was planned to regularize the corneal surface and treat the residual refractive error. Postoperatively, the patient showed a best-corrected visual acuity of logMAR 0 with a refractive error of -1 DC × 90°. Regularization of topography and epithelial thickness was seen along with a reduction in astigmatism and higher order aberrations. We report the use of PTK followed by TCAT as a novel method to treat a case of intraoperative flap loss during laser in situ keratomileusis.


The effect of intraoperative dexmedetomidine on acute kidney injury after pediatric congenital heart surgery: A prospective randomized trial.
Dexmedetomidine has been reported to have a renal protective effect after adult open heart surgery. The authors hypothesized that intraoperative infusion of dexmedetomidine would attenuate the decrease in renal function after pediatric open heart surgery. Twenty-nine pediatric patients (1-6 years) scheduled for atrial or ventricular septal defect repair were randomly assigned to receive either continuous infusion of normal saline (control group, n = 14) or dexmedetomidine (a bolus dose of 0.5 μg/kg and then an infusion of 0.5 μg/kg/h) (dexmedetomidine group, n = 15) from anesthesia induction to the end of cardiopulmonary bypass. Serum creatinine (Scr) was measured before surgery (T0), 10 minutes after anesthesia induction (T1), 5 minutes after cardiopulmonary bypass weaning (T2), 2 hours after T2 (T3), and after postoperative day 1 (POD1) and postoperative day 2 (POD2) and estimated glomerular filtration rates (eGFRs) were calculated. Renal biomarkers were measured at T1, T2, and T3. Acute kidney injury (AKI) was defined as an absolute increase in Scr of ≥ 0.3 mg/dL or a percent increase in Scr of ≥50%. The incidence of AKI during the perioperative period was significantly higher in the control group than in the dexmedetomidine group (64% [9/14] vs 27% [4/15], P = .042). eGFR was significantly lower in the control group than in the dexmedetomidine group at T2 (72.6 ± 15.1 vs 83.9 ± 13.5, P = .044) and T3 (73.4 ± 15.4 vs 86.7 ± 15.9, P = .03). Intraoperative infusion of dexmedetomidine may reduce the incidence of AKI and suppress post-bypass eGFR decline.


Evaluation of musculoskeletal injuries after the 2023 Kahramanmaras earthquake: A local hospital experience.
The aim of this study was to evaluate musculoskeletal injuries, clinical follow-ups and treatments of trauma patients admitted to our hospital after the 2023 Kahramanmaras earthquake. Between February 6th, 2023 and February 16th, 2023, a total of 957 trauma patients (452 males, 505 females; mean age: 36.2±19.9 years; range, 0 to 97 years) who were affected by the earthquake were retrospectively analyzed. Age, sex, presence of orthopedic consultation, diagnosis of open/closed fracture, diagnosis of dislocation, presence and classification of soft tissue injury, additional system injury, preoperative and postoperative neurovascular examination status, presence of compartment syndrome, conservative/surgical applications, operation side, fasciotomy surgery and level, amputation surgery and level, length of stay in the hospital and intensive care unit (ICU), the Mangled Extremity Severity Score (MESS) score were collected. A total of 811 of the survivors were Turkish and 146 were Syrians. Of 957 earthquake victims, 40% had soft tissue injuries, 19% had closed fractures, 8.9% had other system injuries, 7.7% had crush injuries, 4.1% had nerve injuries, 2.1% had compartment syndrome, 2.1% had vascular injury, 1.8% had dislocation, and 1.7% had open fracture. Surgical or conservative treatments were applied to 574 patients with musculoskeletal injuries. Conservative treatment was applied to 322 of 574 patients and surgical procedure was applied to 252 patients. The highest patient density is experienced within the first 24 h after a devastating earthquake. The most common injuries due to high-energy trauma are isolated soft tissue injuries and fractures. The definition of the demographic characteristics and clinical outcomes of earthquake patients is critical to the development of preparedness, response, and recovery policies for future disasters..


Chemistry and Enzymology of Disulfide Cross-Linking in Proteins.
Cysteine thiols are among the most reactive functional groups in proteins, and their pairing in disulfide linkages is a common post-translational modification in proteins entering the secretory pathway. This modest amino acid alteration, the mere removal of a pair of hydrogen atoms from juxtaposed cysteine residues, contrasts with the substantial changes that characterize most other post-translational reactions. However, the wide variety of proteins that contain disulfides, the profound impact of cross-linking on the behavior of the protein polymer, the numerous and diverse players in intracellular pathways for disulfide formation, and the distinct biological settings in which disulfide bond formation can take place belie the simplicity of the process. Here we lay the groundwork for appreciating the mechanisms and consequences of disulfide bond formation in vivo by reviewing chemical principles underlying cysteine pairing and oxidation. We then show how enzymes tune redox-active cofactors and recruit oxidants to improve the specificity and efficiency of disulfide formation. Finally, we discuss disulfide bond formation in a cellular context and identify important principles that contribute to productive thiol oxidation in complex, crowded, dynamic environments.


Revisiting the energy-economy-environment relationships for attaining environmental sustainability: evidence from Belt and Road Initiative countries.
The Belt and Road Initiative (BRI) is an ambitious development project initiated by the Chinese government to foster economic progress worldwide. In this regard, this study aims to investigate the dynamics of energy, economy, and environment among 42 BRI developing countries using an annual frequency panel dataset from 1995 to 2019. The major findings from the econometric analyses revealed that higher levels of energy consumption, economic growth, population growth rate, and FDI inflows exhibit adverse environmental consequences by boosting the CO2 emission figures of the selected developing BRI member nations. However, it is interesting to observe that exploiting renewable energy sources, which are relatively cleaner compared to the traditionally-consumed fossil fuels, and fostering agricultural sector development can significantly improve environmental well-being by curbing the emission levels further. On the other hand, financial development is found to be ineffective in explaining the variations in the CO2 emission figures of the selected countries. Besides, the causality analysis shows that higher energy consumption, FDI inflows, and agricultural development cause environmental pollution by boosting CO2 emissions. However, economic growth, technology development, financial progress, and renewable energy consumption are evidenced to exhibit bidirectional causal associations with CO2 emissions. In line with these findings, several relevant policies can be recommended for the BRI to be environmentally sustainable.


Dairy fat blend improves brain DHA and neuroplasticity and regulates corticosterone in mice.
Mimicking the breast milk lipid composition appears to be necessary for infant formula to cover the brain's needs in n-3 PUFA. In this study, we evaluated the impact of partial replacement of vegetable oil (VL) in infant formula by dairy fat (DL) on docosahexaenoic acid (DHA) brain level, neuroplasticity and corticosterone in mice. Mice were fed with balanced VL or balanced DL diets enriched or not in DHA and arachidonic acid (ARA) from the first day of gestation. Brain DHA level, microglia number, neurogenesis, corticosterone and glucocorticoid receptor expression were measured in the offsprings. DL diet increased DHA and neuroplasticity in the brain of mice at postnatal day (PND) 14 and at adulthood compared to VL. At PND14, ARA and DHA supplementation increased DHA in VL but not in DL mice brain. Importantly, DHA and ARA supplementation further improved neurogenesis and decreased corticosterone level in DL mice at adulthood. In conclusion, dairy lipids improve brain DHA level and neuroplasticity.


[Ranking of cerclage in prophylaxis of premature births].
The results of 196 cases after operation for cerclage are reported. In 133 patients the operation was performed because of cervical incompetence with opening of the cervical canal without contractions. In 63 patients a prophylactic operation was performed for anamnestic reasons. In the group of cervical incompetence the operation resulted in 103 (94.5%) deliveries, 12 of which occurred before the 35th week of gestation. Following prophylactic cerclage, 46 (78.0%) pregnancies ended with a delivery. In the latter group, the rate of abortions was four times higher than in the group with cervical incompetence. In 82.6% the birth weight was higher than 2,500 g; 4.7% of the newborn only had a body weight below 1,500 g. Before performing cerclage in the 196 patients the abortion rate had been 50.5%, which dropped subsequently to 11.2%. Childbirth at term could be achieved after operation in 73.2% of the patients, compared to the previous figure of 34.4% only.


Assessing the validity and reliability of the Turkish version of the Trunk Impairment Scale in stroke patients.
To determine the validity and reliability of the Turkish version of the Trunk impairment scale (TIS), used in the evaluation of somatic, motor, and coordination disturbances in stroke patients, and provide a culturally adapted version for use in the Turkish population. A total of 80 patients who were either hospitalized at our facility and rehabilitated for stroke or admitted at our outpatient clinics were included in this study. Reliability was evaluated by the internal consistency (Cronbach α) and test reproducibility [intra-class correlation coefficient (ICCC)] methods, and validity was evaluated by the correlation between subgroups and the total scores of the TIS and Berg Balance Scale (BBS), Brunnstrom phases, Barthel index (BI), Rivermead mobility index (RMI), and Short Form-36 (SF-36) scores. The mean age of the patients was 63.00±12.1 years. Out of a total of 80 subjects, 34 were female and 46 were male. The reliability of the scale was evaluated by the internal consistency, inter- and intra-observer reliability, and test reproducibility. The findings showed that the Turkish form of the scale was reliable at a good level. The test values were as follows; Cronbach α: >0.70, ICCC: 0.969-1, subgroups and total score comparison: 0. The correlation between TIS and BBS was considerably high in the validity analysis (p<0.001). Further, significant associations among the BI, RMI, KF-36, Brunnstrom, and TIS scores were found (p<0.001), which indicate the structural validity of this scale. TIS is a scale used in measuring the motor derangement that develops after a stroke. It has sufficient reliability, internal consistency, and validity for use in clinical practice and stroke investigations. Our study has shown that TIS used for the evaluation of body balance is valid and reliable for the Turkish population.


