ED Assembly: Introducing a Simple Method of Bringing Emergency Department Staff Together to Facilitate Improvement; A Report of a Real Experience.
The emergency department (ED) at Ashford and St Peter's Hospitals NHS Foundation Trust (ASPH) is a medium size department which sees around 260-300 patients per day. As a result of sustained demand, we continue to struggle to meet the four hour waiting target and face similar challenges of those of ED's nationally. Working in a busy ED is challenging and demanding. specific challenges around communication and risks arise directly from the unique contextual demands of the ED environment. Aim being to improve the productivity of the ED team and find a mechanism to create a more supportive and enjoyable working environment within the department. Our clinical leadership started looking for answer to improve communication among team members and to create a platform where there was no hierarchy and all team members could be directly involved in problem solving. With the support of the quality improvement (QI) team, ED assembly was born.The assembly is a simple method of regularly bringing together staff to facilitate improvement and better team working. It is a platform for effective communication and innovation, in which there is no hierarchy and everyone is encouraged to contribute. The assembly runs to a routine; every other Wednesday at 11am, the team come together for just half an hour. The agenda is set by the team in advance and everyone is encouraged to contribute their ideas and items they wish to contribute to others. Here are some examples of the quality improvement initiatives that have been born out of ED assembly: ED board rounds, coding information, overdose proforma, timely completion of standard investigations, access to fracture clinic appointments, nil-by-mouth communication, safety huddles, patient safety and sepsis, inclusive improvement, adoption of the ED assembly model by other teams and etc. ED assembly has supported many small but effective QI initiatives and regular communications support timely feedback on progress and update on plan-do-study-act (PDSA) cycles, resulting in changes in the everyday practice and improved pathways of patient care.


Severe cutaneous reactions among American travelers using pyrimethamine-sulfadoxine (Fansidar) for malaria prophylaxis.
In 1982, the fixed combination of pyrimethamine and sulfadoxine (Fansidar) became available in the United States, and was recommended for use in travelers at risk of acquiring chloroquine-resistant Plasmodium falciparum. Prior to that time, no reports of severe cutaneous reactions had appeared in the medical literature despite widespread use for more than 8 years in both Europe and malarious areas of the developing world. In the fall of 1984, the Centers for Disease Control received reports of 4 cases of toxic epidermal necrolysis (including 3 fatalities) among Americans who had used pyrimethamine-sulfadoxine (PYR/SDX) for the prevention of malaria. Subsequent investigation into severe cutaneous reactions associated with the use of this drug by American travelers detected 24 cases of erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis. Twenty-three of the 24 patients concurrently used chloroquine. Seven patients died. No risk factors in the development of these reactions other than the use of PYR/SDX could be identified. Among American travelers, we estimate that these reactions occur in 1 per 5,000-8,000 users, and that fatal reactions occur in 1 per 11,000-25,000 users. This higher than expected incidence necessitates that the use of PYR/SDX for the prevention of malaria be reconsidered. In the United States it is now recommended that the routine weekly use of the drug be reserved for those travelers at highest risk of acquiring chloroquine-resistant P. falciparum, when alternate prophylactic regimens are not deemed appropriate.


Milk peptides and blood pressure.
Epidemiological studies suggest that milk consumption and dietary intake of dairy proteins are inversely related to the risk for hypertension. Also, some intervention studies have shown a blood pressure-lowering effect of milk products and dairy proteins. Milk peptides are formed from milk proteins by enzymatic breakdown by digestive enzymes or by the proteinases formed by lactobacilli during the fermentation of milk. Several milk peptides have been shown to have antihypertensive effects in animal and in clinical studies. The most studied mechanism underlying the antihypertensive effects of milk peptides is inhibition of angiotensin-converting enzyme. Milk peptides may also have other additional mechanisms to lower blood pressure such as opioid-like activities and mineral-binding and antithrombotic properties. The future challenge is to identify the antihypertensive components in milk and their mechanisms of action and thus to find more possibilities for using these constituents and products as a dietary treatment of hypertension.


Characterisation and Antibiotic Susceptibility Profile of Clostridioides (Clostridium) Difficile Isolated from Chicken Carcasses.
Clostridioides (Clostridium) difficile is a Gram+, anaerobic, spore-forming, rod-shaped bacterium that can produce toxins, and it is mainly because its virulence is attributed. The objective of this study was to evaluate the presence of C. difficile and hyper virulent ribotypes in chicken carcasses and the antibiotic susceptibility of isolated strains. C. difficile was isolated from chicken carcasses by microbiological methods, its ribotypes were identified by means of PCR, the toxin production ability was defined by ELISA, and the susceptibility of the isolates to selected antibiotics was determined by minimum inhibitory concentration evaluator strips. The bacterium was isolated from 69 out of 185 (37.3%) examined chicken carcass samples, and six out of the 69 (8.7%) isolates were identified as ribotype 027. All isolates were susceptible to amoxicillin-clavulanic acid (100.0%), vancomycin (97.1%), metronidazole (88.4%), and tetracycline (95.7%), whereas they were resistant to cefotaxime (97.1%) and imipenem (89.9%). The results of this study demonstrate the presence of toxigenic C. difficile isolates such as ribotype 027 (one of the most common causes of C. difficile infection in humans) in chicken carcasses. Although there is no case for stating that C. difficile is a food-borne pathogen, the presence of C. difficile in chicken may be considered to be a potential risk to consumers.


Factors affecting the lactate dehydrogenase isoenzyme pattern of cultured kidney-cortex cells.
1. The lactate dehydrogenase isoenzyme pattern of cultured calf kidney-cortex cells was correlated to growth phase, changes in oxygen supply, mean generation time and changes in nutritional supply. 2. During culture of free cells and intact explants the lactate dehydrogenase isoenzyme pattern changed towards a dominance of isoenzymes containing the M subunit. 3. Of the shift in monomer proportion, 58% occurred during the lag phase and 42% during the initial part of the exponential growth phase. During the stationary phase the shift in monomer proportion reversed slightly. It was possible to relate the observed shift in monomer proportion to the glycolytic rate. 4. Factors that depressed glycolysis decreased the shift in monomer proportion. Oxygen was found to limit the decrease in the H subunit/M subunit ratio caused by anaerobic culture in vitro. 5. The results obtained support the view that the altered lactate dehydrogenase isoenzyme pattern of urine in renal ischaemia may be explained by anaerobic changes in the lactate dehydrogenase isoenzyme pattern of cortical tubule cells.


Acute fatal coronary artery dissection following exercise-related blunt chest trauma.
Coronary artery injury such as acute coronary dissection is an uncommon and potentially life-threatening complication after blunt chest trauma. The authors report an unusual autopsy case of a 43-year-old healthy man who suddenly collapsed after receiving a punch to the chest during the practice of kung fu. The occurrence of the punch was supported by the presence of one recent contusion on the left lateral chest area at the external examination and by areas of hemorrhage next to the left lateral intercostal spaces at the internal examination. The histological examination revealed the presence of an acute dissection of the proximal segment of the left anterior descending coronary artery. Only few cases of coronary artery dissection have been reported due to trauma during sports activities such as rugby and soccer games, but never during the practice of martial arts, sports usually considered as safe and responsible for only minor trauma.


Echocardiographic design of a multicenter investigation of free-living elderly subjects: the Cardiovascular Health Study.
The Framingham study has shown by M-mode echocardiography that left ventricular hypertrophy is a powerful, independent predictor for the development of coronary heart disease and that increased left atrial dimension has been associated with an increased risk of stroke. No previous population-based study has evaluated the risk factor correlates and predictive value for coronary heart disease and stroke of two-dimensional and Doppler, as well as M-mode, echocardiography. The Cardiovascular Health Study is a multi-year prospective epidemiologic study of 5201 men and women older than 65 recruited from four geographic sites in the United States. The main objectives of incorporating echocardiography were to determine whether echocardiographic indices, or changes in these indices, are (1) correlated with traditional risk factors for coronary heart disease and stroke; and (2) independent predictors of morbidity and mortality for coronary heart disease and stroke. Echocardiographic measurements of interest include those related to global and segmental left ventricular systolic and diastolic structure and function and left atrial size. For each subject, a baseline echocardiogram was recorded in super-VHS tape using a standard protocol and equipment. All studies were sent to a reading center where images were digitized and measurements were made using customized computer algorithms. Calculated data and images were stored on optical disks to facilitate retrieval and future comparisons in longitudinal studies. A second echocardiogram is scheduled in year 7, with a goal of determining whether changes in cardiac anatomy or function over a 5-year period are important predictors of morbidity or mortality from coronary heart disease and stroke. Quality control measures included standardized training of echocardiography technicians and readers, technician observation by a trained echocardiographer, periodic blind duplicate readings with reader review sessions, phantom studies, and quality control adults.


Use of palivizumab in primary practice.
To describe the implementation of a program for the use of palivizumab in a general pediatrics office and evaluate adherence to the 2009 American Academy of Pediatrics (AAP) guidelines. Pediatricians in a large practice were educated in the diagnosis and management of bronchiolitis, with specific attention to the AAP's palivizumab administration guidelines. During the 2009-2010 and 2010-2011 respiratory syncytial virus seasons, children were systematically identified and enrolled for palivizumab administration. Indication for administration was determined by gestational age, age at the beginning of the respiratory syncytial virus season, pertinent diagnoses, and presence of risk factors. In the 2009-2010 season, 161 children were enrolled to receive palivizumab, 86 of whom (53%) conformed with AAP guidelines. In contrast, in 2010-2011, a total of 85 children were enrolled to receive palivizumab, and 73 (86%) conformed with the guidelines. As a consequence, the total cost of palivizumab (US $: 511 559 vs 1 500 670) and the cost per child (US $: 6018 vs 9438) were lower in 2010-2011 than in 2009-2010. However, of the children selected within the AAP guidelines, only 29% received the appropriate number of doses, whereas 62% and 9% received fewer or excessive doses, respectively; these findings were similar for the 2 seasons. In a primary practice, use of palivizumab outside of the AAP guidelines was frequent and manifested as inadequate indications or inadequate number of doses. The former improved with education and standardization of care (suggesting provider problems), while the latter did not (suggesting system problems). Additional interventions are required.


