[Application of a Fotonic Sensor for measurement of chronotropy and contractility in cultured rat cardiac myocytes].
We used a Fotonic Sensor, a fiber optic displacement measurement instrument, to measure the chronotropy and the contractility of cultured neonatal rat cardiac myocytes. The principle of the measurement is to detect changes in the distance between the probe and myocytes vertically extruded by the contraction. A fiber optic probe consists of adjacent pairs of light-transmitting and light-receiving fibers. The ratio of reflected light to transmitted light changes proportionally to the distance between the probe and an object at a certain range shown in a calibration curve. The analogue output from the sensor was transferred to a personal computer through an analogue/digital converter and analyzed. The sensor was able to detect the rate of myocyte beating, i.e., chronotropy, with a high correlation to the frequency of electrically stimulated beating and agreed well with the beating rate counted visually under a microscope. The contractility was evaluated by the maximum contraction velocity (Vm) by the first derivatives of the contraction curves obtained by the sensor. Norepinephrine (NE) and isoproterenol (ISO) increased the contractility in cultured myocytes in a dose-dependent fashion. In the preparation of rat ventricular papillary muscle, NE- and ISO-induced increase in the Vm in the radial direction significantly correlated with the increase in tension measured with a force-displacement transducer. These results indicate that the Fotonic Sensor is an appropriate instrument for evaluating the chronotropy and the contractility of cultured myocytes.


The Implementation of Restorative Care and Factors Associated with Resident Outcomes in Long-Term Care Facilities in Taiwan.
This study aimed to analyze how restorative care is implemented in long-term care facilities and factors associated with resident outcomes in Taiwan. A one-group pre-test and post-test design was adopted in 24 long-term care facilities by collecting a sample of 310 participants at the baseline and 210 at six months. Participants were residents aged 65 or over, and were being constrained, used diapers, or were bedridden, or a combination of these. Their physical and mental functions were measured using Activities of Daily Living (ADLs), Instrumental Activities of Daily Living (IADLs), Mini-Mental State Examination (MMSE), Geriatric Depression Scale-15 (GDS-15), and EuroQol-5D (EQ-5D). Mean differences in the outcomes were analyzed, and mixed effect models were used to examine influencing factors. The results showed that most of the participants had good family support. However, participants with better family support were more likely to drop out. Improvements were found in the residents' outcomes on physical function, depression and quality of life. Social support was a significant influencing factor on most of the outcomes. In conclusion, restorative care was found to have positive effects on residents' physical function and helped maintain mental function. Sufficient support and communication between participants, families, and staff in facilities are key factors leading to positive outcomes.


Analysis of definitions of general practice, family medicine, and primary health care: a terminological analysis.
There are numerous definitions of general practice/family medicine (GP/FM) and primary health care (PHC), but the distinction between the two concepts is unclear. To conduct a terminological analysis of a set of definitions of GP/FM and of PHC, to clarify the commonalities and differences between these two concepts. Sets of 20 definitions were collected in two 'bags of words' (one for GP/FM and one for PHC terms). A terminological analysis of these two collections was performed to prioritise the terms and analyse their universe of discourse. The two collections were extracted with VocabGrabber, configured in two 'term clouds' using Wordle, and further explored for similarities using Tropes. The main terms were analysed using the Aristotelian approach to the categorisation of things. Although continuity of care (characterised by a person-centred approach and shared decision making) is common to both sets, the two sets of definitions differ greatly in content. The main terms specific to GP/FM (community, medicine, responsibility, individual, problem, and needs) are different from those specific to PHC (home, team, promotion, collaborator, engagement, neighbourhood, and medical centre). Terminological analysis of the definitions for GP/FM and PHC shows two overlapping but distinct entities, necessitating a different taxonomic approach and different bibliographic search strategies.


[Oral health on the public agenda: an analysis of Municipal Health Council records in cities from the 17th Regional Health Division in the State of Paraná, Brazil].
The present study analyzes interventions pertaining to oral health recorded in the minutes of meetings held by 15 Municipal Health Councils in cities from the 17th Regional Health Division of the State of Paraná, Brazil. Document analysis was performed by identifying health themes, emphasizing categorization of issues related to interventions in oral health. The most frequently analyzed themes were records concerning the programming and organization of oral health services, followed by health budget issues. In 90 of the 591 minutes studied, 134 records pertaining to oral health interventions were identified. An analysis of the latter showed that oral health interventions involve reports of actions already implemented and lack the characteristics of proposals when analyzed from the health planning perspective. This study highlights the need for dentists to expand their representation in such forums in order to play a broader role in the planning process and support oral health as a basic citizen's right.


[Contact lenses. 2: Contact lens associated infections].
Contact lens wearers, especially those who wear soft or extended wear contact lenses, are at increased risk of suffering from keratitis. Among the causes of corneal infections, an inadequate hygiene or overextended wear play an important role. An insufficient cleaning and disinfection leads to contamination with pathological germs. Sites of entry for these germs are corneal microlesions, caused by the setting and removal of contact lenses, and epithelial defects, as a result of the wearing of old or defective contact lenses. Primary eye diseases of patients who wear contact lenses can be altered by their wearing, and vice-versa. Even more, miscellaneous infections may lead to infectious corneal ulcerations. Having an adequate hygiene, a proper patient orientation during the medical visit, and a regular control are therefore of great importance for the reduction in the frequency of such infections by patients who wear contact lenses.


Concomitant tickborne encephalitis and human granulocytic ehrlichiosis.
We report a patient with febrile illness and epidemiologic and clinical findings consistent with human granulocytic ehrlichiosis and tickborne encephalitis, in whom infection with Anaplasma phagocytophilum was demonstrated by polymerase chain reaction and seroconversion. Tickborne encephalitis virus infection was established by serum immunoglobulin (Ig) M and IgG antibodies.


North Atlantic forcing of tropical Indian Ocean climate.
The response of the tropical climate in the Indian Ocean realm to abrupt climate change events in the North Atlantic Ocean is contentious. Repositioning of the intertropical convergence zone is thought to have been responsible for changes in tropical hydroclimate during North Atlantic cold spells, but the dearth of high-resolution records outside the monsoon realm in the Indian Ocean precludes a full understanding of this remote relationship and its underlying mechanisms. Here we show that slowdowns of the Atlantic meridional overturning circulation during Heinrich stadials and the Younger Dryas stadial affected the tropical Indian Ocean hydroclimate through changes to the Hadley circulation including a southward shift in the rising branch (the intertropical convergence zone) and an overall weakening over the southern Indian Ocean. Our results are based on new, high-resolution sea surface temperature and seawater oxygen isotope records of well-dated sedimentary archives from the tropical eastern Indian Ocean for the past 45,000 years, combined with climate model simulations of Atlantic circulation slowdown under Marine Isotope Stages 2 and 3 boundary conditions. Similar conditions in the east and west of the basin rule out a zonal dipole structure as the dominant forcing of the tropical Indian Ocean hydroclimate of millennial-scale events. Results from our simulations and proxy data suggest dry conditions in the northern Indian Ocean realm and wet and warm conditions in the southern realm during North Atlantic cold spells.


The Association Between Use of Brain CT for Atraumatic Headache and 30-Day Emergency Department Revisitation.
The purpose of this article is to describe the association between initial CT for atraumatic headache and repeat emergency department (ED) visitation within 30 days of ED discharge. A retrospective observational study was performed at an academic urban ED with more than 85,000 annual visits. All adult patients with a chief complaint of headache from January through December 2010 who were discharged after ED evaluation were included in the analysis. Patients were excluded if they were transferred, died in the ED, or had a diagnosis indicating a traumatic mechanism. A propensity score-matched logistic regression model was used to determine whether the use of brain CT was associated with the primary outcome of ED revisitation within 30 days, controlling for potential confounding variables. Of 80,619 total patient visits to the ED during the study period, 922 ED discharges with a chief complaint of headache were included. A total of 139 (15.1%) patients revisited within 30 days. The return rate was 11.2% among patients who underwent CT at their initial visit and 21.1% among those who did not. In the adjusted analysis, controlling for age, race, sex, insurance status, triage vital signs, laboratory values, and triage pain level, the odds ratio for revisitation given CT performance was 0.49 (95% CI, 0.27-0.86). After adjustment for clinical factors, we found that patients who underwent a brain CT examination for atraumatic headache at an initial ED visit were less likely to return to the ED within 30 days. Future appropriate use quality metrics regarding ED imaging use may need to incorporate downstream health care use.


Phase behavior of the lecithin/water/isooctane and lecithin/water/decane systems.
The isothermal pseudo-ternary-phase diagram was determined at 25 degrees C for systems composed oflecithin, water, and, as oil, either isooctane or decane. This was accomplished by a combination of polarizing microscopy, small-angle X-ray scattering, and NMR techniques. The lecithin-rich region of the phase diagram is dominated by a lamellar liquid-crystalline phase (Lalpha). For lecithin contents less than 60% and low hydration (mole ratio water/lecithin = W0 < 5.5), the system forms a viscous gel of branched cylindrical reverse micelles. With increase in the water content, the system phase separates into two phases, which is either gel in equilibrium with essentially pure isooctane (for lecithin < 25%) or a gel in equilibrium with Lalpha (for lecithin > 25%). These two-phase regions are very thin with respect to water dilution. For 8 < W0 < 54 very stable water-in-oil emulsions form. It is only after ripening for more than 1 year that the large region occupied by the emulsion reveals a complex pattern of stable phases. Moving along water dilution lines, one finds (i) the coexistence of gel, isooctane and Lalpha, (ii) equilibrium between reverse micelles and spherulites, and, finally, (iii) disconnected reverse micelles that fail to solubilize water for W0 > 54. This results in a Winsor II phase equilibrium at low lecithin content, while for lecithin > 20% the neat water is in equilibrium with a reverse hexagonal phase and an isotropic liquid-crystalline phase. The use of the decane as oil does not change the main features of the phase behavior.


What can genome-wide association studies tell us about the genetics of common disease?
The success of genome-wide association studies relies on much of the risk of common diseases being due to common genetic variants; but evidence for this is inconclusive. The results of published genome-wide association studies are examined to see what can be learnt about the distribution of disease-associated variants and how this might influence future study design. Although replicated disease-associated variants tend to be very common and frequency is inversely correlated with estimated effect size, our simulations suggest that such observations are the result of power. We find that for studies conducted to date, the frequency and effect size of significantly associated alleles are likely to be similar to those of the underlying disease alleles that they represent. Little of the genetic variation of disease has been explained so far, but current studies are only adequately powered to detect very common alleles unless they greatly increase disease risk. Thus, although the truth of the common disease / common variant hypothesis remains undecided, recent successes suggest that there are many more common genetic disease-associated variants, requiring larger studies to be identified.


