Does alcohol involvement increase the severity of intimate partner violence?
Most studies that have examined alcohol use immediately prior to intimate partner violence (IPV) have been limited to male-to-female partner violence (MFPV) and are subject to a number of methodological limitations. We add new information concerning the relationship between alcohol involvement and severity of IPV, MFPV, and female-to-male partner violence (FMPV). We analyzed data from a 1995 U.S. national population-based survey of couples > or = 18 years old. We examined 436 couples who reported IPV and had information on alcohol involvement with IPV. We measured IPV using a revised Conflict Tactics Scale, Form R that asked respondents about 11 violent behaviors in the past year. Respondents were classified into mutually exclusive categories as having experienced mild only or mild + severe ("severe") IPV, MFPV or FMPV. Respondents were also asked if they or their partner were drinking at the time the violent behavior occurred and were classified as exposed to IPV with or without alcohol involvement. We estimated proportions, odds ratios, 95% confidence intervals, and p-values of the proposed associations, accounting for the complex survey design. Overall, 30.2% of couples who reported IPV reported alcohol involved IPV; 69.8% reported no alcohol involvement. In adjusted analyses, those reporting severe (vs. mild only) IPV were more than twice as likely to report alcohol involvement. In adjusted analyses, those reporting severe (vs. mild) MFPV or FMPV were more likely to report female but not male alcohol involvement. Though estimates were positive and strong, most confidence intervals were compatible with a wide range of estimates including no association. Our findings suggest alcohol involvement of either or both in the couple increases the risk of severe IPV. Our findings also suggest female alcohol use may play an important role in determining the severity of IPV, MFPV or FMPV.


Concepts in U.S. Food and Drug Administration Regulation of Artificial Intelligence for Medical Imaging.
OBJECTIVE. Although extensive attention has been focused on the enormous potential of artificial intelligence (AI) technology, a major question remains: how should this fundamentally new technology be regulated? The purpose of this article is to provide an overview of the pathways developed by the U.S. Food and Drug Administration to regulate the incorporation of AI in medical imaging. CONCLUSION. AI is the new wave of innovation in health care. The technology holds promising applications to revolutionize all aspects of medicine.


Endogenous Na+, K+-ATPase inhibitors and CSF [Na+] contribute to migraine formation.
There is strong evidence that neuronal hyper-excitability underlies migraine, and may or may not be preceded by cortical spreading depression. However, the mechanisms for cortical spreading depression and/or migraine are not established. Previous studies reported that cerebrospinal fluid (CSF) [Na+] is higher during migraine, and that higher extracellular [Na+] leads to hyper-excitability. We raise the hypothesis that altered choroid plexus Na+, K+-ATPase activity can cause both migraine phenomena: inhibition raises CSF [K+] and initiates cortical spreading depression, while activation raises CSF [Na+] and causes migraine. In this study, we examined levels of specific Na+, K+-ATPase inhibitors, endogenous ouabain-like compounds (EOLC), in CSF from migraineurs and controls. CSF EOLC levels were significantly lower during ictal migraine (0.4 nM +/- 0.09) than from either controls (1.8 nM +/- 0.4) or interictal migraineurs (3.1 nM +/- 1.9). Blood plasma EOLC levels were higher in migraineurs than controls, but did not differ between ictal and interictal states. In a Sprague-Dawley rat model of nitroglycerin-triggered central sensitization, we changed the concentrations of EOLC and CSF sodium, and measured aversive mechanical threshold (von Frey hairs), trigeminal nucleus caudalis activation (cFos), and CSF [Na+] (ultra-high field 23Na MRI). Animals were sensitized by three independent treatments: intraperitoneal nitroglycerin, immunodepleting EOLC from cerebral ventricles, or cerebroventricular infusion of higher CSF [Na+]. Conversely, nitroglycerin-triggered sensitization was prevented by either vascular or cerebroventricular delivery of the specific Na+, K+-ATPase inhibitor, ouabain. These results affirm our hypothesis that higher CSF [Na+] is linked to human migraine and to a rodent migraine model, and demonstrate that EOLC regulates them both. Our data suggest that altered choroid plexus Na+, K+-ATPase activity is a common source of these changes, and may be the initiating mechanism in migraine.


Analysis of treatment for isolated zygomaticomaxillary complex fractures.
The purpose of this study was to evaluate the adequacy of reduction and stability of fixation of isolated zygomaticomaxillary complex (ZMC) fractures treated by various methods over a 5-year period. Forty-eight patients with isolated, unilateral ZMC fractures that had at least 6 weeks' clinical follow-up were studied. Demographic information and methods of treatment were obtained from the medical records. Quality of reduction was assessed by examination of postoperative images. Stability of the repositioned ZMC was assessed by comparing immediate postoperative images with those obtained at least 5 weeks later. Cosmetic outcomes were assessed by clinical assessment and examination of photographs. A variety of surgical approaches and fixation sites were used in the sample. All patients but five had satisfactory reductions performed during surgery. In two of the latter, no noticeable facial deformity was apparent. No patient showed postsurgical change in position of the reduced ZMC. Three patients showed postsurgical enophthalmos at longest follow-up. Approximately 20% of those having lower eyelid incisions had some amount of scleral show at longest follow-up. A variety of techniques can be used to produce a satisfactory outcome. Based on the results and a review of the literature, recommendations for treatment are proposed.


Biosynthesis of nuclear proteins after stimulation of quiescent Swiss mouse 3T3 cells.
Stimulation of quiescent Swiss mouse 3T3 fibroblasts either by serum or by the low molecular weight hormones, prostaglandin F2 alpha and insulin, induces DNA synthesis after a lag period of about 15 h. Following restimulation by serum or these pure hormones there is an overall increase of two- to fourfold in the rate of biosynthesis of nuclear proteins. In addition, there is a relative decrease in some proteins (Mr = 200 X 10(3), pI 6.0-6.5), while others increase (e.g. actin). Two polypeptides show specific correlations with the exit from G0. The synthesis of p30 (Mr = 30 X 10(3), pI 5.2) is at a maximum within 5 h of restimulation, while the synthesis of p36 (Mr = 36 X 10(3), pI = 4.25) is first seen at 10-20 h after restimulation. Synthesis of p36 correlates well with the initiation of DNA synthesis. The synthesis of both proteins is stimulated by serum and by the hormones. Thus there are common biosynthetic responses to different stimuli indicating convergent pathways leading to DNA biosynthesis. Addition of hydrocortisone with the growth-stimulatory hormones inhibits both entry into the S phase and biosynthesis of p36. In contrast, hydrocortisone does not alter the biosynthesis of p30. This 'early' protein, p30, is different from the products of both c-fos and c-myc. Therefore, we have identified two specific components that might participate in the regulation of cell proliferation.


Association of daily step counts and step intensity with fear of falling in Chinese community-dwelling older women.
This study aimed to investigate the relationship between objectively measured step counts, step intensity and FOF in community-dwelling older Chinese women. Cross-sectional analyses were conducted on pooled data (n = 1101) from the baseline survey of the Physical Activity and Health Study (PAHIOWS). Step counts and step intensity were measured using wGT3X-BT accelerometers, and FOF was categorized into two levels (low and high) for logistic regression analysis. Higher step counts were significantly and negatively associated with FOF; however, after adjusting for step intensity, the association was no longer statistically significant. On the contrary, higher step intensity was negatively associated with FOF independent of step counts. This finding may provide new insights into the physical activity management of FOF in older women.


From bedside to bench - In vivo and in vitro evaluation of mechanically assisted cough treatment in a patient with bulbar Amyotrophic Lateral Sclerosis.
When the ability to cough is impaired, secretion clearance may be assisted and augmented by Mechanical Insufflation-Exsufflation (MI-E) treatment. In patients with Amyotrophic Lateral Sclerosis, the efficacy of MI-E may be hampered by counterproductive upper airway responses. Careful adjustment of MI-E settings can be beneficial. During the disease progression, a 41-year-old woman with bulbar Amyotrophic Lateral Sclerosis experienced that treatment with MI-E was exhausting and inefficient. Despite adjustments of settings, all treatment led to retching. A change of MI-E device led to more effective treatment. A bench test revealed variations in flow and pressure waveforms in the two devices. When MI-E treatment fails, differences in equipment delivery need to be considered in addition to the adjustment of MI-E settings.


CD141+ dendritic cells produce prominent amounts of IFN-α after dsRNA recognition and can be targeted via DEC-205 in humanized mice.
Functional differences between human dendritic cell (DC) subsets and the potential benefits of targeting them with vaccines remain poorly defined. Here we describe that mice with reconstituted human immune system components (huNSG mice) develop all human conventional and plasmacytoid DC compartments in lymphoid organs. Testing different Toll-like receptor agonists for DC maturation in vivo, we found that IL-12p70 and interferon (IFN)-α production correlated with the maturation of CD141+ (BDCA3+) conventional DCs in huNSG mice. Furthermore, depletion of CD141+ DCs before stimulation significantly reduced IFN-α levels in vivo. This DC subset produced similar total amounts but different subtypes of IFN-α in response to synthetic double-stranded RNA compared with plasmacytoid DCs in response to a single-stranded RNA equivalent. Moreover, synthetic double-stranded RNA as adjuvant and antigen targeting to the endocytic receptor DEC-205, a combination that focuses antigen presentation for T-cell priming on CD141+ DCs, stimulated antigen-specific human CD4+ T-cell responses. Thus, the human CD141+ DC subset is a prominent source of IFN-α and interleukin-12 production and should be further evaluated for vaccine development.


