Effect of infancy-onset dietary intervention on salivary cholesterol of children: a randomized controlled trial.
This study investigated salivary cholesterol of children from 6 to 16 years of age in response to dietary intervention. One thousand sixty-two infants started in the prospective, randomized project. At 3 years of age, every fifth child was invited into the study (n=178). Of these, 148 enrolled, and 86 completed the oral sub-study at 16 years of age. The intervention aimed at restricting the child's saturated fat and cholesterol intake. Control children received no special recommendations. Every third year, paraffin-stimulated saliva samples (10.0 mL) were collected for cholesterol assays. Nutrient intakes and serum total cholesterol concentrations were regularly followed up by means of 4-day food records and blood samples. Intake of saturated fatty acids (SAFA) was lower in the intervention than in the control group (p<0.001). Salivary cholesterol concentration increased from 1.9 (±1.1) µmol/L at 6 years of age to 16.0 (±9.0) µmol/L at 16 years of age. The increase was smaller in the intervention than in the control group (p<0.001). The ratios of salivary to serum cholesterol concentrations tended to be higher in boys than in girls (p=0.07). Thus, dietary intervention was reflected in children's salivary cholesterol values more sensitively than in serum cholesterol values. (clinicaltrials.gov NCT00223600).


Mining Hierarchies and Similarity Clusters from Value Set Repositories.
A value set is a collection of permissible values used to describe a specific conceptual domain for a given purpose. By helping to establish a shared semantic understanding across use cases, these artifacts are important enablers of interoperability and data standardization. As the size of repositories cataloging these value sets expand, knowledge management challenges become more pronounced. Specifically, discovering value sets applicable to a given use case may be challenging in a large repository. In this study, we describe methods to extract implicit relationships between value sets, and utilize these relationships to overlay organizational structure onto value set repositories. We successfully extract two different structurings, hierarchy and clustering, and show how tooling can leverage these structures to enable more effective value set discovery.


Ureteritis cystica presenting with atrophic kidney: report of a case.
Ureteritis cystica is a rare proliferative condition that is found predominantly in the bladder, renal pelvis, and upper ureter. It may occlude the ureteral lumen and should be considered in the reasons for an atrophic kidney. A 65-year-old-female with a 2-year history of right flank pain that increased in the last 2 months was presented. Abdominal ultrasonography revealed right-sided atrophic kidney. Nephroureterectomy was performed. On the gross examination, along the ureter wall, there were numerous polyps, 0.5 cm in maximum diameter, protruding into the lumen. On the histopathological evaluation, ureteritis cystica and chronic pyelonephritis was detected. In conclusion, ureteritis cystica is a benign and indolent lesion that needs to be kept in mind among the causes of renal atrophy.


Evaluation and management of geriatric depression in primary care.
Geriatric depression is a common but frequently unrecognized or inadequately treated condition in the elderly population. Manifestations of major depression in elderly persons may hinder early detection; anxiety, somatic complaints, cognitive impairment, and concurrent medical and neurologic disorders are more frequent. Like major depression, minor depression, which is often ignored, produces morbidity for elderly persons. Both major and minor depression are associated with high mortality rates if left untreated. This article reviews the important aspects of geriatric depression for the nonpsychiatric clinician: the etiology of depressive conditions in the elderly population, the unique clinical features of depression in older people, important evaluation considerations in a population with many medical and neurologic comorbidities, and the nonpharmacological and pharmacological treatment options for managing depression in the geriatric population.


In situ formation of a ZnO/ZnSe nanonail array as a photoelectrode for enhanced photoelectrochemical water oxidation performance.
In this study, a ZnO/ZnSe nanonail array was prepared via a two-step sequential hydrothermal synthetic route. In this synthetic process, the ZnO nanorod array was first grown on a fluorine-doped tin oxide (FTO) substrate using a seed-mediated growth approach via the hydrothermal process. Then, the ZnO nanonail array was obtained via in situ growth of ZnSe nano caps onto the ZnO nanorod array via a hydrothermal process in the presence of a Se source. The surface morphology and amount of ZnSe grown on the surface of the ZnO nanorods can be regulated by varying the reaction time and reactant concentration. Compared with pure ZnO nanorods, this unique nanonail array heterostructure exhibits enhanced visible light absorption. The transient photocurrent condition, in combination with steady-state and time-resolved photoluminescence spectroscopy, reveals that the ZnO/ZnSe nanonail array electrode has the highest charge separation rate, highest electron injection efficiency, and highest chemical stability. The photocurrent density of the ZnO/ZnSe nanonail array heterostructure reaches 1.01 mA cm(-2) at an applied potential of 0.1 V (vs. Ag/AgCl), which is much higher than that of the ZnO/ZnSe nanorod array (0.71 mA cm(-2)), the pristine ZnO nanorod array (0.39 mA cm(-2)), and the ZnSe electrode (0.21 mA cm(-2)), indicating its significant visible light driven activities for photoelectrochemical water oxidation. This unique morphology of nail-capped nanorods might be important for providing better insight into the correlation between heterostructure and photoelectrochemical activity.


[Application of modern radiotherapy in lung cancer].
Lung cancer is known for its outstanding incidence and mortality rates. One of the cornerstones of the treatment of this disease is radiation therapy. A remarkable development was observed in this field through the latest decades. Intensity-modulated and image-guided radiotherapy (IMRT and IGRT) are now widely accessible in Hungarian centers, and should be increasingly applied in case of thoracic irradiations as well. Application of modern radiotherapy techniques in the treatment of lung cancer allows better clinical results and lower rates of side effects. In this work the authors give an overview of this above mentioned development regarding different clinical stages.


Unacceptable disparities--do they exist in the adult education movement?
In spite of the tremendous movement and excitement in adult education, there is growing evidence to support the premise that existing adult education programs are not reaching members of minority groups who seem to need them most. Over the past two decades positive strides have been made to bring about equal educational opportunities for all persons regardless of race, sex, or socioeconomic circumstances. Unfortunately these strides have not occurred in continuing or adult education. The purpose of this paper is to: 1) present the current trend in adult education's clientele (re: race, income, and educational attainment); 2) reflect if the movement is bridging or widening the gaps between black and white, poor and rich, and uneducated; and 3) provide a forum for discussion of the issues by current and potential adult educators.


Multivalent display of minimal Clostridium difficile glycan epitopes mimics antigenic properties of larger glycans.
Synthetic cell-surface glycans are promising vaccine candidates against Clostridium difficile. The complexity of large, highly antigenic and immunogenic glycans is a synthetic challenge. Less complex antigens providing similar immune responses are desirable for vaccine development. Based on molecular-level glycan-antibody interaction analyses, we here demonstrate that the C. difficile surface polysaccharide-I (PS-I) can be resembled by multivalent display of minimal disaccharide epitopes on a synthetic scaffold that does not participate in binding. We show that antibody avidity as a measure of antigenicity increases by about five orders of magnitude when disaccharides are compared with constructs containing five disaccharides. The synthetic, pentavalent vaccine candidate containing a peptide T-cell epitope elicits weak but highly specific antibody responses to larger PS-I glycans in mice. This study highlights the potential of multivalently displaying small oligosaccharides to achieve antigenicity characteristic of larger glycans. The approach may result in more cost-efficient carbohydrate vaccines with reduced synthetic effort.


Pathological entity of dementia with Lewy bodies and its differentiation from Alzheimer's disease.
We reclassified the pathological subtypes of dementia with Lewy bodies (DLB), based on both Lewy pathology and Alzheimer pathology, to clarify the pathological entity of DLB and the boundary between DLB and Alzheimer's disease (AD) in autopsied cases, using both pathological and immunohistochemical methods. DLB was classified as either limbic type or neocortical type according to the degree of Lewy pathology including Lewy bodies (LB) and LB-related neurites by our staging, and was classified as pure form, common form or AD form according to the degree of Alzheimer pathology including neurofibrillary tangles (NFT) and amyloid deposits by Braak staging. These combined subtypes were lined up on a spectrum, not only with Lewy pathology but also with other DLB-related pathologies including Alzheimer pathology, neuronal loss in the substantia nigra, spongiform change in the transentorhinal cortex and LB-related neurites in the CA2-3 region. In contrast, the Lewy pathology of AD did not meet the stages of Lewy pathology in DLB, and there were scarcely any similarities in other DLB-related pathologies between AD and DLB. In addition, the Lewy pathology of AD had characteristics different from that of DLB, including the coexistence rate of LB with NFT, and the immunohistochemical and immunoelectron microscopic findings of LB and LB-related neurites. These findings suggest that DLB is a distinctive pathological entity that can be differentiated from AD, although it shows some pathological subtypes.


Transgenic Xenopus laevis for live imaging in cell and developmental biology.
The stable transgenesis of genes encoding functional or spatially localized proteins, fused to fluorescent proteins such as green fluorescent protein (GFP) or red fluorescent protein (RFP), is an extremely important research tool in cell and developmental biology. Transgenic organisms constructed with fluorescent labels for cell membranes, subcellular organelles, and functional proteins have been used to investigate cell cycles, lineages, shapes, and polarity, in live animals and in cells or tissues derived from these animals. Genes of interest have been integrated and maintained in generations of transgenic animals, which have become a valuable resource for the cell and developmental biology communities. Although the use of Xenopus laevis as a transgenic model organism has been hampered by its relatively long reproduction time (compared to Drosophila melanogaster and Caenorhabditis elegans), its large embryonic cells and the ease of manipulation in early embryos have made it a historically valuable preparation that continues to have tremendous research potential. Here, we report on the Xenopus laevis transgenic lines our lab has generated and discuss their potential use in biological imaging.