Colorectal cancer: speculations on the role of intraperitoneal therapy.
Treatment of colorectal cancer beyond surgical resection has had only minimal success in the past. Studies are therefore examining the most advantageous use of currently available treatment methods. Most experience with colorectal cancer has involved 5-fluorouracil; alternatives for adjuvant therapy include combination therapy, immunotherapy, and locoregional therapy. Some success has also been reported with portal vein infusion or intraperitoneal administration of chemotherapeutic agents. Comparison of recurrence data indicates that approximately one third of patients with extrapelvic colorectal cancer can be expected to have peritoneal seeding. Many factors, including selection of patients and chemotherapeutic agents, method of administration, devices used, and techniques for monitoring patients affect the results of any clinical study. Future directions for the adjuvant treatment of colorectal cancer might involve the addition of other agents to the intraperitoneal regimen or of whole abdominal or liver radiation, and also concomitant systemic or portal vein 5-fluorouracil.


Effects of electrocardiograph frequency filters on P-QRS-T amplitudes of the feline electrocardiogram.
OBJECTIVE--To determine whether standard manual frequency filters in the ON and OFF settings affected P-QRS-T voltages, discover whether recorded P-QRS-T voltages vary between commercial electrocardiographs, assess effects of frequency filters on base-line artifact, and evaluate ECG frequency content by high-fidelity recordings subjected to digital filters with variable frequencies. DESIGN--Sequential 10-lead ECG were recorded in 30 cats, using 3 commercial electrocardiographs to assess effects of manual frequency filters on the P-QRS-T wave forms. Three clinically normal cats were evaluated for ECG frequency content. ANIMALS--Thirty cats (13 with hypertrophic cardiomyopathy; 4 with restrictive cardiomyopathy; 3 hyperthyroid; 1 with ventricular septal defect; 1 with aortic stenosis; and 8 with no detectable cardiovascular disease). Three additional clinically normal cats were studied for effects of frequency filters on the ECG frequency content. PROCEDURES--Ten-lead ECG were recorded on each cat by use of 3 commercial electrocardiographs sequentially. For each machine, a recording was made with manual filters ON, immediately followed by a recording with manual filters OFF. High-fidelity lead-II ECG recordings were made with filters set with their rolloff frequency at 0.1 Hz and 3.0 kHz; output voltage (0.2 mV/V) was fed to an analog-to-digital converter, then to attendant software, which sampled the signal at 6 kHz with a 12-bit sampler, and were digitally filtered at various corner frequencies. RESULTS--Voltages recorded by all 3 electrocardiographs were greatest when filters were OFF (most prominent on R- and S-wave voltages). In all recorded leads, R-wave voltage was significantly greater when filters were OFF than ON. Comparison of voltages indicated significant (P < 0.05) differences between R-wave voltages recorded in all leads with manual filters ON, but not with filters OFF. With filters ON, each electrocardiograph produced a smaller percentage of recordings with moderate to severe baseline artifact than with filters OFF. R-Wave amplitudes of high-fidelity lead-II ECG were significantly decreased with digital filters set at corner frequencies < 150 Hz. CONCLUSIONS--Significant (P < 0.05) voltage attenuation was recorded by each of the 3 commercial electrocardiographs when frequency filters were ON, compared with OFF. Comparison of waveform voltages among electrocardiographs with filters ON indicated significant variation in R-wave amplitudes in all leads. With manual filters ON, each electrocardiograph recorded a smaller percentage of recordings with baseline artifact than with filters OFF. Substantial frequency components > or = 150 Hz are present in the feline ECG waveform. Thus, filters with frequencies < 150 Hz markedly attenuate the feline R wave. CLINICAL RELEVANCE--Attenuation of feline ECG signals occurs with use of commercial electrocardiographs and varies greatly between manufacturers. This is attributable largely to internal manual frequency filters. These consequences may be important when applying standard feline reference values or when equivocal voltage measurements are recorded.


Clinical application of ghrelin administration for gastric cancer patients undergoing gastrectomy.
Loss of body weight is a common (and the most serious) sequela after gastrectomy. It impairs quality of life, increases various diseases including infection, and may affect long-term survival. Ghrelin, an intrinsic ligand of the growth hormone secretagogue receptor, was discovered in the stomach in 1999. In addition to growth hormone secretion, ghrelin has pleiotropic functions including appetite stimulation, increasing bowel movement and absorption, and anti-inflammatory reactions. In consequence, ghrelin comprehensively leads positive energy balance and weight gain. The fundic gland of the stomach produces the majority of ghrelin, and plasma ghrelin declines to 10-30 % of the preoperative level after total gastrectomy and 50-70 % after distal gastrectomy. Although plasma ghrelin is never restored after total gastrectomy, it gradually recovers to the preoperative level within a few years after distal gastrectomy. Chronic gastritis due to Helicobacter pylori infection and vagotomy are additional factors that perturb the ghrelin secretion of gastric cancer patients after gastrectomy. A randomized clinical trial that revealed that recombinant ghrelin administration successfully increased both food intake and appetite, and ameliorated weight loss after total gastrectomy. Ghrelin administration could thus be a promising strategy to transiently improve the nutritional status of patients who who have undergone gastrectomy, but its effect in the long term remains unclear. Further studies are warranted to elucidate the mechanism of ghrelin and to create and evaluate the analogs that could be administered orally or subcutaneously.


Schistosomiasis among young children in Usoma, Kenya.
Although schistosomiasis burden is greatest among school-age children (SAC) (6-15 years of age), infection among preschool-age children (PSAC) (1-5 years), may be underestimated in endemic areas. We conducted a cross-sectional study evaluating Schistosoma mansoni infection among children 1-15 years of age in a highly endemic community in Kenya. Diagnostic tests included stool exam (Kato/Katz technique), serum testing for schistosome-specific antibodies, and urine testing for circulating cathodic antigen (CCA). Overall, 268 SAC and 216 PSAC were enrolled; prevalence increased with age, with 14% of 1 year olds and more than 90% of children > 10 years of age infected. Stool exam was more sensitive among SAC than PSAC, but performance was similar after adjusting for infection intensity (based on CCA). Schistosomiasis poses a threat to PSAC in endemic areas, and stool exam may underestimate the prevalence of infection. Control programs in such areas should consider PSAC in addition to SAC.


Role of CB2 receptors in neuroprotective effects of cannabinoids.
CB2 receptors, the so-called peripheral cannabinoid receptor type, were first described in the immune system, but they have been recently identified in the brain in healthy conditions and, in particular, after several types of cytotoxic stimuli. Specifically, CB2 receptors were identified in microglial cells, astrocytes and, to a lesser extent, in certain subpopulations of neurons. Given the lack of psychoactivity demonstrated by selective CB2 receptor agonists, this receptor becomes an interesting target for the treatment of neurological diseases, in particular, the case of certain neurodegenerative disorders in which induction/up-regulation of CB2 receptors has been already demonstrated. These disorders include Alzheimer's disease, Huntington's chorea, amyotrophic lateral sclerosis and others. Interestingly, in experimental models of these disorders, the activation of CB2 receptors has been related to a delayed progression of neurodegenerative events, in particular, those related to the toxic influence of microglial cells on neuronal homeostasis. The present article will review the evidence supporting that CB2 receptors might represent a key element in the endogenous response against different types of cytotoxic events, and that this receptor type may be a clinically promising target for the control of brain damage in neurodegenerative disorders.


[The role of adrenergic mechanisms in the anticonvulsive action of the new preparation acetylaminoazaleptin].
In mice experiments the effects of adrenergic drugs (anaprilin, pirroxan, fetanol and alupent) on anticonvulsive activity of acetylaminoazaleptin (AAA) using the test of maximal electroshock and AAA effect on phenamin-induced manifestation (stereotypy and hyperthermia) were studied. It was demonstrated that anaprilin significantly (6-fold) increased anticonvulsive activity of AAA. The other drugs did not change AAA activity. In the experiments with phenamin AAA slightly weaken stereotypy and significantly reduced hyperthermia manifestation.


Are There Racial Differences in the Rate of Surgical Site Infection Based on Surgical Subspecialty?
Background: Surgical site infection (SSI) is a common, morbid post-operative complication. We hypothesized the presence of racial differences in SSI rates, comparing black/African American (BAA) to white non-Hispanic (WNH) patients. Patients and Methods: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2017), BAA and WNH surgery patients across 10 surgical specialties were identified: general surgery (GS), vascular surgery (VS), cardiac surgery (CS), thoracic surgery (TS), orthopedics (OS), neurosurgery (NS), urology (US), otolaryngology (ENT), plastic surgery (PS), and gynecology (GYN). The primary outcome was SSI rate (superficial, deep incisional, or organ/space). The secondary outcome was rate of non-surgical infection. Pearson χ2 and Fisher exact tests were used to test group differences of categorical variables. Continuous variables were tested with the Student t-test, or Mann-Whitney U test, with statistical significance set at a value of p < 0.05. Multivariable logistic regression models were conducted to analyze the association between race/ethnicity and the infection outcomes. Results: A total of 740,144 patients were included: 99,425 (13.4%) BAA and 640,749 (86.6%) WNH, distributed as follows; 32,2976 GS, 17,6175 OS, 44,383 VS, 2,227 CS, 9,645 TS, 42,298 NS, 42,726 US, 18,518 ENT, 20,709 PS, and 60,517 GYN cases. Surgical site infection rates were higher among WNH in GS (4.4% vs. 4.1%; p = 0.003) and TS (3.1% vs. 1.7%; p = 0.015); lower in VS (3.2% vs. 4.4%; p < 0.001), OS (1.2% vs.1.6%; p < 0.001), and GYN (2.4% vs. 3%; p < 0.001); and similar between WNH and BAA in ENT (1.8% vs 1.8%; p = 0.76), and US (1.9% vs. 1.9%; p = 0.90). Non-surgical infection was higher in BAA in NS (3.2% vs. 2.5%; p = 0.003), and higher in WNH in GYN (2.6% vs. 2%; p < 0.001), OS (1.7% vs. 1.1%; p < 0.001), US (4.4% vs. 3.6%; p = 0.014), and VS (3.4% vs. 2.6%; p < 0.001). Conclusions: Variation exists in SSI rates between WNH and BAA patients among surgical subspecialties. Further research is required to understand these differences and address racial disparities in outcomes.