A detector response function design in pinhole SPECT including geometrical calibration.
Clinical single photon emission computed tomography (SPECT) equipped with pinhole collimators have a magnification factor that results in high spatial resolution images for small animal imaging. Using Monte Carlo simulations to model the acquisition process and the propagation of the photons from their point of emission to their detection point then integrating the model into an iterative reconstruction algorithm improves the signal-to-noise ratio, the contrast and the spatial resolution in the reconstructed images. However, pinhole SPECT systems are known to be very sensitive to geometrical misalignments. Geometrical misalignments are defined as the radial or axial shift of the collimator pinhole and/or twist and tilt of the detector heads and are introduced in the system each time the collimation device is changed (pinhole to parallel holes or vice versa). In this work, we present a flexible detector response function table (DRFT) design that takes into account the geometrical misalignments and avoids performing new Monte Carlo simulations for each exam in order to calculate a geometrical study-dependent system matrix. The utilization of the DRFT for the calculation of the system matrix speeds up its computation time by two orders of magnitude making it acceptable for preclinical and clinical applications.


Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect.
Thiazolidinediones (TZDs), a class of insulin-sensitizing agents used clinically to treat type 2 diabetes, are also antiatherogenic. This study was designed to elucidate the relationship between the antiatherogenic and antidiabetic effects of pioglitazone, a TZD, in type 2 diabetic patients. A total of 136 Japanese type 2 diabetic patients were included and divided into two groups: the pioglitazone-treated group (30 mg daily for 3 months) (n = 70) and the untreated control group (n = 66). The changes in glycolipid metabolism as well as plasma high-sensitivity C-reactive protein (CRP), leptin, adiponectin, and pulse wave velocity (PWV) were monitored to analyze the relationship between the antiatherogenic and antidiabetic effects of pioglitazone. The pioglitazone treatment significantly reduced hyperglycemia, hyperinsulinemia, and HbA(1c) levels and increased plasma adiponectin concentrations relative to the control group (P < 0.01). It also significantly decreased CRP and PWV (P < 0.01). The antiatherogenic effect was observed in both the nonresponders showing <1% of reduction in HbA(1c) (n = 30) and responders showing >1% of reduction (n = 40). ANCOVA revealed that treatment with pioglitazone was associated with a low CRP and PWV, independent of the changes in parameters related to glucose metabolism. This study represents the first demonstration of the antiatherogenic effect of pioglitazone in both nonresponders and responders with respect to its antidiabetic effect and suggests that pioglitazone can exert its antiatherogenic effect independently of its antidiabetic effect.


Circulating adrenomedullin in erythrocopietin-induced hypertension.
Levels of adrenomedullin (AM) have been shown to be elevated in hypertension and chronic renal failure, suggesting that AM plays a role in the pathogenesis of these diseases. The objective of the present study was to investigate whether circulating AM is involved in erythropoietin (Epo)-induced hypertension in patients with renal anemia due to progressive renal disease. Following treatment with 6,000 IU of Epo once a week, the hematocrit (Ht) rose significantly from 25.9+/-4.0 to 33.4+/-3.3% (n=54, p<0.001) with an overall rate of increase in Ht of 0.43+/-0.04%/week. In response to treatment with Epo, a rise in mean blood pressure of >10 mmHg (Epo-induced hypertension) was found in 22% (12/54 cases) of the patients enrolled. There was no difference in the rate of Ht increase between patients with and without Epo-induced hypertension. There was a significant positive correlation between mature AM and serum creatinine (Cr) concentration before treatment with Epo. However, no correlation was found between the plasma concentration of total AM and serum Cr concentration. Long-term treatment with Epo did not influence plasma concentration of either mature AM or total AM in patients developing hypertension during the study period. These results suggest that circulating AM may play a role in the progression of renal disease. However, the present study does not support the notion that circulating AM is associated with the pathogenesis of Epo-induced hypertension. It is too early yet to claim that there is no AM-mediated mechanism in Epo-induced hypertension.


Chikungunya-induced cell death is limited by ER and oxidative stress-induced autophagy.
It has been recognized that macroautophagy constitutes an important survival mechanism that allows both the maintenance of cellular homeostasis and the regulation of programmed cell death pathways (e.g., apoptosis). Although several pathogens have been described to induce autophagy, the prosurvival function of this process in infectious models remains poorly characterized. Our recent studies on chikungunya virus (CHIKV), the causative agent of major epidemics in India, Southeast Asia and southern Europe, reveal a novel mechanism by which autophagy limits the cytopathic effects of CHIKV by impinging upon virus-induced cell death pathways.


Nonlinear unsharp masking for mammogram enhancement.
This paper introduces a new unsharp masking (UM) scheme, called nonlinear UM (NLUM), for mammogram enhancement. The NLUM offers users the flexibility 1) to embed different types of filters into the nonlinear filtering operator; 2) to choose different linear or nonlinear operations for the fusion processes that combines the enhanced filtered portion of the mammogram with the original mammogram; and 3) to allow the NLUM parameter selection to be performed manually or by using a quantitative enhancement measure to obtain the optimal enhancement parameters. We also introduce a new enhancement measure approach, called the second-derivative-like measure of enhancement, which is shown to have better performance than other measures in evaluating the visual quality of image enhancement. The comparison and evaluation of enhancement performance demonstrate that the NLUM can improve the disease diagnosis by enhancing the fine details in mammograms with no a priori knowledge of the image contents. The human-visual-system-based image decomposition is used for analysis and visualization of mammogram enhancement.


Molecular Mechanism of Depolarization-Dependent Inactivation in W366F Mutant of Kv1.2.
Voltage-gated potassium channels play crucial roles in regulating membrane potential. They are activated by membrane depolarization, allowing the selective permeation of K+ ions across the plasma membrane, and enter a nonconducting state after lasting depolarization, a process known as inactivation. Inactivation in voltage-activated potassium channels occurs through two distinct mechanisms, N-type and C-type inactivation. C-type inactivation is caused by conformational changes in the extracellular mouth of the channel, whereas N-type inactivation is elicited by changes in the cytoplasmic mouth of the protein. The W434F-mutated Shaker channel is known as a nonconducting mutant and is in a C-type inactivation state at a depolarizing membrane potential. To clarify the structural properties of C-type inactivated protein, we performed molecular dynamics simulations of the wild-type and W366F (corresponding to W434F in Shaker) mutant of the Kv1.2-2.1 chimera channel. The W366F mutant was in a nearly nonconducting state with a depolarizing voltage and recovered from inactivation with a reverse voltage. Our simulations and three-dimensional reference interaction site model analysis suggested that structural changes in the selectivity filter upon membrane depolarization trap K+ ions around the inner mouth of the selectivity filter and prevent ion permeation. This pore restriction is involved in the molecular mechanism of C-type inactivation.


The Rare Sugar Tagatose Differentially Inhibits the Growth of Phytophthora infestans and Phytophthora cinnamomi by Interfering With Mitochondrial Processes.
Rare sugars are monosaccharides with limited availability in nature and their biological functions are largely unknown. Among them, tagatose was developed as a low-calorie sweetener and showed beneficial effects on human health. Tagatose is metabolized by only certain microbial taxa and inhibits the growth of important crop pathogens (e.g., Phytophthora infestans), but its mode of action and the microbial responses are unknown. The aim of this study was to understand the tagatose mode of action against Phytophthora spp., with the final aim of developing new plant protection products. Tagatose inhibited P. infestans growth in vitro and caused severe ultrastructural alterations, with the formation of circular and concentric mitochondrial cristae. Decreased ATP content and reduced oxygen consumption rate (OCR) were found in tagatose-incubated P. infestans as compared to the control, with the consequent accumulation of reactive oxygen species (ROS) and induction of genes related to apoptosis and oxidative stress response. On the other hand, tagatose did not, or only slightly, affect the growth, cellular ultrastructure and mitochondrial processes in Phytophthora cinnamomi, indicating a species-specific response to this rare sugar. The mode of action of tagatose against P. infestans was mainly based on the inhibition of mitochondrial processes and this rare sugar seems to be a promising active substance for the further development of eco-friendly fungicides, thanks to its anti-nutritional properties on some phytopathogens and low risk for human health.


Use of health care claims data to study patients with ophthalmologic conditions.
To describe what information is or is not included in health care claims data, provide an overview of the main advantages and limitations of performing analyses using health care claims data, and offer general guidance on how to report and interpret findings of ophthalmology-related claims data analyses. Systematic review. Not applicable. A literature review and synthesis of methods for claims-based data analyses. Not applicable. Some advantages of using claims data for analyses include large, diverse sample sizes, longitudinal follow-up, lack of selection bias, and potential for complex, multivariable modeling. The disadvantages include (a) the inherent limitations of claims data, such as incomplete, inaccurate, or missing data, or the lack of specific billing codes for some conditions; and (b) the inability, in some circumstances, to adequately evaluate the appropriateness of care. In general, reports of claims data analyses should include clear descriptions of the following methodological elements: the data source, the inclusion and exclusion criteria, the specific billing codes used, and the potential confounding factors incorporated in the multivariable models. The use of claims data for research is expected to increase with the enhanced availability of data from Medicare and other sources. The use of claims data to evaluate resource use and efficiency and to determine the basis for supplementary payment methods for physicians is anticipated. Thus, it will be increasingly important for eye care providers to use accurate and descriptive codes for billing. Adherence to general guidance on the reporting of claims data analyses, as outlined in this article, is important to enhance the credibility and applicability of findings. Guidance on optimal ways to conduct and report ophthalmology-related investigations using claims data will likely continue to evolve as health services researchers refine the metrics to analyze large administrative data sets.