Massive Ca-induced membrane fusion and phospholipid changes triggered by reverse Na/Ca exchange in BHK fibroblasts.
Baby hamster kidney (BHK) fibroblasts increase their cell capacitance by 25-100% within 5 s upon activating maximal Ca influx via constitutively expressed cardiac Na/Ca exchangers (NCX1). Free Ca, measured with fluo-5N, transiently exceeds 0.2 mM with total Ca influx amounting to approximately 5 mmol/liter cell volume. Capacitance responses are half-maximal when NCX1 promotes a free cytoplasmic Ca of 0.12 mM (Hill coefficient approximately 2). Capacitance can return to baseline in 1-3 min, and responses can be repeated several times. The membrane tracer, FM 4-64, is taken up during recovery and can be released at a subsequent Ca influx episode. Given recent interest in signaling lipids in membrane fusion, we used green fluorescent protein (GFP) fusions with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) and diacylglycerol (DAG) binding domains to analyze phospholipid changes in relation to these responses. PI(4,5)P(2) is rapidly cleaved upon activating Ca influx and recovers within 2 min. However, PI(4,5)P(2) depletion by activation of overexpressed hM1 muscarinic receptors causes only little membrane fusion, and subsequent fusion in response to Ca influx remains massive. Two results suggest that DAG may be generated from sources other than PI(4,5)P in these protocols. First, acylglycerols are generated in response to elevated Ca, even when PI(4,5)P(2) is metabolically depleted. Second, DAG-binding C1A-GFP domains, which are brought to the cell surface by exogenous ligands, translocate rapidly back to the cytoplasm in response to Ca influx. Nevertheless, inhibitors of PLCs and cPLA2, PI(4,5)P(2)-binding peptides, and PLD modification by butanol do not block membrane fusion. The cationic agents, FM 4-64 and heptalysine, bind profusely to the extracellular cell surface during membrane fusion. While this binding might reflect phosphatidylserine (PS) "scrambling" between monolayers, it is unaffected by a PS-binding protein, lactadherin, and by polylysine from the cytoplasmic side. Furthermore, the PS indicator, annexin-V, binds only slowly after fusion. Therefore, we suggest that the luminal surfaces of membrane vesicles that fuse to the plasmalemma may be rather anionic. In summary, our results provide no support for any regulatory or modulatory role of phospholipids in Ca-induced membrane fusion in fibroblasts.


Carcinogenecity of the N-acyl derivatives of N-hydroxy-trans-4-aminostilbene in CD rats.
Carcinogenicities of the N-formyl (N-OH-FAS), N-acetyl (N-OH-AAS) and N-propionyl (N-OH-PAS) derivatives of N-hydroxy-trans-4-aminostilbene (N-OH-AS) were investigated in male and female CD rats. They were injected, i.p. 10 mumol/kg body weight (bwt) twice a week for 6 weeks, and they were killed at the end of 62 weeks. The N-formyl, N-acetyl and N-propionyl derivatives of N-hydroxy-4-aminobiphenyl (N-OH-ABP) were similarly injected at a dose of 100 mumol/kg bwt for comparison in female CD rats. Tumors of the liver, mammary gland and ear duct were produced in the female rats by these N-OH-AS derivatives. N-OH-AAS and N-OH-PAS were more active in the induction of mammary and ear duct tumors than N-OH-FAS. These N-OH-AS derivatives produced more tumors than did the N-OH-ABP derivatives, even at 1/10 dose of the N-OH-ABP derivatives. In male CD rats, these N-OH-AS derivatives produced peritesticular mesothelioma and tumors of the pancreas and ear duct. N-OH-PAS also produced tumors of the small intestine and lung. The acetyl and propionyl derivatives were more carcinogenic than the formyl derivative of N-OH-AS for both male and female CD rats, suggesting that cytosolic acetyltransferases may be more important than the microsomal ones in activating these carcinogens.


[Identification of factors influencing hospital admission delay after ischemic cerebrovascular stroke. Study of a rural population].
We studied the time of arrival of 235 consecutive patients admitted to the emergency department of a University Hospital located in a rural area after the first symptoms of ischemic stroke or TIA. Among the following factors, we determined those that might be involved in delayed admission: place of symptom onset, time and place of onset of the first symptoms, contact with a general practitioner before admission time, mode of transportation, clinical score, impairment of consciousness, presence of seizures, heart complaints or headache, age and past medical history of cerebrovascular, cardiovascular and hypertension diseases. Half of the patients arrived within 4 h 10 of symptom discovery and 55 p. cent arrived within 6 hours. The percentage of patients arriving within 3 h (p = 0.001) and 6 h (p = 0.001) was higher for those who had a stroke during the day (8 a.m.-8 p.m.) than during the evening and night. The other characteristics associated with a shorter delay included a low neurological score on the Mathew's Stroke Scale (p < 0.001 at 3 h and p = 0.001 at 6 h) and younger age (p = 0.015 at 3 h). Presence of headache delayed admission (p = 0.010). Forty-five percent of patients arrive at the hospital 6 hours after the discovery of symptoms, too late to receive optimal stroke therapy. Widespread public education on stroke is necessary to reduce the delay of admission, particularly for old patients and in case of mild to moderate deficits.


[Endoscopic retrograde cholangiopancreatography prior to laparoscopic cholecystectomy in patients with suspected choledocholithiasis].
Laparoscopic cholecystectomy is the treatment of choice for patients with symptomatic gallstones. The management of choledocholithiasis in these patients remains controversial. Endoscopic retrograde cholangiopancreatography (ERCP) with ductal stone clearance prior to laparoscopic cholecystectomy is one of the options. To evaluate the results of ERCP prior to laparoscopic cholecystectomy in patients with suspected ductal stones. We performed a retrospective study from patients who underwent ERCP prior to laparoscopic cholecystectomy in a four years period. ERCP was successful in 86 out of 88 patients (97.7%). Common bile duct (CBD) stones were found in 34 patients (39.5%). Sixty two of 86 patients had symptomatic gallstones with abnormal liver function test and/or ultrasound. CBD stones were found in 25 of the 62 symptomatic patients (40.3%). Twenty four patients had acute biliary pancreatitis. CBD stones were found in nine of these patients (37.5%). All patients with CBD stones underwent stone extraction after endoscopic sphincterotomy (ES). Sixteen other patients underwent ES for suspected obstruction at the ampulla. Stone extraction was successful in 100% of patients. There were six patients with complications (6.9%). Four patients had pancreatitis (4.6%), one patient hemorrhage (1.1%) and one patient cholangitis (1.1%). Analysis using logistic regression model showed that CBD stones on ultrasonography was the only variable significantly associated with choledocholithiasis (P < 0.001). Preoperative ERCP is useful in the management of CBD stones prior to laparoscopic cholecystectomy.


Behaviour of Medial Rectus Motoneurons in the Alert Cat.
The activity of identified medial rectus motoneurons was recorded in alert cats during spontaneous and vestibular induced eye movements. Medial rectus motoneurons fired a burst of spikes slightly preceding adducting saccades and increased their discharge rate linearly with successive eye positions in the adducting direction. Conduction velocity (21.3 - 98.2 m/s), eye position sensitivity (ks, 7.1 +/- 1.5 spikes/s/deg), and eye velocity sensitivity (rs, 1 +/- 0.2 spikes/s/deg/s) during spontaneous eye movements, and time constants calculated from phase lead analysis (To, 135 +/- 36 ms) showed values similar to those described previously for cat abducens motoneurons. The firing rate during repeated fixation of the same eye position was affected significantly by the direction of the preceding saccade and by the animal's level of alertness. Eye velocity sensitivity was not significantly affected by changes in the animal's level of alertness. A weak negative relationship (coefficient of correlation=-0.56) was observed between eye velocity sensitivity (rv) and sinusoidal rotational frequency, with no change in eye position sensitivity (kv) with stimulus frequency. The subsequent changes in the time constant (Tv) calculated as Tv=rv/kv in relation to stimulus frequency suggests that the oculomotor system deviates from a (linear) first-order model.


Performance evaluation of five commercial real-time PCR reagent systems using TaqMan assays for B. anthracis detection.
Real-time PCR assay sensitivity is affected by the choice and concentrations of reaction mix constituents among other factors such as primers, probes, and analytical assay platforms. Commercially available reagent mixes facilitate PCR assay set-up with fewer steps and timeliness. However, determination of analytical assay framework is important for ready-to-use real-time PCR reagent systems for rapid, quantitative and accurate detection of bioterror pathogens such as Bacillus anthracis. In this study, performance characteristics of five commercially available quantitative PCR reagent mixes were evaluated using TaqMan-based real-time PCR. The reagent systems were tested for compatibility on the ABI 7000 assay platform and compared for their distinctive analytical characteristics using the B. anthracis rpoB and pag gene real-time PCR assays. Knowledge of distinctive assay performance characteristics of commercially available qPCR reagent mixes is critical for carefully designing analytical assay systems. The ABI, ABgene and Eppendorf reagent systems performed consistently overall for the two TaqMan assays for B. anthracis detection that were used in the current study. However, the use of Eppendorf reagent system requires shorter thermal cycling time. In addition, while the ABI and Eppendorf systems have similar assay sensitivity for both the rpoB and pag assays, the Eppendorf system achieves the same with lower C(T) values.


Diagnostic Value of SjR2 Gene in Colonic Tissue from Schistosoma Japonicum Infected Hosts.
BACKGROUND The prevalence and intensity of schistosomiasis infection in China has decreased markedly in recent years. Therefore, more accurate methods are critically needed to ensure further control of low-intensity schistosomiasis infection. For chronic schistosomiasis patients, the detection of schistosome eggs in colorectal mucosa tissues is commonly used. This work aimed to explore differences in sensitivity of the Schistosoma japonicum (S. japonicum) retrotransposon (SjR2) gene in colon tissue from S. japonicum infected hosts and to develop an ideal method for genetic diagnosis of low-intensity schistosomiasis. MATERIAL AND METHODS Serum and colon samples were collected from mice at different time points, either post-infection (PI) or post-treatment (PT). Colorectal biopsy specimens from outpatients with schistosomiasis were collected. All samples from mice and patients, including serum as well as colon tissue containing eggs and tissue containing no eggs, were examined using the polymerase chain reaction technique. RESULTS The results showed that the SjR2 gene could be detected in all colon tissue containing at least one egg, except for when the egg was completely degraded. The positive rate of gene detection in serum was low. The results from egg-free colon tissue from around the eggs were more consistent with the actual parasitism in vivo. CONCLUSIONS The results indicate that detection of the gene in colon tissue located within a 0.5 cm distance from the eggs would be a practical and ideal method for genetic diagnosis of schistosomiasis. After the colorectal biopsy, this method can be a sensitive assisted examination to the clinical diagnosis of low-intensity schistosomiasis infection.


The Experience of Alzheimer's Disease Family Caregivers in a Latino Community: Expectations and Incongruences in Support Services.
Current theoretical constructs on the utilization of formal support for Latino caregivers focus on familism and exclude the cultural values represented in the service system. The purpose of this paper is to highlight the experience of care for Latino family caregivers to persons with Alzheimer's disease and related dementias (ADRD). We also examine the cultural congruence between provider perspectives with the expectations of Latino ADRD caregivers. We conducted extended interviews with 24 Latino ADRD caregivers and 10 service providers. Interview transcripts were coded and analyzed using a grounded theory approach. Our study provides a deeper understanding of Latino caregiving experiences and highlights some of the structural and systematic issues in current systems of caregiver support. While Latino families have very specific notions of care, by upholding notions of familism, there is a tendency to not look deeper into how they may be better supported in caregiving and fall into the "culture trap." The assumption that family should be the natural support network for older adults may lead to health and social systems of care to ignore the specific needs of the Latino population. Services are being provided under a model that was established four decades ago and may not reflect current realities. The concept of "an ethics of care" allows us to move beyond familism and explain that underutilization of services may also be due in part to the cultural incongruence between what service providers offer and the perceived needs of Latino caregivers.