[Serum angiotensin converting enzyme in the diagnosis of sarcoidosis and other lung diseases].
The serum angiotensin-converting enzyme activity (ACE) was studied in 198 patients (116 had sarcoidosis and 82 pulmonary diseases with sarcoidosis-like X-ray picture). Rise of ACE activity in sarcoidosis patients was clearly associated with the process phase (93% in active sarcoidosis and 35.7% in nonactive). Rise of serum ACE activity was found in 46.3% of the patients having sarcoidosis-like diseases (in 41% with tuberculosis 56.3% with nonspecific inflammatory diseases and also in patients with fibrosing alveolitis, histiocytosis X and pneumoconiosis). Though the blood serum ACE activity has a high rate of the increase in sarcoidosis, this test should be considered only in the general complex of differential diagnosis signs. This can be explained by a sufficiently high probability of ACE activity rise in all diseases that most commonly require differentiation with sarcoidosis.


Reducing classroom temperature in a tropical climate improved the thermal comfort and the performance of elementary school pupils.
A two-week-long intervention study was performed in two classrooms in an elementary school in Costa Rica. Split-cooling air-conditioning (AC) units were installed in both classrooms. During the first week, the air temperature was reduced in one classroom while in the other (placebo) classroom the fans were operated but no cooling was provided. During the second week, the conditions were exchanged to create a 2 × 2 crossover design in which each pupil was their own control. A total of 37 children performed tasks similar to school work and completed questionnaires reporting their thermal sensation and perceptions. Operating the AC units reduced classroom temperature by about 5 K, from about 30 to 25°C. Thermal sensations changed from hot to neutral and slightly cold, and the percentage of children rating the thermal conditions as acceptable increased significantly. Neutral temperature was estimated to be about 27°C. The 11-year-old children performed the language and logical-thinking tasks significantly better in terms of speed at the lower temperature, while the less able pupils performed better on all tasks at the lower temperature. There were no significant effects on accuracy. These results confirm published findings from moderate climates and extend their validity to the tropics. They indicate that acclimatization can increase the optimal temperature for learning.


Rapid Screening of CAR T Cell Functional Improvement Strategies by Highly Multiplexed Single-Cell Secretomics.
The functional fitness of CAR T cells plays a crucial role in determining their clinical efficacy. Several strategies are being explored to increase cellular fitness, but screening these approaches in vivo is expensive and time-consuming, limiting the number of strategies that can be tested at one time. The presence of polyfunctional CAR T cells has emerged as a critical parameter correlating with clinical responses. However, even sophisticated multiplexed secretomic assays often fail to detect differences in cytokine release due to the functional heterogeneity of CAR T cell products. Here, we describe a highly multiplexed single-cell secretomic assay based on the IsoLight platform to rapidly evaluate the impact of new pharmacologic or gene-engineering approaches aiming at improving CAR T cell function. As a key study, we focus on CD19-specific CAR CD8+ T cells modulated by miR-155 overexpression, but the protocol can be applied to characterize other functional immune cell modulation strategies.


Mitochondrial morphology in the mouse adrenal cortex: Influence of chronic psychosocial stress.
Mitochondria within the adrenal cortex play a key role in synthesizing steroid hormones. The adrenal cortex is organized in three functionally specialized zones (glomerulosa, fasciculata, and reticularis) that produce different classes of steroid hormones in response to various stimuli, including psychosocial stress. Given that the functions and morphology of mitochondria are dynamically related and respond to stress, we applied transmission electron microscopy (TEM) to examine potential differences in mitochondrial morphology under basal and chronic psychosocial stress conditions. We used the chronic subordinate colony housing (CSC) paradigm, a murine model of chronic psychosocial stress. Our findings quantitatively define how mitochondrial morphology differs among each of the three adrenal cortex zones under basal conditions, and show that chronic psychosocial stress mainly affected mitochondria in the zona glomerulosa, shifting their morphology towards the more typical glucocorticoid-producing zona fasciculata mitochondrial phenotype. Analysis of adrenocortical lipid droplets that provide cholesterol for steroidogenesis showed that chronic psychosocial stress altered lipid droplet diameter, without affecting droplet number or inter-organellar mitochondria-lipid droplet interactions. Together, our findings support the hypothesis that each adrenal cortex layer is characterized by morphologically distinct mitochondria and that this adrenal zone-specific mitochondrial morphology is sensitive to environmental stimuli, including chronic psychosocial stressors. Further research is needed to define the role of these stress-induced changes in mitochondrial morphology, particularly in the zona glomerulosa, on stress resilience and related behaviors.


Effect of intravenous ascorbic acid in hemodialysis patients with EPO-hyporesponsive anemia and hyperferritinemia.
Although erythropoietin (EPO)-hyporesponsive anemia in hemodialysis patients most commonly results from iron deficiency, the contributory role of chronic inflammation and oxidative stress in its pathogenesis is poorly understood. We conducted an open-label prospective study to assess the effect of vitamin C, an antioxidant, on EPO-hyporesponsive anemia in hemodialysis patients with unexplained hyperferritinemia. Forty-six of 262 patients in an inner-city hemodialysis center met the inclusion criteria (administration of intravenous iron and EPO for > or = 6 months at a dose > or = 450 U/kg/wk, average 3-month hemoglobin [Hb] level < or = 11.0 g/dL [< or = 110 g/L], ferritin level > or = 500 ng/mL (microg/L), and transferrin saturation [TSAT] < or = 50%). Patients were excluded if they had a clear explanation for the EPO hyporesponsiveness. Four patients refused to participate. The remaining patients were randomly assigned; 20 patients to receive standard care and 300 mg of intravenous vitamin C with each dialysis session (group 1) and 22 patients to receive standard care only (group 2). Study duration was 6 months. During the study, 1 patient from group 1 was removed (upper gastrointestinal bleeding) from final analysis. Monthly assessment included Hb level, mean corpuscular volume, iron level, iron-binding capacity, ferritin level, TSAT, and Hb content in reticulocytes. In addition, biointact parathyroid hormone, aluminum, C-reactive protein (CRP), and liver enzymes were measured every 3 months. Age, sex, race, and time on dialysis therapy were similar in both groups. At 6 months, Hb levels significantly increased from 9.3 to 10.5 g/dL (93.0 to 105.0 g/L) in group 1, but not group 2 (9.3 to 9.6 g/dL [93.0 to 96.0 g/L]; P = 0.0001). Similarly, TSAT increased from 28.9% to 37.3% in group 1, but not group 2 (28.7% to 29.3%; P = 0.0001). EPO dose (477 to 429 versus 474 to 447 U/kg/wk), iron-binding capacity (216 to 194 versus 218 to 257 microg/dL [38.7 to 34.7 versus 39 to 46 micromol/L]), and CRP level (2.8 to 0.9 versus 2.8 to 2.2 mg/dL) decreased significantly in group 1, but not in controls. Changes in Hb content in reticulocytes and ferritin level also were statistically significant in group 1. There was no change in biointact parathyroid hormone levels. Although serum iron levels and intravenous iron doses changed within each group, changes were equal between the 2 groups. In hemodialysis patients with refractory anemia and hyperferritinemia, vitamin C improved responsiveness to EPO, either by augmenting iron mobilization from its tissue stores or through antioxidant effects.


Generalized synchronization in relay systems with instantaneous coupling.
We demonstrate the existence of generalized synchronization in systems that act as mediators between two dynamical units that, in turn, show complete synchronization with each other. These are the so-called relay systems. Specifically, we analyze the Lyapunov spectrum of the full system to elucidate when complete and generalized synchronization appear. We show that once a critical coupling strength is achieved, complete synchronization emerges between the systems to be synchronized, and at the same point, generalized synchronization with the relay system also arises. Next, we use two nonlinear measures based on the distance between phase-space neighbors to quantify the generalized synchronization in discretized time series. Finally, we experimentally show the robustness of the phenomenon and of the theoretical tools here proposed to characterize it.


Effect of calcium on transport characteristics of cultured proximal renal cells.
We examined the effects of acute changes in extracellular and intracellular calcium on transport processes in primary culture of proximal rabbit renal cells. A change in extracellular calcium from 0 to 3 mM inhibited amiloride-sensitive sodium uptake by 30%, and this effect was maximal at 1 mM calcium. Other polyvalent cations (Mn2+, Mg2+, La3+, and Ba2+) produced quantitatively similar inhibition of amiloride-sensitive sodium uptake compared with calcium. An increase in cytosolic calcium produced by calcium loading (20 mM) or by A23187 (20 microM) resulted in an inhibition of 25-40% of amiloride-sensitive sodium uptake. Moreover, quinidine (10(-4)M) and ruthenium red (3 microM), agents presumed to increase cytosolic calcium, inhibited amiloride-sensitive sodium uptake by 20-60%. Both these agents also inhibited sodium-dependent phosphate uptake by 20% but had no effect on ouabain-sensitive 86Rb+ uptake or on sodium-dependent alpha-methylglucoside uptake. Our data indicate that increases in extracellular calcium inhibit amiloride-sensitive sodium uptake and increases in cytosolic calcium inhibit sodium-dependent phosphate and amiloride-sensitive sodium uptakes. The effect of extracellular calcium may be due to charge screening and/or binding to the negatively charged plasma membrane or due to alterations in membrane fluidity.


Controlling chaos by GA-based reinforcement learning neural network.
This paper proposes a TD (temporal difference) and GA (genetic algorithm) based reinforcement (TDGAR) neural learning scheme for controlling chaotic dynamical systems based on the technique of small perturbations. The TDGAR learning scheme is a new hybrid GA, which integrates the TD prediction method and the GA to fulfill the reinforcement learning task. Structurely, the TDGAR learning system is composed of two integrated feedforward networks. One neural network acts as a critic network for helping the learning of the other network, the action network, which determines the outputs (actions) of the TDGAR learning system. Using the TD prediction method, the critic network can predict the external reinforcement signal and provide a more informative internal reinforcement signal to the action network. The action network uses the GA to adapt itself according to the internal reinforcement signal. This can usually accelerate the GA learning since an external reinforcement signal may only be available at a time long after a sequence of actions have occurred in the reinforcement learning problems. By defining a simple external reinforcement signal, the TDGAR learning system can learn to produce a series of small perturbations to convert chaotic oscillations of a chaotic system into desired regular ones with a periodic behavior. The proposed method is an adaptive search for the optimum control technique. Computer simulations on controlling two chaotic systems, i.e., the Hénon map and the logistic map, have been conducted to illustrate the performance of the proposed method.


Decreased interpretation of nonverbal cues in rape victims.
The ability to receive nonverbal facial cues was tested in twelve female victims of multiple nonserial rapes and matched controls. Subjects attempted to interpret nonverbal messages transmitted by male and female senders who were covertly taped while involved in a gambling task. Rape victims had significantly decreased ability to interpret the nonverbal facial cues of both male and female senders.