Phase measurement of fast light pulse in electromagnetically induced absorption.
We report the phase measurement of a fast light pulse in electromagnetically induced absorption (EIA) of the 5S₁/₂ (F = 2)-5P₃/₂ (F' = 3) transition of ⁸⁷Rb atoms. Using a beat-note interferometer method, a stable measurement without phase dithering of the phase of the probe pulse before and after it has passed through the EIA medium was achieved. Comparing the phases of the light pulse in air and that of the fast light pulse though the EIA medium, the phase of the fast light pulse at EIA resonance was not shifted and maintained to be the same as that of the free-space light pulse. The classical fidelity of the fast light pulse according to the advancement of the group velocity by adjusting the atomic density was estimated to be more than 97%.


Spectrum of biological properties of human immunodeficiency virus (HIV-1) isolates.
In vitro assessment of biological properties of 14 independent isolates of human immunodeficiency virus type 1 (HIV-1) was performed in order to gain insight into the spectrum of behavioral diversity of HIV-1s and to attempt to identify phenotypic traits that may be eventually correlated with in vivo pathogenesis. All of these biologically cloned isolates were found to spread very slowly in most cell cultures, requiring 8-10 weeks for virus to spread from a few infected cells to around 10(5) cells. If viral synergistic activity was also present, as in HTLV-1-infected cells, HIV-1 spread was greatly accelerated. The isolates varied in their cellular tropisms, having as much as 100,000-fold difference in their tropisms for various human CD4-positive cell lines. Several HIV isolates were dual-tropic for both T and promonocytic cells, but some of these isolates did not readily infect U937 promonocytes while readily infecting THP-1 promonocytes. Both the slow spread and extreme tropisms of HIV-1 isolates have practical implications for titering HIVs and for initiating any studies examining the interaction between a given isolate and any given cell. Some isolates did not score readily by reverse transcriptase assays while others did and this did not reflect the amount of infectious virus produced. These findings raise questions about the reliability of HIV quantitation by RT assay. The HIV isolates further varied in their ability to kill and/or fuse cells, whereas some induced cytopathology more efficiently in a given cell line than others, even though the latter appeared to replicate as well. Finally, most isolates killed cells without syncytia formation, demonstrating that cell-to-cell fusion is a minor mechanism of cytopathology. The properties observed for each HIV isolate appeared to be stable phenotypes for that virus and the diversity of biological behavior raises the possibility that independent HIV isolates may differ in their virulence properties in vivo as well.


Asthma therapy during the first 8 years of life: a PIAMA cohort study.
Many studies evaluated asthma medication use in children in a cross-sectional manner, yet little is known about longitudinal use patterns. This study describes the formation of a longitudinal data set on asthma medication use and shows first results regarding the prevalence and incidence of medication use. The PIAMA (Prevention and Incidence of Asthma and Mite Allergy) study is a prospective birth cohort study among 3963 Dutch children. Recruitment took place in 1996-1997. The data of the PIAMA birth cohort study were complemented with pharmacy data. Prescription information of family members was used to determine whether medication histories were complete from birth until age 8. The prevalence and incidence of asthma medication use was studied in children for whom complete medication histories were available. A first prescription for asthma medication was filled before age 8 by 280 (36%) children, with 88% starting therapy before age 5. Of all children who started therapy, 91.1% received short-acting beta(2)-agonists and 61.1% inhaled corticosteroids. The applied method of data collection rendered a data set including 777 children with complete medication histories for their first 8 years of life. This data set provides the opportunity to study longitudinal medication use patterns. First analyses show that asthma medication is initiated in a rather high percentage of children in this cohort and mainly at an age at which an asthma diagnosis cannot yet be firmly established.


Regional and Temporal Trends in the Outcomes of Repairs for Acute Type A Aortic Dissections.
Little information exists regarding the use of arch operations for repair of acute type A aortic dissections (AADs) despite increasing interest in this strategy and its potential impact on outcomes. We aimed to determine the relationship between extent of aortic repair, US geographic regions, and outcome. We queried The Society of Thoracic Surgeons database for patients who underwent AAD repair from January 1, 2004 to December 31, 2016 and grouped patients by ascending-only operations and operations involving the arch. We identified 25,462 patients (mean age, 59.8 ± 14.2; 66.7% men) who underwent AAD repair. Operations involving the ascending aorta only were performed in 54% of patients; 46% had repair additionally involving the arch. The 30-day mortality was 18.9% for patients who underwent ascending-only operations vs 19.8% for patients who underwent arch operations (P = .09). In multivariable analysis older age (P < .001), earlier year of operation (P < .001), diabetes mellitus (P < .001), severe chronic lung disease (P < .001), prior cerebrovascular disease (P < .001), and longer bypass time (P < .001) were independently associated with 30-day mortality. There was regional variation in 30-day mortality (P < .001), and incidence of arch repair varied from 38.6% to 52.6% in 9 geographic regions (P < .001). In this analysis of cardiac surgical practice in the United States, repair of AADs included a portion of the aortic arch in 46% of patients. Early mortality remained high throughout the current era regardless of extent of aortic resection. Regional variation in perioperative mortality may signal an opportunity for practice improvement.


Neurogenesis within the juvenile zebra finch telencephalic ventricular zone: a map of proliferative activity.
Localized regions of increased cellular proliferation within the ventricular zone (VZ) of juvenile male songbirds may contain progenitor cells that give rise to song-control neurons and, thereby, contribute to the construction of brain areas important for song learning. The purpose of this study was to examine levels of cell division throughout the telencephalic VZ of juvenile birds. A single pulse of [(3)H]thymidine was administered to 30-day male and female zebra finches, and the birds were killed 2 hours later. The VZ was divided into segments throughout the entire anterior-posterior and dorsal-ventral neuraxes, and levels of thymidine labeling were measured within each subdivision. By subdividing the VZ into segments, we were able to construct a "map" of proliferation throughout the telencephalic VZ, thereby allowing us to compare levels of mitotic activity within corresponding locations of the VZ between males and females. Our map revealed two major findings: (1) proliferation in both juvenile males and females was spatially differentiated throughout the VZ, suggesting that mitotic activity is differentially regulated across the neuraxis; (2) sex differences in proliferation were present in 30-day-old birds, but were highly restricted. The most robust sexual dimorphism occurred within the ventral aspect of the VZ at rostral levels of the song-control nucleus Area X, with males demonstrating an increased number of dividing cells compared with females. This result raises the possibility that Area X neurons in males are derived from committed progenitors within the adjacent VZ in close proximity to this nucleus.


Recent trends in fertility and nuptiality in china.
The State Family Planning Commission of China has conducted two large-scale fertility surveys, in 1982 and 1988, covering sample households containing 1 million and 2 million persons, respectively. These surveys obtained lifetime histories, including age at first marriage and at each birth for female members of the households from ages 15 to 67 in the first survey and from 15 to 57 in the second. The data provide detailed information on the extraordinary decline in the rate of childbearing in China (by 60% from 1970 to 1980). Because rising age at marriage played a significant role in this decline, the effect of changes in the pattern of entry into marriage on childbearing since 1980 was examined. There was a sharp increase in overall fertility (the total fertility rate) from 1980 to 1982; after falling to slightly below the 1980 level in 1985, the rate rose in 1985 and 1986 to well above that of 1980. A major factor in this arrested and partially reversed decline was a boom in marriage that followed a relaxation in 1980 of locally administered restrictions on marriage before the officially designated desirable age. In fact, the total fertility rate of married women (summed over duration of marriage rather than age) averaged much lower in the mid-1980s than in 1980. The summary rate of bearing second children increased markedly in the 1980s when calculated by age of women, but declined when calculated by duration of marriage, given the inflated number of recently married women.


Requirement for the SRS2 DNA helicase gene in non-homologous end joining in yeast.
Mitotic cells experience double-strand breaks (DSBs) from both exogenous and endogenous sources. Since unrepaired DSBs can result in genome rearrangements or cell death, cells mobilize multiple pathways to repair the DNA damage. In the yeast Saccharomyces cerevisiae, mitotic cells preferentially use a homologous recombination repair pathway. However, when no significant homology to the DSB ends is available, cells utilize a repair process called non-homologous end joining (NHEJ), which can join ends with no homology through resection to uncover microhomologies of a few nucleotides. Although components of the homologous recombination repair system are also involved in NHEJ, the rejoining does not involve all of the homologous recombination repair genes. The SRS2 DNA helicase has been shown to be required for DSB repair when the homologous single-stranded regions are short. Here it is shown that SRS2 is also required for NHEJ, regardless of the cell mating type. Efficient NHEJ of sticky ends requires the Ku70 and Ku80 proteins and the silencing genes SIR2, SIR3 and SIR4. However, NHEJ of blunt ends, while very inefficient, is not further reduced by mutations in YKU70, SIR2, SIR3, SIR4 or SRS2, suggesting that this rejoining process occurs by a different mechanism.