The Cost-Effectiveness of HIV/STI Prevention in High-Income Countries with Concentrated Epidemic Settings: A Scoping Review.
The purpose of this scoping review is to establish the state of the art on economic evaluations in the field of HIV/STI prevention in high-income countries with concentrated epidemic settings and to assess what we know about the cost-effectiveness of different measures. We reviewed economic evaluations of HIV/STI prevention measures published in the Web of Science and Cost-Effectiveness Registry databases. We included a total of 157 studies focusing on structural, behavioural, and biomedical interventions, covering a variety of contexts, target populations and approaches. The majority of studies are based on mathematical modelling and demonstrate that the preventive measures under scrutiny are cost-effective. Interventions targeted at high-risk populations yield the most favourable results. The generalisability and transferability of the study results are limited due to the heterogeneity of the populations, settings and methods involved. Furthermore, the results depend heavily on modelling assumptions. Since evidence is unequally distributed, we discuss implications for future research.


Effect of duration of upper- and lower-extremity rehabilitation sessions and walking speed on recovery of interlimb coordination in hemiplegic gait.
The effects of different durations of rehabilitation sessions for the upper extremities (UEs) and lower extremities (LEs) on the recovery of interlimb coordination in hemiplegic gait in patients who have had a stroke were investigated. Fifty-three subjects who had strokes involving their middle cerebral arteries were assigned to rehabilitation programs with (1) an emphasis on the LEs, (2) an emphasis on the paretic UE, or (3) a condition in which the paretic arm (UE) and leg (LE) were immobilized with an inflatable pressure splint (control treatment). The 3 treatment regimens were applied for 30 minutes, 5 days a week, during the first 20 weeks after onset of stroke. All subjects also participated in a rehabilitation program 5 days a week that consisted of 15 minutes of UE exercises and 15 minutes of LE exercises in addition to a weekly 11/2-hour session of training in activities of daily living. A repeated-measures design was used. Differences among the 3 treatment regimens were evaluated in terms of comfortable and maximal walking speeds. In addition, mean continuous relative phase (CRP) between paretic arm and leg (PAL) movements and nonparetic arm and leg (NAL) movements and standard deviations of CRP of both limb pairs as a measurement of stability (variability) were evaluated. Comfortable walking speed improved in the group that received interventions involving the LEs compared with the group that received interventions involving the UEs and the group that received the control treatment. No differences among the 3 treatment conditions were found for the mean CRP of NAL and PAL as well as the standard deviation of CRP of both limb pairs. With the exception of an improved comfortable walking speed as a result of a longer duration of rehabilitation sessions, no differential effects of duration of rehabilitation sessions for the LEs and UEs on the variable we measured related to hemiplegic gait were found. Increasing walking speed, however, resulted in a larger mean CRP for both limb pairs, with increased stability and asymmetry of walking, indicating that walking speed influences interlimb coordination in hemiplegic gait.


Robust autofocusing method for multi-wavelength lensless imaging.
Lensless imaging based on multi-wavelength phase retrieval becomes a promising technology widely used as it has simple acquisition, miniaturized size and low-cost setup. However, measuring the sample-to-sensor distance with high accuracy, which is the key for high-resolution reconstruction, is still a challenge. In this work, we propose a multi-wavelength criterion to realize autofocusing modulation, i.e., achieving much higher accuracy in determining the sample-to-sensor distance, compared to the conventional methods. Three beams in different spectrums are adopted to illuminate the sample, and the resulting holograms are recorded by a CCD camera. The patterns calculated by performing back propagation of the recorded holograms, with exhaustively searched sample-to-sensor distance value, are adopted to access the criterion. Image sharpness can be accessed and the optimal sample-to-sensor distance can be finely determined by targeting the valley of the curve given by the criterion. Through our novel multi-wavelength based autofocusing strategy and executing further phase retrieval process, high-resolution images can be finally retrieved. The applicability and robustness of our method is validated both in simulations and experiments. Our technique provides a useful tool for multi-wavelength lensless imaging under limited experimental conditions.


It's not what you say but the way that you say it: an fMRI study of differential lexical and non-lexical prosodic pitch processing.
This study aims to identify the neural substrate involved in prosodic pitch processing. Functional magnetic resonance imaging was used to test the premise that prosody pitch processing is primarily subserved by the right cortical hemisphere.Two experimental paradigms were used, firstly pairs of spoken sentences, where the only variation was a single internal phrase pitch change, and secondly, a matched condition utilizing pitch changes within analogous tone-sequence phrases. This removed the potential confounder of lexical evaluation. fMRI images were obtained using these paradigms. Activation was significantly greater within the right frontal and temporal cortices during the tone-sequence stimuli relative to the sentence stimuli. This study showed that pitch changes, stripped of lexical information, are mainly processed by the right cerebral hemisphere, whilst the processing of analogous, matched, lexical pitch change is preferentially left sided. These findings, showing hemispherical differentiation of processing based on stimulus complexity, are in accord with a 'task dependent' hypothesis of pitch processing.


Nuquantus: Machine learning software for the characterization and quantification of cell nuclei in complex immunofluorescent tissue images.
Determination of fundamental mechanisms of disease often hinges on histopathology visualization and quantitative image analysis. Currently, the analysis of multi-channel fluorescence tissue images is primarily achieved by manual measurements of tissue cellular content and sub-cellular compartments. Since the current manual methodology for image analysis is a tedious and subjective approach, there is clearly a need for an automated analytical technique to process large-scale image datasets. Here, we introduce Nuquantus (Nuclei quantification utility software) - a novel machine learning-based analytical method, which identifies, quantifies and classifies nuclei based on cells of interest in composite fluorescent tissue images, in which cell borders are not visible. Nuquantus is an adaptive framework that learns the morphological attributes of intact tissue in the presence of anatomical variability and pathological processes. Nuquantus allowed us to robustly perform quantitative image analysis on remodeling cardiac tissue after myocardial infarction. Nuquantus reliably classifies cardiomyocyte versus non-cardiomyocyte nuclei and detects cell proliferation, as well as cell death in different cell classes. Broadly, Nuquantus provides innovative computerized methodology to analyze complex tissue images that significantly facilitates image analysis and minimizes human bias.


ESTIMATION OF CONSTANT AND TIME-VARYING DYNAMIC PARAMETERS OF HIV INFECTION IN A NONLINEAR DIFFERENTIAL EQUATION MODEL.
Modeling viral dynamics in HIV/AIDS studies has resulted in deep understanding of pathogenesis of HIV infection from which novel antiviral treatment guidance and strategies have been derived. Viral dynamics models based on nonlinear differential equations have been proposed and well developed over the past few decades. However, it is quite challenging to use experimental or clinical data to estimate the unknown parameters (both constant and time-varying parameters) in complex nonlinear differential equation models. Therefore, investigators usually fix some parameter values, from the literature or by experience, to obtain only parameter estimates of interest from clinical or experimental data. However, when such prior information is not available, it is desirable to determine all the parameter estimates from data. In this paper, we intend to combine the newly developed approaches, a multi-stage smoothing-based (MSSB) method and the spline-enhanced nonlinear least squares (SNLS) approach, to estimate all HIV viral dynamic parameters in a nonlinear differential equation model. In particular, to the best of our knowledge, this is the first attempt to propose a comparatively thorough procedure, accounting for both efficiency and accuracy, to rigorously estimate all key kinetic parameters in a nonlinear differential equation model of HIV dynamics from clinical data. These parameters include the proliferation rate and death rate of uninfected HIV-targeted cells, the average number of virions produced by an infected cell, and the infection rate which is related to the antiviral treatment effect and is time-varying. To validate the estimation methods, we verified the identifiability of the HIV viral dynamic model and performed simulation studies. We applied the proposed techniques to estimate the key HIV viral dynamic parameters for two individual AIDS patients treated with antiretroviral therapies. We demonstrate that HIV viral dynamics can be well characterized and quantified for individual patients. As a result, personalized treatment decision based on viral dynamic models is possible.


Stimulation of protein kinase C-dependent and -independent signaling pathways by bistratene A in intestinal epithelial cells.
The marine toxin bistratene A (BisA) potently induces cytostasis and differentiation in a variety of systems. Evidence that BisA is a selective activator of protein kinase C (PKC) delta implicates PKC delta signaling in the negative growth-regulatory effects of this agent. The current study further investigates the signaling pathways activated by BisA by comparing its effects with those of the PKC agonist phorbol 12-myristate 13-acetate (PMA) in the IEC-18 intestinal crypt cell line. Both BisA and PMA induced cell cycle arrest in these cells, albeit with different kinetics. While BisA produced sustained cell cycle arrest in G(0)/G(1) and G(2)/M, the effects of PMA were transient and involved mainly a G(0)/G(1) blockade. BisA also produced apoptosis in a proportion of the population, an effect not seen with PMA. Both agents induced membrane translocation/activation of PKC, with BisA translocating only PKC delta and PMA translocating PKC alpha, delta, and epsilon in these cells. Notably, while depletion of PKC alpha, delta, and epsilon abrogated the cell cycle-specific effects of PMA in IEC-18 cells, the absence of these PKC isozymes failed to inhibit BisA-induced G(0)/G(1) and G(2)/M arrest or apoptosis. The cell cycle inhibitory and apoptotic effects of BisA, therefore, appear to be PKC-independent in IEC-18 cells. On the other hand, BisA and PMA both promoted PKC-dependent activation of Erk 1 and 2 in this system. Thus, intestinal epithelial cells respond to BisA through activation of at least two signaling pathways: a PKC delta-dependent pathway, which leads to activation of mitogen-activated protein kinase and possibly cytostasis in the appropriate context, and a PKC-independent pathway, which induces both cell cycle arrest in G(0)/G(1) and G(2)/M and apoptosis through as yet unknown mechanisms.


