[A study on the Shin Man's life and idea of medicine in Juchonsinbang].
For the purpose of understanding the feature of medicine in the late Chosun Dynasty, I investigated Shin Man (1620-1669)'s life and his idea of medicine in Juchonsinbang. Shin Man was a scholar who lived in the middle of the Chosun dynasty. He was famous for his resistance against Ching dynasty in Byeongjahoran, and for his chivalrous spirit. He was daring, inflexible and unrestricted by nature. And his character was reflected in his medical ideas. He studied along Song Si-yeol and started his official career together. Both worked for King Hyojong who strongly wanted to send an expedition to conquer the North. But after the sudden death of King Hyojong, the project to conquer the North had went for nothing. And Shin Man went back to the rural life in Juchon, Jinjam. On the one hand, he lived the life of pursuit of learning Seong Confucianism in Juchon, and on the other hand, he wrote the original form of Juchonsinbang. Shin Man wanted to establish and spread the universal and popularized medicine. So he set a goal to publish a simple and plain prescription book, which corresponds to his idea of medicine which deals with curing people. The currently remaining editions of Juchonsinbang are 3 types. One is the lead printed edition. The others are the dissimilar 2 transcribed editions. There are considerable differences between the lead printed edition and the transcribed editions. The lead printed edition focused on the human being, and divided the category of human being as 3 parts, which are infant, womenkind and adult. Whereas the transcribed editions focused on disorders and aimed at universalization and simplification of medicine. Thus the main viewpoint of medicine changed from disorders to human being. By the way, there are many occult prescriptions in Juchonsinbang. And they aren't distorted with the standpoint of those days. While the time of writing Juchonsinbang has many questionable problems. And there is no historical material which shows the exact time of writing.


Investigation of some immunological functions in a group of asphalt workers exposed to polycyclic aromatic hydrocarbons.
To investigate the effects of polycyclic aromatic hydrocarbons (PAHs) on the human immune system, analyses were performed on T-cell subsets (CD4+, CD8+), B-cells (CD19+), serum immunoglobulin levels (IgG, IgM, IgA) and white blood cell percentages of 16 male workers who were employed in road paving operations and compared to 12 unexposed male controls. PAH exposure was assessed using urinary 1-hydroxy-pyrene (1-OHP) levels and was found to be significantly higher in workers than in the controls. While the CD4+ cell percentage and the CD4+/CD8+ ratio were significantly higher in the PAH-exposed group, the percentages of CD8+ and CD19+ cells were unchanged. There was also a significant enhancement in serum IgG levels and the percentage of monocytes in the workers compared to the control group. These data suggest that chronic exposure to PAHs may affect some immune functions in humans.


Computer-aided diagnosis with temporal analysis to improve radiologists' interpretation of mammographic mass lesions.
The purpose of this study was to evaluate the effect of independent reading with computer-aided diagnosis (CAD) and independent double reading on radiologists' performance to characterize mass lesions on serial mammograms. Six radiologists rated 198 cases, 99 benign and 99 malignant. For each case, the mammograms from two consecutive screening rounds were available. The mass was visible on the prior view in 40% of the cases. Independently, a CAD programe also rated each mass lesion making use of information from prior and current views. The following reading situations were compared: single reading, independent reading with CAD, and independent double reading. Independent reading with CAD was implemented by averaging the scaled ratings from each radiologist and the scaled CAD scores. We implemented independent double reading by averaging the scaled scores from two radiologists. Results were evaluated using receiver-operating characteristic (ROC) methodology and multiple reader multiple case analysis. The average performance, measured as the area under the ROC curve (A(z) value), was 0.80 for the single-reading mode. For independent double reading, the average performance improved to 0.81. This improvement was not significant. For independent interpretation with CAD, the average performance significantly increased to 0.83 (P < 0.05). We conclude that CAD technology with temporal analysis has the potential to help radiologists with the task of discriminating between benign and malignant masses.


Hybrid approaches in atrial fibrillation ablation: why, where and who?
Hybrid strategies involving surgical and catheter ablation of atrial fibrillation (AF) are rapidly evolving. Hybrid techniques may improve procedural success and minimize risks by combining the strengths and minimizing limitations of either surgical or catheter ablation alone. Further study, including randomized controlled trials, will be necessary to determine the optimal approach to hybrid ablation.


Microtubule-organizing centres in binucleate cells and homosynkaryons.
Immunofluorescence studies showed that most binucleate Vero cells formed by virus-induced fusion or by inhibition of cytokinesis had a single microtubule-organizing centre (MTOC) when examined during the reassembly of microtubules after chilling, but two or more organizing centres when examined after exposure to colcemid. These findings suggest that although binucleate cells initially contain more MTOC than mononucleate cells, the extra MTOC are normally aggregated, so that the number of MTOC in binucleate cells tends to be reduced very quickly to that in mononucleate cells.


A global risk assessment of primates under climate and land use/cover scenarios.
Primates are facing an impending extinction crisis, driven by extensive habitat loss, land use change and hunting. Climate change is an additional threat, which alone or in combination with other drivers, may severely impact those taxa unable to track suitable environmental conditions. Here, we investigate the extent of climate and land use/cover (LUC) change-related risks for primates. We employed an analytical approach to objectively select a subset of climate scenarios, for which we then calculated changes in climatic and LUC conditions for 2050 across primate ranges (N = 426 species) under a best-case scenario and a worst-case scenario. Generalized linear models were used to examine whether these changes varied according to region, conservation status, range extent and dominant habitat. Finally, we reclassified primate ranges based on different magnitudes of maximum temperature change, and quantified the proportion of ranges overall and of primate hotspots in particular that are likely to be exposed to extreme temperature increases. We found that, under the worst-case scenario, 74% of Neotropical forest-dwelling primates are likely to be exposed to maximum temperature increases up to 7°C. In contrast, 38% of Malagasy savanna primates will experience less pronounced warming of up to 3.5°C. About one quarter of Asian and African primates will face up to 50% crop expansion within their range. Primary land (undisturbed habitat) is expected to disappear across species' ranges, whereas secondary land (disturbed habitat) will increase by up to 98%. With 86% of primate ranges likely to be exposed to maximum temperature increases >3°C, primate hotspots in the Neotropics are expected to be particularly vulnerable. Our study highlights the fundamental exposure risk of a large percentage of primate ranges to predicted climate and LUC changes. Importantly, our findings underscore the urgency with which climate change mitigation measures need to be implemented to avert primate extinctions on an unprecedented scale.


Evaluation of chromosome 11p imbalances in aniridia and Wilms tumor patients.
Newborn sporadic aniridia patients with an 11p13 deletion including the WT1 gene have an increased risk to develop Wilms tumor. At present a risk for Wilms tumor cannot be estimated in patients with deletions not extending into, but ending close to WT1. Therefore, it is important to determine the distance of deletion endpoints from the WT1 gene and survey these patients for a longer follow-up time to obtain a more defined risk estimation. Using molecular methods, such as Multiplex Ligation-dependent Probe Amplification (MLPA), deletion endpoints can be mapped more accurately than with FISH. We describe here the analysis of six aniridia patients, in two of these the deletions extend close to the 3' end of WT1. At the ages of 3.8 and 4 years they have not developed a Wilms tumor, suggesting a low tumor risk in such patients. In addition we have studied 24 non-AN cases with a higher likelihood for WT1 alterations with MLPA and found no deletions. In conclusion newborns with aniridia should be studied with molecular methods that can determine deletion endpoints in 11p13 exactly. For a better Wilms tumor risk estimation cases with deletion endpoints close to WT1 should be followed for at least 4-5 years. Furthermore germ line intragenic deletions affecting WT1 in patients with a higher likelihood for a WT1 association, for example, bilateral tumors, genitourinary aberrations, or nephrotic syndrome, were not found in this study, suggesting that deletions are rare events.


Association of Social Integration with Cognitive Status in a Multi-Ethnic Cohort: Results From the Kaiser Healthy Aging and Diverse Life Experiences Study.
We evaluated overall and race-specific relationships between social integration and cognition in older adults. Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort participants included 1343 Asian, Black, Latino, or non-Latino White Kaiser Permanente Northern California members. We estimated the effect of social integration on verbal episodic memory, semantic memory, and executive function derived from the Spanish and English Neuropsychological Assessment (SENAS) Scales. Social integration scores included marital status; volunteer activity; and contact with children, relatives, friends, and confidants. We estimated covariate-adjusted linear mixed-effects models for baseline and 17-month follow-up cognition. Social integration was associated with higher baseline cognitive scores (average β = 0.066 (95% confidence interval: 0.040, 0.092)) overall and in each racial/ethnic group. The association did not vary by race/ethnicity. Social integration was not associated with the estimated rate of cognitive change. In this cohort, more social integration was similarly associated with better late-life cognition across racial/ethnic groups.


[Microcirculatory bed of the human duodenum].
In preparations impregnated with silver nitrate (25 corpses of mature persons), the hemomicrocirculatory bed of the intestine wall tunics has been stated to possess a layer-by-layer organization. The most powerful submucosal vascular plexus, formed by branches of the arteries perforating the external tunics of the intestine, supplies with blood all the layers of the intestinal wall and their main working and integrating elements: intestinal and duodenal glands, villi, neural ganglia and trunks of the submucosal and intermuscular plexuses. Summarizing morphometrical criteria for estimating the capillary bed of the tunics of all the anatomical parts and the large duodenal papilla, it is clear that there are specific conditions in microvascularization of the upper part of the organ.


A monoclonal antibody (NKI-L16) directed against a unique epitope on the alpha-chain of human leukocyte function-associated antigen 1 induces homotypic cell-cell interactions.
In the present study a unique antibody (NKI-L16) reacting with the alpha-chain of the human leukocyte function-associated Ag-1 (LFA-1) is described, which stimulates homotypic cell-cell interactions in a manner very similar to 12-O-tetradecanoyl-phorbol-13-acetate (TPA), in contrast to other anti-LFA-1 mAb which inhibit cell aggregation. The induction of aggregate formation of EBV-transformed B cells (JY) and CTL clones by TPA or NKI-L16 is not accompanied by an increase in the expression of LFA-1. Nevertheless, this cluster formation is LFA-1 dependent, inasmuch as anti-LFA-1 antibodies, other than NKI-L16, completely abrogate aggregation. Simultaneous addition of NKI-L16 and TPA did not result in a further increase of the speed of cluster formation, suggesting that a similar pathway is activated. Immunoprecipitation and enzyme digestion studies revealed that NKI-L16 recognizes a unique epitope on the alpha-chain of LFA-1, most likely situated close to the transmembrane segment of the molecule. It is hypothesized that NKI-L16 or TPA can cause the LFA-1 molecule to convert from an inactive to an active configuration, thereby permitting binding of LFA-1 to its natural ligand.