Angiomyolipoma of kidney.
Angiomyolipoma of the kidney is a clonal neoplasm, apparently part of a family of neoplasms derived from perivascular epithelioid cells. Early angiomyolipomas are small nodules composed of HMB-45-reactive spindle cells in the renal capsule, cortex, or medulla. Most angiomyolipomas are asymptomatic, and they are more common than previously appreciated, approaching 13 per 10,000 adults. They are much more prevalent in patients with tuberous sclerosis, where they often are accompanied by cysts and occasionally by renal cell carcinoma. That they are rarely diagnosed before puberty in patients without tuberous sclerosis, that large ones are more common in women than men, and that they occasionally grow rapidly during pregnancy suggest that hormones may play a role in stimulating the growth of angiomyolipoma. Pathologists should recognize that the presence of multiple angiomyolipomas is, at the least, presumptive evidence for the diagnosis of tuberous sclerosis and include this in their reports. Typical angiomyolipomas are benign but may have alarming properties: nuclear pleomorphism and mitotic activity, extension into the vena cava (21 cases), and spread to regional lymph nodes (39 cases), without malignant progression. The most common serious complication of renal angiomyolipoma is hemorrhage. Epithelioid angiomyolipoma is a recently recognized variant with malignant potential. Angiomyolipoma and lymphangiomyoma are closely related, and tumors with features of both have occurred. Angiomyolipomas have occurred in other organs in association with renal angiomyolipoma.


Open anastomosis of extracardiac conduit for total cavopulmonary connection decreases post-operative pleural effusion.
The goal of this study was to see whether the open anastomosis technique using vacuum-assisted venous drainage at the time of the Fontan procedure was associated with decreased post-operative pleural effusion. We analysed a subgroup of patients with a functional single ventricle who underwent non-fenestrated total cavopulmonary connection completion with the insertion of an extracardiac conduit as the sole or predominant procedure conducted by a single surgeon at a single institute, using either an open or closed anastomosis technique. Median age and weight were 2.3 years, with a range from 1.3 to 27.6 years and 11.4 kilograms, with a range from 9.7 to 43 kilograms, respectively. The open anastomosis technique was associated with a shorter bypass run (p = 0.015), decreased surgical duration (p = 0.032), fewer pleural effusion days (p = 0.049), and lesser pleural effusion (p = 0.013) than closed anastomosis. Correlation analysis demonstrated a significant relationship between the amount of pleural effusion and surgical duration (correlation efficient, 0.535; p = 0.033). A logistic regression model showed that the open technique was associated with a 20-fold increase in the likelihood of having a total chest tube discharge of less than 300 millilitres (p = 0.027). The open anastomosis technique shortens operative duration and bypass run, which in turn might contribute to decreased pleural effusion soon after the modified Fontan procedure.


Impaired STAT phosphorylation in T cells from melanoma patients in response to IL-2: association with clinical stage.
To assess the extent of signal transducer and activator of transcription (STAT) activation in response to interleukin 2 (IL-2) in melanoma patients' T cells, along with clinical stage of tumor progression. T lymphocytes from peripheral blood of healthy donors and of American Joint Committee on Cancer stage I to IV melanoma patients, as well as from metastatic lymph nodes of patients, were evaluated for responsiveness to IL-2. CFSE assays and single-cell phospho-STAT-specific flow cytometry screening were used. Results. T cells from advanced melanoma patients, in comparison with healthy donors, showed reduced proliferation to IL-2 and IL-15, but not to anti-CD3 monoclonal antibody. Impaired response occurred in CCR7(+) and CCR7(-) T-cell subsets, but not in CD3(-) CD8(+) natural killer (NK) cells, and was not explained by induction of apoptosis, increased cytokine consumption, or altered IL-2R subunit expression in patients' T lymphocytes. By phospho-specific flow cytometry, defective STAT1 and STAT5 activation in response to IL-2 was found mainly in T lymphocytes from peripheral blood and/or tumor site of American Joint Committee on Cancer stage III and IV patients, compared with stage I and II patients and to donors, and in melanoma antigen-specific T cells isolated from metastatic lymph nodes. At tumor site, impaired STAT activation in T cells did not correlate with frequency of CD4(+) CD25(+) Foxp3(+) T cells. Serum from advanced melanoma patients inhibited IL-2-dependent STAT activation in donors' T cells and a neutralizing monoclonal antibody to transforming growth factor beta1 counteracted such inhibition. These results provide evidence for development of impaired STAT signaling in response to IL-2, along with clinical evolution of the disease, in melanoma patients' T cells.


Conserved cysteine residues determine substrate specificity in a novel As(III) S-adenosylmethionine methyltransferase from Aspergillus fumigatus.
Methylation of inorganic arsenic is a central process in the organoarsenical biogeochemical cycle. Members of every kingdom have ArsM As(III) S-adenosylmethionine (SAM) methyltransferases that methylates inorganic As(III) into mono- (MAs(III)), di- (DMAs(III)) and tri- (TMAs(III)) methylarsenicals. Every characterized ArsM to date has four conserved cysteine residues. All four cysteines are required for methylation of As(III) to MAs(III), but methylation of MAs(III) to DMAs(III) requires only the two cysteines closest to the C-terminus. Fungi produce volatile and toxic arsines, but the physiological roles of arsenic methylation and the biochemical basis is unknown. Here they demonstrate that most fungal species have ArsM orthologs with only three conserved cysteine residues. The genome of Aspergillus fumigatus has four arsM genes encoding ArsMs with only the second, third and fourth conserved cysteine residues. AfArsM1 methylates MAs(III) but not As(III). Heterologous expression of AfarsM1 in an Escherichia coli conferred resistance to MAs(III) but not As(III). The existence of ArsMs with only three conserved cysteine residues suggest that the ability to methylate MAs(III) may be an evolutionary step toward enzymes capable of methylating As(III), the result of a loss of function mutation in organisms with infrequent exposure to inorganic As(III) or as a resistance mechanism for MAs(III).


Dynein associates with oskar mRNPs and is required for their efficient net plus-end localization in Drosophila oocytes.
In order for eukaryotic cells to function properly, they must establish polarity. The Drosophila oocyte uses mRNA localization to establish polarity and hence provides a genetically tractable model in which to study this process. The spatial restriction of oskar mRNA and its subsequent protein product is necessary for embryonic patterning. The localization of oskar mRNA requires microtubules and microtubule-based motor proteins. Null mutants in Kinesin heavy chain (Khc), the motor subunit of the plus end-directed Kinesin-1, result in oskar mRNA delocalization. Although the majority of oskar particles are non-motile in khc nulls, a small fraction of particles display active motility. Thus, a motor other than Kinesin-1 could conceivably also participate in oskar mRNA localization. Here we show that Dynein heavy chain (Dhc), the motor subunit of the minus end-directed Dynein complex, extensively co-localizes with Khc and oskar mRNA. In addition, immunoprecipitation of the Dynein complex specifically co-precipitated oskar mRNA and Khc. Lastly, germline-specific depletion of Dhc resulted in oskar mRNA and Khc delocalization. Our results therefore suggest that efficient posterior localization of oskar mRNA requires the concerted activities of both Dynein and Kinesin-1.


Clostridium hiranonis sp. nov., a human intestinal bacterium with bile acid 7alpha-dehydroxylating activity.
The Clostridium-like organisms TO-931T and HD-17, isolated from human faeces, have high levels of bile acid 7alpha-dehydroxylating activity. Sequencing of their 16S rDNA demonstrated that they belong to cluster XI of the genus Clostridium and that they represent a new and distinct line of descent. Clostridium bifermentans and Clostridium sordellii in cluster XI also possess bile acid 7alpha-dehydroxylating activity. DNA-DNA hybridization experiments with the isolates, TO-931T and HD-17, and C bifermentans and C. sordellii revealed that the isolates are a single species distinct from C. bifermentans and C sordellii. On the basis of phylogenetic analysis, using 16S rDNA sequences, and DNA-DNA hybridization analysis, it is concluded that strains TO-931T and HD-17 are members of a new species of the genus Clostridium, for which the name Clostridium hiranonis is proposed. The type strain is strain TO-931T (= JCM 10541T = DSM 13275T).


Impact of high dietary zinc on zinc accumulation, enzyme activity and proteomic profiles in the pancreas of piglets.
The exocrine pancreas plays an important role in zinc homeostasis. Feeding very high (2000-3000mgzinc/kg diet) levels of zinc oxide to piglets for short periods is a common practice in the swine industry to improve performance and prevent diseases. The impact on pancreatic function and possible side effects during long-term feeding of high dietary zinc levels are still poorly understood. A total of 54 weaned piglets were either fed with low (57mg/kg, LZn), normal (164mg/kg, NZn) or high (2425mg/kg, HZn) zinc concentration in the diets. After 4 weeks of feeding, ten piglets per treatment were euthanized and pancreas samples were taken. Tissue zinc concentration and metallothionein abundance was greater with HZn compared with NZn and LZn (P<0.05). Similarly, activity of α-amylase, lipase, trypsin and chymotrypsin was higher with HZn as compared with NZn and LZn diets (P<0.05), whereas elastase activity was unchanged. Total trolox equivalent antioxidative capacity of pancreas tissue was higher with HZn diets compared with the other treatments (P<0.05). Pancreatic protein profiles of NZn and HZn fed piglets were obtained by 2D-DIGE technique and revealed 15 differentially expressed proteins out of 2100 detected spots (P<0.05). The differentially expressed proteins aldose reductase, eukaryotic elongation factor II and peroxiredoxin III were confirmed by immunoblotting. Identified proteins include zinc finger-containing transcription factors and proteins mainly associated with oxidative stress response and signal transduction in HZn compared with NZn pigs. Histologic examination however showed no morphologic changes. The results suggest that long-term supply of very high dietary zinc increases zinc and metallothionein concentration, and digestive enzyme activity, but also triggers oxidative stress reactions in the pancreas of young pigs. The data provide new insights into pancreatic function under outbalanced zinc homeostasis.