Disparities in housing status among veterans with general medical, cognitive, and behavioral health conditions.
The study explored disparities in housing status among veterans with general medical, cognitive, and behavioral health conditions. Multinomial mixed-effects models estimated the relationship between medical, cognitive, and behavioral health comorbidities and housing instability among veterans enrolled in the Veterans Health Administration (VHA) (N=1,582,125) who responded to the Homelessness Screening Clinical Reminder for homelessness and risk during a three-month period. Veterans were two or more times as likely to screen positive for homelessness or risk if they had a diagnosis of a cognitive or behavioral health conditions in the study. Findings related to general medical conditions were inconsistent. The study found disparities in housing instability among VHA outpatients with cognitive and behavioral health conditions, suggesting the need to identify veterans with these conditions experiencing housing instability and the need to develop appropriate interventions to mitigate homelessness or risk.


Uncovering Modern Clinical Applications of Fuzi and Fuzi-Based Formulas: A Nationwide Descriptive Study With Market Basket Analysis.
Background: As time evolved, traditional Chinese medicine (TCM) became integrated into the global medical system as complementary treatments. Some essential TCM herbs started to play a limited role in clinical practices because of Western medication development. For example, Fuzi (Aconiti Lateralis Radix Praeparata) is a toxic but indispensable TCM herb. Fuzi was mainly used in poor circulation and life-threatening conditions by history records. However, with various Western medication options for treating critical conditions currently, how is Fuzi used clinically and its indications in modern TCM are unclear. This study aimed to evaluate Fuzi and Fuzi-based formulas in modern clinical practices using artificial intelligence and data mining methods. Methods: This nationwide descriptive study with market basket analysis used a cohort selected from the Taiwan National Health Insurance database that contained one million national representatives between 2003 and 2010 used for our analysis. Descriptive statistics were performed to demonstrate the modern clinical indications of Fuzi. Market basket analysis was calculated by the Apriori algorithm to discover the association rules between Fuzi and other TCM herbs. Results: A total of 104,281 patients using 405,837 prescriptions of Fuzi and Fuzi-based formulas were identified. TCM doctors were found to use Fuzi in pulmonary (21.5%), gastrointestinal (17.3%), and rheumatologic (11.0%) diseases, but not commonly in cardiovascular diseases (7.4%). Long-term users of Fuzi and Fuzi-based formulas often had the following comorbidities diagnosed by Western doctors: osteoarthritis (31.0%), peptic ulcers (29.5%), hypertension (19.9%), and COPD (19.7%). Patients also used concurrent medications such as H2-receptor antagonists, nonsteroidal anti-inflammatory drugs, β-blockers, calcium channel blockers, and aspirin. Through market basket analysis, for the first time, we noticed many practical Fuzi-related herbal pairs such as Fuzi-Hsihsin (Asari Radix et Rhizoma)-Dahuang (Rhei Radix et Rhizoma) for neurologic diseases and headache. Conclusion: For the first time, big data analysis was applied to uncover the modern clinical indications of Fuzi in addition to traditional use. We provided necessary evidence on the scientific use of Fuzi in current TCM practices, and the Fuzi-related herbal pairs discovered in this study are helpful to the development of new botanical drugs.


A family study of spina bifida and anencephalus in Belfast, Northern Ireland (1964 to 1968).
The parents of 226 of the 360 patients with anencephalus or spinal bifida or both, born in Belfast 1964 to 1968, were visited to document the occurrence of these malformations among other relatives. The proportions of sibs with anencephalus and spina bifida were 10.41% for spina bifida index patients and 6.4% for anencephalus. For patients born after the index patients, the proportions were 12.19% and 6.35%, respectively. The overall incidence of either malformation among sibs was 8.87%. This estimate is higher than the 4 to 5% commonly reported and is probably related to the specific background of the Northern Ireland population, which is known to have the highest incidence of CNS malformations in the United Kingdom. The substantial size of this risk indicates the importance of amniocentesis for monitoring subsequent pregnancies of women who have had one child with a CNS malformation.


Mediterranean diet and cardiovascular disease: historical perspective and latest evidence.
The concept that the Mediterranean diet was associated with a lower incidence of cardiovascular disease (CVD) was first proposed in the 1950s. Since then, there have been randomized controlled trials and large epidemiological studies that reported associations with lower CVD: in 1994 and 1999, the reports of the intermediate and final analyses of the trial Lyon Diet Heart Study; in 2003, a major epidemiological study in Greece showing a strong inverse association between a Mediterranean score and the risk of cardiovascular complications; in 2011-2012, several reports showing that even non-Mediterranean populations can gain benefits from long-term adhesion to the Mediterranean diet; and in 2013, the PREDIMED trial showing a significant risk reduction in a low-risk population. Contrary to the pharmacological approach of cardiovascular prevention, the adoption of the Mediterranean diet has been associated with a significant reduction in new cancers and overall mortality. Thus, in terms of evidence-based medicine, the full adoption of a modern version of the Mediterranean diet pattern can be considered one of the most effective approaches for the prevention of fatal and nonfatal CVD complications.


Endoscopic-assisted craniofacial resection: a case series and post-operative outcome.
Craniofacial resection is commonly performed in the surgical resection of sinonasal tumours involving anterior skull base. It entails a bicoronal scalp flap with lateral rhinotomy or an extended lateral rhinotomy to expose the anterior skull base. Transfacial approach is necessary in the resection of the nasal part of the tumour. The choice of surgical approach is based heavily on the surgeon's experience and training. The results of endoscopic-assisted craniofacial resection for sinonasal tumours performed in our center in eight patients from 1998 to 2005 were reviewed. There were seven males and one female with age ranging from 18 to 62 years (mean 42.4 years). There was each a case of mature teratoma, poorly differentiated squamous cell carcinoma, undifferentiated squamous cell carcinoma, olfactory neuroblastoma, fibrous dysplasia, inverted papilloma and two cases of sinonasal neuroendocrine carcinoma. The mean follow up duration for these eight patients post surgery was 21.4 months. Out of eight patients, five underwent surgery with no adverse complications. The complications encountered were a cerebrospinal leak and a postoperative transient V and VI cranial nerve palsy. One patient with sinonasal undifferentiated carcinoma died of lung metastasis at 11 months post-surgery. The endoscopic-assisted craniofacial resection is a highly useful surgical technique to avoid the unsightly facial scar of the lateral rhinotomy or the Weber-Ferguson incision, postoperative paranasal sinuses infection and avoidance of tracheostomy in selected cases. We found that this approach has lower morbidity rate in selected cases.


[Preparation and properties of stretched polytene chromosomes. 2. Mechanism of stretching].
Isolated polytene chromosomes were stretched in a 0.125 M NaCl solution with constant speed, by constant force and by cyclically changing force. For each regime, the dependence of chromosome length on the time and force magnitude were recorded. From this it may be concluded that three processes are involved in chromosome stretching: viscoelastic deformation, viscous flow of DNP segments, and cristallization, i.e. intermolecular cross-linking of neighbour segments. At a high rate stretching (V greater than Vo) chromosome may be torn like at small deformation; when rate is V greater than Vo chromosome deformation is mostly viscoelastic; at rates V approximately Vo viscous flow of DNP segments if predominant. We estimate Vo approximately less than 3--6 mum/s. Electron microscopy shows that during chromosome stretching its DNP fibers are oriented along chromosome axis without detectable breaks.


Associations between mental health disorder and management of physical chronic conditions in China: a pooled cross-sectional analysis.
Physical non-communicable diseases (NCDs) and mental health disorders are a rapidly increasing health burden in low-and middle-income countries. This study aims to examine the relationships between mental health disorders and cascade of care in managing four common physical NCDs (hypertension, diabetes, dyslipidemia, chronic kidney disease) in China. We utilized two waves of nationally-representative China Health and Retirement Longitudinal Study (CHARLS 2011, 2015) of older adult population aged 45 and above. A series of unadjusted and adjusted mixed-effect logistic regression was applied to evaluate the association between presence of mental health disorder and physical chronic disease awareness, treatment, and control. We found that the odds of dyslipidemia (AOR 1.81, 95% CI 1.36-2.39) and kidney disease awareness (AOR 2.88, 95% CI 2.12-3.92) were higher for individuals with mental chronic conditions, compared to those without mental chronic conditions. The odds of having hypertension treatment was higher for subjects with mental health disorder, compared to those without (AOR 1.32, 95% CI 1.02-1.70). The odds of having physical chronic conditions controlled was not significantly associated with having mental chronic conditions (P > 0.05). These results indicated that adults with mental health disorder have a greater likelihood of awareness of having dyslipidemia and kidney disease, and receiving treatment for hypertension. Strategies to address the growing burden of physical-mental NCDs in China should include efforts to improve management of patients with comorbid health condition and improve access to continual high-quality treatment after the first diagnosis.


Performance of Predictive Equations Specifically Developed to Estimate Resting Energy Expenditure in Ventilated Critically Ill Children.
To determine, based on indirect calorimetry measurements, the biases of predictive equations specifically developed recently for estimating resting energy expenditure (REE) in ventilated critically ill children, or developed for healthy populations but used in critically ill children. A secondary analysis study was performed using our data on REE measured in a previous prospective study on protein and energy needs in pediatric intensive care unit. We included 75 ventilated critically ill children (median age, 21 months) in whom 407 indirect calorimetry measurements were performed. Fifteen predictive equations were used to estimate REE: the equations of White, Meyer, Mehta, Schofield, Henry, the World Health Organization, Fleisch, and Harris-Benedict and the tables of Talbot. Their differential and proportional biases (with 95% CIs) were computed and the bias plotted in graphs. The Bland-Altman method was also used. Most equations underestimated and overestimated REE between 200 and 1000 kcal/day. The equations of Mehta, Schofield, and Henry and the tables of Talbot had a bias ≤10%, but the 95% CI was large and contained values by far beyond ±10% for low REE values. Other specific equations for critically ill children had even wider biases. In ventilated critically ill children, none of the predictive equations tested met the performance criteria for the entire range of REE between 200 and 1000 kcal/day. Even the equations with the smallest bias may entail a risk of underfeeding or overfeeding, especially in the youngest children. Indirect calorimetry measurement must be preferred.


Trends in Renal-Cell Carcinoma Incidence and Mortality in the United States in the Last 2 Decades: A SEER-Based Study.
Renal-cell carcinoma (RCC) is one of the common malignancies in the United States. RCC incidence and mortality have been changing for many reasons. We performed a thorough investigation of incidence and mortality trends of RCC in the United States using the cell Surveillance, Epidemiology, and End Results (SEER) database. The 13 SEER registries were accessed for RCC cases diagnosed between 1992 and 2015. Incidence and mortality were calculated by demographic and tumor characteristics. We calculated annual percentage changes of these rates. Rates were expressed as 100,000 person-years. A total of 104,584 RCC cases were reviewed, with 47,561 deaths. The overall incidence was 11.281 per 100,000 person-years. Incidence increased by 2.421% per year (95% confidence interval, 2.096, 2.747; P < .001) but later became stable since 2008. However, the incidence of clear-cell subtype continued to increase (1.449%; 95% confidence interval, 0.216, 2.697; P = .024). RCC overall mortality rates have been declining since 2001. However, mortality associated with distant RCC only started to decrease in 2012, with an annual percentage change of 18.270% (95% confidence interval, -28.775, -6.215; P = .006). Despite an overall increase in the incidence of RCC, there has been a recent plateau in RCC incidence rates with a significant decrease in mortality.