Reassessing Diagrams of Cardiac Mechanics: From Otto Frank and Ernest Starling to Hiroyuki Suga.
This article explores the importance of diagrams in the history of the understanding of cardiac function, by comparing Ernest Starling's famous "Law of the Heart" (1918) with the mathematically based view of cardiac mechanics put forward by Otto Frank (1897). Whereas Frank's diagrams gained influence in German cardio-physiological publications, they were widely unknown abroad until 1969, when Hiroyuki Suga began to present similar approaches for warm-blooded animals as Frank had done for the frog. Suga succeeded in correlating the pressure volume area (PVA)-a composite of Frank's work loop plus the area of remaining potential energy-with the oxygen consumption of the beating heart. With the concept of time-varying elastance as an index of cardiac contractility, Suga's approach became attractive for clinical applications, and Daniel Burkhoff and colleagues were able to use these insights for real-time, interactive simulations of the cardiovascular system. Such tools can be used for exploring basic hemodynamic principles and, thanks to technical developments of miniature pumps within the same time frame (Καιρός, the "right moment," or "the opportune"), to test the effects of device-based treatment for heart failure. These outcomes confirm that old analyses of the heart's activity may still be useful today.


The carboxyl terminus of heat shock protein 70-interacting protein (CHIP) participates in high glucose-induced cardiac injury.
The carboxyl terminus of heat shock protein 70-interacting protein (CHIP) is confirmed to have a protective effect on the myocardium, but its effect on diabetic cardiomyopathy is unclear. Small interfering RNA (siRNA) was used for knockdown experiments in neonatal rat cardiomyocytes to examine the function of CHIP in high glucose-induced injury. High glucose stimulated the production of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate oxidase (NOX), interleukin-1β (IL-1β), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) production. However, cardiomyocytes lacking CHIP suffered from increased oxidative stress and inflammatory responses. High glucose increased the expression of Bax and caspase-3 mRNAs, decreased the expression of Bcl-2 mRNA, and up-regulated the expression of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) proteins. However, upon CHIP knockdown, the expression of Bax and caspase-3 mRNAs increased even further, and the expression of Bcl-2 mRNA was further suppressed. The expression of the phosphorylated p65 and p38 proteins (p-p65 and p-p38) was also further enhanced. Thus, CHIP is a potent cardioprotective molecule.


[Summary of questionnaires on slit skin smear test in clinics, hospitals, and university hospitals].
We have performed a questionnaire to survey the present conditions of the slit skin smear test, a method to diagnose leprosy. The answer was obtained from 40 (93.0%) out of 43 clinics, department of dermatology of university and other hospitals and leprosy sanatoriums. Slit skin smear test was carried out in most institutions. However, when inspection frequency was low, a laboratory technician performed Ziehl-Neelsen staining or its variation using a normal slide glass. A few institutions carried out fluorescence staining. Both physician and technician examined the slides in most cases, however, in more than half of the leprosy sanatoriums, technician was the only person examined. Bacterial index was evaluated in most institutions, while only for the presence of bacteria was examined 5 institutions. Slit skin smear test is simple and easy, but accuracy is different with skills, glass slides to be used and methods for staining and inspection. Supply of the glass slide with a marker, the spread of staining methods, technical improvement of an inspection are demanded in future.


Evaluation of the spiral plating system for the routine assessment of indicator microorganisms in raw ewe's milk.
The numbers of members of different microbial groups in bulk raw ewe's milk used for cheesemaking (46 samples, taken on receipt at the dairy over 1 year) were assayed by the spiral plating system to determine the effectiveness of this method compared with that of widely accepted conventional methods in providing counts. The results indicated that for ewe's milk, the suitability of the spiral plating system depends to a great extent on the microbial group studied. Although "spiral" counts of mesophiles, psychrotrophs, coliforms, and Enterobacteriaceae could be considered equivalent to those obtained by conventional techniques (r > or = 0.90; variance between replicate platings approximately 0.005), the automated method was found not to be suitable for the assessment of other groups of indicator bacteria (thermodurics and enterococci). Counts of lactic acid bacteria and yeasts and molds were affected significantly (P < 0.05) by the plating method, although other statistical parameters were more favorable (r = 0.88 and r = 0.82, respectively; 95% confidence limits within 0.5 log units). Finally, counts of staphylococci, particularly on Baird-Parker medium, showed less variation and higher reproducibility with the spiral method. Nevertheless, for the routine microbiological analysis of ewe's milk, the spiral plating system, with its time-, effort-, and material-saving advantages, is preferred over the conventional method.


Alum and Rainfall Effects on Ionophores in Runoff from Surface-Applied Broiler Litter.
Polyether ionophores, monensin, and salinomycin are commonly used as antiparasitic drugs in broiler production and may be present in broiler litter (bird excreta plus bedding material). Long-term application of broiler litter to pastures may lead to ionophore contamination of surface waters. Because polyether ionophores break down at low pH, we hypothesized that decreasing litter pH with an acidic material such as aluminum sulfate (alum) would reduce ionophore losses to runoff (i.e., monensin and salinomycin concentrations, loads, or amounts lost). We quantified ionophore loss to runoff in response to (i) addition of alum to broiler litter and (ii) length of time between litter application and the first simulated rainfall event. The factorial experiment consisted of unamended (∼pH 9) vs. alum-amended litters (∼pH 6), each combined with simulated rainfall at 0, 2, or 4 wk after litter application. Runoff from alum-amended broiler litter had 33% lower monensin concentration ( < 0.01), 57% lower monensin load ( < 0.01), 48% lower salinomycin concentration ( < 0.01), and 66% lower salinomycin load ( < 0.01) than runoff from unamended broiler litter when averaged across all events of rainfall. Ionophore losses to runoff were also less when rainfall was delayed for 2 or 4 wk after litter application relative to applying rainfall immediately after litter application. While the weather is difficult to predict, our data suggest that ionophore losses in runoff can be reduced if broiler litter applications are made to maximize dry time after application.


Chinese Herbal Medicines Might Improve the Long-Term Clinical Outcomes in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: Results of a Decision-Analytic Markov Model.
Aims. The priority of Chinese herbal medicines (CHMs) plus conventional treatment over conventional treatment alone for acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI) was documented in the 5C trial (chictr.org number: ChiCTR-TRC-07000021). The study was designed to evaluate the 10-year effectiveness of CHMs plus conventional treatment versus conventional treatment alone with decision-analytic model for ACS after PCI. Methods and Results. We constructed a decision-analytic Markov model to compare additional CHMs for 6 months plus conventional treatment versus conventional treatment alone for ACS patients after PCI. Sources of data came from 5C trial and published reports. Outcomes were expressed in terms of quality-adjusted life years (QALYs). Sensitivity analyses were performed to test the robustness of the model. The model predicted that over the 10-year horizon the survival probability was 77.49% in patients with CHMs plus conventional treatment versus 77.29% in patients with conventional treatment alone. In combination with conventional treatment, 6-month CHMs might be associated with a gained 0.20% survival probability and 0.111 accumulated QALYs, respectively. Conclusions. The model suggested that treatment with CHMs, as an adjunctive therapy, in combination with conventional treatment for 6 months might improve the long-term clinical outcome in ACS patients after PCI.


A historical overview of combat stress control units of the U.S. Army.
Combat stress control units have been deployed to the Gulf War, Somalia, Haiti, Guantanamo Bay, Bosnia, and Kosovo. They have been very flexible and useful mental health tools for commanders in both combat and peacekeeping operations for the past decade. In their operational role they have been effective, but their garrison mission remains unclear. This article summarizes the uses, missions, and lessons learned from the various combat stress control missions around the world.


Toward an Earlier Diagnosis of Primary Ciliary Dyskinesia. Which Patients Should Undergo Detailed Diagnostic Testing?
Primary ciliary dyskinesia (PCD) is a rare, heterogeneous, recessive, genetic disorder of motile cilia, leading to chronic upper and lower respiratory symptoms. Prevalence is estimated at around 1:10,000, but many patients remain undiagnosed, whereas others receive the label incorrectly. Proper diagnosis is complicated by the fact that the key symptoms, such as wet cough, chronic rhinitis, and recurrent upper and lower respiratory infection, are common and nonspecific. There is no single gold standard test to diagnose PCD. Currently, the diagnosis is made in patients with a compatible medical history after a demanding combination of tests including nasal nitric oxide, high-speed video microscopy, and transmission electron microscopy and genetic and ciliary culture testing. These tests are costly and need sophisticated equipment and experienced staff, restricting use to highly specialized centers. Therefore, it would be desirable to have a screening test for identifying those patients who should undergo detailed diagnostic testing. Three recent studies focused on potential screening tools: one study assessed the validity of nasal nitric oxide for screening, and two studies developed new symptom-based screening tools. These simple tools are welcome, and it is hoped that they will assist physicians in determining whom to refer for definitive testing. However, they have been developed in tertiary care settings, where 10 to 50% of tested patients have PCD. The sensitivity and specificity of the tools are reasonable, but positive and negative predictive values may be poor in primary or secondary care settings. Although these studies are an important step toward an earlier diagnosis of PCD, more remains to be done before we have tools tailored to different health care settings.


[Social control and social support in conditions of community psychiatric care].
Social control and social support are important aspects of psychiatric care. Modern psychiatric care in an area close to the residential quarters of patients requires attentive and self-critical observation, especially of the subtle forms of social control. The concepts of social control and social support are explained; basing on own investigations by the authors, as well as on own experiences and literature, some aspects of social support of schizophrenics and alcoholics are described from the viewpoint of local care.


[X-ray computed tomography in the study of fractures of the calcaneus].
In a series of 28 calcaneal fractures, computed tomography scanning has shown axial deformities in the coronal and horizontal (plantar) planes not previously recognized. Two-thirds of the fractures investigated showed a deformity in at least two planes. A combination of dorsiflexion, valgus and adduction was present in one-third of the cases. This examination allowed a precise measure to be made of the enlargement of the calcaneus which very frequently occurs and was greater than 25 per cent in two-thirds of the cases. It makes it possible to visualize subtalar and calcaneocuboid incongruence with great precision and, in particular, to determine the size of the incongruous surface and its severity. Computed tomography scanning showed the existence of subtalar incongruity without depression of the thalamus, which is a concept which is not well recognized. It shows incongruity which is not evident on normal radiographs or, conversely, which may be falsely interpreted from deceptive pictures. The results of this study indicate that the usual classifications based on radiological examination are inadequate and need to be revised. The accuracy of this examination leads to the hope of more precise indications for treatment in the future.