Measuring Social Isolation in the National Health and Aging Trends Study.
The objectives of the current study were to describe the development of a social isolation measure based on Berkman and Syme's Social Network Index domains with data from the National Health and Aging Trends Study. A descriptive correlational design was used, establishing convergent and divergent validity of the measure with depression risk and well-being. Depression risk was measured with the Patient Health Questionnaire-2 and an ordinal well-being measure was developed based on measures in MIDUS-Midlife in the U.S.-A Study of National Health and Well-Being. Participants who scored ≥4 (cutoff point) on the social isolation measure represented 21.9% (N = 7,609) of the sample (95% confidence interval [20.6, 23.3]). Spearman's correlation with depression was 0.23 (p < 0.001) and -0.24 (p ≤ 0.001) with well-being. The weighted data complex samples general linear model with depression (R = 0.22, p ≤ 0.001) and well-being (R = -0.26, p ≤ 0.001) confirm the relationships. This measure offers conceptual clarity and measurement consistency for developing the components and targets for future social isolation intervention research. [Res Gerontol Nurs. 2017; 10(6):277-287.].


Comparison of maternal blood and fetal liver selenium concentrations in cattle in California.
Selenium concentration was measured in paired maternal blood samples and fetal liver specimens collected at a San Joaquin County, Calif, slaughterhouse (beef = 19, dairy = 54) and from bovine aborted fetuses submitted to the California Veterinary Diagnostic Laboratory System (CVDLS; beef = 20, dairy = 20). Of the slaughterhouse samples and specimens, dairy maternal blood selenium concentration was significantly (P < 0.001) higher (mean +/- SD; 0.22 +/- 0.056 microgram/ml) than that for beef breeds (0.137 +/- 0.082 microgram/ml). The CVDLS mean maternal blood selenium concentration for the dairy-breed samples (0.192 +/- 0.028 microgram/ml) was similar to that for the slaughterhouse dairy-breed samples, but was greater than that for the slaughterhouse beef-breed samples. Slaughterhouse mean fetal liver selenium content also was higher (P < 0.001) for the dairy breeds (0.777 +/- 0.408 microgram/g), compared with the beef breeds (0.443 +/- 0.038 microgram/g). Mean fetal liver selenium content for slaughterhouse specimens was higher (P < 0.002) than that for the CVDLS specimens (beef, 0.244 +/- 0.149 microgram/g; dairy, 0.390 +/- 0.165 microgram/g). At the CVDLS, dairy fetal liver content was greater (P < 0.001) than that for beef breeds. Mean ratio of fetal liver selenium content to maternal blood selenium concentration was 3.53 +/- 1.89 for dairy breeds at the slaughterhouse (liver-to-blood correlation [r] = 0.38), and was 2.11 +/- 1.00 for dairy breeds at the CVDLS (r = 0.31) and 3.43 +/- 1.50 for beef breeds (r = 0.58). Both slaughterhouse breed ratios were significantly (P < 0.002) greater than the CVDLS dairy-breed ratio. On the basis of these results, breed and source location should be taken into account when interpreting selenium values. Fetal liver selenium content should only be used as a screening test and combined with whole blood selenium concentration from clinically normal herdmates to evaluate herd selenium status.


Real-time pickup method for a three-dimensional image based on integral photography.
We studied integral photography (IP), which creates three-dimensional autostereoscopic images. In particular we studied the possibility of a new method that uses a television camera to shoot directly numerous real images produced by a lens array. Unlike the conventional IP method in which the film is placed immediately behind a lens array, this method employs a television camera, which enables us to shoot moving pictures. Of a number of factors affecting the process of image pickup, we examined some optical factors and compared them with those obtained by the conventional IP method. The results show that with this new direct pickup method that uses a television camera, we can obtain an IP image like those obtained by using the conventional IP method. Further, we conducted an experiment with an high-definition TV camera, confirming the production of an autostereoscopic image by using a display device that combines a liquid-crystal panel and pinholes.


A new family of Greek origin maps to the CRD locus for autosomal dominant cone-rod dystrophy on 19q.
Retinal photoreceptor dystrophies (RD) are a highly heterogeneous group of genetic disorders of the retina, representing the most frequently inherited form of visual handicap, affecting approximately 1.5 million people world wide. To date, more than 40 genetic loci have been implicated in RD. One of them, the CORD2 locus, for an autosomal dominant form of cone-rod dystrophy (CRD), maps to chromosome 19q and has previously been reported in a single large family of British origin. We now report a new family with severe early onset CRD, phenotypically very similar to the British family, which also maps to 19q, but is of Greek origin. Haplotype data of the Greek family showed no recombination between and including markers D19S219 and D19S246 and linkage analysis gave a lod score of 2.7 (at theta=0) with marker D19S412, confirming the data obtained in the British family.


Neohesperidin dihydrochalcone is not a taste enhancer in aqueous sucrose solutions.
Neohesperidin dihydrochalcone (NHDC) is an intensive sweetener, obtained by alkaline hydrogenation of neohesperidin. In this investigation a supposed taste enhancing effect of this substance was tested. A three-step procedure was used. In the first experiment, using a pool of 31 subjects, NHDC and sucrose detection thresholds were measured. In the second experiment, psychophysical functions for both tastants were determined. Then, 15 participants closest to the group threshold who, in addition, had produced monotonic psychophysical taste functions were selected to participate in the next two experiments. In the third experiment, taste enhancement was tested. Three psychophysical sucrose functions were constructed, one with a near-threshold amount of NHDC added to each of seven sucrose concentrations, one with a near-threshold amount of sucrose added (control 1) and one without any addition (control 2). No difference was found between the NHDC-enriched sucrose function and the sucrose-enriched sucrose function. Finally, in experiment 4, differential threshold functions were constructed with either NHDC or sucrose added. Neither the overall shape of the functions nor a comparison of the points of subjective equality showed enhancement. It was concluded that weak NHDC does not enhance the taste of aqueous sucrose solutions.


Increased radiosensitivity of a subpopulation ot T-lymphocyte progenitors from patients with Fanconi's anemia.
In vitro radiation survival of peripheral blood T lymphocytes was studied in 15 clinically normal adults and 4 patients with Fanconi's anemia. Tritiated thymidine incorporation in a whole blood lymphocyte stimulation test (LST) and a newly developed whole blood T-lymphocyte colony assay were used to measure lymphocyte blastogenesis and colony formation in response to phytohemagglutinin (PHA) or concanavalin-A (Con-A) stimulation. Lymphocyte colony formation was found to be consistently more sensitive than the LST for detection of low-level radiation effects using both normal cells and lymphocytes from Fanconi's anemia patients. Lymphocytes from patients with Fanconi's anemia were significantly more sensitive to in vitro x-irradiation than lymphocytes from clinically normal individuals as measured by their ability to divide when stimulated by PHA in the LST (patients, D37 = 198 R; normals, D37 = 309 R, p = 0.057) and colony formation assay (patients, D37 = 53 R; normals, D37 = 109 R, p = 0.016). No significant difference in the radiosensitivity of the Con-A response was observed between the two groups. The PHA-responsive T-lymphocyte subpopulation in Fanconi's anemia patients appears to be intrinsically defective. The nature of this defect, significance in the disease process, and relevancy of these findings to the establishment of radiation protection standards are discussed.


Clinical Predictors of Incomplete ST-Segment Resolution in the Patients With Acute ST Segment Elevation Myocardial Infarction.
The failure of ST-segment resolution (STR) after primary percutaneous coronary intervention (pPCI) is associated with adverse clinical outcomes. However, the clinical predictors on admission for incomplete STR are poorly known. Patients undergoing pPCI (n=101, 79 males and 22 females, mean age 60.0 years) were divided into complete STR group (>/=70%, n=58) and incomplete STR group (<70%, n=43). The groups were compared according to clinical factors including history, electrocardiographic (ECG) patterns, angiographic features and laboratory data. The incomplete STR group contained more frequent hypertensive patients (p=0.04) and patients displaying longer tendency in total chest pain duration (p=0.08). This group was associated with worse clinical factors such as low ejection fraction (p=0.06), higher Killip class (p=0.08) and more death (p=0.042). Grade 3 ischemia pattern of ECG and precordial ST elevation (i,e anterior myocardial infarction) at admission were more frequent in the incomplete STR group (p=0.001 and 0.002, respectively). Initial troponin I, creatinin kinase -MB and brain natriuretic peptide levels were higher in the incomplete STR group (p=0.001, 0.002, and 0.043, respectively). Coronary angiography showed that culprit lesions were more frequent in left anterior descending artery than other arteries in the incomplete STR group of patients (p=0.002). Thrombolysis In Myocardial Infarction (TIMI) flow grades 2 or less before PCI was more frequent in the incomplete STR group (p=0.029). However, TIMI flow grade after PCI was not appreciably different between the two groups. Logistic regression analysis demonstrated that TIMI flow grade 2 or less was most powerful predictor for incomplete STR {odds ratio (OR)=12.12, 95% confidence interval (CI) 1.23-119.35, p=0.032}. Other independent predictors were anterior infarction (OR=3.39, CI 1.46-10.57, p=0.007), ischemia grade 3 ECG at admission (OR=3.87, CI 1.31-11.41, p=0.014), and hypertensive patients (OR=3.03, CI 1.13-8.15, p=0.027). Incomplete STR after pPCI is associated with poor prognostic clinical factors. TIMI flow grade 2 or less before pPCI, ST elevation on precordial leads, ischemia grade 3 pattern of initial ECG, and hypertensive patients are independent predictors for incomplete STR in the early stage.


Entrapment of Water at the Transmembrane Helix-Helix Interface of Quiescin Sulfhydryl Oxidase 2.
Little is known about how a membrane can regulate interactions between transmembrane helices. Here, we show that strong self-interaction of the transmembrane helix of human quiescin sulfhydryl oxidase 2 rests on a motif of conserved amino acids comprising one face of the helix. Atomistic molecular dynamics simulations suggest that water molecules enter the helix-helix interface and connect serine residues of both partner helices. In addition, an interfacial tyrosine can interact with noninterfacial water or lipid. Dimerization of this transmembrane helix might therefore be controlled by membrane properties controlling water permeation and/or by the lipid composition of the membrane.