The rationale for caries prevention through the use of sugar substitutes.
The emergence of S. mutans in the plaque flora appears to have depended upon the ability of the organism to sequester sucrose from dietary sources, particularly from between-meal, snack-type foods. S. mutans appears to have a pH optimum at about the pH required for tooth solution to begin. This specialization which makes S. mutans cariogenic, also makes it vulnerable to dietary regimens that contain few or no sucrose snacks. As snacks are consumed by youngsters, primarily for pleasure, the use of pleasant tasting sucrose substitutes, that cannot be fermented by the plaque flora and especially by S. mutans, constitutes a viable tactic for caries control. The potential of this approach was demonstrated by the 80 per cent reduction of caries relative to a sucrose control which was observed with a xylitol chewing gum in the Turku study.


Exploring positive hospital ward soundscape interventions.
Sound is often considered as a negative aspect of an environment that needs mitigating, particularly in hospitals. It is worthwhile however, to consider how subjective responses to hospital sounds can be made more positive. The authors identified natural sound, steady state sound and written sound source information as having the potential to do this. Listening evaluations were conducted with 24 participants who rated their emotional (Relaxation) and cognitive (Interest and Understanding) response to a variety of hospital ward soundscape clips across these three interventions. A repeated measures ANOVA revealed that the 'Relaxation' response was significantly affected (n(2) = 0.05, p = 0.001) by the interventions with natural sound producing a 10.1% more positive response. Most interestingly, written sound source information produced a 4.7% positive change in response. The authors conclude that exploring different ways to improve the sounds of a hospital offers subjective benefits that move beyond sound level reduction. This is an area for future work to focus upon in an effort to achieve more positively experienced hospital soundscapes and environments.


An overview of Indian novel traditional medicinal plants with anti-diabetic potentials.
Diabetes mellitus is a global metabolic epidemic affecting essential biochemical activities in almost every age group. Indian literatures like Ayurveda have already mentioned herbal remediation for a number of human ailments. Among Indian traditional medicinal plants several potential anti-diabetic plants and herbs are being used as part of our diet since prehistoric time. India has a long list of native medicinal plants with confirmed blood sugar lowering property. Some of these have proved remarkable for cure of diabetes and its complications. The current paper is aimed at providing a review on clinical and experimental studies carried out on the most effective and commonly used hypoglycemic plants and herbs species from traditional Indian flora. This write-up includes hypoglycemic and anti-hyperglycemic activities of plants, active hypoglycemic compounds and constituents along with their available toxicity status.


GABP cooperates with c-Myb and C/EBP to activate the neutrophil elastase promoter.
Neutrophil elastase (NE) is a serine protease that is transcriptionally regulated during early myeloid differentiation. The murine NE (mNE) promoter contains functionally important c-Myb, C/EBP, and ets binding sites. Deletion of the ets site reduced promoter activity by 90%. Although the ets transcription factor, PU.1, bound to this ets site, it only modestly activated the mNE promoter. Here, we show that a second transcription factor from myeloid cells-GABP-binds to the mNE ets site but strongly activates the mNE promoter. GABP is a heteromeric transcription factor complex that consists of GABP alpha, an ets factor, and GABP beta, a Notch-related protein. GABP alpha bound to the mNE ets site and, in turn, recruited GABP beta to form a transcriptionally active complex. GABP alpha and PU.1 competed with each other for binding to the mNE ets site. GABP increased the activity of the mNE promoter sevenfold in U937 myeloid cells. GABP cooperated with c-Myb and C/EBP alpha to activate the mNE promoter more than 85-fold in otherwise nonpermissive, nonhematopoietic NIH 3T3 cells. Thus, GABP binds to the crucial mNE promoter ets site and powerfully activates its expression alone and in cooperation with the transcription factors c-Myb and C/EBP.


Gentamicin resistance in clinical-isolates of Pseudomonas aeruginosa associated with diminished gentamicin accumulation and no detectable enzymatic modification.
Three strains of Pseudomonas aeruginosa resistant to gentamicin obtained as representative gentamicin-resistant clinical isolates from the University of Alberta Hospital (UAH) in Edmonton, Canada were characterized to determine their mechanism of resistance. All strains showed wide aminoglycoside resistance (tobramycin, sisomicin, amikacin, streptomycin, kanamycin, SCH 20569) but contained no evidence of gentamicin-acetylating, adenylating or phosphorylating activity. Gentamicin inhibited amino-acid incorporation in cell-free systems equally well with either ribosomes or soluble cell fractions obtained from either resistant or sensitive strains. Plasmid DNA was detected in two strains but resistance could not be transferred by conjugation to either P. aeruginosa or Escherichia coli recipients. The resistant strains showed a marked reduction in energy-dependent accumulation of gentamicin compared to a sensitive strain. These strains which are common at UAH are most likely resistant due to a failure of gentamicin to be transported across the cytoplasmic membrane to ribosomal sites until relatively high external gentamicin concentrations.


[Use of surgical simulators in further education-A nationwide analysis in Germany].
In addition to learning theoretical knowledge, the medical specialist training in surgery necessitates the acquisition of practical surgical competences. Simulation-based teaching concepts represent an alternative to education and advanced training on patients. The aim of this study was to analyze the distribution and implementation of surgical simulators in German hospitals. The data analysis was carried out based on an individual on-line questionnaire with a total of 19 standardized questions. This was sent to the senior surgeons in hospitals and clinics via the email distributors of specialist societies for surgery in Germany. A total of 267 complete datasets were analyzed (response rate 12%). Of the participants 84% reported that they were active in a teaching hospital. At the time of the investigation 143 surgical simulators were in use at 35% of the hospitals and clinics included in the evaluation. There were clear regional differences between the individual federal states. Of the participants, 21.1% did not have a simulator at the hospital but the acquisition of one was planned. Simulation training was most frequently used by students (41.1%) and physicians during further education (32.5%). Simulators were not integrated into advanced surgical training in 81.8%. Of the participating hospitals, 94% showed an interest in integration into surgical specialist training in the future. The results of this survey confirmed the special importance of simulation-based training for surgical education in German hospitals; however, at the same time there were clear deficits in information concerning user behavior and a deficiency in the perceived integration of simulation training in advanced training for surgery.


A higher prevalence of endometriosis among Asian women does not contribute to poorer IVF outcomes.
The purpose of the study was to determine whether diagnosis of endometriosis or endometriosis with endometrioma influences in vitro fertilization (IVF) outcomes in an ethnically diverse population. Women undergoing a first IVF cycle (n = 717) between January 1, 2008 and December 31, 2009, at a university-affiliated infertility clinic, were retrospectively assessed for an endometriosis diagnosis. Differences in prevalence of endometriosis by ethnicity were determined, as well as differences in IVF success by ethnicity, with a focus on country of origin for Asian women. A multivariate model was generated to assess the relative contributions of country of origin and endometriosis to chance of clinical pregnancy with IVF. Endometriosis was diagnosed in 9.5% of participants; 3.5% also received a diagnosis of endometrioma. Endometriosis prevalence in Asian women was significantly greater than in Caucasians (15.7 vs. 5.8%, p < 0.01). Women of Filipino (p < 0.01), Indian (p < 0.01), Japanese (p < 0.01), and Korean (p < 0.05) origin specifically were more likely to have endometriosis than Caucasian women, although there was no difference in endometrioma presence by race/ethnicity. Oocyte quantity, embryo quality, and fertilization rates did not relate to endometriosis. Clinical pregnancy rates were significantly lower for Asian women, specifically in Indian (p < 0.05), Japanese (p < 0.05), and Korean (p < 0.05) women, compared to Caucasian women, even after controlling for endometriosis status. The prevalence of endometriosis appears to be higher in Filipino, Indian, Japanese, and Korean women presenting for IVF treatment than for Caucasian women; however, the discrepancy in IVF outcomes was conditionally independent of the presence of endometriosis. Future research should focus on improving pregnancy outcomes for Asian populations whether or not they are affected by endometriosis, specifically in the form of longitudinal studies where exposures can be captured prior to endometriosis diagnoses and infertility treatment.


Increased neuronal injury in clock gene Per-1 deficient-mice after cerebral ischemia.
Transient, severe global ischemia that arises in humans as a consequence of cardiac arrest or cardiac surgery or that is induced experimentally in animals, leads to selective and delayed neuronal death, particularly in the hippocampus. Especially, in this brain structure, clock genes are rhythmically expressed, for instance the inducible and archetypical clock gene is Period1 (Per1). An eventual involvement of its trans-activating protein products in the daytime-dependent severity of ischemia-induced cell damage is not excluded. Probably, neurons may exhibit endogenously a daytimedependent variation in the expression of predictive cell death proteins. We therefore compared the cell death machinery in the hippocampus between Per1(-/-)- and wildtype (WT) mice upon cerebral ischemia. Neuronal death in the hippocampal CA1-subfield, was observed in both types of mice, but the density of damaged cells in Per1(-/-)-mice was increased by more than 23% as compared to wildtype mice. To explore the mechanisms underlying the excessive vulnerability of the hippocampus in Per1(-/-)-mice and to address if hippocampal susceptibility inherits a daytime component, the expression of both, apoptotic and autophagic predictors of cell death was monitored. In Per1(-/-)-mice, the expression of apoptotic/autophagic markers are altered and higher levels of the proapoptotic factors such as cytochrome c and Apaf-1 were observed as compared to WT mice. Moreover, the autophagy marker LC3B was dramatically reduced in Per1(-/-)- mice. Our data suggests that basal activities of apoptosis and autophagy seem to be modulated by PER1, and that the autophagic machinery is probably slowed down when this clock gene is absent. These alterations may be causal for the observed innate vulnerability of Per1(-/-)-mice to cerebral ischemia.