Imaging spectrum of spinal dysraphism on magnetic resonance: A pictorial review.
Congenital malformations of spine and spinal cord are collectively termed as spinal dysraphism. It includes a heterogeneous group of anomalies which result from faulty closure of midline structures during development. Magnetic resonance imaging (MRI) is now considered the imaging modality of choice for diagnosing these conditions. The purpose of this article is to review the normal development of spinal cord and spine and reviewing the MRI features of spinal dysraphism. Although imaging of spinal dysraphism is complicated, a systematic approach and correlation between neuro-radiological, clinical and developmental data helps in making the correct diagnosis.


Spectroscopic properties of the methyl esters of chlorophenoxy acid herbicides.
The mass and infrared spectra of the methyl esters of 9 chlorophenoxy acid herbicides are presented. Ultraviolet data are discussed and proton magnetic resonance spectra are tabulated. Because of the sensitivity of the technique, the mass spectra are most useful for the identification of those compounds in residues, especially by combined gas chromatography-mass spectrometry. The pure herbicides used for the recording of the spectra were obtained by synthesis and recrystallization.


Crystallization and preliminary X-ray diffraction studies of a novel ferredoxin involved in the dioxygenation of carbazole by Novosphingobium sp. KA1.
Novosphingobium sp. KA1 uses carbazole 1,9a-dioxygenase (CARDO) as the first dioxygenase in its carbazole-degradation pathway. The CARDO of KA1 contains a terminal oxygenase component and two electron-transfer components: ferredoxin and ferredoxin reductase. In contrast to the CARDO systems of other species, the ferredoxin component of KA1 is a putidaredoxin-type protein. This novel ferredoxin was crystallized at 293 K by the hanging-drop vapour-diffusion method using PEG MME 550 as the precipitant under anaerobic conditions. The crystals belong to space group C222(1) and diffraction data were collected to a resolution of 1.9 A (the diffraction limit was 1.6 A).


X-linked clinical anophthalmos. Localization of the gene to Xq27-Xq28.
A Northern Ireland family is reported on, in which there is X-linked inheritance of clinical anophthalmos. Multi-point linkage analysis suggests that the gene is localized to the Xq27-28 region (Z = 1.9, Theta = 0.08), though not between the DNA markers DX13 and Factor VIII.


Treatment of Community-Acquired Pneumonia: A Case Report and Current Treatment Dilemmas.
Resistance to macrolides is rising in the USA and warrants careful consideration when confronted with a patient with suspected pneumonia in the urgent care clinic. This case study exemplifies the potentially serious consequences of treatment failure following prescription of a macrolide for community-acquired bacterial pneumonia. Furthermore, the consequential treatment dilemmas currently faced by physicians are briefly discussed.


Effects of chronic exposure to dietary selenomethionine on the physiological stress response in juvenile white sturgeon (Acipenser transmontanus).
Selenium (Se) is an essential micronutrient, but at low concentrations can be toxic to aquatic organisms. Selenomethionine (SeMeth) is the primary dietary form of Se aquatic organisms are exposed to and is an environmental concern because it persists and bioaccumulates. White sturgeon (WS) might be particularly susceptible to bioaccumulative toxicants, such as SeMeth, due to their longevity and benthic lifestyle. Se exposure is known to have adverse effects on the physiological stress response in teleosts, but these effects are unknown in WS. Therefore, the goal of this study was to determine effects of dietary SeMeth on the ability of WS to mount a stress response. Juvenile WS were administered food spiked with 1.4, 5.6, 22.4 and 104.4μg Se/g dry mass (dm) for 72days. Lower doses were chosen to represent environmentally relevant concentrations, while the high dose represented a worst case scenario exposure. On day 72, fish were subjected to a 2min handling stressor, and they were sampled at 0, 2 and 24h post-stressor. Cortisol, glucose and lactate concentrations were quantified in blood plasma and glycogen concentrations were quantified in muscle and liver. Transcript abundance of genes involved in corticosteroidogenesis and energy metabolism were determined using qPCR. Under basal conditions, WS fed 104.4μg Se/g dm had significantly greater concentrations of plasma cortisol and lactate, and significantly lower concentrations of plasma glucose and liver glycogen, compared to controls. Corticosteroid 11-beta dehydrogenase 2 (hsd11b2) abundance was lower in WS fed 22.4 and 104.4μg Se/g dm, indicating less conversion of cortisol to cortisone. Abundance of the glucocorticoid receptor (gcr) was significantly lower in high dose WS, suggesting lower tissue sensitivity to glucocorticoids. The increasing trend in phosphoenolpyruvate carboxykinase (pepck) abundance, with increasing SeMeth exposure, was consistent with greater cortisol and glucose concentrations in high dose WS. Exposure to an acute handling stressor elicited a typical cortisol response, but the magnitude of the response appeared to be significantly lower than those typically observed in teleosts. SeMeth also did not appear to modulate the cortisol response to a secondary stressor. However, WS exposed to 22.4μg Se/g dm and sampled 2h post-stressor, had significantly higher concentrations of muscle glycogen compared to controls, indicating effects on their ability to utilize muscle glycogen for energy. Overall, the results indicate that chronic exposure to dietary SeMeth concentrations >22.4μg/g can affect cortisol dynamics and mobilization of energy substrates in juvenile WS.


Five points to consider when reading a translational machine-learning paper.
Machine-learning techniques are used in this BJPsych special issue on precision medicine in attempts to create statistical models that make clinically relevant predictions for individual patients. In this primer, we outline five key points that are helpful for a new reader to consider in order to engage with the field and evaluate the literature. These points include the consideration of why we are interested in new statistical approaches, how they may produce individualised predictions, what caveats need to be kept in-mind and why the interest and engagment of clinicians and clinical researchers is critical to successful model development and implementation. We hope that the following primer will provide shared understanding to encourage dialogue between clinical and methodological fields.


Severe pepper allergy in a young child.
Spices are ingredients to confer improved taste to foods. As they are derived from plants, they have the potential for inducing allergic reactions. There is a lack of studies to accurately determine the rate of pepper allergy in children. Allergic reactions to pepper in children are rare. This case illustrates such a reaction. Patient is a 17-month-old boy with mild eczema who developed urticaria, conjunctivitis, facial swelling, and severe cough immediately after ingesting venison prepared in a Southwest/mesquite marinade containing a variety of spices including black and cayenne pepper. His food was not routinely peppered. A similar but less severe reaction with facial urticaria and conjunctivitis occurred after eating roast beef in the same marinade while reintroduction of venison without marinade did not result in recurrence of symptoms. Skin tests to cayenne and black pepper extracts were positive. Skin testing to crude extracts of the food marinades was negative as well as commercial extracts of onion, garlic, paprika, thyme, and tomato. IgE radioallergosorbent results showed undetectable levels to black pepper, chili pepper, lemon, tomato, garlic, onion, green pepper, and white pepper. Specific IgE to cayenne pepper was detected at 0.11 kU/L.


Two ligand-functionalized Pb(II) metal-organic frameworks: structures and catalytic performances.
A microporous Pb(II) metal-organic framework (MOF) [PbL(2)]·2DMF·6H(2)O (1) has been assembled from a N-oxide and amide doubly functionalized ligand HL (= N-(4-carboxyphenyl)isonicotinamide 1-oxide). Complex 1 features a three-dimensional (3D) framework possessing one-dimensional (1D) rhombic channels with dimensions of 13 × 13 Å(2). The 3D framework is built up from 1D PbO(2) chains that link ligands in parallel fashion to construct single-wall channels. When recrystallizing 1 in a DMSO-DMF mixture (3 : 5 v/v), a new coordination polymer, [PbL(2)]·DMF·2H(2)O (2), was obtained. Complex 2 is also a 3D framework containing 1D rectangular channels, but the channel dimensions become reduced in size to 13 × 8 Å(2) due to reorganization of the Pb(ii) coordination environment. The PbO(2) chains in 2 are reformed to link ligands in a double-wall fashion, significantly reducing the channel size. Even though, the guest exchange study indicates that the DMF molecules in 2 could be replaced with benzene molecules when immersing in benzene solvent, showing single-crystal-to-single-crystal (SC-SC) guest exchange in the solid state and leading to a daughter crystal [PbL(2)]·0.5C(6)H(6)·2H(2)O (2'). Desolvated 1 and 2 display preferential adsorption behaviors of water vapour over CO(2) due to the hydrophilic nature of the channels and the strong host-guest interactions. Catalytic tests indicate that desolvated 1 and 2 have size-selective catalytic activity towards the Knoevenagel condensation reaction.


Growth and survival among Hawaiian corals outplanted from tanks to an ocean nursery are driven by individual genotype and species differences rather than preconditioning to thermal stress.
The drastic decline in coral coverage has stimulated an interest in reef restoration, and various iterations of coral nurseries have been used to augment restoration strategies. Here we examine the growth of two species of Hawaiian Montipora that were maintained in mesocosms under either ambient or warmed annual bleaching conditions for two consecutive years prior to outplanting to determine whether preconditioning aided coral restoration efforts. Using coral trees to create a nearby ocean nursery, we examined whether: (1) previous ex situ mesocosm growth would mirror in situ coral tree nursery growth; and (2) thermal ex situ stress-hardening would predict future success during natural warming events in situ for corals moved from tanks to trees. For Montipora capitata, we found that variation in growth was explained primarily by genotype; growth rates in the mesocosms were similar to those in situ, irrespective of preconditioning. Variation in M. flabellata growth, however, was explained by both genotype and culture method such that an individual M. flabellata colony that grew well in the tanks did not necessarily perform as well on the coral trees. For both species, previous exposure to elevated temperatures in the mesocosms provided no benefit to either growth or survival during a warming event in the coral tree nursery compared to those grown in ambient temperatures. Overall, M. capitata performed better in the tree nursery with higher net growth, lower mortality, and was subject to less predation than M. flabellata. Our results show little benefit of the additional cost and time of stress-hardening these corals prior to outplanting because it is unlikely to aid resilience to future warming events. These results also suggest that selecting corals for restoration based on long-term genotype growth performance may be more effective for optimal outcomes but should be weighed against other factors, such as coral morphology, in situ nursery method, location, and other characteristics.