NAD+ and sirtuins in aging and disease.
Nicotinamide adenine dinucleotide (NAD(+)) is a classical coenzyme mediating many redox reactions. NAD(+) also plays an important role in the regulation of NAD(+)-consuming enzymes, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38/157 ectoenzymes. NAD(+) biosynthesis, particularly mediated by nicotinamide phosphoribosyltransferase (NAMPT), and SIRT1 function together to regulate metabolism and circadian rhythm. NAD(+) levels decline during the aging process and may be an Achilles' heel, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies. Restoring NAD(+) by supplementing NAD(+) intermediates can dramatically ameliorate these age-associated functional defects, counteracting many diseases of aging, including neurodegenerative diseases. Thus, the combination of sirtuin activation and NAD(+) intermediate supplementation may be an effective antiaging intervention, providing hope to aging societies worldwide.


Using GRADE as a framework to guide research on the sexual and reproductive health and rights (SRHR) of women living with HIV - methodological opportunities and challenges.
In March 2016, WHO reviewed evidence to develop global recommendations on the sexual and reproductive health and rights (SRHR) of women living with HIV. Systematic reviews and a global survey of women living with HIV informed the guideline development decision-making process. New recommendations covered abortion, Caesarean section, safe disclosure, and empowerment and self-efficacy interventions. Identification of key research gaps is part of the WHO guidelines development process, but consistent methods to do so are lacking. Our method aimed to ensure consistency and comprised the systematic application of a framework based on GRADE (Grading of Recommendations, Assessment, Development and Evaluation) to the process. The framework incorporates the strength and quality rating of recommendations and the priorities reported by women in the survey to inform research prioritisation. For each gap, we also articulated: (1) the most appropriate and robust study design to answer the question; (2) alternative pragmatic designs if the ideal design is not feasible; and (3) the methodological challenges facing researchers through identifying potential biases. We found 12 research gaps and identified five appropriate study designs to address the related questions: (1) Cross-sectional surveys; (2) Qualitative interview-driven studies; (3) Registries; (4) Randomised controlled trials; and (5) Medical record audit. Methodological challenges included selection, recruitment, misclassification, measurement and contextual biases, and confounding. In conclusion, a framework based on GRADE can provide a systematic approach to identifying research gaps from a WHO guideline. Incorporation of the priorities of women living with HIV into the framework systematically ensures that women living with HIV can shape future policy decisions affecting their lives. Implementation science and participatory research are appropriate over-arching approaches to enhance uptake of interventions and to ensure inclusion of women living with HIV at all stages of the research process.


Measurement of radial profiles of density ratio of helium to hydrogen ion using charge exchange spectroscopy with two-wavelength spectrometer.
Radial profiles of density ratio of helium to hydrogen ions are measured using the charge exchange spectroscopy technique with the two-wavelength spectrometer system in the large helical device. The two-wavelength spectrometer system consists of a dichroic mirror box, a spectrometer with two grating and two camera lenses, and one CCD detector. The dichroic mirror box is used to divide the light of one fiber from the plasma to two fibers, one for HeII (λ = 468.6 nm) and the other for H(α) (λ = 656.3 nm), that are connected to the entrance slit of the spectrometer to eliminate the interference between the HeII and the H(α) spectra on the CCD. This system provides a simultaneous measurement of helium and hydrogen ion density ratio at 8 exact same locations (8 spatial channels) with a time resolution of >40 ms in the wide range of the density ratio of 0.05-5.


Portable Visual Photoelectrochemical Biosensor Based on a MgTi2O5/CdSe Heterojunction and Reversible Electrochromic Supercapacitor for Dual-Modal Cry1Ab Protein Detection.
Reversible electrochromic supercapacitors (ESCs) have attracted considerable interest as visual display screens. The use of ESCs in combination with a photoelectrochemical (PEC) biosensor promises to improve the detection efficiency. Herein, a visual PEC biosensor is developed by introducing a circuit module between a PEC-sensing platform (PSP) and a reversible ESC for Cry1Ab protein detection. In PSP, a type II MgTi2O5/CdSe heterojunction effectively drives charge separation by their cross-matched band gap structures, generating an amplified photocurrent. Next, the circuit module is designed to connect the PSP and ESC, realizing the signal conversion from photocurrent to voltage. ESC, as a visual display screen, produces reversible color changes with different voltages. As the concentration of Cry1Ab increases, the photocurrent decreases due to the specific binding between the aptamer and Cry1Ab in PSP, while the color of the reversible ESC changes from green to blue. To improve the integrity of the device, a portable PEC biosensor is further constructed via three-dimensional printing for dual-modal Cry1Ab protein detection, thus collecting both PEC and visual signals. The linear ranges are 0.3-3000 ng mL-1 for PEC mode and 1-1000 ng mL-1 for visual mode. This work presents a portable, efficient, sensitive, and visualized detection system, providing an important reference for practical visualization applications.


[Significance of antiphospholipid syndrome and antiphospholipid antibodies in patients with systemic lupus erythematosus in estimation of risk of subclinical atherosclerosis development].
Atherosclerosis is an important clinical problem in patients with systemic lupus erythematosus (SLE), because of very severe cardiovascular and central nervous system manifestations. Estimation if antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPL) are risk factors for subclinical atherosclerosis in patients with SLE. We examined 103 patients with SLE and 30 healthy volunteers, included as the control group. Coexistence of APS was confirmed in 35 patients. Evaluation of subclinical atherosclerosis was done on the basis of measurement of intima-media thickness (IMT) in B-mode ultrasound examination. We considered classical atherosclerotic risk factors and determined profile of aPL: anti-cardiolipine antibodies (aCL), anti beta2 glycoprotein-I antibodies, antiprothrombin antibodies (aPT), anti-oxidized low-density lipoprotein antibodies and lupus anticoagulant (LA). Statistical analysis was performed with chi2 Yates, chi2 Pearson and R rang Spearman tests. Multivariate regression analysis was also done. Thickened IMT was significantly more frequent in patients with SLE than in controls (p = 0.0002). We found that coexistence of APS is a risk factor for moderate thickening of IMT (OR: 3.41; 95% CI: 1.0-11.5). We also confirmed that the presence of aPL is significantly correlated with IMT ranging from 0.66 to 0.86 mm. The highest risk was found in patients with the presence of aPT IgA (OR: 5.50; 95% CI: 1.1-30.2), aCL IgM (OR: 4.36; 95% CI: 1.1-20.7), LA (OR: 4.02; 95% CI: 1.1-19.4) and aCL IgG (OR: 2.99; 95% CI: 1.1-9.7). Moreover, we found that ischaemic heart disease, nephropathy and myocardial infarction were significantly more frequent in patients with thickened IMT. Patients with SLE develop subclinical atherosclerosis significantly more frequent than the general population. Coexistence of APS and presence of aPL are risk factors for subclinical atherosclerosis development in patients with SLE. Thickened intima-media in patients with SLE is significantly associated with an increased risk of cardiovascular manifestations.


When less means more: dehydration improves innate immunity in rattlesnakes.
Immune function can vary based on availability of resources, and most studies of such influences have focused on the co-investment of energy into immune and other physiological functions. When energy resources are limited, trade-offs exist, which can compromise immunity for other functions. As with energy, water limitation can also alter various physiological processes, yet water has received little consideration for its possible role in modulating immune functions. We examined the relationship between immunocompetence and hydration state using the western diamond-backed rattlesnake (Crotalus atrox). This species is known to undergo substantial seasonal fluctuations in water availability with extreme limitations during the hot-dry season. We collected blood samples from free-ranging C. atrox to compare osmolality and innate immune function (lysis, agglutination and bacterial growth inhibition) during the milder and relatively moister early spring season, the hot-dry season and the hot-wet season. To isolate effects of dehydration from other possible seasonal influences, we complemented this field study with a laboratory study in which we withheld food and water from individually housed adult C. atrox for up to 16 weeks. We collected blood samples from each snake as it dehydrated and collected a final sample after the snake was given water ad libitum at the end of the experiment. Our results demonstrate that C. atrox experience significant dehydration during the hot-dry season, and that, in general, innate immune function is highly correlated with osmolality, whether natural or artificially manipulated.


Computed tomography of lobar collapse: 1. Endobronchial obstruction.
The computed tomographic (CT) appearance of lobar collapse has yet to be defined. In an attempt to determine the characteristic appearance of collapse 95 cases were reviewed retrospectively in a wide variety of clinical settings over a 3 year period ending January 1983. In this report 38 cases of lobar collapse secondary to endobronchial occlusion are analyzed; the appearance of collapse without endobronchial obstruction forms the basis of a subsequent report. Computed tomography was accurate in determining the site of bronchial occlusion in all cases. In 36 of 38 cases collapse was caused by endobronchial tumors, including bronchogenic carcinoma, bronchial carcinoids, endobronchial metastases, and lymphoma. Differentiation between these tumors was not feasible with CT. Most cases of collapse were caused by central tumor. In those cases in which a bolus of contrast material was used differentiation between tumor mass and collapsed pulmonary parenchyma was possible. Two of 38 cases were found to have benign bronchial occlusion. In one case a mucous plug obstructing the left lower lobe bronchus was accurately defined. In another case a bronchial stricture occluded the right lower lobe bronchus. This represented the only false positive case in this series. It is concluded that CT is an accurate means for establishing the diagnosis of endobronchial obstruction. In most cases the diagnosis of neoplasia was possible, provided a bolus of contrast material was used to define tumor mass. The potential role of CT in evaluating patients with lobar collapse is discussed.