Melatonin for pre- and postoperative anxiety in adults.
Anxiety in relation to surgery is a well-known problem. Melatonin offers an atoxic alternative to benzodiazepines in ameliorating this condition in the pre- and postoperative period. To assess the effect of melatonin on pre- and postoperative anxiety in adults when comparing melatonin with placebo or when comparing melatonin with benzodiazepines. The following databases were searched on 19 April 2013: CENTRAL, MEDLINE, EMBASE, CINAHL and Web of Science. For ongoing trials and protocols we searched clinicaltrials.gov, Current Controlled Trials and the World Health Organization (WHO) International Clinical Trials Registry Platform. We reran the search in October 2014. We will deal with any studies of interest when we update the review. Randomized, placebo-controlled or standard treatment-controlled, or both, studies that evaluated the effect of preoperatively administered melatonin on preoperative or postoperative anxiety. We included adult patients of both genders (15 to 90 years of age) undergoing any kind of surgical procedure in which it was necessary to use general, regional or topical anaesthesia. Data were extracted independently by two review authors. Data extracted included information about study design, country of origin, number of participants and demographic details, type of surgery, type of anaesthesia, intervention and dosing regimen, preoperative anxiety outcome measures and postoperative anxiety outcome measures. This systematic review identified 12 randomized controlled trials (RCTs) including 774 patients that assessed melatonin for treating preoperative anxiety, postoperative anxiety or both. Four of the 12 studies compared melatonin, placebo and midazolam, whereas the remaining eight studies compared melatonin and placebo only.The quality of the evidence for our primary outcome (melatonin versus placebo for preoperative anxiety) was high. More than half of the included studies had a low risk of selection bias and at least 75% of the included studies had a low risk of attrition, performance and detection bias. Most of the included studies had an unclear risk of reporting bias.Eight out the 10 studies that assessed the effect of melatonin on preoperative anxiety using a visual analogue scale (VAS) (ranging from 0 to 100 mm, higher scores indicate greater anxiety) showed a reduction compared to placebo. The reported estimate of effect (relative effect -13.36, 95% confidence interval (CI) -16.13 to -10.58; high quality evidence) was based on a meta-analysis of seven studies. Two studies did not show any difference between melatonin and placebo. Two studies comparing melatonin with midazolam using a VAS found no evidence of a difference in preoperative anxiety between the two groups (relative effect -1.18, 95% CI -2.59 to 0.23; low quality evidence).Eight studies assessed the effect of melatonin on postoperative anxiety. Four of these studies measuring postoperative anxiety 90 minutes postoperatively using a VAS did not find any evidence of a difference between melatonin and placebo (relative effect -3.71, 95% CI -9.26 to 1.84). Conversely, two studies showed a reduction of postoperative anxiety measured six hours after surgery using the State-Trait Anxiety Inventory (STAI) when comparing melatonin with placebo (relative effect -5.31, 95% CI -8.78 to -1.84; moderate quality evidence). Two studies comparing melatonin with midazolam using a VAS did not find any evidence of a difference between the two groups in postoperative anxiety (relative effect -2.02, 95% CI -5.82 to 1.78). When compared to placebo, melatonin given as premedication (tablets or sublingually) can reduce preoperative anxiety in adults (measured 50 to 100 minutes after administration). Melatonin may be equally as effective as standard treatment with midazolam in reducing preoperative anxiety in adults (measured 50 to 100 minutes after administration). The effect of melatonin on postoperative anxiety (measured 90 minutes and 6 hours after surgery) in adults is mixed but suggests an overall attenuation of the effect compared to preoperatively.


Patients pathways before and after treatments in emergency departments: A retrospective analysis of secondary data in Germany.
Increasing emergency department (ED) utilization induces considerable pressure on ED staff and organization in Germany. Reasons for certain ED attendances are seen partly in insufficient continuity of care outside of hospitals. To explore the health care patterns before and after an ED attendance in Germany, we used claims data from nine statutory health insurance funds, covering around 25 % of statutory health insurees (1). We descriptively analyzed ED attendances for adult patients in 2016 according to their sociodemographic characteristics and diagnoses (2). Based on the ED attendance as initial event, we investigated health care provider utilization 180 days before and after the respective ED treatment and are presented by means of Sankey diagrams. In total, 4,757,536 ED cases of 3,164,343 insured individuals were analyzed. Back pain was the most frequent diagnosis in outpatient ED cases (5.0 %), and 80.2 % of the patients visited primary care physicians or specialists 180 days before and 78.8 % 180 days after ED treatment. Among inpatient cases, heart failure (4.6 %) was the leading diagnosis and 74.6 % used primary care physicians or specialists 180 days before and 65.1 % 180 days after ED treatment. The ED re-attendance slightly increased for back pain (4.9 % to 7.9 %) and decreased for heart failure (13.4 % to 12.6 %).


Results of using the serological method of epidemiological investigation of plague foci in the Muyunkum and Eastern Kyzylkum deserts in 1978-1982.
Results of serological examination of 81,853 mammals from the Muyunkum and 26,303 from the Eastern Kyzylkum deserts were compared with results of a corresponding bacteriological examination for plague. In both foci and in all phases throughout the epizootic of plague, the serological method made it possible to detect infected animals 6-10 times more frequently in comparison with the bacteriological method. The big meriones mice, i.e., the basic carriers of plague in natural foci, were found to be infected considerably more (in percentage) frequently than the meridian meriones. Differences in the reactivity of meriones to the invasion of plague microbe were observed in both foci (the indices of titres in the antigen neutralization reaction were considerably higher in the Eastern Kyzylkums). The serological method of investigation is highly informative in evaluating both the present state of epizootic activity of a plague focus and its activity in the past.


A Prospective Comparative Study of 18 F-FDOPA PET/CT Versus 123 I-MIBG Scintigraphy With SPECT/CT for the Diagnosis of Pheochromocytoma and Paraganglioma.
This study aimed to compare the diagnostic performances of 18 F-FDOPA PET/CT and 123 I-MIBG scintigraphy with SPECT/CT for detection of pheochromocytoma and paraganglioma (PPGL). We conducted a prospective, single-institution comparative study. Patients suspected of having PPGL or those showing recurrence and/or distant metastasis of PPGL were enrolled. The primary objective was to affirm the noninferiority of 18 F-FDOPA PET/CT for diagnostic sensitivity. Both 123 I-MIBG scintigraphy with SPECT/CT (at 4 and 24 hours) and 18 F-FDOPA PET/CT (at 5 and 60 minutes after radiotracer administration) were performed. The final diagnosis was established either pathologically or via clinical follow-up. Nuclear physicians, unaware of the clinical data, undertook image analysis. Thirty-two patients were evaluated: 14 of 21 with an initial diagnosis and 9 of 11 with recurrence/metastasis had PPGLs in their final diagnoses. In patient-based analyses, 18 F-FDOPA PET/CT (95.7%) exhibited noninferior sensitivity compared with 123 I-MIBG SPECT/CT (91.3%), within the predetermined noninferiority margin of -12% by a 95% confidence interval lower limit of -10%. Both modalities showed no significant difference in specificity (88.9% vs 88.9%). In the region-based analysis for the recurrence/metastasis group, 18 F-FDOPA PET/CT demonstrated significantly higher sensitivity compared with 123 I-MIBG SPECT/CT (86.2% vs 65.5%, P = 0.031) and superior interobserver agreement (κ = 0.94 vs 0.85). The inclusion of an early phase in dual-phase 18 F-FDOPA PET/CT slightly improved diagnostic performance, albeit not to a statistically significant degree. 18 F-FDOPA PET/CT demonstrated noninferior sensitivity and comparable specificity to 123 I-MIBG SPECT/CT in the diagnosing PPGL. Notably, in the assessment of PPGL recurrence and metastasis, 18 F-FDOPA PET/CT outperformed 123 I-MIBG SPECT/CT in terms of both sensitivity and interobserver agreement.


A comparison of decision analysis and second opinions for surgical decisions.
Second opinions and decision analysis, a mathematical process the decision maker can use to represent and solve problems, were compared in hypothetical surgical situations. Fifty expert surgeons gave opinions and provided the information necessary to solve the problems by decision analyses. Each surgeon's opinion was randomly selected again as a second opinion. In six difficult cases, 59% of the individual opinions were correct when compared with previously determined answers. For two surgical second-opinion protocols, the accuracies were 54% and 60%. The accuracy of the decision analyses was 69%. Improvement from second-opinion protocols can be predicted mathematically and is limited. Improvement from decision analysis is not limited by mathematical constraints. Decision analysis may be preferable to second opinions in verifying surgical decisions.


Bioavailability assessment of a contaminated field sediment from Patrick Bayou, Texas, USA: toxicity identification evaluation and equilibrium partitioning.
Contaminated sediments are commonly found in urbanized harbors. At sufficiently high contaminant levels, sediments can cause toxicity to aquatic organisms and impair benthic communities. As a result, remediation is necessary and diagnosing the cause of sediment toxicity becomes imperative. In the present study, six sediments from a highly industrialized area in Patrick Bayou (TX, USA) were subjected to initial toxicity testing with the mysid, Americamysis bahia, and the amphipod, Ampelisca abdita. All sediments were toxic to the amphipods, while sites PB4A, PB6A, and PB9 were the only sites toxic to mysids. Due to its toxicity to both test organisms, site PB6A was chosen for a marine whole sediment phase I toxicity identification evaluation (TIE). Results of the TIE found toxicity to amphipods was primarily due to nonionic organic contaminants (NOCs), rather than cationic metals or ammonia. Causes of mysid toxicity in the TIE were less clear. An assessment of metal bioavailability using equilibrium partitioning (EqP) approaches supported the results of the TIE that cationic metals were not responsible for observed toxicity in PB6A for either organism. Toxic units (TU) calculated on measured concentrations of NOCs in the sediment yielded a total TU of 1.25, indicating these contaminants are contributing to the observed sediment toxicity. Using a combination of these TIE and EqP assessment tools, this investigation was capable of identifying NOCs as the likely class of contaminants causing acute toxicity to amphipods exposed to Patrick Bayou sediment. The cause of mysid toxicity was not definitively determined, but unmeasured NOCs are suspected.