Kriging atomic properties with a variable number of inputs.
A new force field called FFLUX uses the machine learning technique kriging to capture the link between the properties (energies and multipole moments) of topological atoms (i.e., output) and the coordinates of the surrounding atoms (i.e., input). Here we present a novel, general method of applying kriging to chemical systems that do not possess a fixed number of (geometrical) inputs. Unlike traditional kriging methods, which require an input system to be of fixed dimensionality, the method presented here can be readily applied to molecular simulation, where an interaction cutoff radius is commonly used and the number of atoms or molecules within the cutoff radius is not constant. The method described here is general and can be applied to any machine learning technique that normally operates under a fixed number of inputs. In particular, the method described here is also useful for interpolating methods other than kriging, which may suffer from difficulties stemming from identical sets of inputs corresponding to different outputs or input biasing. As a demonstration, the new method is used to predict 54 energetic and electrostatic properties of the central water molecule of a set of 5000, 4 Å radius water clusters, with a variable number of water molecules. The results are validated against equivalent models from a set of clusters composed of a fixed number of water molecules (set to ten, i.e., decamers) and against models created by using a naïve method of treating the variable number of inputs problem presented. Results show that the 4 Å water cluster models, utilising the method presented here, return similar or better kriging models than the decamer clusters for all properties considered and perform much better than the truncated models.


Farming, pesticide use and hairy-cell leukemia.
This paper analyzes the role of farming and pesticide exposures in the occurrence of hairy-cell leukemia (HCL). The study included 226 men with HCL and 425 matched hospital referents. Pesticide exposure was assessed by expert review of detailed interview data on occupational histories and agricultural activities and exposures. Altogether, 77 cases and 116 referents had farmed for at least six months, giving an odds ratio (OR) of 1.5 [95% confidence interval (95% CI) 1.0-2.2]. Forage growing was reported by 20.8% of the cases and 11.1% of the referents and was associated with HCL (OR 2.8, 95% CI 1.6-4.9), even among farmers who had never handled pesticides (OR 3.4, 95% CI 1.0-11.0). A significant association was found between HCL and pesticide use, the overall odds ratios for insecticide, fungicide, and herbicide use ranging from 1.5 to 2.4. Organophosphorus insecticides were the only agrochemicals with a positive association with HCL after other pesticide exposures, smoking, and forage growing were accounted for. A clear-cut negative interaction was found between smoking and exposure to organophosphorus insecticides. A multivariate analysis yielded odds ratio estimates of 2.8 (95% CI 1.4-5.6) for exposure to forage and 7.5 (95% CI 0.9-61.5) for nonsmokers exposed to organophosphorus insecticides. The present study argues for a role of organophosphorus insecticides in HCL among nonsmoking farmers and shows an unexpected association with forage growing. No evidence of an association with phenoxyacetic acids, triazines, or organochlorine insecticides was found.


1,2H hyperfine spectroscopy and DFT modeling unveil the demethylmenasemiquinone binding mode to E. coli nitrate reductase A (NarGHI).
The quinol oxidation site QD in E. coli respiratory nitrate reductase A (EcNarGHI) reacts with the three isoprenoid quinones naturally synthesized by the bacterium, i.e. ubiquinones (UQ), menaquinones (MK) and demethylmenaquinones (DMK). The binding mode of the demethylmenasemiquinone (DMSK) intermediate to the EcNarGHI QD quinol oxidation site is analyzed in detail using 1,2H hyperfine (hf) spectroscopy in combination with H2O/D2O exchange experiments and DFT modeling, and compared to the menasemiquinone one bound to the QD site (MSKD) previously studied by us. DMSKD and MSKD are shown to bind in a similar and strongly asymmetric manner through a short (~1.7 Å) H-bond. The origin of the specific hf pattern resolved on the DMSKD field-swept EPR spectrum is unambiguously ascribed to slightly inequivalent contributions from two β-methylene protons of the isoprenoid side chain. DFT calculations show that their large isotropic hf coupling constants (Aiso ~12 and 15 MHz) are consistent with both (i) a specific highly asymmetric binding mode of DMSKD and (ii) a near in-plane orientation of its isoprenyl chain at Cβ relative to the aromatic ring, which differs by ~90° to that predicted for free or NarGHI-bound MSK. Our results provide new insights into how the conformation and the redox properties of different natural quinones are selectively fine-tuned by the protein environment at a single Q site. Such a fine-tuning most likely contributes to render NarGHI as an efficient and flexible respiratory enzyme to be used upon rapid variations of the Q-pool content.


[Latent ceruloplasmin activity in the frontal lobe of albino rat brains].
Latent ceruloplasmin activity was revealed in 5% of homogenates of the frontal lobes of the albino rats' brain. While assessing the activity of this enzyme in the investigated assays in the dynamics of their storage at 4-8 degrees C, the value under study continuously increased and on the 14th day of the experiment it reached 137% of the initial values. 1-Triphenylphosphoniomethylnafthalene bromide did not exert any effect on the dynamics of changes of ceruloplasmin activity in biological assays.


Pyrolysis-free synthesis of a high-loading single-atom Cu catalyst for efficient electrocatalytic CO2-to-CH4 conversion.
Electrocatalytic CO2-to-CH4 conversion provides a promising means of addressing current carbon resource recycling and intermittent energy storage. Cu-based single-atom catalysts have attracted extensive attention owing to their high intrinsic activity toward CH4 production; however, they suffer from uncontrollable metal loading and aggregation during the conventional pyrolysis process of carbon-based substrates. Herein, we developed a pyrolysis-free method to prepare a single-atom Cu catalyst anchored on a formamide polymer substrate with a high loading amount and well atomic dispersion through a mild polycondensation reaction. Owing to the isolation of copper active sites, efficient CO2-to-CH4 conversion is achieved over the single-atom Cu catalyst, along with the significant suppression of C-C coupling. As a result, the optimal single-atom catalyst with 5.87 wt% of Cu offers high CH4 faradaic efficiencies (FEs) of over 70% in a wide current density range from 100 to 600 mA cm-2 in the flow cell, together with a maximum CH4 partial current density of 415.8 mA cm-2. Moreover, the CH4 FE can reach 74.2% under optimized conditions in a membrane electrode assembly electrolyzer. This work provides new insights into the subtle design of highly efficient electrocatalyst for CO2 reduction.


Model for Predicting Central Nervous System Relapse in Diffuse Large B-Cell Lymphoma and Discussion of Prophylaxis Measures.
Relapse of the central nervous system (CNS) is a rare but fatal complication in diffuse large B-cell lymphoma (DLBCL). The purpose of this study is to learn how to identify high-risk patients and take effective preventive measures. We retrospectively analyzed 1,290 adult patients with DLBCL at Peking University Cancer Hospital and Shanxi Bethune Hospital between 2010 and 2020. There were 55 patients with CNS relapse who had a median follow-up of 5 years. The risk of CNS relapse was 1.58% in the low-risk group, 5.66% in the moderate-risk group, and 11.67% in the high-risk group based on CNS International Prognostic Index (CNS-IPI). We found that CNS-IPI and testicular involvement were risk factors for CNS relapse, with OR 1.913 (95% CI: 1.036∼3.531; P = 0.038) versus. OR 3.526 (95% CI: 1.335∼9.313; P = 0.011), respectively. Intrathecal MTX and/or cytarabine prophylaxis was used in 166 patients (13.94%), intravenous (IV) high-dose methotrexate (HD-MTX) prophylaxis in 8 patients (0.67%), and intrathecal plus intravenous prophylaxis in 15 patients (1.26%). There was no significant difference in CNS relapse risk between IT, HD-MTX, and no prophylaxis recipients (12.7% vs. 0% vs. 23.6%, respectively, P = 0.170). The risk of CNS relapse was similar whether or not patients accepted prophylaxis (5-year risk 4.1% vs. 2.2%, P = 0.140). Central nervous system (CNS) relapse is associated with high risk CNS-IPI and testicular involvement. Therefore, it is necessary to pursue novel prophylactic strategies for CNS relapse.


Expression of EAAT1 reflects a possible neuroprotective function of reactive astrocytes and activated microglia following human traumatic brain injury.
Glutamate-mediated excitotoxicity is known to cause secondary brain damage following stroke and traumatic brain injury (TBI). However, clinical trials using NMDA antagonists failed. Thus, glial excitatory amino acid transporters (EAATs) might be a promising target for therapeutic intervention. We examined expression of EAAT1 (GLAST) and EAAT2 (Glt-1) in 36 TBI cases by immunohistochemistry. Cortical expression of both EAATs decreased rapidly and widespread throughout the brain (in lesional, adjacent and remote areas) following TBI. In the white matter numbers of EAAT1+ parenchymal cells increased 39-fold within 24h (p<0.001) and remained markedly elevated till later stages in the lesion (90-fold, p<0.01) and in peri-lesional regions (86-fold, p<0.01). In contrast, EAAT2+ parenchymal cells and EAAT1+ or EAAT2+ perivascular cells did not increase significantly. Within the first days following TBI mainly activated microglia and thereafter mainly reactive astrocytes expressed EAAT1. Perivascular monocytes and foamy macrophages lacked EAAT1 immunoreactivity. We conclude that following TBI i) loss of cortical EAATs contributes to secondary brain damage, ii) glial EAAT1 expression reflects a potential neuroprotective function of microglia and astrocytes, iii) microglial EAAT1 expression is restricted to an early stage of activation, iv) blood-derived monocytes do not express EAAT1 and v) pharmacological modification of glial EAAT expression might further limit neuronal damage.