Race, Ethnicity, and Clinical Outcomes in Hormone Receptor-Positive, HER2-Negative, Node-Negative Breast Cancer in the Randomized TAILORx Trial.
Black race is associated with worse outcomes in early breast cancer. We evaluated clinicopathologic characteristics, the 21-gene recurrence score (RS), treatment delivered, and clinical outcomes by race and ethnicity among women who participated in the Trial Assigning Individualized Options for Treatment. The association between clinical outcomes and race (White, Black, Asian, other or unknown) and ethnicity (Hispanic vs non-Hispanic) was examined using proportional hazards models. All P values are 2-sided. Of 9719 eligible women with hormone receptor-positive, HER2-negative, node-negative breast cancer, there were 8189 (84.3%) Whites, 693 (7.1%) Blacks, 405 (4.2%) Asians, and 432 (4.4%) with other or unknown race. Regarding ethnicity, 889 (9.1%) were Hispanic. There were no substantial differences in RS or ESR1, PGR, or HER2 RNA expression by race or ethnicity. After adjustment for other covariates, compared with White race, Black race was associated with higher distant recurrence rates (hazard ratio [HR] = 1.60, 95% confidence intervals [CI] = 1.07 to 2.41) and worse overall survival in the RS 11-25 cohort (HR = 1.51, 95% CI = 1.06 to 2.15) and entire population (HR = 1.41, 95% CI = 1.05 to 1.90). Hispanic ethnicity and Asian race were associated with better outcomes. There was no evidence of chemotherapy benefit for any racial or ethnic group in those with a RS of 11-25. Black women had worse clinical outcomes despite similar 21-gene assay RS results and comparable systemic therapy in the Trial Assigning Individualized Options for Treatment. Similar to Whites, Black women did not benefit from adjuvant chemotherapy if the 21-gene RS was 11-25. Further research is required to elucidate the basis for this racial disparity in prognosis.


Synthesis of macrocyclic, potential protease inhibitors using a generic scaffold.
A generic macrocyclic peptide structure 2 was designed as a potential inhibitor of a range of proteinases, by using as a basis for the design the known structures of a series of enzyme-inhibitor complexes. The macrocyclic nature of the target 2 was chosen so as to reduce the entropic advantage in the hydrolytic enzymatic step, and thereby to inhibit the function of the enzyme. The nature of the linking group was identified as a benzoxazole by molecular modeling, so as to preserve the recognized conformation of the peptide chain. The specificity of the potential inhibitor was tuned by variation of the P(1) group (by incorporating phenylalanine, aspartic acid, or lysine), to allow recognition by different enzyme classes. The targets were prepared from the bis-amino acid derivative 5, itself prepared using the Pd-catalyzed coupling of an organozinc reagent with the iodobenzothiazole 7 and subsequent macrocyclization of the open-chain derivatives 22-24 using HATU. None of the macrocylic compounds 25, 28-30, and 32 inhibited their target enzymes. NMR and MS studies on the interaction of macrocycle 29 and chymotrypsin established that compound 29 was in fact a substrate of the enzyme. This result indicated that while the design had been partially successful in identifying a compound that bound, the reduction in entropic advantage due to its macrocyclic nature was not sufficient to allow 29 to act as an inhibitor.


Trabecular bone architecture in the distal radius using magnetic resonance imaging in subjects with fractures of the proximal femur. Magnetic Resonance Science Center and Osteoporosis and Arthritis Research Group.
To determine whether magnetic resonance (MR)-derived measures of trabecular bone architecture in the distal radius are predictive for prevalent hip fractures, 20 subjects with hip fractures and 19 age-matched postmenopausal controls were studied. Bone mineral density (BMD) measures at the hip (dual-energy X-ray absorptiometry, DXA) and the distal radius (peripheral quantitative computed tomography, pQCT) were also obtained. We compared the MR-based structural measures derived in the radius with those in the calcaneus of the same patients. In the radius, images were acquired at an in-plane resolution of 156 microm and a slice thickness of 0.5 mm. Stereologic measures such as the apparent trabecular thickness (app. Tb.Th), fractional trabecular bone volume (app. BV/TV), trabecular spacing (app. Tb.Sp) and trabecular number (app. Tb.N) were derived from the images. Measures of app. Tb.Sp and app. Tb.N in the distal radius showed significant (p<0.05) differences between the two groups, as did hip BMD measures. However, radial trabecular BMD measures showed only a marginal difference (p = 0.05). Receiver operating curve analysis was used to determine the diagnostic efficacy of BMD, structural measures and a combination of the two. The area under the curve (AUC) for total hip BMD was 0.73, and for radial trabecular BMD was 0.69. AUC for most of the measures of trabecular bone structure at the distal radius was lower than for hip BMD measures; however, AUC for app. Tb.N at the radius was 0.69, comparable to trabecular BMD using pQCT. The AUC for combined BMD (hip) and structure measures was higher (0.87) when radius and calcaneus structure was included. Measures of trabecular architecture derived from MR images combined with BMD measures improve the discrimination between subjects with hip fractures and normal age-matched controls.


Evidence for the association of human papillomavirus infection and cutaneous squamous cell carcinoma in immunocompetent individuals.
The aim of our study was to evaluate human papillomavirus (HPV) infection as a risk factor for cutaneous squamous cell carcinoma (SCC) in immunocompetent individuals. Hospital-based case-control study. Referral center for dermatologic diseases for central and southern Italy. Consecutive patients with histologically confirmed cutaneous SCC (n = 46) and control subjects (n = 84) chosen by frequency matching (age and sex) among patients admitted with unrelated diseases. Infection with epidermodysplasia verruciformis-related HPV types, blindly assessed by serologic testing (viruslike particle enzyme-linked immunosorbent assay). Information was obtained on known potentially confounding risk factors (family history, history and signs of sun exposure, and pigmentary traits) and on history of HPV-related lesions and diseases, assessed by interview and examination by a dermatologist. Positive serologic findings for HPV type 8 were associated with SCC (odds ratio, 3.2; 95% confidence interval, 1.3-7.9) independently of other risk factors, whereas positive serologic findings for HPV type 15 were negatively associated with SCC (odds ratio, 0.4; 95% confidence interval, 0.2-0.9). Other variables significantly associated with the tumor were family history of skin cancer, professional or recreational sun exposure, light eye color, high number of solar keratoses and seborrheic keratoses on the body surface, and residency in radon-emitting buildings. Positive serologic findings for HPV type 8 are associated with SCC occurrence in immunocompetent individuals. Viral infection could act as a cofactor in the tumor development, along with genetic predisposition, solar radiation, and other environmental exposures. If confirmed, these findings could open new perspectives for treatment and prevention of SCC.


Rehabilitation following cancer treatment.
Cancer survivorship is increasing. However, life-saving treatments often leave people with physical, cognitive and emotional sequelae that contribute to activity and participation limitations. The purpose of this review is to summarize current evidence regarding rehabilitation interventions to address problems during survivorship. Best evidence synthesis. The review took as its starting point a systematic review of patient needs and supportive care interventions following cancer treatment. The study team identified the needs which could be addressed by rehabilitation and suggested others not originally included. Then they built on the earlier review's conclusions regarding effective intervention through extraction of results from subsequent systematic reviews and randomized controlled trials. Evidence regarding the effectiveness of potential rehabilitation interventions was reviewed for physical functioning, fatigue, pain, sexual functioning, cognitive functioning, depression, employment, nutrition and participation. With the exception of physical rehabilitation interventions following breast cancer, this literature tends to focus on psychoeducational interventions, which have demonstrated limited effectiveness for rehabilitation outcomes. Most of the knowledge available regarding potential rehabilitation interventions comes from psychosocial oncology literature. While there are limitations, this literature provides an excellent starting point to examine the potential effectiveness of rehabilitation interventions within cancer survivorship programs. Good evidence exists for the use of exercise/physical rehabilitation in reducing fatigue after treatment for most cancers, and improving upper extremity functioning following treatment for breast cancer. Preliminary evidence exists in a number of areas that may be improved by rehabilitation interventions, such as pain, sexual functioning, cognitive functioning and return to work, but further research is needed. No intervention studies addressing participation limitations were identified. Rehabilitation professionals are encouraged to take the lead in exploring participation limitations among cancer survivors and developing suitable interventions.


Identification by shotgun sequencing, genomic organization, and functional analysis of a fourth arylsulfatase gene (ARSF) from the Xp22.3 region.
We recently reported the isolation of two new members of the sulfatase gene family, arylsulfatase D (ARSD) and E (ARSE), located approximately 50 kb from each other in the Xp22.3 region. Mutation analysis indicated ARSE as the gene responsible for X-linked recessive chondrodysplasia punctata. Expression of the ARSE gene in COS cells resulted in a heat-labile arylsulfatase activity that was inhibited by warfarin. At the same time, we detected the presence of a 1.2-kb fragment located at approximately 60 kb from ARSD and ARSE with significant homology to these two genes, suggesting the existence of another sulfatase gene, arylsulfatase F (ARSF), in Xp22.3. We have used a combined approach of long-range genomic sequencing and screening of cDNA libraries to isolate the ARSF gene. Expression of the ARSF cDNA in COS cells resulted in a heat-labile arylsulfatase activity that is not inhibited by warfarin, supporting our hypothesis that only ARSE is specifically inhibited by warfarin and is most likely involved in warfarin embryopathy. Genomic analysis revealed that ARSF has an intron/exon organization highly similar to those of ARSD and ARSE, which is also shared by another Xp22.3 sulfatase gene, ARSC (arylsulfatase C, also known as steroid sulfatase), with the splice sites occurring at the same position in all four genes. The data obtained from sequence analysis and presented in this paper indicate that the ARSC, ARSD, ARSE, and ARSF genes are more similar to each other than to other members of the sulfatase gene family, supporting our hypothesis that they represent a subfamily of related proteins created through duplication events that occurred in an ancestral pseudoautosomal region.