How does the dengue vector mosquito Aedes albopictus respond to global warming?
Global warming has a marked influence on the life cycle of epidemic vectors as well as their interactions with human beings. The Aedes albopictus mosquito as the vector of dengue fever surged exponentially in the last decade, raising ecological and epistemological concerns of how climate change altered its growth rate and population dynamics. As the global warming pattern is considerably uneven across four seasons, with a confirmed stronger effect in winter, an emerging need arises as to exploring how the seasonal warming effects influence the annual development of Ae. albopictus. The model consolidates a 35-year climate dataset and designs fifteen warming patterns that increase the temperature of selected seasons. Based on a recently developed mechanistic population model of Ae. albopictus, the model simulates the thermal reaction of blood-fed adults by systematically increasing the temperature from 0.5 to 5 °C at an interval of 0.5 °C in each warming pattern. The results show the warming effects are different across seasons. The warming effects in spring and winter facilitate the development of the species by shortening the diapause period. The warming effect in summer is primarily negative by inhibiting mosquito development. The warming effect in autumn is considerably mixed. However, these warming effects cannot carry over to the following year, possibly due to the fact that under the extreme weather in winter the mosquito fully ceases from development and survives in terms of diapause eggs. As the historical pattern of global warming manifests seasonal fluctuations, this study provides corroborating and previously ignored evidence of how such seasonality affects the mosquito development. Understanding this short-term temperature-driven mechanism as one chain of the transmission events is critical to refining the thermal reaction norms of the epidemic vector under global warming as well as developing effective mosquito prevention and control strategies.


Pruned receptor surface models and pharmacophores for three-dimensional database searching.
A pharmacophore represents the 3D arrangement of chemical features that are shared by molecules exhibiting activity at a protein receptor. Pharmacophores are routinely used in 3D database searching for identifying potential lead compounds. The lack of shape constraints causes the query to identify compounds that could not fit into the active site. In the absence of structural information, a receptor surface model (RSM) can be used to represent the active site. The RSM consists of a surface that envelops a set of known actives after these have been aligned using their common features. When used for database searching, a RSM is overconstraining as it restricts access to regions that could be occupied by ligands, such as the solvent-protein interface or unexplored pockets. We describe a protocol for developing pruned RSMs using information gleaned from 3D quantitative structure-activity relationship (QSAR) models. We examined the performance of queries that consist of pharmacophores used alone or with pruned or unpruned RSMs by performing searches on six databases containing known actives distributed among inactives. The pruned RSMs yield an average selectivity 1.8 times greater than that for pharmacophore queries, compared to 1.6 times for unpruned RSMs. However, the pruned RSMs retrieve on average 73% of the actives identified using the pharmacophores, compared to 40% for the unpruned RSMs. As such, pruned RSMs represent a useful compromise between the high sensitivity of pharmacophores and the high selectivity of unpruned RSMs.


Adjustment of growth and central metabolism to a mild but sustained nitrogen-limitation in Arabidopsis.
We have established a simple soil-based experimental system that allows a small and sustained restriction of growth of Arabidopsis by low nitrogen (N). Plants were grown in a large volume of a peat-vermiculite mix that contained very low levels of inorganic N. As a control, inorganic N was added in solid form to the peat-vermiculite mix, or plants were grown in conventional nutrient-rich solids. The low N growth regime led to a sustained 20% decrease of the relative growth rate over a period of 2 weeks, resulting in a two- to threefold decrease in biomass in 35- to 40-day-old plants. Plants in the low N regime contained lower levels of nitrate, lower nitrate reductase activity, lower levels of malate, fumarate and other organic acids and slightly higher levels of starch, as expected from published studies of N-limited plants. However, their rosette protein content was unaltered, and total and many individual amino acid levels increased compared with N-replete plants. This metabolic phenotype reveals that Arabidopsis responds adaptively to low N by decreasing the rate of growth, while maintaining the overall protein content, and maintaining or even increasing the levels of many amino acids.


Catheter-guided multilevel epidural blood patches in an adolescent boy.
There is increasing evidence for the use of multilevel epidural catheter-guided blood patches to treat spontaneous cerebrospinal fluid leaks in adults. Yet, there are scarce data for their use in children. Furthermore, higher level epidural blood patches are uncommon in both adult and pediatric populations. An adolescent boy with multilevel cerebrospinal fluid leaks associated with status migrainosus failed conservative pain management treatment. As he remained severely symptomatic, epidural blood patches were required to mitigate his symptoms. Given his multilevel leaks, a catheter-guided blood patch approach was used to treat multiple cervicothoracic and thoracolumbar leaks. After three separate uneventful blood patch procedures, the patient was free of symptoms. Other than some rebound intracranial hypertension, the patient maintained full neurological capacity without further complications. Following the resolution of treatment, he has not sought help for pain since his last blood patch over a year ago. Multilevel catheter-guided blood patches have the potential to be administered to higher level spinal regions to the pediatric population suffering from multiple spontaneous cerebrospinal fluid leaks.


External validation of the breast reconstruction risk assessment calculator.
The Breast reconstruction Risk Assessment (BRA) Score estimates patient-specific risk for postsurgical complications using an individual's unique combination of preoperative variables. In this report, we externally validate the BRA Score models for surgical site infection, seroma, and explantation in a large sample of intra-institutional patients who underwent prosthetic breast reconstruction. We reviewed all initiated tissue expander/implant reconstructions by the senior authors from January 2004 to December 2015. BRA Score risk estimates were computed for each patient and compared against observed rates of complications. Hosmer-Lemeshow goodness-of-fit test, concordance statistic, and Brier score were used to assess the calibration, discrimination, and accuracy of the models, respectively. Of the 1152 patients (1743 breasts) reviewed, 855 patients (1333 breasts) had complete data for BRA-score calculations and were included for analysis. Hosmer-Lemeshow tests for calibration demonstrated a good agreement between observed and predicted outcomes for surgical site infection (SSI) and seroma models (P-values of 0.33 and 0.16, respectively). In contrast, predicted rates of explantation deviated from observed rates (Hosmer-Lemeshow P-value of 0.04). C statistics demonstrated good discrimination for SSI, seroma, and explantation (0.73, 0.69, and 0.78, respectively). In this external validation study, the BRA Score tissue expander/implant reconstruction models performed with generally good calibration, discrimination, and accuracy. Some weaknesses in certain models were identified as targets for future improvement. Taken together, these analyses validate the clinical utility of the BRA score risk models in predicting 30-day outcomes.


Atypical "seizure-like" activity in cortical reverberating networks in vitro can be caused by LPS-induced inflammation: a multi-electrode array study from a hundred neurons.
We show here that a mild sterile inflammation induced by the endotoxin lipopolysaccharide (LPS), in a neuron/astrocyte/microglial cortical network, modulates neuronal excitability and can initiate long-duration burst events resembling epileptiform seizures, a recognized feature of various central nervous neurodegenerative, neurological and acute systemic diseases associated with neuroinflammation. To study this action, we simultaneously analyzed the reverberating bursting activity of a hundred neurons by using in vitro multi-electrode array methods. ∼5 h after LPS application, we observed a net increase in the average number of spikes elicited in engaged cells and within each burst, but no changes neither in spike waveforms nor in burst rate. This effect was characterized by a slow, twofold exponential increase of the burst duration and the appearance of rarely occurring long burst events that were never seen during control recordings. These changes and the time-course of microglia-released proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α), were blocked by pre-treatment with 50 nM minocycline, an established anti-inflammatory agent which was inactive when applied alone. Assay experiments also revealed that application of 60 pM exogenous TNF-α after 12-15 h, produced non-washable changes of neuronal excitability, completely different from those induced by LPS, suggesting that TNF-α release alone was not responsible for our observed findings. Our results indicate that the link between neuroinflammation and hyperexcitability can be unveiled by studying the long-term activity of in vitro neuronal/astrocyte/microglial networks.


Association between immunoglobulin allotypes and pulmonary tuberculosis.
In a sample of n = 133 non-related patients suffering from pulmonary tuberculosis, Gm and Km typings have been carried out and compared with healthy controls from the same geographical area. All the Gm allotypes tested were found to be more preponderant in the patients than in the healthy controls and these differences were found to be statistically significant for Gm (1) and Gm (5) only and not for the other immunoglobulin allotypes e.g. Gm (2). The frequency of Km (1) was lower and that of Km (3) was higher in the patients than in the controls. These differences were, however, statistically not significant.


Comparative evaluation of automated ribotyping and RAPD-PCR for typing of Lactobacillus spp. occurring in dental caries.
A group of 67 Lactobacillus spp. strains containing Lactobacillus casei/paracasei, Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus plantarum, Lactobacillus rhamnosus and Lactobacillus salivarius species isolated from early childhood caries and identified to the species level in a previous study (Svec et al., Folia Microbiol 54:53-58, 2009) was characterized by automated ribotyping performed by the RiboPrinter microbial characterization system and by randomly amplified polymorphic DNA fingerprinting (RAPD-PCR) with M13 primer to evaluate these techniques for characterization of lactobacilli associated with dental caries. Ribotyping revealed 55 riboprints among the analysed group. The automatic identification process performed by the RiboPrinter system identified 18 strains to the species level, however cluster analysis divided obtained ribotype patterns into individual clusters mostly corresponding to the species assignment of particular strains. RAPD-PCR fingerprints revealed by the individual Lactobacillus spp. showed higher variability than the ribotype patterns and the fingerprint profiles generated by the analysed species were distributed among one to four clusters. In conclusion, ribotyping is shown to be more convenient for the identification purposes while RAPD-PCR fingerprinting results indicate this method is a better tool for typing of Lactobacillus spp. strains occurring in dental caries.