Coagulation, fibrinolytic and platelet function in patients on long-term therapy with aspirin 300 mg or 1,200 mg daily compared with placebo.
Aspirin has been shown to be beneficial in the prophylaxis of arterial thromboembolic disease. The rationale for its use as an antithrombotic drug lies in its inhibition of thromboxane A2-dependent platelet function. However, the effect of aspirin on coagulation and fibrinolysis during chronic therapy has not been studied. We have measured a range of haemostatic and platelet functions in 49 patients with transient ischaemic attacks randomly allocated to aspirin 300 mg a day, aspirin 1,200 mg a day or placebo. All had been taking their allocated treatment for between 9 months and 4 years prior to investigation. Bleeding time was prolonged, serum thromboxane diminished and platelet aggregation to arachidonic acid but not ADP was abolished by both 300 mg and 1,200 mg aspirin, in a non-dose dependent fashion. Serum salicylate increased with the dose of aspirin ingested. No effect was seen with either dose of aspirin on urinary thromboxane and 6-keto-PGF1 alpha excretion, or on coagulation. Patients taking 1,200 mg aspirin a day had a lower haemoglobin and packed cell volume, lower resting fibrinopeptide A concentration and lower basal plasminogen activator activity than those on placebo. Response to venous occlusion was normal in all groups. The results suggest 300 mg and 1,200 mg aspirin have an equivalent platelet inhibitory effect but 1,200 mg aspirin causes greater gastro-intestinal blood loss.


The Effector TepP Mediates Recruitment and Activation of Phosphoinositide 3-Kinase on Early Chlamydia trachomatis Vacuoles.
Chlamydia trachomatis delivers multiple type 3 secreted effector proteins to host epithelial cells to manipulate cytoskeletal functions, membrane dynamics, and signaling pathways. TepP is the most abundant effector protein secreted early in infection, but its molecular function is poorly understood. In this report, we provide evidence that TepP is important for bacterial replication in cervical epithelial cells, activation of type I IFN genes, and recruitment of class I phosphoinositide 3-kinases (PI3K) and signaling adaptor protein CrkL to nascent pathogen-containing vacuoles (inclusions). We also show that TepP is a target of tyrosine phosphorylation by Src kinases but that these modifications do not appear to influence the recruitment of PI3K or CrkL. The translocation of TepP correlated with an increase in the intracellular pools of phosphoinositide-(3,4,5)-triphosphate but not the activation of the prosurvival kinase Akt, suggesting that TepP-mediated activation of PI3K is spatially restricted to early inclusions. Furthermore, we linked PI3K activity to the dampening of transcription of type I interferon (IFN)-induced genes early in infection. Overall, these findings indicate that TepP can modulate cell signaling and, potentially, membrane trafficking events by spatially restricted activation of PI3K. IMPORTANCE This article shows that Chlamydia recruits PI3K, an enzyme important for host cell survival and internal membrane functions, to the pathogens inside cells by secreting a scaffolding protein called TepP. TepP enhances Chlamydia replication and dampens the activation of immune responses.


An economic evaluation of two ototopical treatments for acute otitis media in tympanostomy tube patients.
The goal of this research was to determine the cost-effectiveness of ciprofloxacin 0.3%/dexamethasone 0.1% (CD) otic suspension versus ofloxacin 0.3% otic solution (OFX) for treatment of acute otitis media in tympanostomy tube patients. A decision-analytic model was used to emulate the ototopical treatment of acute otitis media in patients with tympanostomy tubes. The economic outcome was the cost per otorrhea-free day (OFD) achieved per episode of care. Three tiers of antimicrobial therapy were modeled, with each successive tier representing the retreatment of clinical failures from the preceding tier. First-tier therapy compared CD and OFX using outcome measures obtained from a randomized clinical trial (n = 599). Second-tier therapy modeled the use of amoxicillin/clavulanate (ACA) using outcome measures obtained from a physician survey and medical literature. Third-tier therapy was modeled as pathogen-specific and curative. It could follow one of three pathways: 1) intramuscular ceftriaxone; 2) oral fluconazole; or 3) hospitalization for intravenous antibiotics. Third-tier outcomes were based on a physician survey. Cost data were obtained from standard references and presented from a payer perspective. The expected therapeutic costs were 249.40 dollars for the CD pathway and 265.44 dollars for the OFX pathway. The estimated number of OFDs per episode of care was 25.88 for the CD pathway and 23.86 for the OFX pathway. The cost-effectiveness ratios for CD and OFX therapies were 9.64 dollars and 11.13 dollars per OFD, respectively. CD is both more effective and less costly than OFX for the treatment of acute otitis media in patients with tympanostomy tubes.


Position coding in two-digit arabic numbers.
Digit position coding in two-digit Arabic numbers was examined in two masked priming experiments. In Experiment 1, participants had to decide whether the presented stimulus was a two-digit Arabic number (e.g., 67) or not (e.g., G7). Target stimuli could be preceded by a prime which (i) shared one digit in the initial position (e.g., 13-18), (ii) shared one digit but in a different position (83-18), and (iii) was a transposed number (81-18). Two unrelated control conditions, equalized in terms of the distance between primes and targets with the experimental conditions, were also included (e.g., 79-18). Results showed a priming effect only when prime and target shared digits in the same position. Experiment 2 employed a masked priming same-different matching task - a task that has been successfully employed in the literature on letter position coding. Results showed faster response times when prime and target shared digits - including the transposed-digit condition - relative to the control conditions. Thus, the identity of each digit in the early stages of visual processing is not associated with a specific position in two-digit Arabic numbers. We examine the implication of these findings for models of Arabic number processing.


Protective Actions of α-Tocopherol on Cell Membrane Lipids of Paraquat-Stressed Human Astrocytes Using Microarray Technology, MALDI-MS and Lipidomic Analysis.
Cellular senescence is one of the main contributors to some neurodegenerative disorders. The early detection of senescent cells or their related effects is a key aspect in treating disease progression. In this functional deterioration, oxidative stress and lipid peroxidation play an important role. Endogenous antioxidant compounds, such as α-tocopherol (vitamin E), can mitigate these undesirable effects, particularly lipid peroxidation, by blocking the reaction between free radicals and unsaturated fatty acid. While the antioxidant actions of α-tocopherol have been studied in various systems, monitoring the specific effects on cell membrane lipids at scales compatible with large screenings has not yet been accomplished. Understanding the changes responsible for this protection against one of the consequences of senescence is therefore necessary. Thus, the goal of this study was to determinate the changes in the lipid environment of a Paraquat-treated human astrocytic cell line, as a cellular oxidative stress model, and the specific actions of the antioxidant, α-tocopherol, using cell membrane microarray technology, MALDI-MS and lipidomic analysis. The stress induced by Paraquat exposure significantly decreased cell viability and triggered membrane lipid changes, such as an increase in certain species of ceramides that are lipid mediators of apoptotic pathways. The pre-treatment of cells with α-tocopherol mitigated these effects, enhancing cell viability and modulating the lipid profile in Paraquat-treated astrocytes. These results demonstrate the lipid modulation effects of α-tocopherol against Paraquat-promoted oxidative stress and validate a novel analytical high-throughput method combining cell cultures, microarray technology, MALDI-MS and multivariate analysis to study antioxidant compounds against cellular senescence.


Age-Related Argonaute Loading of Ribosomal RNA Fragments.
Accumulating evidence points to the functional roles of rRNA derived Fragments (rRFs), often considered degradation byproducts. Small RNAs, including miRNAs and tRNA-derived Fragments (tRFs), have been implicated in the aging process and we considered rRFs in this context. We performed a computational analysis of Argonaute-loaded rRFs in Drosophila melanogaster to study rRF changes with age. We determined rRF abundance in Ago1 and Ago2 at 3 and 30 days to identify Ago1-guided and Ago2-guided fragments. We searched for putative seed sequences in rRFs based on frequent matches of sliding k-mer windows to the conserved regions of 12 Drosophila genomes. We predicted putative targets (containing matches to seeds identified in four rRFs) and studied their functional enrichments using Gene Ontology. We identified precise cleavage sites of distinct rRF isoforms from both nuclear and mitochondrial rRNAs. The most prominent rRF isoforms were enriched in Ago2 at 3 days and that loading strongly decreased with age. For less abundant rRFs, loading of Ago2-guided rRFs generally increased in Ago2, whereas Ago1-guided rRFs revealed diverse patterns. The distribution of seed matches in targets suggested that rRFs may bind to various conserved regions of many genes, possibly via miRNA-like seed-based mechanisms. Our observations suggest that rRFs may be functional molecules, with age-dependent Argonaute loading, comparable to that of miRNAs and tRFs. The putative rRF targets showed significant enrichment in developmental processes and biological regulation, similar to tRFs and consistent with a possible involvement of these newly identified small RNAs in the Drosophila aging.


Clinical Dimensions of Bloating in Functional Gastrointestinal Disorders.
Bloating is common bothersome symptoms and most studies conducted in the Western countries found that bloating was frequently associated with lower gastrointestinal (GI) symptoms but many patients complaint bloating as upper GI symptoms in the clinical setting. This study was conducted to assess the prevalence of bloating, and to identify symptom grouping and finally document the impact of bloating in the diagnosis of functional GI disorders. Participants in a comprehensive health-screening cohort were enrolled. They were asked about demographic, medical, and social history and upper and lower GI symptoms by using a validated questionnaire. Factor analysis with principal component analysis method with varimax rotation was used. Among the total of 1050 subjects (mean age, 44.6 ± 10.2 years; females, 46.4%), significant bloating symptoms were found in 282 (26.9%); the prevalence of functional bloating was 6.9%. Factor analysis revealed a 5-component structure with upper GI symptoms, constipation, diarrhea-predominant irritable bowel syndrome (IBS), constipation-predominant IBS, and fecal incontinence. Abdominal bloating loaded on both the upper GI symptoms (0.51 of loadings) and constipation (0.40). On logistic regression analysis, bloating was more predictable for IBS (OR, 7.5; P < 0.001) than functional dyspepsia (FD; OR, 3.7; P = 0.002). Bloating was more frequently combined with IBS according to their severity, but this association was not detected in patients with FD. Abdominal bloating is common symptom in about a quarter of patients and appears as upper as well as lower GI symptoms. However, abdominal bloating is more predictable for IBS, especially constipation-predominant IBS, than FD.