Effect of massage on pain management for thoracic surgery patients.
Integrative therapies such as massage have gained support as interventions that improve the overall patient experience during hospitalization. Thoracic surgery patients undergo long procedures and commonly have postoperative back, neck, and shoulder pain. Given the promising effects of massage therapy for alleviation of pain, we studied the effectiveness and feasibility of massage therapy delivered in the postoperative thoracic surgery setting. Patients who received massage in the postoperative setting had pain scores evaluated pre and post massage on a rating scale of 0 to 10 (0 = no pain, 10 = worst possible pain). In total, 160 patients completed the pilot study and received massage therapy that was individualized. Patients receiving massage therapy had significantly decreased pain scores after massage (p ≤ .001), and patients' comments were very favorable. Patients and staff were highly satisfied with having massage therapy available, and no major barriers to implementing massage therapy were identified. Massage therapy may be an important additional pain management component of the healing experience for patients after thoracic surgery.


Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives.
Lipid-soluble thiamine precursors have a much higher bioavailability than genuine thiamine and therefore are more suitable for therapeutic purposes. Benfotiamine (S-benzoylthiamine O-monophosphate), an amphiphilic S-acyl thiamine derivative, prevents the progression of diabetic complications, probably by increasing tissue levels of thiamine diphosphate and so enhancing transketolase activity. As the brain is particularly sensitive to thiamine deficiency, we wanted to test whether intracellular thiamine and thiamine phosphate levels are increased in the brain after oral benfotiamine administration. Benfotiamine that is practically insoluble in water, organic solvents or oil was solubilized in 200 mM hydroxypropyl-beta-cyclodextrin and the mice received a single oral administration of 100 mg/kg. Though thiamine levels rapidly increased in blood and liver to reach a maximum after one or two hours, no significant increase was observed in the brain. When mice received a daily oral administration of benfotiamine for 14 days, thiamine derivatives were increased significantly in the liver but not in the brain, compared to control mice. In addition, incubation of cultured neuroblastoma cells with 10 muM benfotiamine did not lead to increased intracellular thiamine levels. Moreover, in thiamine-depleted neuroblastoma cells, intracellular thiamine contents increased more rapidly after addition of thiamine to the culture medium than after addition of benfotiamine for which a lag period was observed. Our results show that, though benfotiamine strongly increases thiamine levels in blood and liver, it has no significant effect in the brain. This would explain why beneficial effects of benfotiamine have only been observed in peripheral tissues, while sulbutiamine, a lipid-soluble thiamine disulfide derivative, that increases thiamine derivatives in the brain as well as in cultured cells, acts as a central nervous system drug. We propose that benfotiamine only penetrates the cells after dephosphorylation by intestinal alkaline phosphatases. It then enters the bloodstream as S-benzoylthiamine that is converted to thiamine in erythrocytes and in the liver. Benfotiamine, an S-acyl derivative practically insoluble in organic solvents, should therefore be differentiated from truly lipid-soluble thiamine disulfide derivatives (allithiamine and the synthetic sulbutiamine and fursultiamine) with a different mechanism of absorption and different pharmacological properties.


One-pot synthesis of hollow superparamagnetic CoPt nanospheres.
Hollow metal nanospheres are of interest for a variety of academic and technological applications, including drug delivery, catalysis, plasmonics, and lightweight structural composites. Despite recent advances in synthesizing metal nanostructures with controlled morphologies, there are very few reports of hollow bimetallic nanospheres, although such systems promise to offer advantages over single-metal systems. Here, were report a one-pot synthetic strategy for accessing hollow CoPt nanospheres with a Co-Pt alloy structure. The approach utilizes an in situ Co template and exploits galvanic displacement reactions to selectively dissolve the Co core while depositing a Pt shell. The combination of reducing conditions and a polymer stabilizer appears to allow the Co and Pt to co-reduce and form a Co-Pt fcc alloy phase with a morphology that is templated by the sacrificial Co core. The hollow CoPt nanospheres, which show magnetic hysteresis at low temperatures, are thermally stable up to 300 degrees C. The approach, which adds to a growing toolbox of reactions that yield morphologically controlled magnetic CoPt and FePt nanomaterials, is likely to be general for a variety of alloy systems.


Early prognoses of 200 renal allografts harvested from non-heart-beating cadavers.
When the concept of brain death is not widely accepted, the viability of renal allografts of non-heart-beating cadaveric donors is one of the serious concerns for transplant surgeons. At our center, 200 kidneys were harvested from cardiac arrest donors using the regional in situ cooling technique, and they were transplanted into recipients treated with cyclosporine (CS). The ages of donors ranged from 7 months to 67 years. At the bedside a specially designed double balloon catheter, 14F, was inserted into the aorta through the femoral artery just before or immediately after the cardiac arrest. A venous drainage tube was also placed in the vena cava. Following the cardiac arrest, both balloons of the aortic catheter were inflated, and regional in situ cooling with cold Lactate Ringer's solution started using the infusion pump at 20 mL/kg/min. In the OR, both kidneys were removed en bloc and preserved in Collins'type solution. They were then transplanted into 200 patients treated with CS and steroid. After the transplant operations, 33 patients (16.5%) had immediate renal function, but 14 grafts (7.0%) were not successful and the patients have never had renal function. When several factors such as donor age, warm ischemic time (WIT; 12.3 ± 14.1 minutes), in situ cooling time (IST; 78.1 ± 18.0 minutes) and total ischemic time (TIT; 619 ± 340 minutes) were associated with the post-transplant renal function, only the donor age had significant correlation both with the posttransplant dialysis period and lowest serum creatine level, as follows: 10.5 days ( ≤ 40 years) vs. 14.6 days ( > 40 years); P < 0.05, and 1.16 mg/dL ( ≤ 30 years) vs. 1.83 mg/dL ( > 50 years) P < 0.001, respectively. Our findings indicate; 1) Due to the in situ cooling technique, the renal grafts of non-heart-beating cadavers can be expected to have relatively good function in the CS-treated recipients; 2) donor age is instrumental in predicting post-transplant renal function as well as the duration of ATN; 3) WIT, 1ST and TIT have no association with the post-transplant renal function if the duration of renal ischemia is within the acceptable range.


Bidirectional motion characteristics of resonant inertial impact rotating piezoelectric motor based on self-clamping structure.
A new working principle for multimodal excitation of a resonant bidirectional rotary inertial impact piezoelectric motor with a self-clamping structure was developed based on previous research on piezoelectric motors. Unlike previous piezoelectric motors that relied on single harmonic waves for unidirectional rotation, in this motor, we can simply change the driving signal characteristics of the motor without changing the structure of the piezoelectric motor to excite multiple vibration modes, thereby achieving rotation in both directions. Compared with other bidirectional resonant motors, the structure and control signal are simpler. The finite element simulation software COMSOL5.5 was used to simulate the working mode of the motor, and the results were in good agreement with the final experiment. During the experiments, the optimal operating frequency of the motor prototype was 900 Hz. The maximum output speed of the motor prototype was 3.9 rad/s, the maximum output torque was 15 N mm, and the maximum resolution was 0.248° under the conditions of 240 Vp-p voltage, 900 Hz frequency, and 7.8 N mm preload torque.


Radiofrequency ablation in treatment of atrial fibrillation.
Beside heart failure and metabolic syndrome, atrial fibrillation is termed the cardiovascular epidemic of the twenty-first century. Its increased morbidity and mortality is alarming. The present, most effective therapy of atrial fibrillation is catheter ablation. Successful ablation of atrial fibrillation prevents the occurrence and progression of electrical, structural and mechanic myocardium remodelling, improves function of the left ventricle, and prevents the risk of thrombembolism. Onset of sinus rhythm activates the reversal remodelling leading to wall reconstruction and atrium reduction. The paper reviews the technique and presents own experience with catheter ablation.


[Effect of stimulation of the head of the caudate nucleus on differentiation of acoustic signals in a defensive situation in the dog].
In chronic experiments with a model of instrumental defensive reflexes, the influence of preliminary low-frequency stimulation of n. caudatus head on differentiation of acoustic signals was studied in six dogs. By their motor behaviour the animals were conditionally divided into two groups: excitable and quiet dogs. In these two groups principally similar results were obtained. It was shown that in defensive situation, the caudate nucleus head stimulation does not change (or slightly changes) the formed type of reactions to both defensive and differentiation signals. Striate inhibitory effects revealed in experiments (mainly in quiet dogs) are probably connected with the intensification of mechanisms of selective attention to significant stimuli. The motor reaction of the animals to a "finer" differentiation signal appeared to approach the responses to "rougher" differentional stimuli.


Elucidating the microbiome of the sustainable peat replacers composts and nature management residues.
Sustainable peat alternatives, such as composts and management residues, are considered to have beneficial microbiological characteristics compared to peat-based substrates. Studies comparing microbiological characteristics of these three types of biomass are, however, lacking. This study examined if and how microbiological characteristics of subtypes of composts and management residues differ from peat-based substrates, and how feedstock and (bio)chemical characteristics drive these characteristics. In addition, microbiome characteristics were evaluated that may contribute to plant growth and health. These characteristics include: genera associated with known beneficial or harmful microorganisms, microbial diversity, functional diversity/activity, microbial biomass, fungal to bacterial ratio and inoculation efficiency with the biocontrol fungus Trichoderma harzianum. Bacterial and fungal communities were studied using 16S rRNA and ITS2 gene metabarcoding, community-level physiological profiling (Biolog EcoPlates) and PLFA analysis. Inoculation with T. harzianum was assessed using qPCR. Samples of feedstock-based subtypes of composts and peat-based substrates showed similar microbial community compositions, while subtypes based on management residues were more variable in their microbial community composition. For management residues, a classification based on pH and hemicellulose content may be relevant for bacterial and fungal communities, respectively. Green composts, vegetable, fruit and garden composts and woody composts show the most potential to enhance plant growth or to suppress pathogens for non-acidophilic plants, while grass clippings, chopped heath and woody fractions of compost show the most potential for blends for calcifuge plants. Fungal biomass was a suitable predictor for inoculation efficiency of composts and management residues.