Broadband, high-resolution spatial heterodyne spectrometer.
Design and performance parameters for a broadband, high-resolution spatial heterodyne spectrometer (SHS) are reported. The Mark 1 SHS achieves more than a factor of 5 in continuous wavenumber coverage with a design resolving power in the hundreds of thousands.


Project AquiLá: Community-engaged Planning to Explore the Relationship between Culture and Health.
Elements of charrette planning were employed to develop and examine the relationship between transnationalism, culture and health. This paper describes the partnership, the first two stages of the planning charrette and lessons learned. During charrette planning phase 1 we collected data through social network interviews (n = 58), cultural conversations (n = 88), and photovoice (n = 9). In the second phase we performed five charrette planning meetings. Data were synthesized by the planning team. The issue centered focus facilitated trust among partners. The holistic, iterative process to planning and interpreting preliminary data provided a deeper understanding of the issues under investigation. Community partners at the table held us accountable to the communities we were studying and infused an undercurrent of social justice in our work. There are advantages in employing a community engaged transdisciplinary team-based approach to the study of transnationalism, culture and health.


Expansion of restricted cellular immune responses to HIV-1 envelope by vaccination: IL-7 and IL-12 differentially augment cellular proliferative responses to HIV-1.
The failure of immune effector mechanisms to control HIV-1 infection has important consequences for the human host. In a randomized cohort of HIV-infected patients, there was striking in vitro restriction of the proliferative response to HIV-1 envelope protein (Env), gp160; only 34% of patients recognized Env. Therapeutic vaccination with recombinant gp160 or gp120 (rgp160, rgp120) reversed the restriction in vitro, with Env recognition rising to 81%. Peripheral blood mononuclear cells (PBMC) from HIV-infected vaccine recipients, placebo recipients, and seronegative volunteers were cultured with exogenous IL-7 or IL-12 and either tetanus toxoid (TT) or gp160. IL-7 significantly augmented proliferative responses to TT and gp160, whereas IL-12 only affected proliferation to gp160. IL-7, but not IL-12, increased the number of HIV-infected placebo recipients who recognized rgp160. IL-12 had its greatest effect in the induction of rgp160-specific responses from seronegative individuals. The data suggest that these two cytokines have differential activity in the relief of restricted cellular immunity to Env; the predominant effect of IL-7 is in individuals who have been primed by exposure to antigen, while the effect of IL-12 is most evident in seronegative, unprimed individuals. Modification of restricted proliferative responses to Env by vaccination or cytokines in vitro suggests that strategies incorporating IL-7 or IL-12 as adjuvants may selectively boost cellular reactivity to HIV-1.


Source and Route of Pyrrolizidine Alkaloid Contamination in Tea Samples.
Toxic pyrrolizidine alkaloids (PAs) are found in tea samples, which pose a threat to human health. However, the source and route of PA contamination in tea samples have remained unclear. In this work, an adsorbent method combined with UPLC-MS/MS was developed to determine 15 PAs in the weed Ageratum conyzoides L., A. conyzoides rhizospheric soil, fresh tea leaves, and dried tea samples. The average recoveries ranged from 78%-111%, with relative standard deviations of 0.33%-14.8%. Fifteen pairs of A. conyzoides and A. conyzoides rhizospheric soil samples and 60 fresh tea leaf samples were collected from the Jinzhai tea garden in Anhui Province, China, and analyzed for the 15 PAs. Not all 15 PAs were detected in fresh tea leaves, except for intermedine-N-oxide (ImNO) and senecionine (Sn). The content of ImNO (34.7 µg/kg) was greater than that of Sn (9.69 µg/kg). In addition, both ImNO and Sn were concentrated in the young leaves of the tea plant, while their content was lower in the old leaves. The results indicated that the PAs in tea were transferred through the path of PA-producing weeds-soil-fresh tea leaves in tea gardens.


Video-Based Neonatal Pain Assessment in Uncontrolled Conditions.
Neonatal pain can have long-term adverse effects on newborns' cognitive and neurological development. Video-based Neonatal Pain Assessment (NPA) method has gained increasing attention due to its performance and practicality. However, existing methods focus on assessment under controlled environments while ignoring real-life disturbances present in uncontrolled conditions. We propose a video-based NPA method, which is robust to four real-life disturbances and adaptively highlights keyframes. Our method involves a region-channel-attention module for extracting facial features under the disturbances of facial occlusion and pose variation; a body language analysis module robust to disturbances from body occlusion and movement interference, which utilizes skeleton sequences to represent the neonate's body; and a keyframes-aware convolution to get rid of information located at non-contributing moments. For evaluation, we built an NPA video dataset of 1091 neonates with disturbance annotations. The results show that our method consistently outperforms state-of-the-art methods on the full dataset and nine subsets, where it achieves an accuracy of 91.04% on the full dataset with an accuracy increment of 6.27%. Contributions: We present the problem of video-based NPA under uncontrolled conditions, propose a method robust to four disturbances, and construct a video NPA dataset, thus facilitating the practical applications of NPA.


Efficient mode conversion in guiding structures with longitudinal modulation of nonlinearity.
We describe power-dependent dynamics of conversion of the guided modes of various guiding structures due to nearly resonant longitudinal modulation of the nonlinear coefficient of the medium. It is shown that the control of the energy exchange integrals, as well as of the input weights of the interacting modes, is especially crucial for efficient mode conversion in the setting considered here. Complex dynamics of conversion incorporates various scenarios, including nonharmonic oscillations of the energy weights, which mimics Jacoby elliptical functions.


Mycobacterium leprae inhibits dendritic cell activation and maturation.
Leprosy presents with a clinical spectrum of skin lesions that span from strong Th1-mediated cellular immunity and control of bacillary growth at one pole to poor Ag-specific T cell immunity with extensive bacillary load and Th2 cytokine-expressing lesions at the other. To understand how the immune response to Mycobacterium leprae is regulated, human dendritic cells (DC), potent inducers of adaptive immune responses, exposed to M. leprae, Mycobacterium tuberculosis (Mtb), and Mycobacterium bovis bacillus Calmette-Guerin (BCG) were studied for their ability to be activated and to prime T cell proliferation. In contrast with Mtb and BCG, M. leprae did not induce DC activation/maturation as measured by the expression of selected surface markers and proinflammatory cytokine production. In MLR, T cells did not proliferate in response to M. leprae-stimulated DC. Interestingly, M. leprae-exposed MLR cells secreted increased Th2 cytokines as well as similar Th1 cytokine levels as compared with Mtb- and BCG-exposed cells. Gene expression analysis revealed a reduction in levels of mRNA of DC activation and maturation markers following exposure to M. leprae. Our data suggest that M. leprae does not induce and probably suppresses in vitro DC maturation/activation, whereas Mtb and BCG are stimulatory.


Fructosamine and diabetes as predictors of mortality among Hispanic and non-Hispanic white breast cancer survivors.
Epidemiologic studies have found that elevated insulin levels and chronic hyperglycemia among breast cancer (BC) survivors are associated with poor prognosis; few of these studies have included Hispanic women in whom diabetes is highly prevalent. We examined the associations between circulating fructosamine-a biomarker of hyperglycemia and blood glucose control, self-reported diabetes, and risk of BC-specific and all-cause mortality among Hispanic and non-Hispanic white (NHW) women diagnosed with invasive BC. A total of 399 BC survivors (96 Hispanic, 303 NHW) contributed baseline data and plasma samples. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable Cox proportional hazards regression models. After a median follow-up time of 13 years, a total of 134 deaths occurred, of which 56 deaths were from BC. Diabetes was associated with BC-specific (HR, 2.89; 95% CI 1.27-6.60) and all-cause (HR, 2.10; 95% CI 1.24-3.55) mortality. Associations were stronger among women with clinically high fructosamine levels (>285 µmol/L) (BC-specific: HR, 4.25; 95% CI 1.67-10.80; all-cause: HR, 2.32; 95% CI 1.30-4.14) compared to women with normal levels (≤285 µmol/L). In mediation analysis, fructosamine explained 47% of the association between diabetes and all-cause mortality and 41% of BC-specific mortality; the largest attenuation was among Hispanics for all-cause mortality (56%). Our results demonstrate that poor glycemic control explains a large extent of the relationship between diabetes and mortality among women with invasive BC, particularly among Hispanic women. The associations we observed for BC mortality should be confirmed in larger studies of ethnically diverse BC patients.


Disclosure of information to adult cancer patients: issues and update.
Clinicians are regularly faced with decisions regarding disclosure of information to cancer patients. Many of these decisions constitute a dilemma between the physician's paternalistic concern for the patient and the patient's right to know as much as possible. This paper reviews changes in the attitudes of physicians over the last several decades, elaborates on the problems that confront the clinician in the process of disclosure, and reviews the available data concerning the documented impact on the patient from receiving or not receiving information. The arguments both supporting and challenging the paternalistic view are discussed, and the necessity for viewing the disclosure of clinical information as a clinical process is offered.


Genetic polymorphisms of beta1 adrenergic receptor and their influence on the cardiovascular responses to metoprolol in a South Indian population.
Beta-blockers show interindividual and interethnic variability in their response. Such variability might be due to the polymorphic variations in the beta1 adrenergic receptor genes viz, Ser49Gly and Arg389Gly. The study evaluated the influence of Ser49Gly and Arg389Gly polymorphisms on the cardiovascular responses to metoprolol in a South Indian population. Forty-one genetically prescreened healthy male volunteers participated in the study. They were divided on the basis of genotype of each polymorphism: Ser49Ser, Ser49Gly, and Gly49Gly and Arg389Arg, Arg389Gly, and Gly389Gly. They were also grouped into combination genotypes viz, S49S R389R, S49G R389R, G49G R389R, S49S R389G, S49S G389G, and S49G R389G. They were subjected to treadmill exercise testing, and cardiovascular parameters were measured before and after metoprolol administration. Metoprolol concentration was determined by reversed phase high-performance liquid chromatography method. The diastolic blood pressure (DBP) was significantly lower in S49S/G389G group when compared to S49S/A389A group. The cardiac parameters were significantly increased in all the genotype groups during treadmill exercise test done for a period of 9 minutes. During predrug treadmill exercise at the end of third and sixth minute, Gly49Gly showed a higher increase in heart rate and volume of oxygen consumption compared to Ser49Ser. Same group showed a higher increase of volume of oxygen consumption at the end of ninth minute of exercise compared to the Ser49Ser. Systolic and diastolic blood pressures were not different between Ser49Gly polymorphisms. However, there was no statistical difference between the genotype groups of both polymorphisms at any stage of post-drug treadmill exercise. The analysis of combination of genotypes showed no significant difference during predrug and postdrug exercise testing. The increase in cardiac responses to treadmill test was influenced by Ser49Gly polymorphism. Nevertheless, the above polymorphisms did not alter the beta-blocker response during treadmill exercise in South Indian population.