Real-time speech-driven face animation with expressions using neural networks.
A real-time speech-driven synthetic talking face provides an effective multimodal communication interface in distributed collaboration environments. Nonverbal gestures such as facial expressions are important to human communication and should be considered by speech-driven face animation systems. In this paper, we present a framework that systematically addresses facial deformation modeling, automatic facial motion analysis, and real-time speech-driven face animation with expression using neural networks. Based on this framework, we learn a quantitative visual representation of the facial deformations, called the motion units (MUs). A facial deformation can be approximated by a linear combination of the MUs weighted by MU parameters (MUPs). We develop an MU-based facial motion tracking algorithm which is used to collect an audio-visual training database. Then, we construct a real-time audio-to-MUP mapping by training a set of neural networks using the collected audio-visual training database. The quantitative evaluation of the mapping shows the effectiveness of the proposed approach. Using the proposed method, we develop the functionality of real-time speech-driven face animation with expressions for the iFACE system. Experimental results show that the synthetic expressive talking face of the iFACE system is comparable with a real face in terms of the effectiveness of their influences on bimodal human emotion perception.


[The role of laparoscopy in ovarian carcinoma].
The role of minimally invasive surgery in the management of gynecologic cancers is continuously expanding. Although few trials have focused on the safety of laparoscopy in oncology, laparoscopy is now widely used for most gynecological malignancies. Laparoscopy is widely used to manage benign ovarian masses, but its role in managing ovarian cancer still needs to be defined. The role of laparoscopy in ovarian cancer surgery may be divided into three following categories: 1) laparoscopic staging of apparent early ovarian cancer; 2) laparoscopic assessment of disease extent and potential for resectability; 3) laparoscopic reassessment, or second-look operation, or rule out recurrence. Laparoscopic approach has shown several advantages like a reduction in operating time, blood loss, hospital stay, and total hospital charges. The limitations of laparoscopic practice include inadequate port-site metastasis, tumour dissemination due to cyst rupture and incomplete staging. In addition, there were limitations in performing extensive laparoscopic sampling of areas of tumor persistence including retroperitoneal lymph nodes. In literature there are no randomized studies assessing the use of laparoscopy in the management of ovarian cancer. Moreover, most of the studies in literature comparing laparoscopy and laparotomy are carried out by surgeons specialized in one of two approaches, so that the results can not be compared.


Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 Inhibitors.
Insertion mutations in EGFR and HER2 both occur at analogous positions in exon 20. Non-small cell lung cancer (NSCLC) patients with tumors harboring these mutations seldom achieve clinical responses to dacomitinib and afatinib, two covalent quinazoline-based inhibitors of EGFR or HER2, respectively. In this study, we investigated the effects of specific EGFR and HER2 exon 20 insertion mutations from NSCLC patients that had clinically achieved a partial response after dacomitinib treatment. We identified Gly770 as a common feature among the drug-sensitive mutations. Structural modeling suggested that this mutation may facilitate inhibitor binding to EGFR. Introduction of Gly770 into two dacomitinib-resistant EGFR exon 20 insertion mutants restored sensitivity to dacomitinib. Based on these findings, we used afatinib to treat an NSCLC patient whose tumor harbored the HER2 V777_G778insGSP mutation and achieved a durable partial response. We further identified secondary mutations in EGFR (T790M or C797S) and HER2 (C805S) that mediated acquired drug resistance in drug-sensitive EGFR or HER2 exon 20 insertion models. Overall, our findings identified a subset of EGFR and HER2 exon 20 insertion mutations that are sensitive to existing covalent quinazoline-based EGFR/HER2 inhibitors, with implications for current clinical treatment and next-generation small-molecule inhibitors. Cancer Res; 77(10); 2712-21. ©2017 AACR.


Acute asthma among pregnant women presenting to the emergency department.
Asthma complicates up to 4% of pregnancies. Our objective was to compare emergency department (ED) visits for acute asthma among pregnant versus nonpregnant women. We performed a prospective cohort study, as part of the Multicenter Asthma Research Collaboration. ED patients who presented with acute asthma underwent a structured interview in the ED, and another by telephone 2 wk later. The study was performed at 36 EDs in 18 states. A total of 51 pregnant women and 500 nonpregnant women, age 18 to 39, were available for analysis. Pregnant women did not differ from nonpregnant women by duration of asthma symptoms (median: 0.75 versus 0.75 d, p = 0.57) or initial peak expiratory flow rate (PEFR) (51% versus 53% of predicted, p = 0.52). Despite this similarity, only 44% of pregnant women were treated with corticosteroids in the ED compared with 66% of nonpregnant women (p = 0.002). Pregnant women were equally likely to be admitted (24% versus 21%, p = 0.61) but less likely to be prescribed corticosteroids if sent home (38% versus 64%, p = 0.002). At 2-wk follow-up, pregnant women were 2.9 times more likely to report an ongoing exacerbation (95% CI, 1.2 to 6.8). Among women presenting to the ED with acute asthma, pregnant asthmatics are less likely to receive appropriate treatment with corticosteroids.


Enhanced Sulfate Production by Nitrate Photolysis in the Presence of Halide Ions in Atmospheric Particles.
Heterogeneous oxidation of SO2 is an effective production pathway of sulfate in the atmosphere. We recently reported a novel pathway for the heterogeneous oxidation of SO2 by in-particle oxidants (OH, NO2, and NO2-/HNO2) produced from particulate nitrate photolysis (Environ. Sci. Technol. 2019, 53, 8757-8766). Particulate nitrate is often found to coexist with chloride and other halide ions, especially in aged sea-salt aerosols and combustion aerosols. Reactive uptake experiments of SO2 with UV-irradiated nitrate particles showed that sulfate production rates were enhanced by a factor of 1.4, 1.3, and 2.0 in the presence of Cl-, Br-, and I-, respectively, compared to those in the absence of halide ions. The larger sulfate production was attributed to enhanced nitrate photolysis promoted by the increased incomplete solvation of nitrate at the air-particle interface due to the presence of surface-active halide ions. Modeling results based on the experimental data showed that the nitrate photolysis rate constants increased by a factor of 2.0, 1.7, and 3.7 in the presence of Cl-, Br-, and I-, respectively. A linear relation was found between the nitrate photolysis rate constant, jNO3-, and the initial molar ratio of Cl- to NO3-, [Cl-]0/[NO3-]0, as jNO3- = 9.7 × 10-5[Cl-]0/[NO3-]0 + 1.9 × 10-5 at [Cl-]0/[NO3-]0 below 0.2. The present study demonstrates that the presence of halide ions enhances sulfate production produced during particulate nitrate photolysis and provides insights into the enhanced formation of in-particle oxidants that may increase atmospheric oxidative capacity.


Elements 112 to 119: were they present in meteorites?
Chondrites contain a small fission xenon component of unexplained origin. Evidence on the geochemical behavior of this component suggests that it was not derived from an actinide element (Z = 89 to 103), or from a transition metal between Z = 104 and 111, but from a more volatile progenitor. The most likely candidates are the superheavy elements between Z = 112 and 119, whose lighter congeners (mercury, tellurium, lead, and the like) are known to be strongly fractionated in meteorites.


The change of the split renal function before and after a nephrectomy using Tc-mercaptoacetyltriglycine (MAG3).
We examined the change in the renal function in the normal side kidney before and after a nephrectomy, by means of a newly developed diuretic renography technique utilizing Tc 99m-mercaptoacetyltriglycine (MAG3). Forty patients who underwent a nephrectomy were evaluated using MAG3 diuretic renography. We measured the effective renal plasma flow (ERPF) and Tmax time before and after a nephrectomy. The effects of the patient age and the preoperative ERPF of ill side kidney on the post operative ERPF were then assessed statistically. The ERPF increased by an average of 44.8 ml/min at 2 weeks after a nephrectomy, but it decreased by an average of 24.3 ml/min at 3 months after a nephrectomy. The Tmax time decreased by an average of 0.58 min at 2 weeks, but thereafter increased by an average of 0.58 min at 3 months after a nephrectomy. The correlation coefficient between the rate of increase in the ERPF and the patient age was 0.197. The rise of renal function in terms of ERPF and the Tmax time was observed at 2 weeks post-nephrectomy. However, this effect disappeared at 3 months post-nephrectomy. These data demonstrated that the rise in the renal function of the normal-side kidney in such patients was only temporary.


Cortical reactivations predict future sensory responses.
Many theories of offline memory consolidation posit that the pattern of neurons activated during a salient sensory experience will be faithfully reactivated, thereby stabilizing the pattern1,2. However, sensory-evoked patterns are not stable but, instead, drift across repeated experiences3-6. Here, to investigate the relationship between reactivations and the drift of sensory representations, we imaged the calcium activity of thousands of excitatory neurons in the mouse lateral visual cortex. During the minute after a visual stimulus, we observed transient, stimulus-specific reactivations, often coupled with hippocampal sharp-wave ripples. Stimulus-specific reactivations were abolished by local cortical silencing during the preceding stimulus. Reactivations early in a session systematically differed from the pattern evoked by the previous stimulus-they were more similar to future stimulus response patterns, thereby predicting both within-day and across-day representational drift. In particular, neurons that participated proportionally more or less in early stimulus reactivations than in stimulus response patterns gradually increased or decreased their future stimulus responses, respectively. Indeed, we could accurately predict future changes in stimulus responses and the separation of responses to distinct stimuli using only the rate and content of reactivations. Thus, reactivations may contribute to a gradual drift and separation in sensory cortical response patterns, thereby enhancing sensory discrimination7.


The current state of empathy, compassion and person-centred communication training in healthcare: An umbrella review.
This umbrella review consolidates evidence available on empathy training, its effectiveness and design mechanisms that contribute to effectiveness. We conducted an umbrella review (review of reviews) of empathy, compassion and person-centred communication training in healthcare published between 2018 and 2022. One reviewer screened titles, abstracts and full-text articles, with a second reviewer at full-text stage. Quality appraisal was done in duplicate. Data extraction was piloted by two reviewers and conducted by one reviewer with a quality check of all extracted data. All reviewers provided input into synthesis of results and analysis. Twenty-five reviews were included. We provide an overview of the definitions of empathy, compassion and person-centred communication, outcome measures used, a synthesis of findings on the mechanisms and effectiveness of training and a summary of review recommendations. For policy and practice, we advise the inclusion of empathic communication into the curriculum; longitudinal and sequenced learning; debriefing, targeted feedback, enabling self-reflection, deliberate practice, experiential learning; improving motivation by teaching the benefits of empathy and teaching sustainable empathy. Future research should involve patients in training and research and study the effect of targeting interventions at healthcare practitioners and patients.