[Biochemical selenocysteine synthesis and the phylogenic study].
Selenium (Se) is an essential trace element. Se is found as selenocysteine (Sec) in Se-proteins. Sec is the 21(st) amino acid, because Sec has its tRNA, the codon UGA and those components in its translational machinery. Sec UGA codon shares with major stop codon UGA. We purified Sec synthesizing enzymes, such as seryl-tRNA synthetase (SerRS), Sec synthetase (SecS) and selenophosphate synthetase (SePS). I described the procedures to prepare Sec tRNA, SerRS, SecS, SePS and [(75)Se]H(2)Se in detail. We clarified that SecS composed of two proteins, SecSalpha and SecSbeta. Sec synthesizing and incorporating systems present in Monela, Animalia and Protoctista but not in Plantae and Fungi. We showed that protozoa had Sec tRNA on which Sec was synthesized from Ser-tRNA by bovine and protozoa SecS. Some worms, such as Caenorhabditis elegans and Fasiola gigantica, also had Sec tRNA on which Sec was synthesized by bovine liver SecS or C. elegans enzymes. We showed recognition sites of mammalian Sec tRNA by SecS. The identity units of Sec tRNA are 9 bp aminoacyl- and 6 bp D-stems. This recognition is not the base-specific manner but the length-specific manner. From comparison of the phylogeny trees of Sec synthesizing system and translation system, we concluded that the evolution of Sec synthesizing system is older than that of the translation system.


Latent transforming growth factor-β binding proteins (LTBP-1 and LTBP-2) and gingiva keratinization.
Transforming growth factor-beta (TGF-β) proteins are involved in epithelial keratinization. The major function of latent TGF-β binding proteins (LTBPs) is modulating TGF-β activity. However, whether LTBP-1 and LTBP-2 play roles in gingiva keratinization remains unclear. Human keratinized gingiva and non-keratinized alveolar mucosa were processed for LTBP-1, LTBP-2, cytokeratin-1 (K1), cytokeratin-4 (K4), and TGF-β immunohistochemical (IHC) staining. Porcine heterotopically transplanted connective tissues and newly grown epithelia were harvested for IHC staining. The expression levels of LTBP-1 and LTBP-2 were compared between differentiated and undifferentiated human normal oral keratinocytes (hNOK). The expression of LTBP-1 and LTBP-2 was knocked down in a cell line (OEC-M1) to evaluate the effects on the expression of K1, K4, and involucrin (INV). In human and porcine specimens, LTBP-2 expression patterns distinguished keratinized and non-keratinized oral epithelia. Western blotting results showed that K1, LTBP-1, and INV proteins were upregulated in differentiated hNOK. In OEC-M1 cells, LTBP-2 knockdown resulted in upregulated the expression of K1 and INV and downregulated the expression of K4. LTBP-1 knockdown resulted in opposite effects. The expression patterns of LTBP-2 differ in keratinized gingiva and non-keratinized mucosa. LTBP-1 and LTBP-2 are involved in the keratinization of oral epithelium; however, the underlying mechanism remains to be elucidated.


Autologous minced muscle grafts improve endogenous fracture healing and muscle strength after musculoskeletal trauma.
The deleterious impact of concomitant muscle injury on fracture healing and limb function is commonly considered part of the natural sequela of orthopedic trauma. Recent reports suggest that heightened inflammation in the surrounding traumatized musculature is a primary determinant of fracture healing. Relatedly, there are emerging potential therapeutic approaches for severe muscle trauma (e.g., volumetric muscle loss [VML] injury), such as autologous minced muscle grafts (1 mm3 pieces of muscle; GRAFT), that can partially prevent chronic functional deficits and appear to have an immunomodulatory effect within VML injured muscle. The primary goal of this study was to determine if repair of VML injury with GRAFT rescues impaired fracture healing and improves the strength of the traumatized muscle in a male Lewis rat model of tibia open fracture. The most salient findings of the study were: (1) tibialis anterior (TA) muscle repair with GRAFT improved endogenous healing of fractured tibia and improved the functional outcome of muscle regeneration; (2) GRAFT repair attenuated the monocyte/macrophage (CD45+CDllb+) and T lymphocyte (CD3+) response to VML injury; (3) TA muscle protein concentrations of MCP1, IL-10, and IGF-1 were augmented in a proregenerative manner by GRAFT repair; (4) VML injury concomitant with osteotomy induced a heightened systemic presence of alarmins (e.g., soluble RAGE) and leukocytes (e.g., monocytes), and depressed IGF-1 concentration, which GRAFT repair ameliorated. Collectively, these data indicate that repair of VML injury with a regenerative therapy can modulate the inflammatory and regenerative phenotype of the treated muscle and in association improve musculoskeletal healing.


National Kidney Foundation Laboratory Engagement Working Group Recommendations for Implementing the CKD-EPI 2021 Race-Free Equations for Estimated Glomerular Filtration Rate: Practical Guidance for Clinical Laboratories.
Recognizing that race is a social and not a biological construct, healthcare professionals and the public have called for removal of race in clinical algorithms. In response, the National Kidney Foundation and the American Society of Nephrology created the Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Diseases to examine the issue and provide recommendations. The final report from the Task Force recommends calculating estimated glomerular filtration rate (eGFR) without a race coefficient using the recently published CKD-EPI 2021 creatinine (cr) and creatinine-cystatin C (cr-cys) equations. The Task Force recommends immediately replacing older eGFRcr equations (MDRD Study and CKD-EPI 2009) with the new CKD-EPI 2021 equation. In a 2019 survey by the College of American Pathologists, 23% of 6200 laboratories reporting eGFRcr used an incorrect equation that is not suitable for use with standardized creatinine measurements, 34% used the CKD-EPI 2009 equation and 43% used the MDRD Study 2006 equation re-expressed for standardized creatinine measurement. Rapid transition to using the CKD-EPI 2021 equation is an opportunity for laboratories to standardize to a single equation to eliminate differences in eGFRcr due to different equations used by different laboratories, and to report eGFR without use of race. We provide guidance to laboratories for implementing the CKD-EPI 2021 equations for both eGFRcr and eGFRcr-cys.


The role of the lens in pigment dispersion syndrome.
In patients with pigment dispersion syndrome, changes of the iris configuration can occur with accommodation, blinking, miotics, and following a laser iridotomy. This observational case series looks at the changes following cataract surgery in 3 eyes with signs of pigment dispersion, symptomatic cataracts, and no previous laser iridotomy that were imaged with optical coherence tomography. The iris was concave posteriorly in dark and light lighting conditions, and became flat following an uncomplicated cataract operation. This may be explained by the elimination of iridolenticular contact, which contributes to the mechanism of reverse pupil block. These iris changes suggest the lens plays an important role in the mechanism of pigment dispersion.


[Aliphatic alcohol sulfates: new polar lipids isolated from various Fucacea].
Four new sulfolipids have been found in the three Fucacea from the coast of Britany P. canaliculata (L) Deen et Thur, F. vesiculosus (L), F. serratus (L). These four polar lipids form a separate group, their structures being very different from those of the glyceride by-products already known. By acid hydrolysis of these substances the aliphatic mono and dialcohols can be separated. The aliphatic hydrocarbons studied by gas chromatography and spectrometric methods (IR, MASS), have been established as being saturated C30 mono or dialcohols, saturated C18 and C20 monoinsaturated dialcohols. SAA are the only substances found: there was no sulfonate or phosphate ester in the three algae studied. The quantity and composition of SAA are not characteristic of the species. Their variations depend on the physiological and biochemical states of the thallus and on the conditions of extraction and purification.


The effects of multiaxial and uniaxial unstable surface balance training in college athletes.
The purpose of this study was to compare the effects of 2 different types of unstable surface balance training (uniaxial on a rocker board [RB] and multiaxial on a dynadisc [DD]) on balance in division 1 collegiate athletes in sports that are at high risk for ankle sprains. Subjects (n = 36) consisted of male soccer players and female volleyball and soccer players who were equally and randomly assigned to 1 of 3 groups (CON, DD, and RB). Balance training consisting of balancing on 1 leg on either the RB or DD, while repeatedly catching a 1-kg ball was performed 3 times per week for 4 weeks. Balance was tested with the Star Excursion Balance Test (SEBT) before, halfway through, and at the completion of the balance training. Control (CON) subjects also were given the balance test but did not participate in the training. A 3-way repeated analysis of variance revealed that no group individually changed SEBT scores from pre (CON, 0.98 +/- 0.086; DD, 0.98 +/- 0.083; RB, 0.97 +/- 0.085) to post (CON, 1.00 +/- 0.090; DD, 1.01 +/- 0.088; RB, 1.02 +/- 0.068) after balance training. When the 2 treatment groups were combined (DD and RB), the p value decreased and came closer to significance (p = 0.136). When all 3 groups were combined, there was a significant difference in SEBT scores from pretraining (CON + DD + RB; 0.98 +/- 0.085) to posttraining (CON + DD + RB; 1.01 +/- 0.082), which likely indicates low statistical power. The increase in physical activity the subjects experienced during the return to in-season activity, may have contributed to the significant differences in SEBT scores over time but not between DD or RB training. Therefore, a threshold level of physical activity may exist that is necessary to maintain balance during the off-season.


[Cloning and tissue expression of CAST transcript Ⅱ in goat].
Calpastatin (CAST) gene is closely related with meat quality in livestock and poultry. Based on the bovine and ovine mRNA sequences, the cDNA of CAST Ⅱ gene in goat was amplified successfully for the first time by using RACE-PCR. Results showed that CAST Ⅱ of goat was 2474 bp in length with an open reading frame (ORF) 1695 bp long and encoded 564 amino acids, and there were four conserved domains and one conserved seven-peptide domain in amino acids sequences. Bioinformation analysis indicated that its secondary structures mainly were random coil and helical regions, and contained rich hydrophobic regions, certain phosphorylation sites, and protein kinase C (PKC) sites. Meanwhile, analysis of tissue expression of the gene in Tianfu meat goat demonstrated it was expressed in seven selected tissues. When the goat was of 6-month age, the highest expression was observed in longissimusdorsi, which was significantly higher than that of crureus (P<0.05) and other internal organ tissues (P<0.01).Furthermore, the expression of CAST II increased with the rise of the age and became the highest when the goat was at three-year age.