A RING-type E3 ligase controls anther dehiscence by activating the jasmonate biosynthetic pathway gene DEFECTIVE IN ANTHER DEHISCENCE1 in Arabidopsis.
Suppression of expression of DAF [DEFECTIVE IN ANTHER DEHISCENCE1 (DAD1)-Activating Factor], a gene that encodes a putative RING-finger E3 ligase protein, causes non-dehiscence of the anthers, alters pollen development and causes sterility in 35S:DAF RNAi/antisense Arabidopsis plants. This mutant phenotype correlates with the suppression of DAF but not with expression of the two most closely related genes, DAFL1/2. The expression of DAD1 was significantly reduced in 35S:DAF RNAi/antisense plants, and complementation with 35S:DAF did not rescue the dad1 mutant, indicating that DAF acts upstream of DAD1 in jasmonic acid biosynthesis. This assumption is supported by the finding that 35S:DAF RNAi/antisense plants showed a similar cellular basis for anther dehiscence to that found in dad1 mutants, and that external application of jasmonic acid rescued the anther non-dehiscence and pollen defects in 35S:DAF antisense flowers. We further demonstrate that DAF is an E3 ubiquitin ligase and that its activity is abolished by C132S and H137Y mutations in its RING motif. Furthermore, ectopic expression of the dominant-negative C132S or H137Y mutations causes similar indehiscence of anthers and reduction in DAD1 expression in transgenic Arabidopsis. This result not only confirms that DAF controls anther dehiscence by positively regulating the expression of DAD1 in the jasmonic acid biosynthesis pathway, but also supports the notion that DAF functions as an E3 ubiquitin ligase, and that the conserved RING-finger region is required for its activity.


Endoscopic carpal tunnel release using the biportal technique.
The clinical study consisted of 27 patients and 30 hands that were operated on with the biportal endoscopic carpal tunnel release technique between 2000 and 2002. The mean follow-up time was 28 months. The time to return to work or complete recovery was found to average 12 days. The rate of functional recovery was 93% (27 hands), and 90% of hands (26 hands) were free of symptoms at the time of publication. According to our study, we conclude that the biportal endoscopic technique is an effective method to attain patient comfort; it is a minimally invasive method with a low complication rate in experienced hands for surgical treatment of carpal tunnel syndrome. Military persons can return to work quickly, without deficits in hand skills, with the use of this technique.


Mechanism of hERG inhibition by gating-modifier toxin, APETx1, deduced by functional characterization.
Human ether-à-go-go-related gene potassium channel 1 (hERG) is a voltage-gated potassium channel, the voltage-sensing domain (VSD) of which is targeted by a gating-modifier toxin, APETx1. APETx1 is a 42-residue peptide toxin of sea anemone Anthopleura elegantissima and inhibits hERG by stabilizing the resting state. A previous study that conducted cysteine-scanning analysis of hERG identified two residues in the S3-S4 region of the VSD that play important roles in hERG inhibition by APETx1. However, mutational analysis of APETx1 could not be conducted as only natural resources have been available until now. Therefore, it remains unclear where and how APETx1 interacts with the VSD in the resting state. We established a method for preparing recombinant APETx1 and determined the NMR structure of the recombinant APETx1, which is structurally equivalent to the natural product. Electrophysiological analyses using wild type and mutants of APETx1 and hERG revealed that their hydrophobic residues, F15, Y32, F33, and L34, in APETx1, and F508 and I521 in hERG, in addition to a previously reported acidic hERG residue, E518, play key roles in the inhibition of hERG by APETx1. Our hypothetical docking models of the APETx1-VSD complex satisfied the results of mutational analysis. The present study identified the key residues of APETx1 and hERG that are involved in hERG inhibition by APETx1. These results would help advance understanding of the inhibitory mechanism of APETx1, which could provide a structural basis for designing novel ligands targeting the VSDs of KV channels.


IL10 and PD-1 Cooperate to Limit the Activity of Tumor-Specific CD8+ T Cells.
Immune checkpoint inhibitors show great promise as therapy for advanced melanoma, heightening the need to determine the most effective use of these agents. Here, we report that programmed death-1(high) (PD-1(high)) tumor antigen (TA)-specific CD8(+) T cells present at periphery and at tumor sites in patients with advanced melanoma upregulate IL10 receptor (IL10R) expression. Multiple subsets of peripheral blood mononucleocytes from melanoma patients produce IL10, which acts directly on IL10R(+) TA-specific CD8(+) T cells to limit their proliferation and survival. PD-1 blockade augments expression of IL10R by TA-specific CD8(+) T cells, thereby increasing their sensitivity to the immunosuppressive effects of endogenous IL10. Conversely, IL10 blockade strengthened the effects of PD-1 blockade in expanding TA-specific CD8(+) T cells and reinforcing their function. Collectively, our findings offer a rationale to block both IL10 and PD-1 to strengthen the counteraction of T-cell immunosuppression and to enhance the activity of TA-specific CD8(+) T cell in advanced melanoma patients.


Attenuation correction and gating synergistically improve the diagnostic accuracy of myocardial perfusion SPECT.
The diagnostic accuracy of myocardial perfusion single photon emission computed tomography is limited by soft tissue attenuation. Artifacts may be reduced by attenuation correction (AC) or compensated for by assessment of wall motion in gated images. We studied the benefit of gating and AC, both separately and combined, in improving accuracy. Sixty-six subjects (27 with > or =50% angiographic stenosis, 5 with <50% stenosis, and 34 Bayesian normal volunteers) underwent gated AC single photon emission computed tomography. Images were reconstructed and independently viewed in 4 ways: static with motion correction (MC) only, gated with MC only, static with MC plus blur correction plus AC (referred to as combined corrections [CC]), and gated with CC. Images were interpreted by 2 blinded observers for overall presence of coronary disease and for vascular territory (left anterior descending [LAD], left circumflex [LCx], and right coronary artery [RCA]). Statistical analysis of sensitivity and normalcy was done by means of the Cochran Q test. Overall diagnostic accuracy showed statistically significant improvement (P =.05 for sensitivity, P <.001 for normalcy), progressing from static MC to gated MC to static CC to gated CC (sensitivity/normalcy = 85%/54%, 78%/62%, 93%/77%, and 96%/85%, respectively, for the 4 reconstruction and viewing approaches). Sensitivity was highest in all 3 vascular territories for the combination of gating and CC; normalcy was also highest with the same combination for the LAD and RCA territories; sensitivity/normalcy with this combination was 85%/87% for the LAD, 69%/87% for the LCx, and 89%/87% for the RCA territory. The combination of gating and CC provides the highest diagnostic accuracy, and gating and AC should thus be considered complementary and synergistic.


Urolithiasis in adults. Clinical and biochemical aspects.
Urolithiasis is a multifactorial recurrent disease of world-wide distribution in rural, urban, industrial and non-industrial regions. Changes in urinary pH is a risk factor especially with hyperuricosuria, hypercalciuria or hyperoxaluria. With recurrence, hypercalcuria and higher urinary oxalate levels are more frequent. Hypercalciuria and hyperuricosuria showed correlation with family history of stones. The ionic relations between various stone forming salts in urine of patients are opposite to that in controls and are well represented in stone composition. Obesity is a risk factor in both genders. Over eating a diet rich in all nutrients was associated with hyperuricosuria while a diet high only in fat was associated with other urinary disturbances. High protein and fat intake are risk factors. High or low calcium diet was associated with urolithiasis and supplemental calcium is not a risk factor. Potassium and magnesium citrate are potent in inhibiting the growth of stone fragments after extracorporeal shock wave lithotripsy. Whether in patients or normal subjects, drinking hard water should be avoided; tap water or low calcium content water is preferable. Seasonal variations in temperature affected urinary volume, pH and relative saturation of uric acid. To prevent recurrence, patients should maintain high fluid intake achieving a urine volume of 2 liters per day.


Myofilament calcium regulation in human myocardium.
We investigated whether decreased myofilament calcium contractile activation may, in part, contribute to heart failure. Calcium concentration required for 50% activation and Hill coefficient for fibers from nonfailing and failing human hearts at pH 7.1 were not different. Maximum calcium-activated force (F(max)) was also not different. However, at pH 6.8 and 6.9, differences were seen in myofilament calcium activation between nonfailing and failing hearts. At lower pH, failing myocardium was shifted left on the calcium axis compared with nonfailing myocardium, which suggested an increase in myofilament calcium responsiveness. Increased inorganic phosphate concentration decreased maximal force development by 56% in nonfailing and 36% in failing myocardium and shifted the calcium-force relationship by 2.01+/-0.22 versus 0.86+/-0.13 micromol/L, respectively (P<0.05). Addition of cAMP resulted in a 0. 56 micromol/L shift toward higher intracellular calcium concentrations in nonfailing myocardium and a 1.04 micromol/L shift in failing myocardium. Protein kinase A in the presence of cAMP resulted in a further rightward shift in nonfailing human myocardium but did not further shift the calcium-force relationship in fibers from failing hearts. cGMP also resulted in a greater decrease in myofilament calcium sensitivity in fibers from failing hearts. We propose that changes at the level of the thin myofilaments result in differential responses to changes in the intracellular milieu in nonfailing versus failing myocardium.


High sensitivity to calcitonin of prolactin-secreting control in lactating rats.
The effects of intracerebroventricular (icv;25ng/rat) or iv (10 micrograms/kg) salmon calcitonin (sCT) on PRL secretion were determined in lactating rats and compared to the effects in intact or ovariectomized-estrogen-treated female rats. The icv or iv injections of sCT 9 days after estrogen treatment did not significantly lower the PRL levels in intact rats. In ovariectomized-estrogen-primed animals, sCT (icv or iv) did not modify the afternoon surge of PRL secretion when injected during the surge, nor did it delay or attenuate the increasing secretory activity when administered (iv) before the afternoon surge had begun. On the contrary, 30 or 60 min after the icv or iv administration of sCT to lactating rats, suckling-induced PRL secretion was prevented. These results and our previous evidence that a greater dose of sCT is needed to decrease the less intense morphine- or stress-induced PRL secretion indicate differential hypoprolactinemic properties of sCT, which are particularly striking during lactation. While the mechanisms underlying these selective activities deserve further investigation, the proposed participation of PRL in the regulation of calcium metabolism during lactation suggests that the potent PRL inhibitory effect of CT in this condition should be regarded as one factor in the complex mechanism that prevents bone loss and protects the maternal skeleton.


Dynamics of soil carbon during deglaciation of the laurentide ice sheet.
Deglaciation of the Laurentide Ice Sheet in North America was accompanied by sequestration of organic carbon in newly exposed soils. The greatest rate of land exposure occurred around 12,000 to 8,000 years ago, and the greatest increase in the rate of carbon sequestration by soils occurred from 8,000 to 4,000 years ago. Sequestration of carbon in deglaciated peat lands continues today, and a steady state has not been reached. The natural rate of carbon sequestration in soils, however, is small relative to the rate of anthropogenic carbon dioxide production.