Antinociceptive pharmacology of N-[[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]methyl]-2-[2-[[(4-methoxy-2,6-dimethylphenyl) sulfonyl]methylamino]ethoxy]-N-methylacetamide, fumarate (LF22-0542), a novel nonpeptidic bradykinin B1 receptor antagonist.
The antinociceptive pharmacology of N-[[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]methyl]-2-[2-[[(4-methoxy-2,6-dimethylphenyl) sulfonyl]methylamino]ethoxy]-N-methylacetamide fumarate (LF22-0542), a novel nonpeptidic B1 antagonist, was characterized. LF22-0542 showed high affinity for human and mouse B1 receptors with virtually no affinity for the human B2 receptor; a selectivity index of at least 4000 times was obtained when LF22-0542 was profiled throughout binding or cell biology assays on 64 other G-protein-coupled receptor, 10 ion channels, and seven enzymes. LF22-0542 was a competitive B1 receptor antagonist and elicited significant antinociceptive actions in the mouse acetic acid-induced writhing assay, as well as in the second phases of formalin-induced nociception in mice and in both the first and second phases of the formalin response in rats. LF22-0542 was active after s.c. but not p.o. administration. In B1 receptor knockout (KO) mice, acetic acid and formalin responses were significantly reduced and LF22-0542 had no additional effects in these animals. LF22-0542 alleviated thermal hypersensitivity in both acute (carrageenan) and persistent inflammatory (complete Freund's adjuvant) pain models in rats. LF22-0542 produced a full reversal of experimental neuropathic thermal hypersensitivity but was inactive in reversing nerve injury-induced tactile hypersensitivity in rats. In agreement with this observation, B1 KO mice subjected to peripheral nerve injury did not show thermal hypersensitivity but developed nerve injury-induced tactile hypersensitivity normally. The data demonstrate the antihyperalgesic actions of a selective systemically administered B1 receptor antagonist and suggest the utility of this class of agents for the treatment of inflammatory pain states and for some aspects of neuropathic pain.


Dynamics and heat diffusion of Abrikosov's vortex-antivortex pairs during an annihilation process.
The manipulation and control of vortex states in superconducting systems are of great interest in view of possible applications, for which mesoscopic materials are good candidates. In this work, we studied the annihilation dynamics and the dissipative aspects of an Abrikosov's vortex-antivortex pair in a mesoscopic superconducting system with a concentric hole. The generalized time-dependent Ginzburg-Landau equations were numerically solved. The main result is the appearance of a phase slip-like line due to the elongation of the vortex and antivortex cores. Under specific circumstances, thermal dissipation might be associated with a sizeable relaxation of the order parameter, so that the energy released in the annihilation of a vortex-antivortex pair might become detectable in measurements of the magnetization as a function of time.


Evidence for concerted electron proton transfer in charge recombination between FADH- and 306Trp• in Escherichia coli photolyase.
Proton-coupled electron-transfer (PCET) is a mechanism of great importance in protein electron transfer and enzyme catalysis, and the involvement of aromatic amino acids in this process is of much interest. The DNA repair enzyme photolyase provides a natural system that allows for the study of PCET using a neutral radical tryptophan (Trp(•)). In Escherichia coli photolyase, photoreduction of the flavin adenine dinucleotide (FAD) cofactor in its neutral radical semiquinone form (FADH(•)) results in the formation of FADH(-) and (306)Trp(•). Charge recombination between these two intermediates requires the uptake of a proton by (306)Trp(•). The rate constant of charge recombination has been measured as a function of temperature in the pH range from 5.5 to 10.0, and the data are analyzed with both classical Marcus and semi-classical Hopfield electron transfer theory. The reorganization energy associated with the charge recombination process shows a pH dependence ranging from 2.3 eV at pH ≤ 7 and 1.2 eV at pH(D) 10.0. These findings indicate that at least two mechanisms are involved in the charge recombination reaction. Global analysis of the data supports the hypothesis that PCET during charge recombination can follow two different mechanisms with an apparent switch around pH 6.5. At lower pH, concerted electron proton transfer (CEPT) is the favorable mechanism with a reorganization energy of 2.1-2.3 eV. At higher pH, a sequential mechanism becomes dominant with rate-limiting electron-transfer followed by proton uptake which has a reorganization energy of 1.0-1.3 eV. The observed 'inverse' deuterium isotope effect at pH < 8 can be explained by a solvent isotope effect that affects the free energy change of the reaction and masks the normal, mass-related kinetic isotope effect that is expected for a CEPT mechanism. To the best of our knowledge, this is the first time that a switch in PCET mechanism has been observed in a protein.


Fibrin deposition in primary and metastatic human brain tumours.
Extravascular, intratumoral fibrin deposition is frequently observed within and around neoplastic tissue and has been implicated in various aspects of tumour growth. This is the first report on the presence and distribution of fibrinogen/fibrin in primary (14 glioblastomas) and metastatic (nine samples of lung cancer origin) human brain tumours detected by immunofluorescent techniques. All tissue samples showed specific staining for fibrinogen/fibrin. In glioblastomas fibrin deposits could be detected within and around tumour foci, while in metastatic brain tumours the tumour cell nodules were surrounded by fibrin deposits localized almost exclusively in the connective tissue compartment of tumours. Double-labelling reactions for von Willebrand factor and fibrinogen/fibrin has revealed that fibrin deposition occurred throughout the tumour stroma independently of tumour vasculature. The overlapping reactions for fibrinogen/fibrin and factor XIII subunit A, as well as the urea-insolubility of the deposits indicate the crosslinked, highly stabilized nature of fibrin both within and around tumours. Staining with Ki M7 monoclonal antibody specific for phagocytosing macrophages showed these cells to be scattered in the nonnecrotic areas in glioblastomas and to be accumulated at the interface of tumorous parenchyma and connective tissue in both primary and metastatic tumours. The close association between fibrin deposition and macrophage accumulation strongly suggests the active participation of tumour associated macrophages in the formation of stabilized intratumoral fibrin network in human brain neoplasms.


Presentation and outcome with second-line treatment in AL amyloidosis previously sensitive to nontransplant therapies.
The management of light chain (AL) amyloidosis has improved in recent years thanks to accurate biomarker-based staging systems and response criteria and availability of novel effective therapies. However, previous studies have focused on newly diagnosed patients, and little is known on relapsed patients, despite the fact that trials of new agents are often performed in this setting. In the present study, we report the outcome of 259 patients who responded to up-front therapy. Ninety-two patients (35%) needed second-line therapy after a median of 49 months. Cardiac and renal progression were observed in 22% and 12% of patients who received second-line therapy, respectively. Complete response after up-front treatment and frontline therapy with combined bortezomib, melphalan, and dexamethasone independently prolonged time to second-line therapy. Median survival of relapsing patients was 59 months. Patients who had a "high-risk dFLC progression," which we defined as a difference between involved and uninvolved free light chains (dFLC) of >20 mg/L, a level >20% of baseline value, and a >50% increase from the value reached at best response, had a shorter survival after initiation of second-line therapy on univariate, but not on multivariate, analysis, where cardiac progression was the only independent predictor of survival after starting rescue treatment. Patients with AL amyloidosis who need second-line therapy after response to up-front treatment generally have a good outcome. A "high-risk dFLC progression" should trigger rescue treatment, and cardiac progression should not be awaited.


INA-CBGs claim versus total hospital cost: A vaginal delivery investigation at Airlangga University Academic Hospital, Indonesia.
Background: Inadequate funding for vaginal delivery can be one of the barriers to reducing the maternal mortality rate. It could be therefore critical to compare the vaginal delivery cost between total hospital cost and INA-CBGs cost in national health insurance. Methods: This was a retrospective cross-sectional study conducted from October to December 2019 in Universitas Airlangga Academic Hospital. It collected data on primary diagnosis, length of stay, total hospital cost, INA-CBGs cost, and counted disparity. The data analyzed statistically using t-test independent sample (or Mann-Whitney test). Results: A total of 149 vaginal delivery claims were found, with the majority having a level II severity (79.87%) and moderate preeclampsia as a primary diagnosis (20.1%). There was a significant disparity in higher total hospital costs compared with government INA-CBGs costs (Rp. 9,238,022.09±1,265,801.88 vs 1,881,521.48±12,830.15; p<0.001). There was also an increase of LOS (p<0.001), total hospital cost (p<0.001), and cost disparity (p<0.01) in a higher severity level of vaginal delivery. Conclusion: Vaginal delivery costs in INA-CBGs scheme are underneath the actuarial value. There was also an increase in total hospital costs and a more significant disparity in the higher severity levels of vaginal delivery.


Correlates of Alcohol Use Likelihood for Latino Immigrant Youth in an Emerging Context.
Using a three-wave prospective longitudinal design spanning 3 years, we assessed alcohol use likelihood trajectories and their correlates among a community sample of Latino immigrant adolescents in the emerging immigrant context of Western Oregon. Results from growth mixture modeling revealed two distinct classes: lower risk youth who reported little likelihood of alcohol use but whose trajectory was increasing, and higher risk youth who reported higher likelihood of alcohol use and whose trajectory was stable. We found significant differences between the two classes such that lower risk youth reported greater levels of Latino cultural orientation and parental monitoring, whereas higher risk youth reported greater levels of family cultural stress and delinquency. Results are discussed in terms of prior research and theory.


[The modification of the M.D. Patsiora's operation by portal hypertension].
The direct transcutaneous transhepatic portography was performed in 85 patients with hystologically confirmed liver cirrhosis, portal hypertension and varices of the esophagus and stomach. It was found out, that the left gastric vein partakes the varicous transformation in 100% of cases. The least had an isolated division in 27% of the studied patients. 68% had the significant dilatation of the posterior gastric vein, whereas 19 (22%) patients had the combined posterior, left and short gastric veins dilatation. The study allowed the modification of the M.D. Patsiora's operation (the azygo-portal disintegration), by supplementing it with the gastric devascularization. The new method increased the 2-years survival from 77 to 97%, improved the hemostatic effect from 51 to 89% and decrease the recurrences from 25 to 5%.