Pneumonia. Pearls for interpreting patients' radiographs.
The chest radiograph can detect pneumonia, but laboratory evaluation is needed to determine the specific causative organism. However, before these results become available, a presumptive diagnosis can be made with the help of chest radiography. A lobar pattern on radiography is usually produced by pneumococcal and Klebsiella infections. A lobular (bronchopneumonia) pattern may be produced by Staphylococcus, gram-negative organisms, and anaerobes. An interstitial pattern results from viral, Mycoplasma, and Pneumocystis carinii infections. Mixed patterns may also occur. There is great variation in the presentation of each infection. However, pertinent clinical information, epidemiologic factors, and associated radiographic findings (eg, adenopathy, pleural effusion, cavitation) are helpful in further limiting diagnostic possibilities.


Is the QbMini a Valid Instrument for ADHD Assessment?
Objective: Few neuropsychological measurement tools of attention can assess preschoolers despite adequate instruments' potential to facilitate early diagnostic processes, which are currently demanding. This study's objective was to evaluate the QbMini, an attention-deficit hyperactive disorder (ADHD) measurement tool for preschoolers. Method: QbMini performances of 37 5-year-old ADHD patients, 55 healthy controls, and 26 children with specific language impairment (SLI) were compared using univariate analyses of variance. The test's predictive power was evaluated using receiver operating characteristics (ROC) analyses and compared to a parental rating scale. Finally, the scales were compared by correlating their respective scores. Results: The QbMini measures ADHD symptoms and reliably differentiates between healthy children and patients, but not between children with ADHD and children with SLI. Conclusion: The QbMini can indicate presence and strength of ADHD symptoms, but fails to diagnose ADHD. It measures symptoms in a different way than parental ratings and might be stronger in distinguishing between hyperactivity and inattention.


A comparison of 1978 and 2006 peak pollen seasons and sampling methods in Missoula, Montana.
A study was conducted in Missoula, Montana to compare local pollen counts from 1978 with those measured nearly 30 years later in 2006 using two different measurement techniques (Durham gravimetric sampler and a Burkard volumetric sampler). Trends in peak pollen times measured during the spring, summer and autumn, respectively, were compared between the two years by Pearson's correlation and frequency of occurrence of plant genus. Meteorological conditions were also examined during each of the two study periods.In comparing the two years, there was a statistically significant linear association between the different counts for the months of April through August, with similar levels of pollen types for any given month. The five predominant pollen types (based on counts) identified in each study were Pinus, Poaceae, Populus, Alnus, and Betula for 2006 and Pinus, Poaceae, Populus, Acer and Artemisia for 1978. In summary most of the genera displayed similar peak pollination timing between the two years, suggesting that results from the Durham (gravimetric) and Burkard (volumetric) sampling methods are comparable when reporting relative frequency of occurrence.


Surfactant volume is an essential element in human toxicity in acute glyphosate herbicide intoxication.
Glyphosate, one of the most commonly used herbicides worldwide, has been considered as minimally toxic to humans. However, clinical toxicologists occasionally encounter cases of severe systemic toxicity. The purpose of this study was to determine the effect of glyphosate-surfactants ("glyphosate-surfactant toxicity") in patients with acute glyphosate intoxication. In all, 107 patients (69 men and 38 women, aged 52.3 ± 15.5 years) with acute glyphosate intoxication were enrolled in this study. From their medical records, we identified the formulation of ingested glyphosate products and derived clinical parameters, which focused on clinical outcome, admission days, duration in the intensive care unit, development of respiratory failure, cardiovascular deterioration, renal failure, altered mental status, and convulsions. The effect of surfactants on clinical complications was also assessed. For surfactant ingestion volumes of 8 mL, the incidence of clinical complications was (in rank order) as follows: hypotension, 47.1%; mental deterioration, 38.6%; respiratory failure, 30.0%; acute kidney injury, 17.1%; and arrhythmia, 10.0%. These complications were influenced by the volume of surfactant and not the type of surfactant-ingredient in the herbicide product. Two patients died of refractory shock, metabolic acidosis, and respiratory failure. However, the final clinical outcomes of the surviving patients were benign, and cardiovascular, respiratory, kidney, and mental functions were fully restored to normal levels. Our results indicate that treatment of patients with acute glyphosate herbicide intoxication should take into account the volume and not the type of surfactants in herbicide formulations.


From the Cover: Teratogenic Effects of in Utero Exposure to Di-(2-Ethylhexyl)-Phthalate (DEHP) in B6:129S4 Mice.
Intrauterine exposure to phthalates is known to cause disorders of male reproductive function including androgen insufficiency, decreased fertility, and germ cell defects in rodents. In this study, we set out to investigate the effects of intrauterine exposure to di-(2-ethylhexyl)-phthalate (DEHP) on fetal development of the B6:129S4 mouse strain. Time-mated pregnant C57BL/6 dams were exposed to 0, 5, 250, or 500 mg/kg DEHP with corn oil as the vehicle via oral gavage from embryonic days (E)7 to 16. Survival and gross morphology of the pups were analyzed one day after the last treatment. Anogenital distance (AGD) and testicular cell functions were examined in male embryos to confirm the known effects of phthalate exposure. DEHP exposure significantly reduced the survival rate of fetuses in the 250 and 500 mg/kg dosage groups compared with the control and 5 mg/kg groups. Exposure to 250 and 500 mg/kg DEHP was teratogenic and induced exencephaly and limb malformations such as polydactyly in the B6:126S4 embryos. No gross malformations were observed in control or 5 mg/kg DEHP groups. In male embryos, exposure to both 5 and 250 mg/kg DEHP in utero was sufficient to induce the formation of multinucleated germ cells in the testes and widespread changes in mRNA expression of germ cell, interstitium and Sertoli cell-associated genes. These findings reveal that intrauterine DEHP exposure has a strong teratogenic, and lethal impact on the fetuses of B6:129S4 mouse strain.


New York State Health Foundation: integrating mental health and substance abuse care.
Roughly half of all people with severe mental disorders also have substance abuse problems. Yet their care is fragmented: They are treated by either the mental health system or the substance abuse system. In New York State only 10 percent of them receive evidence-based treatment for both conditions. Beginning in 2007 the New York State Health Foundation and two state agencies--the Office of Mental Health and the Office of Alcoholism and Substance Abuse Services--began collaborating on ways to integrate the treatment of people with co-occurring disorders. The state agencies removed financial and regulatory barriers to integrated treatment. The foundation provided funding to establish the Center for Excellence in Integrated Care. The center's goal: provide hands-on assistance in implementing best practices to at least half of the state's 1,200 mental health and substance abuse treatment clinics. An evaluation found that the percentage of clinics using best practices doubled after the regulatory and financial changes and the center's intervention. This illustrates the potential that foundations, governments, and nonprofits, working collaboratively, have to improve the care of a neglected and difficult-to-serve population.


Osteomyelitis Risk Factors Related to Combat Trauma Open Femur Fractures: A Case-Control Analysis.
To identify the risk factors for osteomyelitis development in US military personnel with combat-related, open femur fractures? Retrospective observational case-control study. US military regional hospital in Germany and tertiary care hospitals in United States (2003-2009). One hundred three patients with open femur fractures who met diagnostic osteomyelitis criteria (medical record review verification) were classified as cases. Sixty-four patients with open femur fractures who did not meet osteomyelitis diagnostic criteria were included as controls. The main outcome measurements were multivariable odds ratios (ORs) and 95% confidence interval (CI). Among patients with surgical implants, osteomyelitis cases had significantly longer time to definitive orthopaedic surgery compared with controls (median: 21 vs. 13 days). Independent predictors for osteomyelitis risk were Gustilo-Anderson classification (transfemoral amputation OR: 19.3; CI: 3.0-123.0) and Orthopaedic Trauma Association Open Fracture Classification for muscle loss (OR: 5.7; CI: 1.3-25.1) and dead muscle (OR: 32.9; CI: 5.4-199.1). Being injured between 2003 and 2006, antibiotic bead use, and foreign body plus implant(s) at fracture site were also risk factors. Patients with open femur fractures resulting in significant muscle damage have the highest osteomyelitis risk. Foreign body contamination was only significant when an implant was present. Increased risk with antibiotic bead use is likely a surrogate for clinical suspicion of contamination with complex wounds. The timeframe association is likely due to changing trauma system patterns around 2006-2007 (eg, increased negative pressure wound therapy, reduced high-pressure irrigation, decreased crystalloid use, and delayed definitive internal fixations). Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


"Don't eat that, you'll get fat!" Exploring how parents and children conceptualise and frame messages about the causes and consequences of obesity.
Family interactions about weight and health take place against the backdrop of the wider social discourse relating to the obesity epidemic. Parents (and children) negotiate complex and often contradictory messages in constructing a set of beliefs and practices around obesity and weight management. Despite this, very little research attention has been given to the nature of family-unit discourse on the subject of body weight and it's potential influence on the weight-related behaviours of family members. This includes the broad influence that dominant socio-cultural discourses have on family conceptualisations of weight and health. Using in-depth qualitative interviews with 150 family 'groups' comprised of at least one parent and one child in Victoria and South Australia, we explored how parents and children conceptualise and discuss issues of weight- and health-related lifestyle behaviours. Data were analysed using Attride-Stirling's (2001) thematic network approach. Three thematic clusters emerged from the analysis. First, both parents and children perceived that weight was the primary indicator of health. However, parents focused on the negative physical implications of overweight while children focused on the negative social implications. Second, weight and lifestyle choices were highly moralised. Parents saw it as their responsibility to communicate to children the 'dangers' of fatness. Children reported that parents typically used negatively-framed messages and scare tactics rather than positively-framed messages to encourage healthy behaviours. Third was the perception among parents and children that if you were thin, then eating habits and exercise were less important, and that activity could provide an antidote to food choices. Results suggest that both parents and children are internalising messages relating to obesity and weight management that focus on personal responsibility and blame attribution. These views reflect the broader societal discourse, and their consolidation at the family level is likely to increase their potency and make them resistant to change.