Digital divide: variation in internet and cellular phone use among women attending an urban sexually transmitted infections clinic.
We sought to describe: (1) the prevalence of internet, cellular phone, and text message use among women attending an urban sexually transmitted infections (STI) clinic, (2) the acceptability of health advice by each mode of information and communication technology (ICT), and (3) demographic characteristics associated with ICT use. This study is a cross-sectional survey of 200 English-speaking women presenting to a Baltimore City STI clinic with STI complaints. Participants completed a self-administered survey querying ICT use and demographic characteristics. Three separate questions asked about interest in receiving health advice delivered by the three modalities: internet, cellular phone, and text message. We performed logistic regression to examine how demographic factors (age, race, and education) are associated with likelihood of using each modality. The median age of respondents was 27 years; 87% were African American, and 71% had a high school diploma. The rate of any internet use was 80%; 31% reported daily use; 16% reported weekly use; and 32% reported less frequent use. Almost all respondents (93%) reported cellular phone use, and 79% used text messaging. Acceptability of health advice by each of the three modalities was about 60%. In multivariate analysis, higher education and younger age were associated with internet use, text messaging, and cellular phone use. Overall rate of internet use was high, but there was an educational disparity in internet use. Cellular phone use was almost universal in this sample. All three modalities were equally acceptable forms of health communication. Describing baseline ICT access and the acceptability of health advice via ICT, as we have done, is one step toward determining the feasibility of ICT-delivered health interventions in urban populations.


The effect of contraction and Ca2+ removal on the indomethacin-induced increase in tracheal smooth muscle reactivity.
The effect of contraction and Ca2+ on the indomethacin mediated increased tracheal reactivity to histamine was studied in swine isolated tracheal smooth muscle. The potentiating effect of indomethacin was not directly related to the size of muscle contraction. Histamine, but not acetylcholine-induced contractions were partially inhibited in a zero-Ca2+ Krebs solution and almost abolished in zero-Ca2+ Krebs solution containing 0.1 mM EGTA. Indomethacin potentiated histamine but not acetylcholine-induced contractions in the zero-Ca2+ medium. Re-addition of Ca2+ ions caused a further potentiation of the histamine-induced response. The histamine response with indomethacin when EGTA was present was further reduced. Indomethacin had no effect on Ca2+-contractures of tissues bathed in zero-Ca2+ solution containing 80 mM K+. The results demonstrate that histamine-induced tone is largely dependent on labile Ca2+, whereas its potentiation by indomethacin, is only partly dependent on this cation pool.


Acetylcholine receptor clustering in rat myotubes: requirement for CA2+ and effects of drugs which depolymerize microtubules.
The acetylcholine receptor (AChR) clusters which form in the plasma membranes of cultured rat myotubes disappear when the myotubes are exposed to medium depleted of Ca2+. This loss of receptor clusters is reversible and depends both on extracellular Ca2+ concentrations and on temperature. Other divalent cations (Mg2+, Ba2+, Sr2+, Co2+, Mn2+) do not maintain receptor clusters when Ca2+ is absent. Extracellular Na+, which promotes Ca2+ efflux from myotube cultures, is necessary for cluster loss to occur in Ca2+-depleted medium. Experiments using colchicine and other drugs which depolymerize microtubules suggest that the cytoskeleton is involved in AChR clustering. At submicromolar concentrations, these drugs afford partial protection against cluster loss caused by Ca2+ depletion. Colchicine also alters the organization of vinculin in the vicinity of AChR clusters. It is concluded that receptor clustering probably depends on intracellular Ca2+ and on a structure or mechanism indirectly affected by colchicine.


Performance of heterodyne differential phase-shift-keying underwater wireless optical communication systems in gamma-gamma-distributed turbulence.
The analytical expressions for the average bit error rate and the outage probability of a heterodyne differential phase-shift-keying underwater wireless optical communication (UWOC) system are derived with proper consideration of all of the channel-degrading effects, including absorption, scattering, and turbulence-induced fading. The scintillation index of a spherical wave is evaluated in order to quantify the underwater system performance in a strong turbulence regime. The spherical wave propagating through the strong underwater turbulence environment is modeled as gamma-gamma distribution. Then, the system performance is simulated for various variations of the underwater turbulence, i.e., the rate of dissipation of kinetic energy per unit mass of fluid, the ratio of temperature to salinity contributions to the refractive index spectrum, and the UWOC system link length. The results show that the analytical expressions for describing the system performance are valid.


Magnetization transfer imaging of patients with definite MS and negative conventional MRI.
To assess, in a group of patients with clinically or laboratory-supported definite MS and negative conventional MRI scans of the brain, whether magnetization transfer imaging (MTI) is able to detect subtle white matter changes. MTI of the brain in patients with MS frequently demonstrates the presence of microscopic damage to white matter, which appears normal on conventional MRI. Brain MRI and MTI scans were obtained from 11 patients with negative conventional MRIs of the brain, selected from 618 clinically or laboratory-supported definite MS cases scanned in the last 2 years in three Italian MS centers. Compared with control subjects, patients had significantly lower mean MT ratios (MTR) in the pons, cerebellum, and periventricular regions. The percentages of pixels with MTR values below 1, 2, and 3 SD of the mean MTR value of the control subjects were 7.6% (range, 3.2% to 11.8%), 5.2% (range, 2.0% to 8.5%), and 3.6% (range, 1.2% to 6.1%), respectively. They were mainly located in the white matter of the centra semiovalia, and usually were isolated. MTI can detect white matter abnormalities in patients with MS and negative conventional brain MRI scans. The detection of such abnormalities may increase diagnostic confidence in those cases where MS is clinically suspected, but conventional MRI does not suggest the diagnosis.


Properties of a temporal difference reinforcement learning brain machine interface driven by a simulated motor cortex.
Our overall goal is to develop a reinforcement learning (RL) based decoder for brain machine interfaces. As an important step in this process, we determine the basic stability and convergence properties of a Temporal Difference (TD) RL architecture being driven by a simulated motor cortex.


Role of beta-endorphin in the control of body temperature in the rabbit.
There is evidence of release of the opioid peptide beta-endorphin (beta-E) in the hypothalamus during development of fever and stress-induced hyperthermia. In the unanesthetized rabbit, microinjection of beta-E in the preoptic/anterior hypothalamus (POAH) results in peripheral vasoconstriction, inhibition of evaporative heat loss, and a prolonged elevation of body temperature. These reactions are magnified with increases in ambient temperature. Injections of beta-E nearly abolish vasodilation to back heating and also postural enhancement of heat dissipation ( sprawling , limb extension) in a hot environment. beta-E has also been found to reduce the thermal sensitivity of single POAH neurons to ambient heating. However, POAH beta-E injections do not alter metabolic rate at ambient temperatures from 2 to 27 degrees C, and to this extent beta-E-induced hyperthermia is distinct from fever. It is suggested that beta-E reduces sensitivity of POAH neurons to high ambient temperature and that this reduction leads to increased peripheral vasoconstriction, inhibition of evaporative heat loss, and modification of behavioral thermoregulation resulting in a regulated-type elevation in body temperature. A general neural model is proposed to explain the thermoregulatory effects of beta-E in the rabbit.


Chemometric models of template--molecularly imprinted polymer binding.
This report provides the first example of the use of chemometrics to describe and predict the extent of template binding to molecularly imprinted polymers. The binding of bupivacaine to imprinted and reference polymers was examined in different solvent mixtures and at various temperatures using equilibrium binding studies. Data were fitted to third-degree equations using partial least-squares regression, resulting in chemometric models describing template binding in this system. The mathematical models demonstrated good correlation (R = 0.72-0.98) and predictive ability (Q = 0.54-0.99), and binding could be described in terms of temperature and dielectric constant. Binding in a nonpolar, aprotic solvent was unaffected by temperature whereas in more polar solvent mixtures temperature had a greater influence. This was explained by changes in the balance between electrostatic and hydrophobic interactions. Moreover, the results demonstrate that temperature has a greater influence on the nonspecific portion of binding, particularly in water-containing solvent mixtures.


Ginger exosome-like nanoparticles (GELNs) induced apoptosis, cell cycle arrest, and anti-metastatic effects in triple-negative breast cancer MDA-MB-231 cells.
Ginger exosome-like nanoparticles (GELNs) have been extensively implicated in alleviating inflammation, maintaining intestinal microbiome and are considered competent drug delivery vehicles. Despite this, the current knowledge of the GELN interaction with cancer cells is limited. Triple-negative breast cancer (TNBC), an aggressive variant lacking efficient therapeutics, necessitates novel natural counterparts with minimal side effects. This study investigates the action of GELNs isolated from ginger rhizomes against TNBC cells. GELNs were isolated by ultracentrifugation and characterized physicochemically. The interaction of GELNs with TNBC cells (MDA-MB-231) was studied in detail. The GELNs induced a concentration-dependent decrease in cell viability in MDA-MB-231 cells without affecting the normal cell lines tested. GELNs induced apoptosis as indicated by morphological changes, nuclear fragmentation, membrane damage, phosphatidyl serine translocation, ROS generation, drop in mitochondrial membrane potential, expression of apoptotic specific proteins, and increased caspase activity. GELNs also instigated cell cycle arrest, retarded cell migration and colony formation in TNBC cells. These findings report a novel action of GELNs against TNBC cells and a closer look at the underlying molecular mechanism of this interspecies communication. This opens newer prospects for using dietary ELNs to target therapeutically challenging cancers.


Distinguishing potential bacteria-tumor associations from contamination in a secondary data analysis of public cancer genome sequence data.
A variety of bacteria are known to influence carcinogenesis. Therefore, we sought to investigate if publicly available whole genome and whole transcriptome sequencing data generated by large public cancer genome efforts, like The Cancer Genome Atlas (TCGA), could be used to identify bacteria associated with cancer. The Burrows-Wheeler aligner (BWA) was used to align a subset of Illumina paired-end sequencing data from TCGA to the human reference genome and all complete bacterial genomes in the RefSeq database in an effort to identify bacterial read pairs from the microbiome. Through careful consideration of all of the bacterial taxa present in the cancer types investigated, their relative abundance, and batch effects, we were able to identify some read pairs from certain taxa as likely resulting from contamination. In particular, the presence of Mycobacterium tuberculosis complex in the ovarian serous cystadenocarcinoma (OV) and glioblastoma multiforme (GBM) samples was correlated with the sequencing center of the samples. Additionally, there was a correlation between the presence of Ralstonia spp. and two specific plates of acute myeloid leukemia (AML) samples. At the end, associations remained between Pseudomonas-like and Acinetobacter-like read pairs in AML, and Pseudomonas-like read pairs in stomach adenocarcinoma (STAD) that could not be explained through batch effects or systematic contamination as seen in other samples. This approach suggests that it is possible to identify bacteria that may be present in human tumor samples from public genome sequencing data that can be examined further experimentally. More weight should be given to this approach in the future when bacterial associations with diseases are suspected.