The Exponentially Increasing Rate of Patients Infected with COVID-19 in Iran.
Coronavirus, the cause of severe acute respiratory syndrome (COVID-19), is rapidly spreading around the world. Since the number of corona positive patients is increasing sharply in Iran, this study aimed to forecast the number of newly infected patients in the coming days in Iran. The data used in this study were obtained from daily reports of the Iranian Ministry of Health and the datasets provided by the Johns Hopkins University including the number of new infected cases from February 19, 2020 to March 21, 2020. The autoregressive integrated moving average (ARIMA) model was applied to predict the number of patients during the next thirty days. The ARIMA model forecasted an exponential increase in the number of newly detected patients. The result of this study also show that if the spreading pattern continues the same as before, the number of daily new cases would be 3574 by April 20. Since this disease is highly contagious, health politicians need to make decisions to prevent its spread; otherwise, even the most advanced and capable health care systems would face problems for treating all infected patients and a substantial number of deaths will become inevitable.


Temporal effects of topical morphine application on cutaneous wound healing.
Studies have shown that topical administration of exogenous opioid drugs impairs wound healing by inhibiting the peripheral release of neuropeptides, thereby inhibiting neurogenic inflammation. This delay is immediate and peaks during the first days of wound closure. This study examined the effects of topical morphine treatment in a cutaneous wound healing model in the rat. Full-thickness 4-mm-diameter wounds were placed on the periscapular region of rats that subsequently received twice-daily topical applications of IntraSite Gel (Smith+Nephew, Hull, United Kingdom) alone or gel infused with 5 mm morphine sulfate on days 0-3 or 4-10 postwounding or throughout the time course. Wound tissue was taken on days 1, 3, 5, 8, and 18 postwounding and immunostained for myofibroblast and macrophage markers or stained with hematoxylin and eosin. Delays in wound closure observed during morphine application on days 0-3 postwounding mimicked those seen in wounds treated with morphine throughout the entire healing process. However, no significant delays in closure were seen in wounds treated with morphine beginning on day 4 postwounding. Treatment of wounds with morphine significantly reduced the number of myofibroblasts and macrophages in the closing wound. In addition, morphine application resulted in decreases in skin thickness and an increase in residual scar tissue in healed skin. These findings demonstrate the time-dependent and persistent nature of the detrimental effects of topical morphine on cutaneous wound healing. The data identify specific limitations that could be ameliorated to optimize topical opioid administration as an analgesic therapeutic strategy in the treatment of painful cutaneous wounds.


Comparative investigation of concentrations of major and trace elements in organic and conventional Danish agricultural crops. 1. Onions (Allium cepa Hysam) and peas (Pisum sativum ping pong).
210 samples of onions (Allium cepa Hysam) from 11 conventionally and 10 organically cultivated sites and 190 samples of peas (Pisum sativum Ping Pong) from 10 conventionally and 9 organically cultivated sites in Denmark were collected and analyzed for 63 and 55 major and trace elements, respectively, by high-resolution inductively coupled plasma mass spectrometry. Sampling, sample preparation, and analysis of the samples were performed under carefully controlled contamination-free conditions. Comparative statistical tests of the element concentration mean values for each site show significantly (p < 0.05) different levels of Ca, Mg, B, Bi, Dy, Eu, Gd, Lu, Rb, Sb, Se, Sr, Ti, U, and Y between the organically and conventionally grown onions and significantly (p < 0.05) different levels of P, Gd, and Ti between the organically and conventionally grown peas. Principal component analysis (PCA) applied to the 63 elements measured in the individual onion samples from the 21 sites split up the sites into two groups according to the cultivation method when the scores of the first and third principal components were plotted against each other. Correspondingly, for peas, a PCA applied to the 55 elements measured as mean values for each site split up the 19 sites into two groups according to the cultivation method when the scores of the third and fourth principal component were plotted against each other. The methodology may be used as authenticity control for organic cultivation after further method development.


Cardiac resynchronization therapy.
Systolic heart failure is a major problem for Americans today, with 550,000 new cases diagnosed per year, and ultimately contributes to 287,000 deaths annually. While pharmacologic therapy has drastically improved outcomes in patients with systolic heart failure, hospitalizations from systolic heart failure continue to increase and remain a major cost burden. In response to this unmet need, recent years have seen dramatic improvements in device-based therapy targeting one cause of systolic dysfunction: dyssynchronous ventricular contraction. Cardiac resynchronization therapy aims to restore mechanical synchrony by electrically activating the heart in a synchronized manner. This review summarizes the rationale for cardiac resynchronization therapy, evidence for its use, current guidelines, and ongoing and future directions for research.


The Non-Concentration-Quenching Phosphor Ca3Eu2B4O12 for WLED Application.
Commercial white LED devices usually suffer from a high color temperature and poor color rendering. Developing a new, efficient, and stable red phosphor is the key to solving this problem. In this work, a series of pure Ca3Y2-xB4O12:xEu3+ (0 < x ≤ 2) samples, including the new and fully transitional borate phosphor Ca3Eu2B4O12 (CEBO), have been successfully prepared by solid-state reaction synthesis. CEBO is isostructural with Ca3Y2B4O12 (CYBO), belonging to the orthorhombic system with space group Pnma (No. 62). Under optimal 393 nm excitation, this borate exhibits a strong red emission, peaking at 615 nm, with high color purity. Interestingly, the luminescence of CEBO is relatively higher than that of CYBO:Eu3+ phosphors. The quantum yield of this non-concentration-quenching phosphor reaches 95.6%. Furthermore, a warm pc-WLED device has been fabricated by mixing as-prepared CEBO powders and commercial BaMgAl10O17:Eu2+ and (Sr, Ba)2SiO4:Eu2+ phosphors, which exhibits a high color rendering index (Ra = 83.7) along with a color temperature of around 3883 K. The present work indicates that this new borate, with outstanding quantum efficiency and favorable thermal stability, can be used as a red phosphor for application in WLEDs.


Mapping Genetic Influences on Brain Shape using Multi-Atlas Fluid Image Alignment.
In this pilot study, we developed a set of computer vision based surface segmentation and statistical shape analysis algorithms to study genetic influences on brain structure in a database of brain MRI scans of normal twins. A set of manually delineated 3D parametric surfaces, representing the lateral ventricles, was deformed, using a Navier-Stokes fluid image registration algorithm, onto all the images in the database. The geometric transformations thus obtained were used to propagate the segmentation labels to all the other images. 3D radial distance maps were derived to encode anatomical shape differences. The proportion of shape variance attributable to genetic factors, known as the heritability, was estimated from the shape models using a restricted maximum likelihood method to increase statistical power. Segmentation errors associated with projecting labels onto new images were greatly reduced through multi-atlas averaging. The resulting algorithms provide a convenient and sensitive tool to recover and analyze small intra-pair image differences, and will make it easier to detect genetic influences on brain structure.


Tandem inverted repeats in mitochondrial DNA of petite mutants of Saccharomyces cerevisiae.
Denatured mitochondrial DNA (mtDNA) from a grande (wild-type) yeast strain and a series of derived genetically characterized cytoplasmic petite mutants was examined in the electron microscope as DNA-protein monolayers prepared under conditions that permitted little bimolecular renaturation. In the grande and some petite strains, the mtDNA remained predominantly single-stranded. However, in several petite strains, a large proportion of molecules contained double-stranded segments indicative of unimolecular renaturation due to the presence of inverted repeat sequences. The length of the double-stranded segments of strain E41 was compared to the periodicity seen on denaturation maps. A repeat spacing twice the length of the inverted repeats was observed in the denaturation map. Inverted repeat length was similar to contour length of circular mtDNA molecules in this strain. On the basis of these observations most of the mtDNA from petite strain E41 appeared to consist of polymers of tandem inverted repeats interspersed with a small single-stranded "spacer" sequence between the repeat segments. In contrast, petite strain F13 mtDNA had few or no inverted repeats and showed a regular periodicity of 0.14 mum in the denaturation map, similar in length to the 0.13-mum circles present in the isolated mtDNA.


The effect of Pt and Pd alloying additions on the corrosion behavior of titanium in fluoride-containing environments.
In this study, we examined the corrosion behaviors of pure titanium, the alloys Ti-6Al-4V and Ti-6Al-7Nb, and the new experimental alloys Ti-Pt and Ti-Pd using anodic polarization and corrosion potential measurements in an environment containing fluoride. Before and after immersion in the test solutions, we made observations using a scanning electron microscope. The test solutions included an artificial saliva containing 0.2% NaF (corresponding to 905 ppm F) and an artificial saliva with a low concentration of oxygen. Although the surfaces of the Ti-Pt and Ti-Pd alloys were not affected by an acidic environment containing fluoride, the surfaces of the pure titanium, the Ti-6Al-4V alloy, and the Ti-6Al-7Nb alloy were markedly roughened by corrosion. The surfaces of the pure titanium, the Ti-6Al-4V alloy, and the Ti-6Al-7Nb alloy were microscopically damaged by corrosion when they were immersed in the solution containing a low concentration of dissolved oxygen, even with a fluoride concentration included in the commercial dentifrices. In this situation, however, the surfaces of the new Ti-Pt and Ti-Pd alloys were not affected. These alloys are expected to be of use in dental work as new titanium alloys with high corrosion resistances.


Physical and functional interactions between uracil-DNA glycosylase and proliferating cell nuclear antigen from the euryarchaeon Pyrococcus furiosus.
Uracil-DNA glycosylase (UDG) is an important repair enzyme in all organisms to remove uracil bases from DNA. Recent biochemical studies have revealed that human nuclear UDG (UNG2) forms a multiprotein complex in replication foci and initiates the base excision repair pathway by interacting with proliferating cell nuclear antigen (PCNA). Here, we show the physical and functional interactions between UDG and PCNA from the hyperthermophilic euryarchaeon, Pyrococcus furiosus. The physical interaction between the two proteins was identified by a surface plasmon resonance analysis. Furthermore, the uracil glycosylase activity of P. furiosus UDG is stimulated by P. furiosus PCNA (PfuPCNA) in vitro. This stimulatory effect was observed only when wild type PfuPCNA, but not a monomeric PCNA mutant, was present in the reaction. Mutational analyses revealed that our predicted PCNA-binding region (AKTLF) in P. furiosus UDG is actually important for the interaction with PfuPCNA. This is the first report describing the functional interaction between archaeal UDG and PCNA.