Deep Learning-Based Multi-Focus Image Fusion: A Survey and a Comparative Study.
Multi-focus image fusion (MFIF) is an important area in image processing. Since 2017, deep learning has been introduced to the field of MFIF and various methods have been proposed. However, there is a lack of survey papers that discuss deep learning-based MFIF methods in detail. In this study, we fill this gap by giving a detailed survey on deep learning-based MFIF algorithms, including methods, datasets and evaluation metrics. To the best of our knowledge, this is the first survey paper that focuses on deep learning-based approaches in the field of MFIF. Besides, extensive experiments have been conducted to compare the performance of deep learning-based MFIF algorithms with conventional MFIF approaches. By analyzing qualitative and quantitative results, we give some observations on the current status of MFIF and discuss some future prospects of this field.


[Primary signet-ring cell bladder adenocarcinoma].
The authors report a case of primary adenocarcinoma of the bladder, a rare tumor that accounts for 0.5-2% of primary bladder tumors in a 69 years old male patient with a previous history of urothelial tumor that had been treated by TUR and intravesical chemotherapy. The tumor widely infiltrated adjacent structures and biopsy disclosed signet-ring cells. This condition was not amenable to treatment.


Laparoscopic salpingotomy using the floseal hemostatic sealant in patients with tubal pregnancy.
To present our initial experience with laparoscopic salpingotomy using the Floseal™ (Baxter International Corp., Deerfield, IL) hemostatic matrix for tubal pregnancy and to evaluate the efficacy and tubal patency after salpingotomy. A prospective study was conducted on 20 consecutive patients with tubal pregnancy undergoing laparoscopic salpingotomy using the Floseal hemostatic matrix. The outcome measures were treatment success rates and homolateral patency rates. Of 20 cases, 19 cases (95%) were successfully performed without any additional intervention, and 1 case was switched to salpingectomy during the initial surgery. During the mean β-human chorionic gonadotropin resolution time of 17.9±6.4 days, postoperative complications or persistent trophoblasts did not occur. Of 19 salpingotomy patients, only 12 patients received a tubal patency test using hysterosalpingography, and the homolateral tubal patency rate was 75% (9 of 12). The use of Floseal allows laparoscopic salpingotomy to be performed successfully and easily with comparable outcomes.


Shape memory polymers with silicon-containing segments.
Thermoresponsive shape memory polymers are stimuli-responsive materials whose shape is modulated by heat. They have been investigated as smart materials in a variety of biomedical, industrial and aerospace applications. The vast majority of shape memory polymers have been limited to those prepared from organic polymers. In this present work, shape memory polymers comprised of inorganic silicon-containing polymer segments (polydimethylsiloxane, PDMS) and organic poly(ε-caprolactone) (PCL) segments were developed. Because of its low T g, PDMS served as a highly effective soft segment. The photochemical cure of diacrylated PCL n -block-PDMS37-block-PCL n macromers with tailored PCL segment lengths produced networks with excellent mechanical properties, shape fixity, and shape recovery.


Immediate termination of intractable vomiting induced by cisplatin combination chemotherapy using an intensive five-drug antiemetic regimen.
A five-drug parenteral antiemetic regimen was administered to 17 patients experiencing intractable vomiting following treatment with cisplatin-containing combination chemotherapy. The five-drug treatment consisted of metoclopramide (1 mg/kg iv), diphenhydramine (50 mg im), dexamethasone (20 mg iv), diazepam (5 mg iv), and thiethylperazine (10 mg im), given together at the initiation of the regimen and repeated on a predefined schedule. The number of emetic episodes, duration of nausea and vomiting, and adverse effects were recorded by trained observers. In addition, all patients completed standardized evaluation forms on the day after treatment. Thirteen patients (76%) remained free of vomiting and three (18%) had only one emesis after beginning the study treatment. No serious toxicity was encountered. We conclude that intractable vomiting induced by cisplatin-based combination chemotherapy can be successfully terminated with an aggressive parenteral antiemetic regimen.


Innovative reactor technology for selective oxidation of toxic organic pollutants in wastewater by ozone.
Ozonation can be a suitable technique for the pre-treatment of wastewater containing low concentrations of toxic or non-biodegradable compounds that cannot be treated with satisfactory results when only the traditional, less expensive biological techniques are applied. In this case, the oxidation process has to be made as efficient as possible, in order to reduce the coats of ozone addition and use. An efficient oxidation process with ozone can be obtained by focusing the oxidation with ozone selectively on the direct oxidation of toxic pollutants and to minimize ozone losses due to the decay of ozone in water. Supported by data of the rate constants of the reactions involved, a mathematical model was developed. It quantifies the ozone consumption by the process, and the share of ozone consumption by undesired side reactions, in several different reactor systems. Results obtained with this model indicate that a plug flow reactor (PFR) will be the most efficient design for the oxidation reactor. As an alternative, the cascaded tank reactor system (CTR), in which the ozone feed may be realized with less practical problems, might be considered. The traditional continuous flow stirred tank reactor (CFSTR) is shown to be the least efficient system.


COVID-19 knowledge, attitudes, and practices of United Arab Emirates medical and health sciences students: A cross sectional study.
The COVID-19 pandemic is the largest viral pandemic of the 21st century. We aimed to study COVID-19 knowledge, attitudes, and practices (KAP) among medical and health sciences students in the United Arab Emirates (UAE). We performed a cross-sectional study between 2 June and 19 August 2020. The survey was distributed online using Survey Monkey. It was conducted in English and comprised two parts: socio-demographic characteristics, and KAP towards COVID-19. 712 responses to the questionnaire were collected. 90% of respondents (n = 695) were undergraduate students, while 10% (n = 81) were postgraduates. The majority (87%, n = 647) stated that they obtained COVID-19 information from multiple reliable sources. They were highly knowledgeable about the COVID-19 pandemic, but 76% (n = 539) did not recognize its routes of transmission. Medical students were significantly more knowledgeable compared with allied health students (P<0.0001, Mann Whitney U test) but there was no difference in knowledge between undergraduate and postgraduate students (P = 0.14, Mann Whitney U test). Medical students thought that more could be done to mitigate the COVID-19 situation compared with the allied health students (66.2% compared with 51.6%, p = 0.002 Fisher's Exact test). 63% (n = 431) were worried about getting COVID-19 infection, while 92% (n = 633)) were worried that a family member could be infected with the virus. 97% (n = 655) took precautions when accepting home deliveries, 94% (n = 637) had been washing their hands more frequently, and 95% (n = 643) had been wearing face masks. In conclusion, medical and health sciences students in the UAE showed high levels of knowledge and good attitudes and practices towards the COVID-19 pandemic. Nevertheless, they were worried about themselves or their family members becoming infected. Medical students had more knowledge about COVID-19 pandemic which was reflected in their opinion that more can be done to mitigate its effects.


[Preparation and characterization of monoclonal antibodies against Cryptosporidium parvum].
To develop and characterize the monoclonal antibodies(McAbs) against Cryptosporidium parvum (C. parvum). BALB/c mice were immunized with purified oocyst antigens of C. parvum from human isolates and McAbs against C. parvum were prepared by using hybridoma technique. The characterization of McAbs was studied by means of indirect immunofluorescent assay (IFA) and Western blot analysis. Four clones of hybridoma cell lines secreting McAbs against oocyst antigens of C. parvum were obtained. The immunoglobulin subclasses of these four McAbs were identified as IgM (Z4C8,Z3D7) and IgG1(Z2B6,Z3D2) and their light chains were kappa chain. IFA results showed that three McAb (Z4C8, Z3D7 and Z3D2) conjugates produced a diffuse fluorescence in the Cryptosporidium sporozoites (CSP) and one (Z2B6) produced local fluorescence in the oocyst wall of C. parvum. Four McAbs could recognize 4 of 42 polypeptide antigen bands of CSP with molecular weights of 20.5 kDa, 33 kDa, 60.5 kDa and 95 kDa, among which both Z4C8 and Z3D7 could recognize 20.5 kDa band that was defined as a principal antigenic protein of CSP. These four McAbs possess their own characteristics of recognizing antigenic epitopes on CSP, but react specifically against antigens of C. parvum.