The progress and prospect of regulatory T cells in autoimmune diseases.
Regulatory T cells (Treg) are an important immune cell population, playing a crucial role in regulating immune tolerance and preventing autoimmune diseases. These cells consist of various cell sub-populations and generally have an immunoregulatory or suppressive role against immune responses. They also have a different cell heterogeneity and each populations has own biological characteristics. Treg deficiency, reduction, instability, reduced vitality and dysfunction all account for multiple autoimmune diseases. In this review, we have systemically reviewed Treg classification, phenotypic features, regulation of Foxp3 expression, plasticity and stability of Treg as well as their relationship with several important autoimmune diseases. We particularly focus on why and how inflammatory and diet environments affect the functional capacity and underlying mechanisms of Treg cell populations. We also summarize new advances in technologies which help to analyze and dissect these cells in molecular levels in-depth. We also clarify the possible clinical relevance on application of these cells in patients with autoimmune diseases. The advantages and weaknesses have been carefully discussed as well. We also propose the possible approaches to overcome these weaknesses of Treg cells in complicate environments. Thus, we have displayed the updated knowledge of Treg cells, which provides an overall insight into the role and mechanisms of Treg cells in autoimmune diseases.


Perceptions on Competence by Design in urology.
The Royal College of Physicians and Surgeons of Canada has begun implementing Competence by Design (CBD). However, it is unclear how much urology trainees and faculty know about CBD, their attitudes towards this change, and their willingness to embrace and participate in this new model of training. This cross-sectional study was conducted through an online survey, which was administered to all trainees and faculty at Canadian urology programs prior to the implementation of CBD. The final survey consisted of eight demographic questions, 17 five-point Likert items, one visual analog scale question, 11 multiple selection questions, and two open-ended questions. A total of 74 participants (38 faculty and 36 trainees) across 12 universities responded, with a completion rate of 82.4%. This corresponded to an overall response rate of 20.5%. Overall, there was a lack of resounding enthusiasm towards this shift to CBD in urology. Although both trainees and faculty had overall positive perceptions of CBD on assessment, teaching, and readiness, most agreed that this transition will be costly and associated with increased requirements for time, funding, and administrative support. Furthermore, there were significant concerns regarding the lack of valid assessment tools and evidence for the validity of entrustable professional activities. While this survey has demonstrated an appreciation for the benefits of CBD, challenges are equally anticipated. CBD in urology will be a fertile research area; this study has identified several important educational questions regarding the model's effectiveness and consequences, thus, providing collaborative opportunities among all Canadian programs.


Improved experimental model for measuring skin degerming activity on the human hand.
A gloved-hand method is presented for evaluating the interaction of antimicrobial agents with the normal resident bacterial flora of human skin. One of the key features of the experimental model is a simplified technique for sampling the skin, which involves the addition of eluting fluid to the gloved hand. As with other skin sampling techniques, the number of bacteria recovered from the hands showed considerable variation from subject to subject. However, no significant differences were observed between the numbers of bacteria recovered from the right and left hands of individual subjects. The mean number of bacteria recovered from the hand before and after washing with nonmedicated soap was consistent and reproducible over a period of at least 5 consecutive days. The number of recoverable bacteria from the hand was greatly reduced by a single treatment with a surgical scrub preparation containing hexachlorophene. The extent of skin degerming achieved was little affected by the use of a surgical brush, and was maximal at approximately 30 min after contact with the hexachlorophene-containing formulation. It was determined that the level of transient bacteria on the hands could be controlled by a simple wash with nonmedicated soap, resulting in a stabilized base-line level from which treatment interactions with the resident microflora could be measured more precisely. The basic elements of the method presented fulfill the requirements of a satisfactory experimental model for the in vivo evaluation of skin-degerming agents on the hand. The selection of appropriate experimental designs allows treatment comparisons to be made with a high degree of statistical confidence.


[Reactions of antibodies to streptococcus group A antigens with fibroblasts of human heart interstitial connective tissue].
The indirect immunofluorescence method was applied to the study of the serum of rabbits immunized with fractions containing nontype-specific antigens of streptococcus, group A, belonging to the cell wall proteins. Antibodies reacting with fibroblasts of the interstitial connective tissue of the human heart were revealed in the sera. On the basis of the experimental results of absorption a supposition was put forward on the presence of a cross-reacting antigen common with the fibroblast antigen in some hydrochloric extracts obtained from streptococci, groups A and C.


Transposon-derived Brucella abortus rough mutants are attenuated and exhibit reduced intracellular survival.
The O antigen of Brucella abortus has been described as a major virulence determinant based on the attenuated survival of fortuitously isolated rough variants. However, the lack of genetic definition of these mutants and the virulence of naturally occurring rough species, Brucella ovis and Brucella canis, has confused interpretation. To better characterize the role of O antigen in virulence and survival, transposon mutagenesis was used to generate B. abortus rough mutants defective in O-antigen presentation. Sequence analysis of DNA flanking the site of Tn5 insertion was used to verify insertion in genes encoding lipopolysaccharide (LPS) biosynthetic functions. Not surprisingly, each of the rough mutants was attenuated for survival in mice, but unexpected differences among the mutants were observed. In an effort to define the basis for the observed differences, the structure of the rough LPS and the sensitivity of these mutants to individual killing mechanisms were examined in vitro. All of the B. abortus rough mutants exhibited a 4- to 5-log-unit increase, compared to the smooth parental strain, in sensitivity to complement-mediated lysis. Little change was evident in the sensitivity of these organisms to hydrogen peroxide, consistent with an inability of O antigen to exclude relatively small molecules. Sensitivity to polymyxin B, which was employed as a model cationic, amphipathic peptide similar to defensins found in phagocytic cells, revealed survival differences among the rough mutants similar to those observed in the mouse. One mutant in particular exhibited hypersensitivity to polymyxin B and reduced survival in mice. This mutant was characterized by a truncated rough LPS. DNA sequence analysis of this mutant revealed a transposon interruption in the gene encoding phosphomannomutase (pmm), suggesting that this activity may be required for the synthesis of a full-length core polysaccharide in addition to O antigen. B. abortus O antigen appears to be essential for extra- and intracellular survival in mice.


Rapid review on monkeypox policies among the G20 nations: relevance to policy and practitioner.
Background: Monkeypox has been declared as a Public Health Emergency of International Concern (PHEIC) by the WHO Director General (WHO-DG). Most of the G20 nations have reported Monkeypox outbreak. Policies developed and implemented in G20 countries for the prevention and control of monkeypox preparedness and response have global consequences. This rapid review aimed to map the monkeypox prevention and control policies planned and implemented in G20 nations in line with temporary recommendations issued by the WHO-DG. Methods: We mapped monkeypox prevention and control policies in G20 nations based on the WHO-DG recommendations. Medline (through PubMed), Scopus, and ProQuest Health and Medical Complete were searched to understand G20 preventative, diagnostic, and therapeutic policies. We also performed an extensive gray literature search through the Ministry of Health websites and newspaper through Google. The documents/ studies that had an information on prevention, control and management guidelines/policies and published through journal, news articles and health ministry websites of G20 nations on monkeypox were included. We excluded the editorials, opinion, and perspective papers and studies published prior to May 6, 2022. Results: We obtained 671 articles with 10 articles included in the review. Additionally, we identified 55 documents from the gray literature. We included national guidelines of the 18 countries on the control, prevention, and management of monkeypox. National guidelines were compared with the WHO guidelines in terms of implementing coordinated response, engaging and protecting communities, surveillance and public health measures and international travel, clinical management and infection, prevention and control (IPC) measures and medical countermeasures research. Depending on the availability of resources, some recommendations are followed by nations while others are not. Conclusions: Coordinated response among states is key to contain the transmission of monkeypox. To bring a coordinated response, G20 nations are following temporary recommendations that are context specific to their nation.


Ubqln4 Facilitates Endoplasmic Reticulum-to-Cytosol Escape of a Nonenveloped Virus during Infection.
The nonenveloped polyomavirus simian virus 40 (SV40) must penetrate the host endoplasmic reticulum (ER) membrane to enter the cytosol in order to promote infection. How this is accomplished is not entirely clear. Here, we demonstrate that the cytosolic chaperone Ubiquilin4 (Ubqln4) binds directly to the ER membrane J proteins B12 and B14. Strategically localized at the ER-cytosol interface, Ubqln4 captures SV40 emerging from the ER, thereby facilitating escape of the virus from the ER into the cytosol, which leads to infection. Strikingly, Ubqln4 engages the J proteins in a J-domain-independent manner, in contrast to the previously reported Hsc70-Hsp105-SGTA-Bag2 cytosolic complex that also mediates SV40 ER-to-cytosol transport. Our results also reveal that the H domain and STI1 motif (1-2) of Ubqln4 support J protein binding, essential for SV40 infection. Together, these data further clarify the molecular basis by which a nonenveloped virus escapes a host membrane during infectious entry.IMPORTANCE How a nonenveloped virus escapes from a host membrane to promote infection remains enigmatic. In the case of the nonenveloped polyomavirus SV40, penetration of the ER membrane to reach the cytosol is a decisive virus infection step. In this study, we found a new host factor called Ubqln4 that facilitates escape of SV40 from the ER into the cytosol, thereby providing a path for the virus to enter the nucleus to cause infection.


Standard-suspension-test: influence of bovine albumin, saline and water of standard hardness on M.E.-values.
Notwithstanding considerable international agreement upon the principle of the quantitative suspension test differences still exist between the main variants of this test, in particular on the diluent to be used in the test mixture. For this reason the influence of the main variables - i.e. bovine albumin (0.03%), NaCl (physiol. saline) and divalent ions (water of standard hardness) - on the activity of the different classes of disinfectants have been investigated. Using so-called borderline concentrations only a small protein effect of 0.03% bovine albumin was found with a phenolic product, quaternary ammonium compounds and aldehydes. A substantial protein effect was observed only with chlorine compounds. The chlorine consumption in the present Dutch Standard Suspension Test is approx. 20 ppm. In tests without a protein load as well as in the presence of 0.03% bovine albumin M.E.-values using saline as the diluent were usually higher than in tests using water of standard hardness (WSH) or distilled water (DW). M.E.-values of quaternary ammonium compounds in WSH were significantly lower than those in DW, presumably due to the antagonizing effect of divalent cations (Mg++ and Ca++). The different views regarding the aim of quantitative suspension tests are discussed. In The Netherlands the opinion prevails that these tests should have at least some relationship with practical conditions. The use of water of standard hardness as a diluent and the incorporation of a slight protein challenge are in agreement with this standpoint.