Application of moisturizer to neonates prevents development of atopic dermatitis.
Recent studies have suggested that epidermal barrier dysfunction contributes to the development of atopic dermatitis (AD) and other allergic diseases. We performed a prospective, randomized controlled trial to investigate whether protecting the skin barrier with a moisturizer during the neonatal period prevents development of AD and allergic sensitization. An emulsion-type moisturizer was applied daily during the first 32 weeks of life to 59 of 118 neonates at high risk for AD (based on having a parent or sibling with AD) who were enrolled in this study. The onset of AD (eczematous symptoms lasting >4 weeks) and eczema (lasting >2 weeks) was assessed by a dermatology specialist on the basis of the modified Hanifin and Rajka criteria. The primary outcome was the cumulative incidence of AD plus eczema (AD/eczema) at week 32 of life. A secondary outcome, allergic sensitization, was evaluated based on serum levels of allergen-specific IgE determined by using a high-sensitivity allergen microarray of diamond-like carbon-coated chips. Approximately 32% fewer neonates who received the moisturizer had AD/eczema by week 32 than control subjects (P = .012, log-rank test). We did not show a statistically significant effect of emollient on allergic sensitization based on the level of IgE antibody against egg white at 0.34 kUA/L CAP-FEIA equivalents. However, the sensitization rate was significantly higher in infants who had AD/eczema than in those who did not (odds ratio, 2.86; 95% CI, 1.22-6.73). Daily application of moisturizer during the first 32 weeks of life reduces the risk of AD/eczema in infants. Allergic sensitization during this time period is associated with the presence of eczematous skin but not with moisturizer use.


The molecular basis of class II MHC allelic control of T cell responses.
To identify the molecular basis for the effects of MHC molecule polymorphism on T cell responses, we have combined functional T cell response testing with measurements of peptide binding to the class II MHC molecules on transfected cells. Our studies identify a small subset of spatially localized polymorphic residues of the E alpha E beta dimer (strand residue beta 29, and helix residues beta 72 and beta 75) regulating cytochrome c peptide presentation by two distinct mechanisms. The first effect is on quantitative control of net peptide binding. The replacement of the valine found at position beta 29 in E beta k with the glutamic acid found in E beta b results in a selective loss of pigeon cytochrome peptide but not moth cytochrome peptide binding to the resultant mutant E alpha E beta k molecule. Reciprocally, the replacement of glutamic acid at beta 29 in E beta b with valine results in a gain of pigeon peptide binding. These changes in binding parallel changes in T cell responses in vitro to these peptide-E alpha E beta combinations and mirror the in vivo immune response gene phenotypes of mice expressing E alpha E beta k and E alpha E beta b. E alpha E beta s molecules, which have a beta 29 glutamic acid, are nevertheless able to bind and present pigeon cytochrome peptides, and this is due to changes in helix residues beta 72 and beta 75 that compensate for the negative effect of the beta 29 glutamic acid. The second activity is a critical change in the conformation of the peptide bound to the same extent by distinct MHC molecules, as revealed by changes in T cell responses to moth cytochrome peptides presented by two E alpha E beta molecules differing only at position beta 29. Both of these effects can be ascribed to a single polymorphic residue modeled to be inaccessible to TCR contact (beta 29), providing a striking demonstration of how MHC molecule polymorphism can modify T cell-dependent immune responses without direct physical participation in the receptor recognition event.


Alkaptonuric arthropathy with periprosthetic fracture:a case report.
Alkaptonuria or Ochronosis is an autosomal recessive congenital metabolic error due to absence of enzyme homogentisic acid oxidase. Recently, we had an opportunity to diagnose this condition in one of our patients. An old aged man developed a pathological fracture of femur after a trivial fall at home. He was diagnosed to have intracapsular fracture neck of femur. Intraoperatively we noticed blackish discoloration of femoral head which lead us to investigate the case for alkaptonuria. Hemiarthroplasty was done with Austin moore prosthesis. Patient had cutaneous pigmentation and gross arthritic changes at multiple joints including spine. After one and half year patient developed a periprosthetic fracture of the femur for which open reduction and internal fixation was done. A periprosthetic fracture in ochronotic patient has never been reported till date which makes it a rarer entity. This article presents the clinico-radiologic manifestations of the case with surgical management and a follow up of two years.


The myth of the normal, average human brain--the ICBM experience: (1) subject screening and eligibility.
In the course of developing an atlas and reference system for the normal human brain throughout the human age span from structural and functional brain imaging data, the International Consortium for Brain Mapping (ICBM) developed a set of "normal" criteria for subject inclusion and the associated exclusion criteria. The approach was to minimize inclusion of subjects with any medical disorders that could affect brain structure or function. In the past two years, a group of 1685 potential subjects responded to solicitation advertisements at one of the consortium sites (UCLA). Subjects were screened by a detailed telephone interview and then had an in-person history and physical examination. Of those who responded to the advertisement and considered themselves to be normal, only 31.6% (532 subjects) passed the telephone screening process. Of the 348 individuals who submitted to in-person history and physical examinations, only 51.7% passed these screening procedures. Thus, only 10.7% of those individuals who responded to the original advertisement qualified for imaging. The most frequent cause for exclusion in the second phase of subject screening was high blood pressure followed by abnormal signs on neurological examination. It is concluded that the majority of individuals who consider themselves normal by self-report are found not to be so by detailed historical interviews about underlying medical conditions and by thorough medical and neurological examinations. Recommendations are made with regard to the inclusion of subjects in brain imaging studies and the criteria used to select them.


The role of S100A14 in epithelial ovarian tumors.
S100A14 is an EF-hand calcium-binding protein that has been reported to be involved in the progression of many malignancies. However, its role in ovarian cancer has not yet been clarified. In this study, we investigated the significance of S100A14 expression in epithelial ovarian cancers (EOCs) as well as it's mechanism of action. On both RNA and protein levels, S100A14 was overexpressed in transformed cells. Immunohistochemical staining demonstrated that S100A14 expression was associated with advanced stage (P<0.001) and poor tumor grade (P<0.001). Moreover, S100A14 overexpression was an independent prognostic factor for overall survival (HR = 4.53, P = 0.029). We also investigated S100A14's functional role by employing lentiviral-mediated overexpression and knockdown in EOC cells. S100A14 overexpression promoted cell proliferation, tumorigenesis, migration, and invasion, whereas S100A14 knockdown inhibited these properties. TOV112D cells that overexpressed S100A14 also exhibited greater tumor growth potential in xenografted mice. S100A14 promoted such a malignant phenotype in EOC cells through the PI3K/Akt pathway. Taken together, our data indicate that S100A14 has a crucial role in EOC progression, and its overexpression is associated with poor prognosis. Further study of S100A14's molecular mechanisms may lead to the development of a novel therapeutic target for ovarian cancer.


Notch regulates vascular collagen IV basement membrane through modulation of lysyl hydroxylase 3 trafficking.
Collagen type IV (Col IV) is a basement membrane protein associated with early blood vessel morphogenesis and is essential for blood vessel stability. Defects in vascular Col IV deposition are the basis of heritable disorders, such as small vessel disease, marked by cerebral hemorrhage and drastically shorten lifespan. To date, little is known about how endothelial cells regulate the intracellular transport and selective secretion of Col IV in response to angiogenic cues, leaving a void in our understanding of this critical process. Our aim was to identify trafficking pathways that regulate Col IV deposition during angiogenic blood vessel development. We have identified the GTPase Rab10 as a major regulator of Col IV vesicular trafficking during vascular development using both in vitro imaging and biochemistry as well as in vivo models. Knockdown of Rab10 reduced de novo Col IV secretion in vivo and in vitro. Mechanistically, we determined that Rab10 is an indirect mediator of Col IV secretion, partnering with atypical Rab25 to deliver the enzyme lysyl hydroxylase 3 (LH3) to Col IV-containing vesicles staged for secretion. Loss of Rab10 or Rab25 results in depletion of LH3 from Col IV-containing vesicles and rapid lysosomal degradation of Col IV. Furthermore, we demonstrate that Rab10 is Notch responsive, indicating a novel connection between permissive Notch-based vessel maturation programs and vesicle trafficking. Our results illustrate both a new trafficking-based component in the regulated secretion of Col IV and how this vesicle trafficking program interfaces with Notch signaling to fine-tune basement membrane secretion during blood vessel development.


Method for securing a subcuticular suture with minimal buried knot.
Subcuticular, intradermal suturing with retained suture has been performed with a variety of techniques requiring bulky buried knots. This report outlines a new method for closing a skin wound under light to moderate tension with fewer problems of buried knot bulkiness and gapping of the wound ends. The suture method was developed in a porcine model and has been used in clinical suturing with 3-0, 4-0, and 5-0 suture material. Outcomes for 23 cases have been satisfactory with no dehiscences and no exposure of knot material. This technique provides the surgeon with an excellent way to approximate skin wounds with a retained sucuticular suture. A modified technique for small 3- to 10-mm wounds is also described.


Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth.
Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.


Fast room-temperature functionalization of silicon nanoparticles using alkyl silanols.
Silicon nanoparticles (Si NPs) are a good alternative to conventional heavy metal-containing quantum dots in many applications, due to their low toxicity, low cost, and the high natural abundance of the starting material. Recently, much synthetic progress has been made, and crystalline Si NPs can now be prepared in a matter of hours. However, the passivation of these particles is still a time-consuming and difficult process, usually requiring high temperatures and/or harsh reaction conditions. In this paper, we report an easy method for the room-temperature functionalization of hydrogen-terminated Si NPs. Using silanol compounds, a range of functionalized Si NPs could be produced in only 1 h reaction time at room temperature. The coated NPs were fully characterized to determine the efficiency of binding and the effects of coating on the optical properties of the NPs. It was found that Si NPs were effectively functionalized, and that coated NPs could be extracted from the reaction mixture in a straightforward manner. The silanol coating increases the quantum yield of fluorescence, decreases the spectral width and causes a small (∼50 nm) blue-shift in both the excitation and emission spectra of the Si NPs, compared to unfunctionalized particles.