In vitro biomechanical investigation of the stability and stress-shielding effect of lumbar interbody fusion devices.
Interbody fusion devices are rapidly gaining acceptance as a method of ensuring lumbar interbody arthrodesis. Although different types of devices have been developed, the comparative reconstruction stability remains controversial. It also remains unclear how different stress-shielded environments are created within the devices. Using a calf spine model, this study was designed to compare the construct stiffness afforded by 11 differently designed lumbar interbody fusion devices and to quantify their stress-shielding effects by measuring pressure within the devices. Sixty-six lumbar specimens obtained from calves were subjected to anterior interbody reconstruction at L4-5 by using one of the following interbody fusion devices: four different threaded fusion cages (BAK device, BAK Proximity, Ray TFC, and Danek TIBFD), five different nonthreaded fusion devices (oval and circular Harms cages, Brantigan PLIF and ALIF cages, and InFix device); two different types of allograft (femoral ring and bone dowel) were used. Construct stiffness was evaluated in axial compression, torsion, flexion, and lateral bending. Prior to testing, a silicon elastomer was injected into the cages and intracage pressures were measured using pressure needle transducers. No statistical differences were observed in construct stiffness among the threaded cages and nonthreaded devices in most of the testing modalities. Threaded fusion cages demonstrated significantly lower intracage pressures compared with nonthreaded cages and structural allografts. Compared with nonthreaded cages and structural allografts, threaded fusion cages afforded equivalent reconstruction stiffness but provided more stress-shielded environment within the devices.


Immune Thrombocytopenic Purpura Splenectomy in the Context of New Medical Therapies.
As medical therapy improves, splenectomy has been relegated to third- or fourth-line therapy for immune thrombocytopenic purpura (ITP) in many hematologic practices. However, these medications have well-known associated morbidity and changes in treatment algorithms may affect the timing and degree of response to splenectomy as well as complications in heavily treated ITP patients. This is a retrospective study of consecutive patients who underwent ITP splenectomy from January 1994 to June 2017. Nonresponders after splenectomy and those with recurrent disease were compared to complete responders. The cohort included 84 patients. Median number of medications received before splenectomy was 3 (1-6). 14.3% of patients had a medication-related complication, including heart failure, adrenal insufficiency, diabetes mellitus, infection, and osteoporosis. After splenectomy, 83.5% had a complete response, 7.5% partial response, and 9% no response. Complete response was associated with response to steroids before surgery (P < 0.01). Among responders, 19% had recurrent disease, which was associated with lower platelet count at diagnosis (P < 0.01). Forty-four patients (52.0%) had nonelective splenectomies for persistent bleeding or dangerously low platelets despite maximal medical therapy. Ten patients had Clavien-Dindo grade II or higher surgical complications (11.9%). Seven of these complications were related to recurrent or refractory ITP. Many ITP patients have complications related to medication use, and 52.0% required nonelective splenectomy despite maximal medical therapy. Earlier splenectomy may avoid medication-related complications and may reduce the complications from splenectomy. Splenectomy remains an effective and safe treatment for ITP.


Physics of polymer melts.
We have mapped the physics of polymer melts onto a time-dependent Landau-Ginzburg |psi|(4) field theory using techniques of functional integration. Time in the theory is simply a label for the location of a given monomer along the extent of a flexible chain. With this model, one can show that the limit of infinitesimal concentration of a polymer melt corresponds to a dynamic critical phenomenon. The transition to the entangled state is also shown to be a critical point. For larger concentrations, when the role of fluctuations is reduced, a mean-field approximation is justifiably employed to show the existence of tubelike structures reminiscent of Edwards' model.


Waiting list mortality for pediatric deceased donor liver transplantation in a Japanese living-donor-dominant program.
Living donor liver transplantation (LDLT) has become a major life-saving procedure for children with end-stage liver disease in Japan, whereas deceased donor liver transplantation (DDLT) has achieved only limited success. The annual number of pediatric liver transplantations is approximately 100-120, with a patient 20-year survival rate of 81.0%. In 2005, the liver transplantation program at the National Center for Child Health and Development in Tokyo, Japan, was initiated, with an overall number of 560 pediatric patients with end-stage liver disease to date. In July 2010, our center was qualified as a pediatric DDLT center; a total of 132 patients were listed for DDLT up until February 2019. The indications for DDLT included acute liver failure (n = 46, 34.8%), metabolic liver disease (n = 26, 19.7%), graft failure after LDLT (n = 17, 12.9%), biliary atresia (n = 16, 12.1%), and primary sclerosing cholangitis (n = 10, 7.6%). Overall, 25.8% of the patients on the waiting list received a DDLT and 52.3% were transplanted from a living donor. The 5-year patient and graft survivals were 90.5% and 88.8%, respectively, with an overall waiting list mortality of 3.0%. LDLT provides a better survival compared with DDLT among the recipients on the DDLT waiting list. LDLT is nevertheless of great importance in Japan; however, it cannot save all pediatric recipients. As the mortality of children on the waiting list has not yet been reduced to zero, both LDLT and DDLT should be implemented in pediatric liver transplantation programs.


Antimycobacterial activity of chemically defined natural substances from the Caribbean flora in Guadeloupe.
Eight chemically defined, naturally occurring compounds were extracted from the tropical flora of the Caribbean island of Guadeloupe: pilocarpine, an alkaloid from Pilocarpus racemosus; heraclenol and isomeranzin, coumarins from Triphasia trifolia; lochnerin, an indole alkaloid from Rauwolfia biauriculata; ibogaine and voacangine, indole alkaloids from Tabernaemontana citrifolia; texalin, an oxazole from Amyris elemifera; and canellal, a sesquiterpene dialdehyde from Canella winterana. An essential oil fraction from Canella winterana was also tested. The antimycobacterial activity of these substances was tested against Mycobacterium tuberculosis, M. avium and M. kansasii using the Middlebrook 7H11 agar medium, the Bactec 460-TB radiometric methodology, and determination of bacterial viable counts. Three compounds, namely ibogaine, voacangine and texalin, showed antimycobacterial activity. Investigations on the structure-modification and structure-activity relationships of these compounds may help determine new targets for future drug development.


Characterisation of selenium and tellurium nanoparticles produced by Aureobasidium pullulans using a multi-method approach.
Aureobasidium pullulans was grown in liquid culture media amended with selenite and tellurite and selenium (Se) and tellurium (Te) nanoparticles (NPs) were recovered after 30 d incubation. A separation method was applied to recover and characterise Se and Te NPs by asymmetric flow field flow fractionation (AF4) with online coupling to multi-angle light scattering (MALS), ultraviolet visible spectroscopy (UV-Vis), and inductively coupled plasma mass spectrometry (ICP-MS) detectors. Additional characterisation data was obtained from transmission electron microscopy (TEM), and dynamic light scattering (DLS). Solutions of 0.2% Novachem surfactant and 10 mM phosphate buffer were compared as mobile phases to investigate optimal AF4 separation and particle recovery using Se-NP as a model sample. 88% recovery was reported for 0.2% Novachem solution, compared with 50% recovery for phosphate buffer. Different crossflow (Cflow) rates were compared to further investigate optimum separation, with recoveries of 88% and 30% for Se-NPs, and 90% and 29% for Te-NPs for 3.5 mL min-1 and 2.5 mL min-1 respectively. Zeta-potential (ZP) data suggested higher stability for NP elution in Novachem solution, with increased stability attributed to minimised NP-membrane interaction due to PEGylation. Detection with MALS showed monodisperse Se-NPs (45-90 nm) and polydisperse Te-NPs (5-65 nm).Single particle ICP-MS showed mean particle diameters of 49.7 ± 2.7 nm, and 135 ± 4.3 nm, and limit of size detection (LOSD) of 20 nm and 45 nm for Se-NPs and Te-NPs respectively. TEM images of Se-NPs and Te-NPs displayed a spherical morphology, with the Te-NPs showing a clustered arrangement, which suggested electrostatic attraction amongst neighbouring particles. Particle hydrodynamic diameters (dH) measured with dynamic light scattering (DLS) further suggested monodisperse Se-NPs and polydisperse Te-NPs distributions, showing good agreement with AF4-MALS for Se-NPs, but suggests that the Rg obtained from AF4-MALS for Te-NP was unreliable. The results demonstrate a complementary application of asymmetric flow field-flow fractionation (AF4), ICP-MS, light scattering, UV-Vis detection, and microscopic techniques to characterise biogenic Se and Te NPs.


Contraception and Catholicism in the Twentieth Century: Transnational Perspectives on Expert, Activist and Intimate Practices.
This special issue uses Catholicism as a thread to bring together five contributions to the transnational history of contraception. The articles, which cover examples from Western and East-Central Europe, East Africa and Latin America, all explore the complex interplay between users and providers of birth control in contexts marked by prevalence of the Catholic religion and/or strong political position of the Catholic Church. In the countries examined here, Brazil, Belgium, Poland, Ireland and Rwanda, Catholicism was the majority religion during the different moments of the long twentieth century the authors of this special issue focus on. Using transnationalism as a perspective to examine the social history of the entanglements between Catholicism and contraception, this special issue seeks to underscore the ways in which individuals and organisations used, adapted and contested local and transnational ideas and debate around family planning. It also examines the role of experts and activist groups in the promotion of family planning, while paying attention to national nuances in Catholic understandings of birth control. The contributions shed light on the motivations behind involvement in birth control activism and expertise, its modus operandi, networking strategies and interactions with men and women demanding contraceptive information and technology. Moreover, through the use of oral history, as well as other print sources such as women's magazines, this collection of articles seeks to illustrate 'ordinary' men and women's practices in the realm of reproductive health.


CircRNA circPTK2 Might Suppress Cancer Cell Invasion and Migration of Glioblastoma by Inhibiting miR-23a Maturation.
CircRNA circPTK2 plays opposite roles in different cancers, while its role in glioblastoma is unknown. The aim of this study was to explore the involvement of circPTK2 in glioblastoma. Expression of circPTK2, mature miR-23a, and premature miR-23a in paired cancer and non-cancer tissues from glioblastoma patients (n = 60) was analyzed by RT-qPCR. Pearson's correlation coefficient was used to analyze the correlations between gene expressions. The effects of circPTK2 overexpression on miR-23a maturation were analyzed by transfecting circPTK2 expression vector into glioblastoma cells, followed by determining the expression of mature miR-23a and premature miR-23a by RT-qPCR. Transwell assays were carried out to explore the role of circPTK2 and miR-23a in regulating glioblastoma cell invasion and migration. We found that circPTK2 was downregulated in GBM and was inversely correlated with mature miR-23a, but not premature miR-23a. GBM cells transfected with circPTK2 expression vector showed significantly downregulated mature miR-23a, but not premature miR-23a. Transwell assay analysis showed that circPTK2 overexpression decreased cell invasion and migration, while miR-23a increased cell invasion and migration. Moreover, miR-23a overexpression reversed the inhibitory effects of circPTK2 overexpression on cell behaviors. CircPTK2 might suppress cancer cell invasion and migration by inhibiting the maturation of miR-23a.