Postural Communication of Emotion: Perception of Distinct Poses of Five Discrete Emotions.
Emotion can be communicated through multiple distinct modalities. However, an often-ignored channel of communication is posture. Recent research indicates that bodily posture plays an important role in the perception of emotion. However, research examining postural communication of emotion is limited by the variety of validated emotion poses and unknown cohesion of categorical and dimensional ratings. The present study addressed these limitations. Specifically, we examined individuals' (1) categorization of emotion postures depicting 5 discrete emotions (joy, sadness, fear, anger, and disgust), (2) categorization of different poses depicting the same discrete emotion, and (3) ratings of valence and arousal for each emotion pose. Findings revealed that participants successfully categorized each posture as the target emotion, including disgust. Moreover, participants accurately identified multiple distinct poses within each emotion category. In addition to the categorical responses, dimensional ratings of valence and arousal revealed interesting overlap and distinctions between and within emotion categories. These findings provide the first evidence of an identifiable posture for disgust and instantiate the principle of equifinality of emotional communication through the inclusion of distinct poses within emotion categories. Additionally, the dimensional ratings corroborated the categorical data and provide further granularity for future researchers to consider in examining how distinct emotion poses are perceived.


Determination of patient set-up error and optimal treatment margin for intensity modulated radiotherapy using image guidance system.
The geometrical uncertainties in the patient positioning during intensity modulated radiotherapy (IMRT) are crucial as there is potential to underdose the tumor and overdose the nearby critical structures. Image guided techniques provide a solution to assess the patient set-up uncertainties and help determine the optimal planning target volume (PTV) margin to the clinical tumor volume (CTV). A retrospective study was conducted to evaluate patient set-up errors along the three translational directions at different treatment sites such as the brain, the head and neck (H&N) and the prostate. A total of 60 patients' set-up error data was analysed to evaluate the systematic and random errors and the optimal CTV-PTV margin. For brain and H&N sites, more than 90, 80 and about 100% of the total image acquisitions were less than 3 mm in lateral, longitudinal and vertical directions respectively. For the prostate cases, the frequency of patient set-up error to be less than 3 mm were 79.7, 75.6 and 80% in lateral, longitudinal and vertical directions respectively. About 0.6% had more than 7 mm error in the lateral and longitudinal directions for the prostate site. CTV-PTV margin of 3.4, 3.4 and 1.9 mm for brain cases, 3.5, 3 and 1.8 mm for H&N cases and 5, 4.6 and 4.5 mm for the prostate cases in the lateral, longitudinal and vertical directions respectively were determined. Image guidance is an effective method to evaluate the accuracy of IMRT treatment delivery. The optimal CTV-PTV margin can be determined to ensure adequate dose to CTV, specific to the site.


Reading fluency in Spanish patients with Parkinson's disease: A reading prosody examination.
The expressiveness during reading is essential for a fluent reading. Reading prosody has been scarcely studied in an experimental manner, owing to the difficulties in taking objective and direct measures of this reading skill. However, new technologies development has made it possible to analyse reading prosody in an experimental way. Prosodic patterns may vary, not being the same at the beginning of the reading learning process as in adulthood. They may also be altered in disorders such as dyslexia, but little is known about the prosodic characteristics and reading fluency of people with neurodegenerative diseases that cause language impairment, such as Parkinson's disease (PD). The aim of this work was to study reading fluency in PD considering the prosodic characteristics of its reading. The participants were 31 Spanish adults with PD and 31 healthy controls, aged 59-88 years. Two experimental texts were designed that included declarative, interrogative, and exclamatory sentences and experimental verbs and nouns. The manipulability level of the nouns and the motor content of the verbs were considered. The reading of the participants was recorded and analysed with Praat software. A longer reading duration and a greater number of pauses, especially in verbs, were found in the PD group, which also showed less pitch variation than the control group in the experimental sentences. The control group showed a big initial rise in declarative and interrogative sentences, as well as a stronger final declination in declarative and exclamatory ones, when compared to the PD group. The use of experimental methodologies for the analysis of reading fluency allows learning more about the prosodic characteristics of people with different pathologies, such as PD. Scarce pitch variability found in the analysis, together with the great number of pauses and the longer reading duration, leads to poorly expressive reading, which compromises fluency in PD. The exhaustive evaluation of the reading fluency of PD patients will make it possible to design more complete assessment methods that will favour the diagnosis and early detection of this pathology. What is already known on this subject • The speech of people with Parkinson's disease (PD) is often impaired by the appearance of hypokinetic dysarthria. The language of people with PD is usually affected with the progression of the disease, with lexico-semantic impairment which mainly affects verbs. Previous literature on reading fluency in PD usually considers reading speed and accuracy, neglecting prosody. Other neurodegenerative diseases with language impairment, such as Alzheimer's disease, commonly cause reading fluency problems. What this paper adds to existing knowledge • This study provides direct and objective measures of the reading fluency (speed, accuracy and prosody) in patients with PD, by the design of experimental texts. Reading fluency characteristics were found to be altered in these patients, especially in pitch variations and reading duration. The reading of Parkinson's patients showed a more flattened pitch. In addition, a greater number of pauses and longer reading durations were also found in the reading of verbs compared to the control group. What are the potential or actual clinical implications of this work? • The use of experimentally created texts makes it possible to analyse the influence of different psycholinguistic variables (frequency, length, motor content, manipulability) on reading fluency, and how the processing of these stimuli could be affected in PD. The objective analysis of the reading fluency characteristics in PD allows the design of more specific evaluation and diagnostic tasks. More complete assessment methods may allow the early detection of the disease. In the same way, it may favour a differential diagnosis with other neurodegenerative diseases.


Proximity effects in graphene-supported single-atom catalysts for hydrogen evolution reaction.
The interaction between adjacent active sites is crucial to balance the efficiency and utilization of functional atoms in single-atom catalysts. Herein, the catalytic activity of hydrogen evolution reaction at different site (nitrogen coordinated transition metal centers embedded in graphene) distances was comprehensively investigated by density functional theory calculations. The results show that a proximity effect of reactivity and site spacing can be identified in the Co-series single-atom catalysts. Although the proximity effect is more linearly responded with the site spacing along x direction, an optimal distance of ∼0.8 and ∼2.8 nm are found for Co and Rh, Ir atoms, respectively. An in-depth analysis of the electronic property reveals that the proximity effect is caused by the distinct net charge of the active site, which is affected by the dz2 position relative to EF. Subsequently, an excess electron nodal channel in x direction was found to serve as a communication pathway between the active sites. Through the finding in this work, an optimal Fe-N2C2 structure was deliberately designed and has shown prominent proximity effect as Co-series do. The results reported in this work provide a simple and effective tuning method for the reactivity of a single-atom catalyst.


Animal and Cellular Models in Thrombosis and Hemostasis.
STANDARDIZED IN VITRO AND IN VIVO MODEL SYSTEMS TO SIMPLIFY COMPLEXITY-THAT'S HOW WE LEARN: The discovery of new target molecules and translational progress in the development and refinement of antithrombotic therapies as well as the improved treatment of bleeding disorders strongly relies on standardized ex vivo and in vivo models that closely resemble the respective human pathologies. The standardization of these models requires sound training in specialized hemostasis and thrombosis research laboratories as well as a consistent daily routine. In this theme issue of Hämostaseologie-Progress in Haemostasis, four review articles cover key models that have proven instrumental to gain mechanistic insights on thrombogenesis and hemostatic processes. In recent decades, these models have moved our field forward and enabled translation across scales, from cell-based research to isolated flow chamber systems, to mouse thrombosis models reflecting the pathologic situations as observed in patients, to large animal models.


Ligand-inducible dimeric antibody for selecting antibodies against a membrane protein based on mammalian cell proliferation.
A method for selecting antibodies against a membrane protein is important for attaining a variety of antibody-based diagnostics and therapies. In this study, we propose a novel system to select specific antibodies against a membrane protein based on mammalian cell proliferation as a readout. The system employs a chimeric membrane protein in which a target membrane protein of interest is fused to the intracellular signaling domain of a cytokine receptor. The chimeric membrane protein transduces a cell proliferation signal through dimerization when co-expressed with a specific single-chain Fv fused with a mutant of FK-binding protein 12 (scFv-Fk) that can be conditionally dimerized by a synthetic ligand AP20187. To demonstrate this system, ErbB2 and gp130 were chosen as the target membrane protein and cytokine receptor, respectively. Consequently, co-expression of the ErbB2/gp130 chimera and ErbB2-specific scFv-Fk rendered the cells proliferative in response to AP20187. The system also allowed selection of high-affinity binders from a mixture composed of dominant low-affinity binders. This system may be extended to affinity maturation of scFvs by modulating AP20187 concentration in the selection process.