Self-Assembly of Hollow Organic Nanotubes Driven by Arene Regioisomerism.
Arene regioisomerism in low-molecular-weight gelators can be exploited as a tool to modulate the micro-structures of the corresponding xerogel networks by using the three different possible substitution patterns ortho, meta and para. This aromatic regioisomer-driven strategy has been used with a cholesterol-based gelator to prepare hollow self-assembled organic nanotubes (S-ONTs) with inside and outside diameters of ca. 35 and 140 nm, respectively. Electron microscopy imaging and theoretical calculations were employed to rationalize the formation mechanism of these S-ONTs. From the three possible regioisomers, only the ortho-disubstituted cholesteryl-based gelator showed the optimal angle and distance between substituents to afford the formation of the cyclic assemblies required for nanotube growth by assembling 30-40 units of the gelator. This study opens fascinating opportunities to expand the synthesis of controllable and unique microstructures by modulating geometrical parameters through aromatic regioisomers.


Inhibition of NF-κB activation by a novel IKK inhibitor reduces the severity of experimental autoimmune myocarditis via suppression of T-cell activation.
NF-κB, which is activated by the inhibitor of NF-κB kinase (IKK), is involved in the progression of inflammatory disease. However, the effect of IKK inhibition on the progression of myocarditis is unknown. We examined the effect of IKK inhibition on the progression of myocarditis. Lewis rats were immunized with porcine cardiac myosin to induce experimental autoimmune myocarditis (EAM). We administered the IKK inhibitor (IMD-0354; 15 mg·kg(-1)·day(-1)) or vehicle to EAM rats daily. Hearts were harvested 21 days after immunization. Although the untreated EAM group showed increased heart weight-to-body weight ratio, and severe myocardial damage, these changes were attenuated in the IKK inhibitor-treated group. Moreover, IKK inhibitor administration significantly reduced NF-κB activation and mRNA expression of IFN-γ, IL-2, and monocyte chemoattractant protein-1 in myocardium compared with vehicle administration. In vitro study showed that the IKK inhibitor treatment inhibited T-cell proliferation and Th1 cytokines production induced by myosin stimulation. The IKK inhibitor ameliorated EAM by suppressing inflammatory reactions via suppression of T-cell activation.


Novel supercritical carbon dioxide impregnation technique for the production of amorphous solid drug dispersions: a comparison to hot melt extrusion.
The formulation of BCS Class II drugs as amorphous solid dispersions has been shown to provide advantages with respect to improving the aqueous solubility of these compounds. While hot melt extrusion (HME) and spray drying (SD) are among the most common methods for the production of amorphous solid dispersions (ASDs), the high temperatures often required for HME can restrict the processing of thermally labile drugs, while the use of toxic organic solvents during SD can impact on end-product toxicity. In this study, we investigated the potential of supercritical fluid impregnation (SFI) using carbon dioxide as an alternative process for ASD production of a model poorly water-soluble drug, indomethacin (INM). In doing so, we produced ASDs without the use of organic solvents and at temperatures considerably lower than those required for HME. Previous studies have concentrated on the characterization of ASDs produced using HME or SFI but have not considered both processes together. Dispersions were manufactured using two different polymers, Soluplus and polyvinylpyrrolidone K15 using both SFI and HME and characterized for drug morphology, homogeneity, presence of drug-polymer interactions, glass transition temperature, amorphous stability of the drug within the formulation, and nonsink drug release to measure the ability of each formulation to create a supersaturated drug solution. Fully amorphous dispersions were successfully produced at 50% w/w drug loading using HME and 30% w/w drug loading using SFI. For both polymers, formulations containing 50% w/w INM, manufactured via SFI, contained the drug in the γ-crystalline form. Interestingly, there were lower levels of crystallinity in PVP dispersions relative to SOL. FTIR was used to probe for the presence of drug-polymer interactions within both polymer systems. For PVP systems, the nature of these interactions depended upon processing method; however, for Soluplus formulations this was not the case. The area under the dissolution curve (AUC) was used as a measure of the time during which a supersaturated concentration could be maintained, and for all systems, SFI formulations performed better than similar HME formulations.


The evolution of progressive postoperative weight bearing after autologous chondrocyte implantation in the tibiofemoral joint.
Autologous chondrocyte implantation (ACI) has demonstrated good clinical success in the repair of articular cartilage defects in the knee. Postoperative rehabilitation after ACI is considered critical in returning the patient to an optimal level of function by attempting to create the appropriate mechanical environment for cartilage regrowth, and it involves a progressive program that emphasizes full motion, progressive partial weight bearing (PWB), and controlled exercises. While evidence-based research is clearly lacking in all components of ACI rehabilitation, one important element in this treatment algorithm that has been subjected to some early scientific study is the gradual progression of the patient back to full weight-bearing (WB) gait after surgery. With the continual advancement of ACI surgical techniques, along with clinical experience and improved knowledge of histology and of the maturation process of chondrocytes, proposed postoperative WB protocols have evolved to better reflect the nature of the specific ACI surgery. The purpose of this article is to present the varied PWB programs that have been practiced alongside the evolving ACI surgical technique, the experimental basis for such protocols, the issues pertinent to the accurate prescription of WB, and future directions for developing such methods to best return patients to an optimal level of function after ACI.


Attachment style predict compliance, quality of life and renal function in adult patients after kidney transplant: preliminary results.
Aim of this study was to evaluate the association between attachment style, compliance, quality of life and renal function in adult patients after kidney transplantation. A total of 43 adult patients who received a kidney transplant more than 3 months before were enrolled and were asked to complete two Self-Report questionnaires: Attachment Style Questionnaire (ASQ-40) and Short Form Health Survey (SF-36). Also compliance was measured using appropriate questions. Linear regression analysis showed associations between the confidence in relationships (ASQ-40) and compliance [beta = -0.37; B = -0.02; t(41) = -2.51; p = 0.02]; aspects of anxious attachment style (ASQ-40) and creatinine levels [beta = 0.3; B = 0.13; t(41) = 2.03; p = 0.04]; aspects of avoidant attachment style (ASQ-40) and compliance [beta = -0.37; B = -3.15; t(41) = -2.35; p = 0.02]. Patients who exhibited avoidant attachment had a significantly better perception of their own general health than patients with anxious [F(2,37) = 6.8; p < 0.05] or secure attachment; however, they had a worse perception regarding role limitations due to emotional problems, compared to patients with anxious attachment [F(2,37) = 6.4; p < 0.05]. The results of this study suggest that the evaluation of the attachment style in adult kidney transplant patients can contribute to plan a goal-directed psychological support program for these patients, in order to increase their compliance. The association between aspects of anxious attachment style and creatinine level needs more investigations.


Discordance Between Physician Assessment and Patient-Reported Depressive Symptoms in Parkinson Disease.
To assess concordance between physician assessment and patient-reported symptoms when screening for depression in Parkinson disease (dPD). Depression in Parkinson disease is highly prevalent (∼40%) and has a significant impact on quality of life and disability, yet physician recognition and treatment remain inadequate. One thousand seventy-six patients with PD completed the Brief Symptom Inventory-18 (BSI-18), a screening questionnaire for psychiatric symptoms, which was compared to item #3 (depression) on the Unified Parkinson's Disease Rating Scale (UPDRS). The mean BSI-18 depression score was 51.4 (9.7). Of the 170 (16%) patients screening positive for dPD on the BSI-18, 104 (61%) were not recognized as depressed by neurologists on the UPDRS. Factors associated with lower neurologist recognition included male gender, better mental health quality of life, and lack of antidepressant use. More than 60% of patients screening positive for depression on self-report were not recognized by neurologists on the UPDRS. A patient-reported screening tool for depression may improve recognition and management of dPD.


The role of gender in the decision to pursue a surgical career: A qualitative, interview-based study.
Previous literature has explored the underrepresentation of women in surgery. However, this research has often been quantitative or limited by considering only the perspectives and experiences of women at more advanced career stages. Here, we use a qualitative methodology and a sample of women and men across the career continuum to identify the role that gender plays in the decision to pursue a surgical career. We audio-recorded and transcribed semi-structured interviews conducted with 12 women and 12 men ranging in their level of medical training from medical students to residents to staff surgeons. We used Braun and Clarke's six-step approach to thematic analysis to analyze the data, maintaining trustworthiness and credibility by employing strategies including reflexivity and participant input. Our findings suggested that the characteristics of surgery and early exposure to the profession served as important factors in participants' decisions to pursue a surgical career. Although not explicitly mentioned by participants, each of these areas may implicitly be gendered. Gender-based factors explicitly mentioned by participants included the surgical lifestyle and experiences with gender discrimination, including sexual harassment. These factors were perceived as challenges that disproportionately affected women and needed to be overcome when pursuing a surgical career. Our findings suggest that gender is more likely to act as a barrier to a career in surgery than as a motivator, especially among women. This suggests a need for early experiences in the operating room and mentorship. Policy change promoting work-life integration and education to target gender discrimination is also recommended.


Dry suction versus wet suction technique of endoscopic ultrasound-guided fine-needle biopsy for diagnosis of solid pancreatic lesions: study protocol of a multicenter randomized controlled non-inferiority trial.
Studies have shown that the wet suction technique in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) generates better histological diagnostic accuracy and specimen quality than the dry suction technique. However, conclusions of wet suction on the diagnostic accuracy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) are still controversial. Besides, the optimal number of passes for EUS-FNB has not been determined. We aimed to design a large multicenter randomized trial to compare the diagnostic accuracy of dry suction versus wet suction technique in solid pancreatic lesions (SPLs) using 22G Franseen needles and determine the optimal number of passes required for EUS-FNB. This is a multi-center open-label, randomized controlled non-inferiority trial with two parallel groups. Two hundred patients with SPLs will undergo EUS-FNB using 22G Franseen needles in 4 tertiary hospitals in China and will be randomly assigned to the dry suction group and wet suction group in a ratio of 1:1. The primary endpoint is diagnostic accuracy. Secondary endpoints include the optimal number of needle passes, sensitivity, specificity, specimen quality, cytological diagnoses, time of the procedure, and incidence of complications. This study has been designed to determine (i) whether EUS-FNB using 22G Franseen needle with dry suction is non-inferior to wet suction in terms of diagnostic accuracy and (ii) the optimal number of passes during EUS-FNB of SPLs using 22G Franseen needle. ClinicalTrials.gov NCT05549856. Registered on September 22, 2022.