Discovery of C-(1-aryl-cyclohexyl)-methylamines as selective, orally available inhibitors of dipeptidyl peptidase IV.
The successful launches of dipeptidyl peptidase IV (DPP IV) inhibitors as oral anti-diabetics warrant and spur the further quest for additional chemical entities in this promising class of therapeutics. Numerous pharmaceutical companies have pursued their proprietary candidates towards the clinic, resulting in a large body of published chemical structures associated with DPP IV. Herein, we report the discovery of a novel chemotype for DPP IV inhibition based on the C-(1-aryl-cyclohexyl)-methylamine scaffold and its optimization to compounds which selectively inhibit DPP IV at low-nM potency and exhibit an excellent oral pharmacokinetic profile in the rat.


Marine Aerosols and Clouds.
The role of marine bioaerosols in cloud formation and climate is currently so uncertain that even the sign of the climate forcing is unclear. Marine aerosols form through direct emissions and through the conversion of gas-phase emissions to aerosols in the atmosphere. The composition and size of aerosols determine how effective they are in catalyzing the formation of water droplets and ice crystals in clouds by acting as cloud condensation nuclei and ice nucleating particles, respectively. Marine organic aerosols may be sourced both from recent regional phytoplankton blooms that add labile organic matter to the surface ocean and from long-term global processes, such as the upwelling of old refractory dissolved organic matter from the deep ocean. Understanding the formation of marine aerosols and their propensity to catalyze cloud formation processes are challenges that must be addressed given the major uncertainties associated with aerosols in climate models.


Vaginal progesterone pessaries for pregnant women with a previous preterm birth to prevent neonatal respiratory distress syndrome (the PROGRESS Study): A multicentre, randomised, placebo-controlled trial.
Neonatal respiratory distress syndrome, as a consequence of preterm birth, is a major cause of early mortality and morbidity. The withdrawal of progesterone, either actual or functional, is thought to be an antecedent to the onset of labour. There remains limited information on clinically relevant health outcomes as to whether vaginal progesterone may be of benefit for pregnant women with a history of a previous preterm birth, who are at high risk of a recurrence. Our primary aim was to assess whether the use of vaginal progesterone pessaries in women with a history of previous spontaneous preterm birth reduced the risk and severity of respiratory distress syndrome in their infants, with secondary aims of examining the effects on other neonatal morbidities and maternal health and assessing the adverse effects of treatment. Women with a live singleton or twin pregnancy between 18 to <24 weeks' gestation and a history of prior preterm birth at less than 37 weeks' gestation in the preceding pregnancy, where labour occurred spontaneously or in association with cervical incompetence or following preterm prelabour rupture of the membranes, were eligible. Women were recruited from 39 Australian, New Zealand, and Canadian maternity hospitals and assigned by randomisation to vaginal progesterone pessaries (equivalent to 100 mg vaginal progesterone) (n = 398) or placebo (n = 389). Participants and investigators were masked to the treatment allocation. The primary outcome was respiratory distress syndrome and severity. Secondary outcomes were other respiratory morbidities; other adverse neonatal outcomes; adverse outcomes for the woman, especially related to preterm birth; and side effects of progesterone treatment. Data were analysed for all the 787 women (100%) randomised and their 799 infants. Most women used their allocated study treatment (740 women, 94.0%), with median use similar for both study groups (51.0 days, interquartile range [IQR] 28.0-69.0, in the progesterone group versus 52.0 days, IQR 27.0-76.0, in the placebo group). The incidence of respiratory distress syndrome was similar in both study groups-10.5% (42/402) in the progesterone group and 10.6% (41/388) in the placebo group (adjusted relative risk [RR] 0.98, 95% confidence interval [CI] 0.64-1.49, p = 0.912)-as was the severity of any neonatal respiratory disease (adjusted treatment effect 1.02, 95% CI 0.69-1.53, p = 0.905). No differences were seen between study groups for other respiratory morbidities and adverse infant outcomes, including serious infant composite outcome (155/406 [38.2%] in the progesterone group and 152/393 [38.7%] in the placebo group, adjusted RR 0.98, 95% CI 0.82-1.17, p = 0.798). The proportion of infants born before 37 weeks' gestation was similar in both study groups (148/406 [36.5%] in the progesterone group and 146/393 [37.2%] in the placebo group, adjusted RR 0.97, 95% CI 0.81-1.17, p = 0.765). A similar proportion of women in both study groups had maternal morbidities, especially those related to preterm birth, or experienced side effects of treatment. In 9.9% (39/394) of the women in the progesterone group and 7.3% (28/382) of the women in the placebo group, treatment was stopped because of side effects (adjusted RR 1.35, 95% CI 0.85-2.15, p = 0.204). The main limitation of the study was that almost 9% of the women did not start the medication or forgot to use it 3 or more times a week. Our results do not support the use of vaginal progesterone pessaries in women with a history of a previous spontaneous preterm birth to reduce the risk of neonatal respiratory distress syndrome or other neonatal and maternal morbidities related to preterm birth. Individual participant data meta-analysis of the relevant trials may identify specific women for whom vaginal progesterone might be of benefit. Current Clinical Trials ISRCTN20269066.


Aggressive regional surgery for advanced ovarian carcinoma.
Between January 1975 and December 1983 in the Cancer Institute, Montpellier, France, regional surgery (RS) was performed on 18 Stage III and 3 Stage IV patients (International Federation of Gynecology and Obstetrics [FIGO]) with histologically proven cystadenocarcinoma of the ovary. All patients were placed into one of three nonrandomized groups: Group A (9 patients), RS at first-look surgery; Group B (7 patients), RS at second-look surgery; and Group C (5 patients), RS at third-look surgery. Group A was given adjuvant chemotherapy, whereas Group B and C patients underwent nonregional surgery at first- or second-look operation, and received chemotherapy supplemented in some Group C cases by radiotherapy before RS. The adjuvant chemotherapy consisted of: cyclophosphamide plus Alkeran (mephalan) plus 5-fluorouracil (the first 7 patients) and Adriamycin (doxorubicin) plus cisplatin plus hexamethylmelamine (14 additional patients). RS consisted of basic procedures--abdominal hysterectomy; bilateral salpingo-oophorectomy; omentectomy--and specific procedures--abdominal and pelvic peritonectomy; either total or partial colectomy; jejunoilectomy, leaving at least 150 cm of the jejunum; and retroperitoneal lymph node dissection aimed at maximal cytoreduction of tumor mass. There was no operative mortality. The overall postoperative morbidity was 33.3% (seven patients) due to wound sepsis. The survival from the beginning of treatment (absolute survival [AS]) and survival after RS (RSS) were compared. In Group A (AS = RSS) the probability of survival at 112 months (6/9 patients are still alive) was 0.52. In Groups B and C the median survival times (AS and RSS) were 37 and 17 months and 18 and 1 month, respectively. The difference in AS among the three groups of patients was not statistically significant (log-rank test), whereas the RSS was statistically significant between Group A versus Groups B, C, and Groups B and C combined (P less than 0.05).


On the physical origin of linguistic laws and lognormality in speech.
Physical manifestations of linguistic units include sources of variability due to factors of speech production which are by definition excluded from counts of linguistic symbols. In this work, we examine whether linguistic laws hold with respect to the physical manifestations of linguistic units in spoken English. The data we analyse come from a phonetically transcribed database of acoustic recordings of spontaneous speech known as the Buckeye Speech corpus. First, we verify with unprecedented accuracy that acoustically transcribed durations of linguistic units at several scales comply with a lognormal distribution, and we quantitatively justify this 'lognormality law' using a stochastic generative model. Second, we explore the four classical linguistic laws (Zipf's Law, Herdan's Law, Brevity Law and Menzerath-Altmann's Law (MAL)) in oral communication, both in physical units and in symbolic units measured in the speech transcriptions, and find that the validity of these laws is typically stronger when using physical units than in their symbolic counterpart. Additional results include (i) coining a Herdan's Law in physical units, (ii) a precise mathematical formulation of Brevity Law, which we show to be connected to optimal compression principles in information theory and allows to formulate and validate yet another law which we call the size-rank law or (iii) a mathematical derivation of MAL which also highlights an additional regime where the law is inverted. Altogether, these results support the hypothesis that statistical laws in language have a physical origin.


Plasma levels of coagulation and fibrinolysis markers in acute ischemic stroke patients with lone atrial fibrillation.
Atrial fibrillation (AF) is a well-defined risk factor for ischemic stroke. Patients with lone AF represent a subgroup of AF patients with the lowest lifelong stroke risk. Nonvalvular atrial fibrillation (NVAF) confers a hypercoagulable state resulting in an increased risk of thromboembolism. This study was performed to determine the contributory role of alteration in the hemostatic markers of thrombin generation and fibrinolysis in patients with lone AF during acute ischemic stroke episode. We studied thrombin-antithrombin complexes (TAT), prothrombin fragments 1+2 (F1+2), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAI-1) concentrations in patients with acute middle cerebral artery ischemic stroke due to atherosclerotic large artery disease (n=50), lone AF (n=24) and cardioembolism (n=21). The values were compared with those of age-matched control subjects with lone AF and sinus rhythm (n=21 and 15, respectively). The mean F1+2 concentration was higher in the control subjects with lone AF in comparison with those without AF (p=0.014). Patients with stroke due to possible cardioembolism, from lone AF or other causes, had higher TAT (and marginally higher F1+2) concentrations than those with atherosclerotic stroke (p<0.001). tPA concentrations were not different among groups (p=0.89). PAI-I levels were marginally higher in stroke patients with lone AF and atherothrombotic large artery disease compared to the controls without AF (p=0.05). These results suggest that in the acute period of ischemic stroke secondary to lone AF, enhancement of the coagulatory activity occurs as a result of increased thrombin generation, similar to other possible sources of cardioembolism. Observed hemostatic alterations in acute ischemic stroke associated with lone AF may indicate some therapeutic and prognostic implications.