Individual differences in beta-band oscillations predict motor-inhibitory control.
The ability of motor-inhibitory control is critical in daily life. The physiological mechanisms underlying motor inhibitory control deficits remain to be elucidated. Beta band oscillations have been suggested to be related to motor performance, but whether they relate to motor-inhibitory control remains unclear. This study is aimed at systematically investigating the relationship between beta band oscillations and motor-inhibitory control to determine whether beta band oscillations were related to the ability of motor-inhibitory control. We studied 30 healthy young adults (age: 21.6 ± 1.5 years). Stop-signal reaction time (SSRT) was derived from stop signal task, indicating the ability of motor-inhibitory control. Resting-state electroencephalography (EEG) was recorded for 12 min. Beta band power and functional connectivity (including global efficiency) were calculated. Correlations between beta band oscillations and SSRT were performed. Beta band EEG power in left and right motor cortex (MC), right somatosensory cortex (SC), and right inferior frontal cortex (IFC) was positively correlated with SSRT (P's = 0.031, 0.021, 0.045, and 0.015, respectively). Beta band coherence between bilateral MC, SC, and IFC was also positively correlated with SSRT (P's < 0.05). Beta band global efficiency was positively correlated with SSRT (P = 0.01). This is the first study to investigate the relationship between resting-state cortical beta oscillations and response inhibition. Our findings revealed that individuals with better ability of motor inhibitory control tend to have less cortical beta band power and functional connectivity. This study has clinical significance on the underlying mechanisms of motor inhibitory control deficits.


Characterization of acetohexamide reductases purified from rabbit liver, kidney, and heart: structural requirements for substrates and inhibitors.
The structural requirements of acetohexamide reductases purified from rabbit liver, kidney, and heart for substrates and inhibitors were examined. Acetohexamide, an oral antidiabetic drug with a ketone group, and analogs of it with various alkyl groups instead of the cyclohexyl group were used as substrates for these three enzymes. The results obtained as to substrate specificity suggested that the nature of the substrate-binding region of the heart enzyme is markedly different from those of the substrate-binding regions of the liver and kidney enzymes. Tolbutamide, which has no ketone group within its chemical structure, strongly inhibited the heart enzyme, whereas it had little ability to inhibit the liver or kidney enzyme. The inhibition of the heart enzyme by tolbutamide was competitive with respect to acetohexamide and uncompetitive with respect to NADPH. Furthermore, tolbutamide analogs with n-pentyl and n-hexyl groups instead of the n-butyl group exhibited very pronounced inhibition of only the heart enzyme. Therefore, it is reasonable to postulate that the heart enzyme, unlike the liver and kidney ones, has a cleft of a strongly hydrophobic nature near its substrate-binding region, and that this hydrophobic cleft plays a critical role in the interaction of the heart enzyme with the cyclohexyl group of acetohexamide.


Sensitivity and Specificity of US and CT as Diagnostic Tools for Pediatric Lateral Neck Abscesses.
Ultrasound (US) and computed tomography (CT) are commonly used in the diagnosis of pediatric neck abscesses. The objective of this study is to determine the sensitivity and specificity of US and CT in the diagnosis of pediatric lateral neck abscesses, with a secondary objective of evaluating the association of specific clinical features with a positive US or CT scan. Retrospective review of pediatric patients admitted to a tertiary care center from January 1, 2011, to December 31, 2020, with neck abscesses. Tertiary care center. The sensitivity and specificity of US and CT were calculated by comparing imaging performed within 24 h of incision and drainage (I&D). Multiple regression was used to evaluate the association of clinical features with a true positive US or CT. There were 171 patients included in this study, with a median age of 1.5 years (interquartile range [IQR]: 1-5 years). I&D was done in 156 patients (91.2%), while 15 (8.8%) were treated with antibiotics. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of US were 69.5%, 80%, 96.6%, and 24.2%. The sensitivity, specificity, PPV, and NPV of neck CT were 95.5%, 80%, 95.5%, and 57.1%. Length of symptoms, skin erythema, and fluctuance were not significantly associated with a positive US (F(3, 82) = 0.24, p = .9, R2 = 0.01) or CT scan (F(3, 30) = 0.84, p = .5, R2 = 0.08). Neck US has a low sensitivity for diagnosing pediatric neck abscesses, when compared to CT, but remains a useful initial investigation given its high PPV. Clinicians should have a low threshold for pursuing CT if there is a high suspicion of abscess formation. Level 4.


Extraction of bismuth(III) with 2-bromoalkanoic acid in nondonating solvent from highly acidic aqueous solution.
The extraction behaviors of bismuth(III) with carboxylic acid (HL), which have not yet been clearly elucidated, because of the precipitation of hydroxide, were studied using the 2-bromoalkanoic acid in benzene and in hexane systems under aqueous conditions of high acidity at I = 1.0 M ((H,Li)NO3). The extraction equilibria were analyzed based on the-initial concentration of nitric acid and the concentration of bismuth(III) extracted in the organic phase. The extracted species and the logarithmic values of the extraction constant (log Kex) were found to be a single species of BiL3(HL)3 for the systems of 2-bromooctanoic acid/benzene (log Kex = -1.66) and 2-bromohexadecanoic acid/benzene (-1.58), and to be two species of BiL3(HL)4 (-1.01) and Bi3L9HL (-1.62) for the system of 2-bromooctanoic acid/hexane, where the monomer was dominant at a higher reagent concentration.


Maize BIG GRAIN1 homolog overexpression increases maize grain yield.
The Zea Mays BIG GRAIN 1 HOMOLOG 1 (ZM-BG1H1) was ectopically expressed in maize. Elite commercial hybrid germplasm was yield tested in diverse field environment locations representing commercial models. Yield was measured in 101 tests across all 4 events, 26 locations over 2 years, for an average yield gain of 355 kg/ha (5.65 bu/ac) above control, with 83% tests broadly showing yield gains (range +2272 kg/ha to -1240 kg/ha), with seven tests gaining more than one metric ton per hectare. Plant and ear height were slightly elevated, and ear and tassel flowering time were delayed one day, but ASI was unchanged, and these traits did not correlate to yield gain. ZM-BG1H1 overexpression is associated with increased ear kernel row number and total ear kernel number and mass, but individual kernels trended slightly smaller and less dense. The ZM-BG1H1 protein is detected in the plasma membrane like rice OS-BG1. Five predominant native ZM-BG1H1 alleles exhibit little structural and expression variation compared to the large increased expression conferred by these ectopic alleles.


What defines 'low birth weight' in Pacific infants born in New Zealand?
To report the combined and ethnic specific proportions of preterm and low birth weight (LBW) births, and average birth weights, for New Zealand's four major Pacific ethnic groups (Samoan, Tongan, Cook Island Māori, Niuean). Data were gathered from the Pacific Island Families Study (PIFS). Mothers of a cohort of 1398 Pacific infants born in South Auckland New Zealand (NZ) during 2000 were interviewed when their infants were 6 weeks old. Birth outcome data were obtained from hospital records on receipt of full informed consent. Of the Pacific ethnic groups preterm rates ranged from 5.3% to 8.3% (7.3% overall), LBW rates ranged from 3.4% to 5.7% (4.0% overall), and average birth weight of full-term deliveries ranged from 3467 gm to 3751 gm (3664 gm overall). Cook Island and Niuean infants were significantly lighter than Samoan infants. Infants of Pacific born mothers were significantly heavier than infants born to NZ born Pacific mothers. There were no differences observed between infants of 'ethnically homogenous' parents compared 'ethnically heterogeneous' parents. The 10th percentile for all Pacific ethnic groups ranged from 2894 to 3065 grams. These data reaffirm that infants of various Pacific ethnic groups are larger than other New Zealand infants. Furthermore, analyses of the PIFS cohort suggest that a LBW threshold for NZ born Pacific infants of 3000 grams may be more appropriate.


Permanent education in healthcare services: educational activities developed in the state of Minas Gerais, Brazil.
To analyse educational activities carried out in the state of Minas Gerais, Brazil, considered permanent education in healthcare. This is a mixed methods study with a qualitative approach and the participation of 492 municipal health departments. Data were collected in March and October 2014 through interviews available online. The data were tabulated using Excel software. The data were subjected to thematic content analysis and statistic descriptive analysis. The study was approved with opinion 22830812.5.0000.5149. Data analysis revealed the following nine categories: type of practice, theme, method, technological resource, motive, healthcare level, public, financing, and status of the described practice. The activities were not related to a specific educational concept. The researchers found that the subjects that motivated the education activities were based on work and the diagnosis of problems faced by the workers. These principles are characteristic of permanent education in healthcare. In some municipalities, permanent education is being incorporated into the healthcare service routine.


Sex Differences in Neuroanatomy of the Human Mirror Neuron System: Impact on Functional Recovery of Ischemic Hemiparetic Patients.
Considering the higher activity of mirror neuron system in females, they frequently have better performance in empathy, interpersonal sensitivity, and emotional recognition compared to males. The purpose of this study was to assess whether gender difference in neuroanatomy of the human mirror neuron system has any impact on functional recovery of ischemic hemiparetic patients. This single-blind clinical trial was conducted on 24 patients with cerebrovascular accident (CVA) in the age range of 45 - 60 years, referring at a rehabilitation center in Tehran, Iran, during 2013 - 2014. Sampling method was stratified random sampling. The subjects were assigned to 2 groups of 12 males and 12 females. Then, each group was randomly divided into 2 groups (totally 4 groups, n = 6 for each group): women watching functional movies, control women, men watching functional movies, and control men. Movies were shown to patients and then, they were evaluated by Timed Up and Go (TUG), Six-minute walk test (SMW), Barthel index (BI), and Berg balance scale (BBS). Comparison of all variables related to functional activities of all groups before and after watching movies revealed significant differences. The highest percentage of change and improvement was observed in groups 1 and 3 watching the functional movies (P = 0.0001). Percentage of improvement in women of groups 1 and 2 was higher than men in groups 3 and 4 (P = 0.0003). The changes in group of females watching the functional movies (group 1) were significantly greater than in other groups (P < 0.0001). The Sex differences in the neuroanatomy of the human mirror neuron system affect functional recovery of patients with hemiparesis. The improvement in studied women was found to be significantly greater than studied men. The results indicate a higher chance of recovery among hemiparetic women, especially those watching functional movies.