Researcher perspectives on embedding community stakeholders in T1-T2 research: A potential new model for full-spectrum translational research.
Effective community engagement in T3-T4 research is widespread, however, similar stakeholder involvement is missing in T1-T2 research. As part of an effort to embed community stakeholders in T1-T2 research, an academic community partnered team conducted discussion groups with researchers to assess perspectives on (1) barriers/challenges to including community stakeholders in basic science, (2) skills/training required for stakeholders and researchers, and (3) potential benefits of these activities. Engaging community in basic science research was perceived as challenging but with exciting potential to incorporate "real-life" community health priorities into basic research, resulting in a new full-spectrum translational research model.


A bibliometric approach demonstrates the impact of a social care data set on research and policy.
The National Minimum Dataset for Social Care (NMDS-SC) has provided detailed data since 2006 on the workforce for adult social care services in England. In 2012, the organisation responsible for the data set commissioned an evaluation into the impact of the data set on researchers and policymakers. Discusses how a novel wide-ranging bibliometric approach, complemented by interviews of key informants, demonstrated the developing impact of the data set. The evaluation comprised web metrics to assess NMDS-SC-related traffic on relevant websites; bibliometrics to assess the use of NMDS-SC data in scholarly publications and grey literature; telephone interviews with 12 key users of the data set; and an online survey completed by 24 key users of the data set. A theoretical framework for research impact was used. The web metrics demonstrated increase in traffic on the relevant pages of the organisation's website. There were references to the data set in 175 separate publications (15% from academic journals, 50% as policy/practice reports and 35% as media communications. Interviews evidenced many impacts, for example provision of robust data for secondary analysis that challenged conventional views about the social care workforce. Bibliometrics plus interviews provided a rounded picture of the data set's impact.


Radial polydactyly: putting together evolution, development and clinical anatomy.
Evolutionary developmental pathology, a new biological field, connects the study of evolution, development and human pathologies. In radial polydactyly, traditional studies have focused mainly on skeletal anomalies. This study examines anatomical and operative records of 54 consecutive cases of radial polydactyly to investigate whether there is a consistent spatial correlation between muscles, tendons and bones and whether this reflects a link between the mechanisms that generate these structures. The data are explored in the context of two current models of limb development: the modularity and topology models. Autopod (hand) tendons and muscles are more predictable in terms of insertion site, supporting both topology and modularity models. Zeugopod (forearm) tendons are less predictable. Neither model universally predicts the anatomy in radial polydactyly. These observations provide evidence for the complexity of anatomy in radial polydactyly and the difficulty in predicting operative findings based on the level of skeletal duplication alone.


[Mutation analysis of the MMACHC gene in a pedigree with methylmalonic aciduria].
To identify the mutation of the methylmalonic aciduria (cobalamin deficiency) CblC type, with homocystinuria (MMACHC) gene in a pedigree with methylmalonic aciduria. The MMACHC gene mutation was detected using polymerase chain reaction (PCR) and DNA sequencing. The MMACHC gene of 50 healthy people was also sequenced as control. A new mutation of 146_154 del CCTTCCTGG was found in the patient and his father, and was absent in the controls. A new mutation (146_154 del CCTTCCTGG) in the MMACHC gene was detected in a Chinese family with methylmalonic aciduria.


Gastrointestinal emergencies in critically ill cancer patients.
To describe gastrointestinal emergencies in cancer patients. All cancer patients admitted to the medical ICU of Saint-Louis Hospital for an acute abdominal syndrome during the study period (1997-2011) were included. A total of 164 patients were included. The most common diagnoses were: neutropenic enterocolitis (NE) (n=54, 33%), infectious colitis and peritonitis (n=51, 31%), bowel infiltration by malignancy (n=14, 9%), and mucosal toxicity of chemotherapy (n=12, 7%). Microbiologically documented infections were reported in 82 patients (50%), including 12 fungal infections. Twenty-seven patients (16%) underwent urgent surgery. The hospital mortality rate was 35%. Five factors were independently associated with hospital mortality: the Simplified Acute Physiology Score II (SAPS II) score on day 1 (OR 1.03/SAPS II point, 95% CI 1.01 to 1.05), microbiological documentation (OR 0.27, 95% CI 0.11 to 0.64), neutropenia (OR 0.42, 95% CI 0.19 to 0.95), allogenic hematopoietic stem-cell transplantation (HSCT) (OR 5.13, 95% CI 1.71 to 15.4), and mechanical ventilation (OR 3.42, 95% CI 1.37 to 8.51). Gastrointestinal emergencies in cancer patients are associated with significant mortality. Mortality correlated both with the severity of organ failure upon ICU admission and the underlying diagnosis. Interestingly, patients admitted to the ICU with neutropenia had better survival.


A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis.
Several lines of evidence suggest that transcription factors are involved in the pathogenesis of Multiple Sclerosis (MS) but complete mapping of the whole network has been elusive. One of the reasons is that there are several clinical subtypes of MS and transcription factors that may be involved in one subtype may not be in others. We investigate the possibility that this network could be mapped using microarray technologies and contemporary bioinformatics methods on a dataset derived from whole blood in 99 untreated MS patients (36 Relapse Remitting MS, 43 Primary Progressive MS, and 20 Secondary Progressive MS) and 45 age-matched healthy controls. We have used two different analytical methodologies: a non-standard differential expression analysis and a differential co-expression analysis, which have converged on a significant number of regulatory motifs that are statistically overrepresented in genes that are either differentially expressed (or differentially co-expressed) in cases and controls (e.g., V$KROX_Q6, p-value <3.31E-6; V$CREBP1_Q2, p-value <9.93E-6, V$YY1_02, p-value <1.65E-5). Our analysis uncovered a network of transcription factors that potentially dysregulate several genes in MS or one or more of its disease subtypes. The most significant transcription factor motifs were for the Early Growth Response EGR/KROX family, ATF2, YY1 (Yin and Yang 1), E2F-1/DP-1 and E2F-4/DP-2 heterodimers, SOX5, and CREB and ATF families. These transcription factors are involved in early T-lymphocyte specification and commitment as well as in oligodendrocyte dedifferentiation and development, both pathways that have significant biological plausibility in MS causation.


Impairment, disability, and handicap.
It seems clear that the orthopedic surgeon cannot separate impairment from disability. The measurement of impairment is clouded by the inability to measure dynamic function. A range of motion demonstrated by a patient in the doctor's office does not fully describe the functional potential of either the extremity or the spine. Moreover, the rules by which disability is defined are interpreted with a natural sympathy of the physician's care for the patient. The physician may have less sympathy if the individual being reviewed is a client of an insurance company or of an attorney, compared to being a "private" patient. In the future, the orthopedic surgeon would focus on the musculoskeletal handicap rather than disability, or function rather than impairment. Function must be measured in a dynamic manner. The guidelines for definition of function or dysfunction should be similar to those used in sports medicine regarding the decision as to when the athlete can resume sports. What was the capacity before injury? How close to the normal capacity has medical care restored function? This includes measurements of passage of time and consideration of the desire to return to previous activity. The goal is the development of methods that will accurately measure dynamic musculoskeletal function. Visceral organ systems have biochemical standards of measurement; comparable standards must be devised for the musculoskeletal system.


A randomized controlled trial of asthma self-management support comparing clinic-based nurses and in-home community health workers: the Seattle-King County Healthy Homes II Project.
To compare the marginal benefit of in-home asthma self-management support provided by community health workers (CHWs) with standard asthma education from clinic-based nurses. Randomized controlled trial. Community and public health clinics and homes. Three hundred nine children aged 3 to 13 years with asthma living in low-income households. All participants received nurse-provided asthma education and referrals to community resources. Some participants also received CHW-provided home environmental assessments, asthma education, social support, and asthma-control resources. Asthma symptom-free days, Pediatric Asthma Caretaker Quality of Life Scale score, and use of urgent health services. Both groups showed significant increases in caretaker quality of life (nurse-only group: 0.4 points; 95% confidence interval [CI], 0.3-0.6; nurse + CHW group: 0.6 points; 95% CI, 0.4-0.8) and number of symptom-free days (nurse only: 1.3 days; 95% CI, 0.5-2.1; nurse + CHW: 1.9 days; 95% CI, 1.1-2.8), and absolute decreases in the proportion of children who used urgent health services in the prior 3 months (nurse only: 17.6%; 95% CI, 8.1%-27.2%; nurse + CHW: 23.1%; 95% CI, 13.6%-32.6%). Quality of life improved by 0.22 more points in the nurse + CHW group (95% CI, 0.00-0.44; P = .049). The number of symptom-free days increased by 0.94 days per 2 weeks (95% CI, 0.02-1.86; P = .046), or 24.4 days per year, in the nurse + CHW group. While use of urgent health services decreased more in the nurse + CHW group, the difference between groups was not significant. The addition of CHW home visits to clinic-based asthma education yielded a clinically important increase in symptom-free days and a modest improvement in caretaker quality of life.


Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk.
The paramyxovirus hemagglutinin-neuraminidase (HN) protein plays multiple roles in viral entry and egress, including binding to sialic acid receptors, activating the fusion (F) protein to activate membrane fusion and viral entry, and cleaving sialic acid from carbohydrate chains. HN is an oligomeric integral membrane protein consisting of an N-terminal transmembrane domain, a stalk region, and an enzymatically active neuraminidase (NA) domain. Structures of the HN NA domains have been solved previously; however, the structure of the stalk region has remained elusive. The stalk region contains specificity determinants for F interactions and activation, underlying the requirement for homotypic F and HN interactions in viral entry. Mutations of the Newcastle disease virus HN stalk region have been shown to affect both F activation and NA activities, but a structural basis for understanding these dual affects on HN functions has been lacking. Here, we report the structure of the Newcastle disease virus HN ectodomain, revealing dimers of NA domain dimers flanking the N-terminal stalk domain. The stalk forms a parallel tetrameric coiled-coil bundle (4HB) that allows classification of extensive mutational data, providing insight into the functional roles of the stalk region. Mutations that affect both F activation and NA activities map predominantly to the 4HB hydrophobic core, whereas mutations that affect only F-protein activation map primarily to the 4HB surface. Two of four NA domains interact with the 4HB stalk, and residues at this interface in both the stalk and NA domain have been implicated in HN function.