BRCA1 and BRCA2 Gene Mutations and Colorectal Cancer Risk: Systematic Review and Meta-analysis.
Investigations of the associations with colorectal cancer have yielded conflicting results. The aim of our study was to synthesize the research on colorectal cancer risks in BRCA mutation carriers by means of a systematic review and quantitatively by means of meta-analyses overall and in subgroups of BRCA mutation carriers. We searched PubMed/MEDLINE, Embase, Cochrane, Scopus, and ProQuest Dissertation & Theses. Unadjusted odds ratios (ORs) were used to derive pooled estimates of colorectal cancer risk overall and in subgroups defined by mutation type (BRCA1 or BRCA2), cancer type (colorectal or colon cancer), study design (age-sex-adjusted or crude), and ascertainment method (ascertained or inferred genotyping). The associations were evaluated using random-effect models. All statistical tests were two-sided. Eighteen studies were included in the systematic review: five cohort studies with ascertained BRCA mutation, six cohort studies involving pedigree analysis, five case-control studies, and two kin-cohort studies. Of these, 14 were used in the meta-analysis, which revealed a statistically significant increased risk of colorectal cancer in overall BRCA mutation carriers (OR = 1.24, 95% confidence interval (CI) = 1.02 to 1.51, P = .03). In subgroup meta-analyses by BRCA type, BRCA1 mutation was associated with increased risk of colorectal cancer (OR = 1.49, 95% CI = 1.19 to 1.85, P < .001), but BRCA2 was not (OR = 1.10, 95% CI = 0.77 to 1.58, P = .61). In subgroup meta-analyses of studies reporting estimates adjusted for age and sex, an increased risk of colorectal cancer for BRCA1 (OR = 1.56, 95% CI = 1.23 to 1.98, P < .001), but not for BRCA2 (OR = 1.09, 95% CI = 0.75 to 1.58, P = .66) was observed. Analyses stratified by ascertainment method found no association between BRCA mutation and colorectal cancer risk. The meta-analysis results provide clinicians and health-care regulatory agencies with evidence of the increased risk of colorectal cancer in BRCA1 mutation carriers, but not in BRCA2.


Expanding the clinical and genetic spectrum of ALPK3 variants: Phenotypes identified in pediatric cardiomyopathy patients and adults with heterozygous variants.
Biallelic damaging variants in ALPK3, encoding alpha-protein kinase 3, cause pediatric-onset cardiomyopathy with manifestations that are incompletely defined. We analyzed clinical manifestations of damaging biallelic ALPK3 variants in 19 pediatric patients, including nine previously published cases. Among these, 11 loss-of-function (LoF) variants, seven compound LoF and deleterious missense variants, and one homozygous deleterious missense variant were identified. Among 18 live-born patients, 8 exhibited neonatal dilated cardiomyopathy (44.4%; 95% CI: 21.5%-69.2%) that subsequently transitioned into ventricular hypertrophy. The majority of patients had extracardiac phenotypes, including contractures, scoliosis, cleft palate, and facial dysmorphisms. We observed no association between variant type or location, disease severity, and/or extracardiac manifestations. Myocardial histopathology showed focal cardiomyocyte hypertrophy, subendocardial fibroelastosis in patients under 4 years of age, and myofibrillar disarray in adults. Rare heterozygous ALPK3 variants were also assessed in adult-onset cardiomyopathy patients. Among 1548 Dutch patients referred for initial genetic analyses, we identified 39 individuals with rare heterozygous ALPK3 variants (2.5%; 95% CI: 1.8%-3.4%), including 26 missense and 10 LoF variants. Among 149 U.S. patients without pathogenic variants in 83 cardiomyopathy-related genes, we identified six missense and nine LoF ALPK3 variants (10.1%; 95% CI: 5.7%-16.1%). LoF ALPK3 variants were increased in comparison to matched controls (Dutch cohort, P = 1.6×10-5; U.S. cohort, P = 2.2×10-13). Biallelic damaging ALPK3 variants cause pediatric cardiomyopathy manifested by DCM transitioning to hypertrophy, often with poor contractile function. Additional extracardiac features occur in most patients, including musculoskeletal abnormalities and cleft palate. Heterozygous LoF ALPK3 variants are enriched in adults with cardiomyopathy and may contribute to their cardiomyopathy. Adults with ALPK3 LoF variants therefore warrant evaluations for cardiomyopathy.


Virulence properties and characterization of aeromonads isolated from foods of animal origin and environmental sources.
Aeromonas species are increasingly recognized as enteric pathogens, and they possess several virulence factors that may contribute to illness. In this work, the biochemical, enzymatic, and some virulence properties of 73 potentially pathogenic strains of Aeromonas spp. isolated from food and environmental sources were investigated to compare strains from different sources and establish the possible relationships between some phenotypic characters and pathogenicity. Virulence factors (hemolysin and siderophores), biochemical properties (Voges-Proskauer and lysine decarboxylase reactions), and enzymatic properties (lipase, phospholipase, protease, and DNase activities) were examined in these strains. Results indicated that 57% of the strains from environmental sources produced siderophores and hemolysin, whereas 39.0% of strains from food produced siderophores and 60.5% produced hemolysin. Protease, lipase, DNase, and phospholipase activities in strains isolated from food and environmental sources were 69.5 to 94.3, 73.6 to 68.5, 52.6 to 68.6, and 71.0 to 68.4%, respectively. A higher percentage of strains of environmental origin (94.3%) had protease activity, and higher lipase activity (73.6%) was observed in food isolates. For all antimicrobials tested, all strains had the least resistance to meropenem, and high levels of resistance were found to amoxicillin-clavulanic acid and cephalothin. These findings demonstrate the presence of potentially pathogenic and multidrug-resistant Aeromonas spp. in environmental and food sources, thereby indicating a significant risk to public health.


Effects of the nematicide imicyafos on soil nematode community structure and damage to radish caused by Pratylenchus penetrans.
The effects of the non-fumigant nematicide imicyafos on soil nematode community structure and damage to radish caused by Pratylenchus penetrans were evaluated in two field experiments in consecutive years (2007 and 2008). Nematode densities in soil at 0 - 10 cm (the depth of nematicide incorporation) and 10 - 30 cm were measured. The application of imicyafos had a significant impact on the density of P. penetrans at 0 - 10 cm but had no effect on free-living nematode density. PCR-DGGE analysis conducted using extracted nematodes showed that the nematode community structure 12 d after application in 2007 was altered by the application of imicyafos at the 0 - 10 cm depth, but not at 10 - 30 cm. No significant differences were observed in the diversity of the nematode community at harvest (89 and 91 d after application) between the control and imicyafos treatments in both depths and both years. In both years, the damage to radish caused by P. penetrans was markedly suppressed by the nematicide. Overall, the nematicide imicyafos decreased populations of P. penetrans in soil and thereby decreased damage to radish, while having little impact on the soil nematode community.


Enhanced regeneration of osteochondral defects by using an aggrecanase-1 responsively degradable and N-cadherin mimetic peptide-conjugated hydrogel loaded with BMSCs.
Due to the poor self-repair capabilities of articular cartilage, chondral or osteochondral injuries are difficult to be recovered. In this study, an N-cadherin mimetic peptide sequence HAVDIGGGC (HAV) was conjugated to direct cell-cell interactions, and an aggrecanase-1 cleavable peptide sequence CRDTEGE-ARGSVIDRC (ACpep) was used to crosslink hyperbranched PEG-based multi-acrylate polymer (HBPEG) with cysteamine-modified chondroitin sulfate (Cys-CS), obtaining an aggrecanase-1 responsively degradable and HAV-conjugated hydrogel ((HAV-HBPEG)-CS-ACpep). A HBPEG-CS-ACpep hydrogel without the HAV motif was also prepared. The two hydrogels exhibited similar equilibrium swelling ratios, elastic moduli and pore sizes after lyophilization, indicating the negligible influence of conjugated HAV on the crosslinking networks and mechanical properties of the hydrogels. After being degraded in PBS, aggrecanase-1 (ADAMTS4) and trypsin, the HBPEG-CS-ACpep hydrogel exhibited significantly decreased elastic moduli with a much lower value when incubated in enzyme solutions. The two hydrogels could maintain the viability of encapsulated bone marrow-derived mesenchymal stem cells (BMSCs), and the (HAV-HBPEG)-CS-ACpep hydrogel better promoted the cell-cell interactions. After being implanted into osteochondral defects in rabbits for 18 weeks, the two cell-laden hydrogel groups achieved better repair effects than the blank control group. Moreover, hyaline cartilage was formed in the (HAV-HBPEG)-CS-ACpep/BMSCs hydrogel group, while a hybrid of hyaline cartilage and fibrocartilage was found in the HBPEG-CS-ACpep/BMSCs hydrogel group.


[Development of a new type soybean germplasm with null lipoxygenase isozymes].
Soybean protein is a kind of high-quality protein composed of balanced amino acids. It contains all kinds of amino acids, especially eight amino acids necessary for human, but also contains some components that are not good for human and affect food quality, such as Lipoxygenase (Lox) and Trypsin inhibitor (Ti). Nutritional value and processing quality of soybean can be improved by means of development of new variety with null Lox and Ti. In this paper, a new type soybean germplasm with null lipoxygenase isozymes was developed by Institute of Crop Sciences, Chinese Academy of Agricultural Sciences through years of biochemical marker assistant selection for null lipoxygenase by means of isoelectric focusing-polyacrylamid gel electrophoresis (IEF-PAGE) in the hybrid progenies of "96P17" (Female parent, a null lipoxygenase 2.3 line) and "93704" (Male parent, a null lipoxygenase 1.3 line). It is the first new soybean germplasm with null Lox1.2.3 genes in our country, which will contribute to soybean breeding for high quality, soybean production and utilization. In this paper, the development process of new type soybean germplasm is described.


Decreased environmental complexity during development impairs habituation of reinforcer effectiveness of sensory stimuli.
Previous research has shown that rats reared in simple/impoverished environments demonstrate greater repetitive responding for sensory reinforcers (e.g., light onset). Moreover, the brains of these rats are abnormally developed, compared to brains of rats reared in more complex/enriched environments. Repetitive behaviors are commonly observed in individuals with developmental disorders. Some of these repetitive behaviors could be maintained by the reinforcing effects of the sensory stimulation that they produce. Therefore, rearing rats in impoverished conditions may provide an animal model for certain repetitive behaviors associated with developmental disorders. We hypothesize that in rats reared in simple/impoverished environments, the normal habituation process to sensory reinforcers is impaired, resulting in high levels of repetitive behaviors. We tested the hypothesis using an operant sensory reinforcement paradigm in rats reared in simple/impoverished (IC), standard laboratory (SC), and complex/enrichened conditions (EC, treatments including postnatal handling and environmental enrichment). Results show that the within-session habituation of the reinforcer effectiveness of light onset was slower in the IC and SC rats than in the EC rats. A dishabituation challenge indicated that within-session decline of responses was due to habituation and not motor fatigue or sensory adaptation. In conclusion, rearing rats in simple/impoverished environments, and comparing them to rats reared in more complex/enriched environments, may constitute a useful approach for studying certain repetitive behaviors associated with developmental disorders.