Repeatability of 18F-FDG PET/CT in Advanced Non-Small Cell Lung Cancer: Prospective Assessment in 2 Multicenter Trials.
PET/CT with the glucose analog (18)F-FDG has several potential applications for monitoring tumor response to therapy in patients with non-small cell lung cancer (NSCLC). A prerequisite for many of these applications is detailed knowledge of the repeatability of quantitative parameters derived from (18)F-FDG PET/CT studies. The repeatability of the (18)F-FDG signal was evaluated in 2 prospective multicenter trials. Patients with advanced NSCLC (tumor stage III-IV) underwent two (18)F-FDG PET/CT studies while not receiving therapy. Tumor (18)F-FDG uptake was quantified by measurement of the maximum standardized uptake value within a lesion (SUVmax) and the average SUV within a small volume of interest around the site of maximum uptake (SUVpeak). Analysis was performed for the lesion in the chest with the highest (18)F-FDG uptake and a size of at least 2 cm (target lesion) as well as for up to 6 additional lesions per patient. Repeatability was assessed by Bland-Altman plots and calculation of 95% repeatability coefficients (RCs) of the log-transformed SUV differences. Test-retest repeatability was assessed in 74 patients (34 from the ACRIN 6678 trial and 40 from the Merck MK-0646-008 trial). SUVpeak was 11.57 ± 7.89 g/mL for the ACRIN trial and 6.89 ± 3.02 for the Merck trial. The lower and upper RCs were -28% (95% confidence interval [CI], -35% to -23%) and +39% (95% CI, 31% to 54%) in the ACRIN trial, indicating that a decrease of SUVpeak by more than 28% or an increase by more than 39% has a probability of less than 2.5%. The corresponding RCs from the Merck trial were -35% (95% CI, -42% to -29%) and +53% (95% CI, 41% to 72%). Repeatability was similar for SUVmax of the target lesion, averaged SUVmax, and averaged SUVpeak of up to 6 lesions per patient. The variability of repeated measurements of tumor (18)F-FDG uptake in patients with NSCLC is somewhat larger than previously reported in smaller single-center studies but comparable to that of gastrointestinal malignancies in a previous multicenter trial. The variability of measurements supports the definitions of tumor response according to PET Response Criteria in Solid Tumors.


Rapa Nui (Easter Island) monument (ahu) locations explained by freshwater sources.
Explaining the processes underlying the emergence of monument construction is a major theme in contemporary anthropological archaeology, and recent studies have employed spatially-explicit modeling to explain these patterns. Rapa Nui (Easter Island, Chile) is famous for its elaborate ritual architecture, particularly numerous monumental platforms (ahu) and statuary (moai). To date, however, we lack explicit modeling to explain spatial and temporal aspects of monument construction. Here, we use spatially-explicit point-process modeling to explore the potential relations between ahu construction locations and subsistence resources, namely, rock mulch agricultural gardens, marine resources, and freshwater sources-the three most critical resources on Rapa Nui. Through these analyses, we demonstrate the central importance of coastal freshwater seeps for precontact populations. Our results suggest that ahu locations are most parsimoniously explained by distance from freshwater sources, in particular coastal seeps, with important implications for community formation and inter-community competition in precontact times.


Characterization of the electrophoretic mobility mutation in the N protein of the tsD1 mutant of vesicular stomatitis virus New Jersey serotype.
Some isolates of the temperature sensitive mutant tsD1 of complementation group D of vesicular stomatitis virus of New Jersey serotype have a nucleocapsid (N) protein which shows an increased electrophoretic mobility on sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS-PAGE) when compared with wild type. Utilizing techniques involving specific chemical cleavage at tryptophan or methionine residues, as well as enzymatic cleavage with carboxypeptidases A and B, we have determined that residues near the carboxyterminus are responsible for the electrophoretic difference of the mutant protein. We have further shown that there are no differences in the tryptic peptides of the mutant compared with the wild type or a non-ts revertant in this region of the protein. We have identified a tryptic peptide located outside the relevant carboxyterminal region which is distinct in mutant and revertant. We conclude that the mutation producing the aberrant electrophoretic mobility of N protein of the tsD1 mutant is a missense point mutation located at least 40 amino acid residues from the carboxyterminus and which interacts with a more proximal carboxyregion so as to influence electrophoretic mobility on SDS-PAGE.


Molecular comparisons of plasmids isolated from colicinogenic strains of Escherichia coli.
The plasmid content of 14 colicinogenic strains of Escherichia coli has been examined. Four strains contained miniplasmids (1.2-2.0 kb). Small plasmids (4-7 kb) were detected in all the strains specifying group A colicins (colicins A, E1, E2, E3 and K; group I plasmids). Larger plasmids (55-130 kb) were detected in seven out of nine strains specifying group B colicins (colicins B, H, Ia, Ib, M, V and S1; group II plasmids). DNA-DNA hybridization with group II plasmids showed a wide variation in the degree of DNA sequence homology among its members. In contrast little (if any) DNA sequence homology was detected with the group I plasmids when the same group II plasmid DNAs were used as hybridization probes. The results of DNA-DNA hybridization studies with the two small group II plasmids (pcolG-CA46 and pcolD-CA23) suggested that these plasmids are equivalent to deleted forms of larger group II plasmids. Our hybridization data thus support the division of colicin plasmids into the two groups (I and II) that have been previously defined from genetic and physiological studies.


A Semi-supervised Algorithm for Atrial Fibrillation Attack Prediction Using Convolution Auto-encoder of Time Series Signal.
During the initial stages, atrial fibrillation (AF) typically presents as paroxysmal atrial fibrillation (PAF), which may further progress into persistent atrial fibrillation, leading to high-risk diseases such as ischemic stroke and heart failure. Given that the current machine learning algorithms used for predicting AF involve time-consuming and labor-intensive processes of feature extraction and labeling electrocardiogram data, this study proposes a novel two-stage semi-supervised AF attack prediction algorithm. The first stage is designed as unsupervised learning based on convolutional autoencoder (CAE) network when inputting RR interval time series signal, while the second stage is designed as supervised learning using a Long Short-Term Memory (LSTM) model. A training set consisting of 20 segments of PAF and 20 normal heart rates was used to evaluate the performance of the CAE-LSTM combination model. The results showed that the average accuracy and root mean square error of ten-fold cross-validation were 93.56% and 0.004, respectively, with an F1 parameter of 0.9345. In summary, the preliminary results suggest that the combination of unsupervised CAE model and supervised LSTM model can reduce the dimensionality of the input data while using a small amount of labeled data as input for subsequent classification. Furthermore, the proposed algorithm can be used for predicting atrial fibrillation when the sample size is limited.Clinical Relevance- Compared with common supervised methods, our proposed method only requires a small number of tagged ECG signals, which can reduce the workload of clinicians to complete the task of atrial fibrillation attack prediction.


Health in Adapted Youth Sports Study (HAYS): health effects of sports participation in children and adolescents with a chronic disease or physical disability.
In typically developing children, participation in sports has been proven to be positively correlated to both physical and psychosocial health outcomes. In children and adolescents with a physical disability or chronic disease participation in both recreational and competitive sports is often reduced, while for this population an active lifestyle may be even more important in reaching optimal levels of physical and psychosocial health. Therefore, the aim of the Health in Adapted Youth Sports (HAYS) Study is to determine both negative and positive effects of sports on children and adolescents with a chronic disease or physical disability. In this cross-sectional study differences will be compared in regards to physical and psychosocial health, cognitive functioning, school performance, daily physical activity and injuries between children and adolescents with a chronic disease or physical disability who participate in sports and those who do not. Children and adolescents, both ambulatory and wheelchair dependent, in the age of 10-19 years with a physical disability or chronic disease will be included. "Sports" is defined as participation in an organized sport at least two times a week for a duration of 3 months or more prior to the assessment. Parametric and non-parametric statistics will be used to determine the differences between the two groups. This study provides insight in the effects of sports participation in relation to health, psychosocial functioning, physical activity and school performance in children and adolescents (10-19 years) with a chronic disease or physical disability. Results will guide healthcare professionals working with these children to better guide this population in reaching optimal levels of health and physical activity levels.


Risk Factors Associated With All-Cause 30-Day Mortality in Nursing Home Residents With COVID-19.
The coronavirus disease 2019 (COVID-19) pandemic has severely affected nursing homes. Vulnerable nursing home residents are at high risk for adverse outcomes, but improved understanding is needed to identify risk factors for mortality among nursing home residents. To identify risk factors for 30-day all-cause mortality among US nursing home residents with COVID-19. This cohort study was conducted at 351 US nursing homes among 5256 nursing home residents with COVID-19-related symptoms who had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by polymerase chain reaction testing between March 16 and September 15, 2020. Resident-level characteristics, including age, sex, race/ethnicity, symptoms, chronic conditions, and physical and cognitive function. Death due to any cause within 30 days of the first positive SARS-CoV-2 test result. The study included 5256 nursing home residents (3185 women [61%]; median age, 79 years [interquartile range, 69-88 years]; and 3741 White residents [71%], 909 Black residents [17%], and 586 individuals of other races/ethnicities [11%]) with COVID-19. Compared with residents aged 75 to 79 years, the odds of death were 1.46 (95% CI, 1.14-1.86) times higher for residents aged 80 to 84 years, 1.59 (95% CI, 1.25-2.03) times higher for residents aged 85 to 89 years, and 2.14 (95% CI, 1.70-2.69) times higher for residents aged 90 years or older. Women had lower risk for 30-day mortality than men (odds ratio [OR], 0.69 [95% CI, 0.60-0.80]). Two comorbidities were associated with mortality: diabetes (OR, 1.21 [95% CI, 1.05-1.40]) and chronic kidney disease (OR, 1.33 [95%, 1.11-1.61]). Fever (OR, 1.66 [95% CI, 1.41-1.96]), shortness of breath (OR, 2.52 [95% CI, 2.00-3.16]), tachycardia (OR, 1.31 [95% CI, 1.04-1.64]), and hypoxia (OR, 2.05 [95% CI, 1.68-2.50]) were also associated with increased risk of 30-day mortality. Compared with cognitively intact residents, the odds of death among residents with moderate cognitive impairment were 2.09 (95% CI, 1.68-2.59) times higher, and the odds of death among residents with severe cognitive impairment were 2.79 (95% CI, 2.14-3.66) times higher. Compared with residents with no or limited impairment in physical function, the odds of death among residents with moderate impairment were 1.49 (95% CI, 1.18-1.88) times higher, and the odds of death among residents with severe impairment were 1.64 (95% CI, 1.30-2.08) times higher. In this cohort study of US nursing home residents with COVID-19, increased age, male sex, and impaired cognitive and physical function were independently associated with mortality. Understanding these risk factors can aid in the development of clinical prediction models of mortality in this population.