Full-color optically-sectioned imaging by wide-field microscopy via deep-learning.
Wide-field microscopy (WFM) is broadly used in experimental studies of biological specimens. However, combining the out-of-focus signals with the in-focus plane reduces the signal-to-noise ratio (SNR) and axial resolution of the image. Therefore, structured illumination microscopy (SIM) with white light illumination has been used to obtain full-color 3D images, which can capture high SNR optically-sectioned images with improved axial resolution and natural specimen colors. Nevertheless, this full-color SIM (FC-SIM) has a data acquisition burden for 3D-image reconstruction with a shortened depth-of-field, especially for thick samples such as insects and large-scale 3D imaging using stitching techniques. In this paper, we propose a deep-learning-based method for full-color WFM, i.e., FC-WFM-Deep, which can reconstruct high-quality full-color 3D images with an extended optical sectioning capability directly from the FC-WFM z-stack data. Case studies of different specimens with a specific imaging system are used to illustrate this method. Consequently, the image quality achievable with this FC-WFM-Deep method is comparable to the FC-SIM method in terms of 3D information and spatial resolution, while the reconstruction data size is 21-fold smaller and the in-focus depth is doubled. This technique significantly reduces the 3D data acquisition requirements without losing detail and improves the 3D imaging speed by extracting the optical sectioning in the depth-of-field. This cost-effective and convenient method offers a promising tool to observe high-precision color 3D spatial distributions of biological samples.


Secondhand nicotine vaping at home and respiratory symptoms in young adults.
Despite high prevalence of e-cigarette use (vaping), little is currently known regarding the health effects of secondhand nicotine vape exposure. To investigate whether exposure to secondhand nicotine vape exposure is associated with adverse respiratory health symptoms among young adults. We investigated the effect of secondhand nicotine vape exposure on annually reported wheeze, bronchitic symptoms and shortness of breath in the prospective Southern California Children Health Study cohort. Data were collected from study participants (n=2097) with repeated annual surveys from 2014 (average age: 17.3 years) to 2019 (average age: 21.9). We used mixed effect logistic regression to evaluate the association between secondhand nicotine vape and respiratory symptoms after controlling for relevant confounders. Prevalence of secondhand nicotine vape increased from 11.7% to 15.6% during the study period in this population. Prevalence of wheeze, bronchitic symptoms and shortness of breath ranged from 12.3% to 14.9%, 19.4% to 26.0% and 16.5% to 18.1%, respectively, during the study period. Associations of secondhand nicotine vape exposure with bronchitic symptoms (OR 1.40, 95% CI 1.06 to 1.84) and shortness of breath (OR 1.53, 95% CI 1.06 to 2.21) were observed after controlling for vaping, active and passive exposure to tobacco or cannabis, and demographic characteristics (age, gender, race/ethnicity and parental education). Stronger associations were observed when analysis was restricted to participants who were neither smokers nor vapers. There were no associations with wheezing after adjustment for confounders. Secondhand nicotine vape exposure was associated with increased risk of bronchitic symptoms and shortness of breath among young adults.


[Assessment of the diagnostic value of perfusion scintigraphy in diagnosis of pulmonary artery thromboembolism].
The present work was aimed at specifying the place of perfusion scintigraphy of the lungs in the diagnostic algorithm of pulmonary artery thromboembolism (PATE) and at determining sensitivity, specificity, and accuracy of the method concerned. The authors analysed the data regarding a total of 211 patients divided into two groups (Group One with an arbitrary algorithm of investigation, comprising 108 patients and Group Two with the suggested algorithm of «pulmonary roentgenography Doppler ultrasonography perfusion scintigraphy of the lungs») in clinically suspected pulmonary artery thromboembolism and scintigraphy-revealed defects of perfusion. The diagnostic complex included ECG, Doppler ultrasonography of the veins, roentgenography, perfusion scintigraphy of the lungs, and in a series of doubtful cases Echo-CG and CT angiography of the lungs. We revealed reliable signs of pulmonary artery thromboembolism (PATE) by the findings of instrumental diagnostic methods, having demonstrated a considerable increase in specificity and accuracy of perfusion scintigraphy in diagnosing PATE using the proposed diagnostic algorithm, when scintigraphy stands on the third position (specificity increased by 78% and accuracy by 22%). The following recommendations were made: the findings of scintigraphy should be interpreted with due regard for the data of roentgenography and Doppler ultrasonography of the veins; if the patient s condition is severe, the examination may be limited to roentgenography alone prior to performing perfusion scintigraphy of the lungs.


[Patients' self-management of type 2 diabetes: a narrative review].
According to the World Health Organization, the number of people with diabetes mellitus in 2030 will be 366 millions in the whole world, with diabetes mellitus type 2 having the highest prevalence. The current National Chronicity and Diabetes Strategies advocate patients' self-management programs and/or interventions. Nevertheless, lack of knowledge and inadequate attitudes hinder the associative relationship between patients and professionals that is required in these programs. This literature review aims to show the outstanding needs of type 2 diabetes mellitus patients when it comes to managing the illness. Thus, results from this literature review could lay the foundations for the development of effective future programs, helping professionals focus on patients' needs.


Comparison of toxicity and outcomes of concurrent radiotherapy with carboplatin/paclitaxel or cisplatin/etoposide in stage III non-small cell lung cancer.
Concurrent chemoradiotherapy (CCRT) has become the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). The comparative merits of two widely used regimens: carboplatin/paclitaxel (PC) and cisplatin/etoposide (PE), each with concurrent radiotherapy, remain largely undefined. Records for consecutive patients with stage III NSCLC treated with PC or PE and ≥60 Gy chest radiotherapy between 2000 and 2011 were reviewed for outcomes and toxicity. Survival was estimated using the Kaplan-Meier method and Cox modeling with the Wald test. Comparison across groups was done using the student's t and chi-squared tests. Seventy-five (PC: 44, PE: 31) patients were analyzed. PC patients were older (median 71 vs. 63 years; P = 0.0006). Other characteristics were comparable between groups. With PE, there was significantly increased grade ≥3 neutropenia (39% vs. 14%, P = 0.024) and thrombocytopenia (10% vs. 0%, P = 0.039). Radiation pneumonitis was more common with PC (66% vs. 38%, P = 0.033). Five treatment-related deaths occurred (PC: 3 vs. PE: 2, P = 1.000). With a median follow-up of 51.6 months, there were no significant differences in relapse-free survival (median PC 12.0 vs. PE 11.5 months, P = 0.700) or overall survival (median PC 20.7 vs. PE 13.7 months; P = 0.989). In multivariate analyses, no factors predicted for improved survival for either regimen. PC was more likely to be used in elderly patients. Despite this, PC resulted in significantly less hematological toxicity but achieved similar survival outcomes as PE. PC is an acceptable CCRT regimen, especially in older patients with multiple comorbidities.


Route and survey processing of topographical memory during navigation.
We investigated the characteristics of route and survey processing of a unique complex virtual environment both at the behavioral and brain levels. Prior to fMRI scanning, participants were trained to follow a route and to learn the spatial relationships between several places, acquiring both route and survey knowledge from a ground-level perspective. During scanning, snapshots of the environment were presented, and participants were required to either indicate the direction to take to follow the route (route task), or to locate unseen targets (survey task). Data suggest that route and survey processing are mainly supported by a common occipito-fronto-parieto-temporal neural network. Our results are consistent with those gathered in studies concerning the neural bases of route versus survey knowledge acquired either from different perspectives or in different environments. However, rather than arguing for a clear distinction between route and survey processing, "mixed" strategies are likely to be involved when both types of encoding take place in the same environment.


The meaning of radiolucencies in parosteal osteosarcoma.
Parosteal osteosarcoma with either intralesional radiolucencies or extralesional clefts within the tumor was identified in eighteen patients. In each patient, both high-quality radiographs and whole macrosections of the lesions were available for correlative study of the radiolucencies. The intralesional radiolucencies were characterized as either deep or peripheral. Study of the macrosections showed that most of the peripheral lucent areas were comprised of low-grade malignant cartilaginous or fibrous tissue that was mixed with fat and bone trabeculae. The majority (67 per cent) of the high-grade dedifferentiated areas of tumor, however, corresponded to the deep radiolucencies. We think that the presence of a deep radiolucent area on a computed tomographic scan or other preoperative radiographic staging studies must create suspicion that a high-grade (grade-II) dedifferentiated region exists within an otherwise low-grade parosteal osteosarcoma.


Glycolytic and oxidative metabolism in relation to retinal function.
Measurements of lactate production and ATP concentration in superfused rat retinas were compared with extracellular photoreceptor potentials (Fast PIII). The effect of glucose concentration, oxygen tension, metabolic inhibition, and light were studied. Optimal conditions were achieved with 5-20 mM glucose and oxygen. The isolated retina had a high rate of lactate production and maintained the ATP content of a freshly excised retina, and Fast PIII potentials were similar to in vivo recordings. Small (less than 10%) decreases in aerobic and anaerobic lactate production were observed after illumination of dark-adapted retinas. There were no significant differences in ATP content in dark- and light-adapted retinas. In glucose-free medium, lactate production ceased, and the amplitude of Fast PIII and the level of ATP declined, but the rates of decline were slower in oxygen than in nitrogen. ATP levels were reduced and the amplitude of Fast PIII decreased when respiration was inhibited, and these changes were dependent on glucose concentration. Neither glycolysis alone nor Krebs cycle activity alone maintained the superfused rat retina at an optimal level. Retinal lactate production and utilization of ATP were inhibited by ouabain. Mannose but not galactose or fructose produced lactate and maintained ATP content and Fast PIII. Iodoacetate blocked lactate production and Fast PIII and depleted the retina of ATP. Pyruvate, lactate, and glutamine maintained ATP content and Fast PIII reasonably well (greater than 50%) in the absence of glucose, even in the presence of iodoacetate. addition of glucose, mannose, or 2-deoxyglucose to medium containing pyruvate and iodoacetate abolished Fast PIII and depleted the retina of its ATP. It is suggested that the deleterious effects of these three sugars depend upon their cellular uptake and phosphorylation during the blockade of glycolysis by iodoacetate.


Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations.
Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM) in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1); including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders.


Comparison of the antiinflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis.
To assess the clinical efficacy of chondroitin sulfate (CS) in comparison with the nonsteroidal antiinflammatory drug (NSAID) diclofenac sodium (DS) in a medium/longterm clinical study in patients with knee osteoarthritis (OA). This was a randomized, multicenter, double blind, double dummy study. 146 patients with knee OA were recruited into 2 groups. During the first month, patients in the NSAID group were treated with 3 x 50 mg DS tablets/day and 3 x 400 mg placebo (for CS) sachets; from Month 2 to Month 3, patients were given placebo sachets alone. In the CS group, patients were treated with 3 x 50 mg placebo (for diclofenac) tablets/day and 3 x 400 mg CS sachets/day during the first month; from Month 2 to Month 3, these patients received only CS sachets. Both groups were treated with 3 x 400 mg placebo sachets from Month 4 to Month 6. Clinical efficacy was evaluated by assessing the Lequesne Index, spontaneous pain (using the Huskisson visual analog scale), pain on load (using a 4 point ordinal scale), and paracetamol consumption. Patients treated with the NSAID showed prompt and plain reduction of clinical symptoms, which, however, reappeared after the end of treatment; in the CS group, the therapeutic response appeared later in time but lasted for up to 3 months after the end of treatment. CS seems to have slow but gradually increasing clinical activity in OA; these benefits last for a long period after the end of treatment.


Immunomodulation in established murine tumors: response and survival rate enhancement by blood leukocyte-augmenting substance 236 (Cl-), a novel synthetic compound.
Immunomodulation in cancer has obvious appeal. Available data suggest the central role to be played by the host immune response in cancer outcome. Herein, we report a novel compound, Blood Leukocyte Augmenting Substance 236 (Cl(-)) [BLAS 236 (Cl(-))], which is able to restore and/or strengthen immunocompetence, which is critical in host-resistance to malignancy. The effects of several protocols in which BLAS 236 (Cl(-)) was given as single-agent or combined therapy on established murine tumors were evaluated in terms of long-term tumor-free survivors (>1 year). Treatment significantly improved overall complete response and survival rates and prolonged the life span of mice to beyond that of animals receiving placebo. The most outstanding protocols (denoted B3, B6 and D6, D7), were able to flatten tumor-free survival curves at the 80% and 100% levels, respectively (P < 0.001 for each protocol); these results compare favorably with those reported for other preclinical trials. Immunomodulation by BLAS 236 (Cl(-)) is viewed as a new efficient, safe way of potentiating and maintaining host-resistance to malignancy that holds promise as an adjuvant therapy alternative to current immune approaches for the ultimate cure of cancer.


Bilateral Talus and Navicular Fractures accompanied with Unilateral Calcaneal Fracture: A Case Report.
An 18-year old male patient, with a history of paragliding accident, sustaining a coronal shear fracture of the body of the talus, an anterior process fracture of the calcaneus extending to the calcaneocuboid joint and a nondisplaced navicular body fracture at the right foot and a displaced fracture of the navicular body accompanied with posteromedial process fracture of the talus at the left side was referred to our emergency clinic. For the right foot, the coronal plane fracture of the talar body was anatomically reduced and fixed with screws. For the left foot, screw fixation was performed through the lateral aspect to fix the large posteromedial fragment. Small bone fragments were removed from the left navicular fracture, and the main fragments were also fixed with screw. The talo-navicular joint was stabilised with a Kirschner wire. At 36 months follow-up, bilateral foot and ankle functions were satisfactory, Maryland scores of the right and left foot were 85 (good) and 90 (excellent), respectively, and the patient regained his full activity level by the 5th month postoperatively. With reference to the number and types of fractures in this one patient, we present a standard protocol for treatment of isolated talus, navicular and calcaneal fractures presenting together in a single foot injury.


Clarification of the database concept.
Our concern is that nursing databases be structured to improve the efficiency of decision-making in nursing. The selection of database management systems that are compatible with the computer resources in a majority of settings is important to methodology. To facilitate methodological development, we encourage the inclusion of information in the nursing literature that details the investments in personnel, equipment, and facilities required to develop computerized databases. In the current state of affairs, determining the personnel and budgets for the development, update, and maintenance of computerized databases and related data management systems is somewhat like trying to pin the tail on the donkey while blindfolded. However some of the frustrations encountered at the start of new endeavors can be lessened if we share our experiences in project management as we report findings from our work.


Ventricular tachycardia in acute rheumatic fever.
A 19-year-old man presented with fever, migratory polyarthritis, and palpitations; a diagnosis of acute rheumatic fever was made. Twenty-four-hour ambulatory cardiac monitoring (Holter) performed during the patient's hospitalization revealed ventricular tachycardia. Although disturbances in cardiac conduction and rhythm are common during the acute phase of rheumatic fever, malignant ventricular arrhythmias, to our knowledge, have not been described. Recognition of this occurrence emphasizes the need for continuous cardiac monitoring in selected patients.


Assisted reproductive technology in the United States: 1997 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry.
To summarize the procedures and outcomes of assisted reproductive technology (ART) initiated in the United States in 1997. Data were collected electronically by using Society for Assisted Reproductive Technology Clinical Outcome Reporting System software and were submitted to the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. 335 programs submitted data on procedures performed in 1997. Data were collated after November 1998 so that the outcome of all pregnancies established would be known. Incidence of clinical pregnancy, ectopic pregnancy, abortion, stillbirth, delivery, and structural and functional abnormalities. Programs reported initiating 73,069 cycles of ART treatment. Of these, 51,344 cycles involved IVF (with and without micromanipulation), with a delivery rate per retrieval of 27.9%; 1,943 were cycles of GIFT, with a delivery rate per retrieval of 30.0%; and 1,104 were cycles of zygote intrafallopian transfer, with a delivery rate per retrieval of 28.0%. The following additional ART procedures were also initiated: 4,616 donor oocyte cycles, with a delivery rate per transfer of 40.0%; 10,181 frozen embryo transfer procedures, with a delivery rate per transfer of 18.8%; 1,584 frozen embryo transfers using donated oocytes, with a delivery rate per transfer of 22.2%; and 600 cycles using a host uterus, with a delivery rate per transfer of 34.6%. Furthermore, 1,173 cycles were reported as combinations or more than one treatment type, 40 cycles as research, 258 as embryo banking, and 226 as other (unclassified) cycle types. As a result of all procedures, 17,311 deliveries resulting in 25,059 babies were reported. In 1997, more programs reported ART treatment and the number of reported cycles increased significantly (10.9%) compared with 1996. In comparable cycle types, the overall success rate (deliveries per retrieval) increased by 1.8%, which represents an increase of 6.9% compared with the success rate for 1996.


An ultrathin two-dimensional vertical ferroelectric tunneling junction based on CuInP2S6 monolayer.
Ferroelectric (FE) materials, especially ABO3 FE perovskite oxides, have been extensively studied for their important applications in memory devices, electronics and sensors. However, the integration of FE perovskite oxides into miniaturized memory and electronic devices has been impeded by the critical thickness limitation, as out-of-plane ferroelectricity in most FE perovskite oxides will disappear when the oxide thin film thickness is below a critical value. On the other side, CuInP2S6 (CIPS) nano-flake, a prototypical two-dimensional (2D) FE material, has recently been demonstrated to display stable out-of-plane ferroelectricity at the atomic layer thickness by experiment, which offers a new candidate for developing FE devices in the 2D nanoscale regime. Herein, after investigation of the structural and ferroelectric properties of 2D CIPS layers, especially the interactions between out-of-plane polarization and the corresponding depolarization field using first-principles calculations, we reveal that out-of-plane ferroelectricity can even persist in the CIPS monolayer, which is only 3.4 Å in thickness. Moreover, in order to explore the potential application of 2D FE CIPS layers as minimized FE devices, we design an ultrathin ferroelectric tunneling junction (FTJ) composed of a graphene/CIPS monolayer/graphene vertical van der Waals (vdW) heterostructure. Our transport simulations based on the non-equilibrium Green's function formalism predict that such an ultrathin FTJ device can still exhibit the typical tunneling electroresistance (TER) effect, where tunneling current strongly depends on the direction of FE polarization. Our work not only elucidates the origin of stable out-of-plane ferroelectricity appearing in 2D CIPS layers, but also demonstrates the practical application of a CIPS based 2D FTJ as a miniaturized, multi-functional and low-power consumption memory device for modern electronics.


Binding characterization of a putative cGMP transporter in the cell membrane of human erythrocytes.
Cyclic GMP is an intracellular signal molecule whose biological and pharmacological role is not well understood. Recent studies with human erythrocytes and other cell types (normal and transformed) have shown that the extrusion of cGMP is an ATP-dependent and saturable process. In this paper, we present our studies on binding of [3H]-cGMP to human erythrocyte ghost and its solubilized extracts. At 4 degrees C, an apparent dissociation constant of 0.15 microM was found in the samples. Maximum specific binding values in ghost and solubilized extracts were 9.0 pmol/mg of protein and 1.0 pmol/mg of protein, respectively. The low dissociation constant was confirmed by kinetic studies with a value of 0.16 microM. Specific [3H]-cGMP binding was inhibited by cAMP, cGMP, and cIMP with KD values of 0.22 microM, 0.09 microM, and 0.17 microM, respectively. Unlabeled cGMP and cIMP inhibited [3H]-cGMP binding completely whereas cAMP inhibited only 70%. The membrane-localized cGMP-binding protein discriminates between cyclic and noncyclic nucleotides, since GMP, IMP, and AMP were unable to displace [3H]-cGMP. A zwitterionic detergent, CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfate), was able to solubilize a protein with identical binding affinity. The results of this study show that erythrocyte ghosts possess a cGMP-binding protein which is not a kinase (due to a similar affinity for cAMP, cGMP, and cIMP) or phosphodiesterase (due to the inability of IBMX, 3-isobutyl-1-methylxanthine, to inhibit specific [3H]-cGMP binding). We hypothesize that this protein is the cell membrane cGMP transporter.