The system neurophysiological basis of non-adaptive cognitive control: Inhibition of implicit learning mediated by right prefrontal regions.
Cognitive control is adaptive in the sense that it inhibits automatic processes to optimize goal-directed behavior, but high levels of control may also have detrimental effects in case they suppress beneficial automatisms. Until now, the system neurophysiological mechanisms and functional neuroanatomy underlying these adverse effects of cognitive control have remained elusive. This question was examined by analyzing the automatic exploitation of a beneficial implicit predictive feature under conditions of high versus low cognitive control demands, combining event-related potentials (ERPs) and source localization. It was found that cognitive control prohibits the beneficial automatic exploitation of additional implicit information when task demands are high. Bottom-up perceptual and attentional selection processes (P1 and N1 ERPs) are not modulated by this, but the automatic exploitation of beneficial predictive information in case of low cognitive control demands was associated with larger response-locked P3 amplitudes and stronger activation of the right inferior frontal gyrus (rIFG, BA47). This suggests that the rIFG plays a key role in the detection of relevant task cues, the exploitation of alternative task sets, and the automatic (bottom-up) implementation and reprogramming of action plans. Moreover, N450 amplitudes were larger under high cognitive control demands, which was associated with activity differences in the right medial frontal gyrus (BA9). This most likely reflects a stronger exploitation of explicit task sets which hinders the exploration of the implicit beneficial information in case of high cognitive control demands. Hum Brain Mapp 37:4511-4522, 2016. © 2016 Wiley Periodicals, Inc.


Inguinal draining-lymph node in 18F-FDG PET/CT images could be a new indicator for the diagnosis of fracture-related infection in the lower extremities.
The imaging diagnosis of fracture-related infection is often challenging. The aim of this study was to evaluate the value of 18F-FDG PET/CT for the diagnosis of fracture-related infection (FRI) with internal fixation after orthopedic surgery in lower extremities. A total of 254 consecutive patients who underwent 18F-FDG PET/CT scans with suspected FRI with internal fixation in lower extremities were retrospectively investigated 18F-FDG PET/CT images were semiquantitatively evaluated with multiple metabolic parameters. Additionally, morphological information of the inguinal draining lymph nodes (DLN) with the highest SUV value was also collected and analyzed. Patients were divided into two groups according to final diagnosis: the infected (N=197) and the non-infected group (N=57). The differences in the inguinal DLN-related parameters, including the long diameter, short diameter, maximum cross-sectional area, maximum standardized uptake value (SUVmax), metabolic volume (MV) 60%, MV70%, MV80%, total lesional glycolysis (TLG) 60%, TLG70%, TLG80%, and the infection suspected area related parameters, including SUVmax, MV25%, MV30%, MV35%, MV40%, MV50%, and TLG70%, between the two groups were statistically significant. We then compared the highest area under the curves (AUCs) among the morphological parameters of DLN, metabolic parameters of DLN, and metabolic parameters of the suspected infection area. The result demonstrated that SUVmax of the inguinal DLN showed the best diagnostic performance with an AUC of 0.939 (P<0.05). Semiquantitative analysis (especially SUVmax) of the inguinal DLN in 18F-FDG PET/CT images could be a promising method for the diagnosis of suspected FRI with internal fixation after orthopedic surgery in lower extremities.


Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia.
Profiling of the kinase-binding capabilities of an aminopyrimidine analogue detected in a cellular screen of the St. Jude small-molecule collection led to the identification of a novel series of FMS-like tyrosine kinase 3 (FLT3) inhibitors. Structure-activity relationship studies led to the development of compounds exhibiting good potency against MV4-11 and MOLM13 acute myelogenous leukemia cells driven by FLT3, regardless of their FLT3 mutation status. In vitro pharmacological profiling demonstrated that compound 5e shows characteristics suitable for further preclinical development.


Brown algal morphogenesis: atomic force microscopy as a tool to study the role of mechanical forces.
Over the last few years, a growing interest has been directed toward the use of macroalgae as a source of energy, food and molecules for the cosmetic and pharmaceutical industries. Besides this, macroalgal development remains poorly understood compared to other multicellular organisms. Brown algae (Phaeophyceae) form a monophyletic lineage of usually large multicellular algae which evolved independently from land plants. In their environment, they are subjected to strong mechanical forces (current, waves, and tide), in response to which they modify rapidly and reversibly their morphology. Because of their specific cellular features (cell wall composition, cytoskeleton organization), deciphering how they cope with these forces might help discover new control mechanisms of cell wall softening and cellulose synthesis. Despite the current scarcity in knowledge on brown algal cell wall dynamics and protein composition, we will illustrate, in the light of methods adapted to Ectocarpus siliculosus, to what extent atomic force microscopy can contribute to advance this field of investigation.


Treatment of an Early Kaposi's Sarcoma Case Post Kidney Transplantation by Sirolimus: A Case Report.
Kaposi᾽s sarcoma (KS) can develop in 0.06% to 4.1% of kidney transplant recipients. Here we describe a case of 50-year-old man who developed KS a few months after kidney transplantation. After transplantation, he had delayed graft function and was managed by anti-thymocyte globulin (ATG) for five days. At the discharge, his immunosuppressive therapy was prednisolone 20 mg/day, tTacrolimus (Pprograf®) 4 mg/day, and mycophenolate mofetil (MMF) 2 gr/day, while he also took Vvalcyte and diltiazem. Once diagnosed with KS, the Prograf® (tacrolimus) was replaced by prednisolone (5 mg/day) and sirolimus (2 mg/day). Gradually the skin nodule on the patient arm disappeared, and the others nodule on the right his leg was decreased. It seems that the examination of skin should be a part of regular follow-up and dermatologist examination is recommended every 6 months.


Assessing the neurological status of patients with head injuries.
The aim of this article is to inform staff who are new to emergency care settings how to use the Glasgow Coma Scale (GCS) when managing patients with head injuries. It may also be useful as a refresher for experienced staff and a helpful teaching tool. It emphasises the need for continual, standardised assessment of neurological status and emphasises how the GCS is seen as best practice nationally and internationally.


Development of a deep learning model for classifying thymoma as Masaoka-Koga stage I or II via preoperative CT images.
Accurate thymoma staging via computed tomography (CT) images is difficult even for experienced thoracic doctors. Here we developed a preoperative staging tool differentiating Masaoka-Koga (MK) stage I patients from stage II patients using CT images. CT images of 174 thymoma patients were retrospectively selected. Two chest radiologists independently assessed the images. Variables with statistical differences in univariate analysis were adjusted for age, sex, and smoking history in multivariate logical regression to determine independent predictors of the thymoma stage. We established a deep learning (DL) 3D-DenseNet model to distinguish the MK stage I and stage II thymomas. Furthermore, we compared two different methods to label the regions of interest (ROI) in CT images. In routine CT images, there were statistical differences (P<0.05) in contour, necrosis, cystic components, and the degree of enhancement between stage I and II disease. Multivariate logical regression showed that only the degree of enhancement was an independent predictor of the thymoma stage. The area under the receiver operating characteristic curve (AUC) of routine CT images for classifying thymoma as MK stage I or II was low (AUC =0.639). The AUC of the 3D-DenseNet model showed better performance with a higher AUC (0.773). ROIs outlined by segmentation labels performed better (AUC =0.773) than those outlined by bounding box labels (AUC =0.722). Our DL 3D-DenseNet may aid thymoma stage classification, which may ultimately guide surgical treatment and improve outcomes. Compared with conventional methods, this approach provides improved staging accuracy. Moreover, ROIs labeled by segmentation is more recommendable when the sample size is limited.


Hypocupremia associated with prior vitamin B12 deficiency.
Clinical similarities between vitamin B(12) and copper deficiencies prompted us to investigate if hypocupremia is present in patients receiving vitamin B(12) supplementation. Our pilot study results indicate that a significant number of elderly patients with prior diagnosis of vitamin B(12) deficiency have also undiagnosed hypocupremia.


[Pulmonary involvement in collagen tissue diseases].
Collagen tissue diseases are multisystem and heterogeneous group disease mediated inflammatory disorders. The pulmonary manifestations is more common and all elements of the lung are involved. However, symptoms of the respiratory system may be masked by exercise limitation due to involvement of the musculoskeletal system. The involvement may be subclinical or determined fulminant and life-threatening dimension. In this review, the pulmonary involvement of the more common collagen tissue diseases are reviewed.


Exploring the Mechanism of Hepatotoxicity Induced by Dictamnus dasycarpus Based on Network Pharmacology, Molecular Docking and Experimental Pharmacology.
The root bark of Dictamnus dasycarpus Turcz is a traditional Chinese medicine, Dictamni Cortex (DC), which is mainly used in the clinical treatment of skin inflammation, eczema, rubella, rheumatism, and gynecological inflammation. Unexpectedly, there are some cases of liver injury after the administration of DC. However, the mechanism of hepatotoxicity remains ambiguous. The aim of this study was to explore the mechanism and substance bases of DC hepatotoxicity based on network pharmacology and molecular docking, verified through pharmacological experiments. Partial prototype components and metabolites in vivo of quinoline alkaloids from DC were selected as candidate compounds, whose targets were collected from databases. Network pharmacology was applied to study the potential hepatotoxic mechanism after correlating the targets of candidate compounds with the targets of hepatotoxicity. Molecular docking was simulated to uncover the molecular mechanism. Furthermore, the hepatotoxicity of the extract and its constituents from DC was evaluated in vivo and in vitro. We constructed the "potential toxic components-toxic target-toxic pathway" network. Our results showed that the targets of DC included CYP1A2 and GSR, participating in heterologous steroid metabolism, REDOX metabolism, drug metabolism, heterocyclic metabolic processes, the synthesis of steroid hormone, cytochrome P450 metabolism, chemical carcinogens and bile secretion pathways. In vitro and in vivo experiments displayed that DC could result in a decrease in GSH-Px and oxidative stress, simultaneously inhibiting the expression of CYP1A2 and inducing hepatotoxicity. These results further indicated the mechanism of hepatotoxicity induced by Dictamnus dasycarpus, providing a basic theory to explore and prevent hepatotoxicity in the clinical usage of Dictamnus dasycarpus.