Repeated Measures Correlation.
Repeated measures correlation (rmcorr) is a statistical technique for determining the common within-individual association for paired measures assessed on two or more occasions for multiple individuals. Simple regression/correlation is often applied to non-independent observations or aggregated data; this may produce biased, specious results due to violation of independence and/or differing patterns between-participants versus within-participants. Unlike simple regression/correlation, rmcorr does not violate the assumption of independence of observations. Also, rmcorr tends to have much greater statistical power because neither averaging nor aggregation is necessary for an intra-individual research question. Rmcorr estimates the common regression slope, the association shared among individuals. To make rmcorr accessible, we provide background information for its assumptions and equations, visualization, power, and tradeoffs with rmcorr compared to multilevel modeling. We introduce the R package (rmcorr) and demonstrate its use for inferential statistics and visualization with two example datasets. The examples are used to illustrate research questions at different levels of analysis, intra-individual, and inter-individual. Rmcorr is well-suited for research questions regarding the common linear association in paired repeated measures data. All results are fully reproducible.


Astroglial ER-mitochondria calcium transfer mediates endocannabinoid-dependent synaptic integration.
Intracellular calcium signaling underlies the astroglial control of synaptic transmission and plasticity. Mitochondria-endoplasmic reticulum contacts (MERCs) are key determinants of calcium dynamics, but their functional impact on astroglial regulation of brain information processing is unexplored. We found that the activation of astrocyte mitochondrial-associated type-1 cannabinoid (mtCB1) receptors determines MERC-dependent intracellular calcium signaling and synaptic integration. The stimulation of mtCB1 receptors promotes calcium transfer from the endoplasmic reticulum to mitochondria through a specific molecular cascade, involving the mitochondrial calcium uniporter (MCU). Physiologically, mtCB1-dependent mitochondrial calcium uptake determines the dynamics of cytosolic calcium events in astrocytes upon endocannabinoid mobilization. Accordingly, electrophysiological recordings in hippocampal slices showed that conditional genetic exclusion of mtCB1 receptors or dominant-negative MCU expression in astrocytes blocks lateral synaptic potentiation, through which astrocytes integrate the activity of distant synapses. Altogether, these data reveal an endocannabinoid link between astroglial MERCs and the regulation of brain network functions.


Do Grip Strength Dynamometer Readings Improve After Cervical Spine Surgery?
Retrospective, cohort study. Hand function can be difficult to objectively assess perioperatively. In patients undergoing cervical spine surgery by a single-surgeon, we sought to: (1) use a hand dynamometer to report pre/postoperative grip strength, (2) distinguish grip strength changes in patients with radiculopathy-only vs myelopathy, and (3) assess predictors of grip strength improvement. Demographic and operative data were collected for patients who underwent surgery 2015-2018. Hand dynamometer readings were pre/postoperatively at three follow-up time periods (0-3 m, 3-6 m, 6-12 m). 262 patients (mean age of 59 ± 14 years; 37% female) underwent the following operations: ACDF (80%), corpectomy (25%), laminoplasty (19%), and posterior cervical fusion (7%), with 81 (31%) patients undergoing multiple operations in a single anesthetic setting. Radiculopathy-only was seen in 128 (49%) patients, and myelopathy was seen 134 (51%) patients. 110 (42%) had improved grip strength by ≥10-lbs, including 69/128 (54%) in the radiculopathy-only group, and 41/134 (31%) in the myelopathy group. Those most likely to improve grip strength were patients undergoing ACDF (OR 2.53, P = .005). Patients less likely to improve grip strength were older (OR = .97, P = .003) and underwent laminoplasty (OR = .44, 95% CI .23, .85, P = .014). Patients undergoing surgery at the C2/3-C5/6 levels and C6/7-T1/2 levels both experienced improvement during the 0-3-month time range (C2-5: P = .035, C6-T2: P = .015), but only lower cervical patients experienced improvement in the 3-6-month interval (P = .030). Grip strength significantly improved in 42% of patients. Patients with radiculopathy were more likely to improve than those with myelopathy. Patients undergoing surgery from the C2/3-C5/6 levels and the C6/7-T1/2 levels both significantly improved grip strength at 3-month postoperatively.


Increased Serum Levels of Soluble TNF-α Receptor Is Associated With ICU Mortality in COVID-19 Patients.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected over 112M patients and resulted in almost 2.5M deaths worldwide. The major clinical feature of severe COVID-19 patients requiring ventilation is acute respiratory distress syndrome (ARDS) possibly associated with a cytokine storm. To elucidate serum levels of TNF-α and soluble TNF-Receptor 1 (sTNFR1) in patients with severe and mild COVID-19 disease as determinants of disease severity. We determined serum TNF-α and sTNFR1 concentrations in 46 patients with laboratory-confirmed COVID-19 (17 patients with severe disease within the intensive care unit [ICU] and 29 non-severe, non-ICU patients) and 15 healthy controls upon admission using ELISA. Subjects were recruited between March-May 2020 at the Masih Daneshvari Hospital Tehran, Iran. Serum levels of sTNFRI were significantly higher in ICU patients (P<0.0001) and non-ICU patients (P=0.0342) compared with healthy subjects. Serum sTNFR1 were significantly higher in ICU patients than in non-ICU patients (P<0.0001). Serum TNF-α levels were greater in ICU and non-ICU patients than in the healthy subjects group (p<0.0001). The sTNFRI concentration in ICU (r=0.79, p=0.0002) and non-ICU (r=0.42, p=0.02) patients positively correlated with age although serum sTNFRI levels in ICU patients were significantly higher than in older healthy subjects. The sTNFRI concentration in ICU patients negatively correlated with ESR. The study demonstrates higher sTNFRI in ICU patients with severe COVID-19 disease and this be a biomarker of disease severity and mortality. Future studies should examine whether lower levels of systemic sTNFR1 at admission may indicate a better disease outcome.


Niclosamide inhibits ovarian carcinoma growth by interrupting cellular bioenergetics.
Background: Ovarian carcinoma is a common malignant tumor of the female reproductive organs with an incidence rate second only to cervical and endometrial cancers. In the past 10 years, anticancer therapy has focused on Niclosamide, an anthelmintic teniacide that is commonly used against tapeworms and has been approved for use in humans for nearly 50 years. Importantly, Niclosamide has been confirmed to target the Wnt/β-catenin, mTOR, STAT3, NF-κB, and Notch pathways has been widely investigated in multiple cancer types. However, the potential benefits of Niclosamide therapy for treatment of ovarian carcinoma have not been established. Methods: CCK-8 colony formation assays were performed to evaluate cell viability and tumor growth. Cell apoptosis was measured by flow cytometry. A Seahorse XF96 analyzer was used to measure cellular bioenergetics. Mito-tracker stained mitochondria were visualized by confocal microscopy. Western blotting was used to detect expressed proteins. A nude mouse transplanted-tumor model was used to evaluate the antitumor activity of Niclosamide in ovarian carcinoma. Result: Niclosamide treatment significantly suppressed ovarian carcinoma growth and induced cell apoptosis by inactivating MEK1/2-ERK1/2 mediated signal transduction. Overall, mitochondrial respiration and aerobic glycolysis were both decreased by Niclosamide treatment. Niclosamide dramatically enhanced ROS-activated and JNK-mediated apoptosis in cells subjected to glucose deprivation. Niclosamide also showed in vivo antitumor activity in the nude mouse transplanted-tumor model. Conclusion: Collectively, these data highlight a novel anti-tumor mechanism of Niclosamide that involves an interruption of cell metabolism. The finding also indicates a potential for the application of Niclosamide in ovarian carcinoma therapy.


Increased expression of calreticulin is linked to ANG IV-mediated activation of lung endothelial NOS.
This study demonstrates that ANG IV-induced activation of lung endothelial cell nitric oxide synthase (ecNOS) is mediated through mobilization of Ca(2+) concentration and by increased expression and release of the Ca(2+) binding protein calreticulin in pulmonary artery endothelial cells (PAEC). In Ca(2+)-free medium and in the presence of the ANG II AT(1) and AT(2) receptor antagonists losartan and PD-123319 (1 microM each), respectively, ANG IV (5, 50, and 500 nM) significantly increased intracellular Ca(2+) release in PAEC (P < 0.05 for all concentrations). In contrast, ANG IV-mediated activation of ecNOS was abolished by the intracellular Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM. ANG IV stimulation resulted in significantly increased expression of calreticulin in cells as well as release of calreticulin into the medium of cells as early as 2 h after ANG IV stimulation (P < 0.05). Catalytic activity of purified ecNOS in the absence of calmodulin was increased in a concentration-dependent fashion by calreticulin. Immunocoprecipitation studies revealed that ecNOS and calreticulin were coprecipitated in ANG IV-stimulated PAEC. These results demonstrate that ANG IV-mediated activation of ecNOS is regulated by intracellular Ca(2+) mobilization and by increased expression of calreticulin, which appears to involve interaction of ecNOS and calreticulin proteins in PAEC.


Concentrations of selected vitamins and selenium in bison cuts.
We analyzed individual cuts from clod (Triceps brachii), ribeye (Longissimus thoracis), top round (semimembranosus), and top sirloin (Gluteus medius) from 12 fed bison bulls for content of selected vitamins and selenium. The bulls came from producers in the United States and Canada and had consumed concentrate diets plus hay free choice for at least 180 d. The mean nutrient concentrations of all of the bison cuts combined were as follows (per 100 grams of wet weight): .045 mg thiamin, .253 mg vitamin B6, 2.131 microg vitamin B12, no detectable vitamin C, .848 microg vitamin A, .047 mg alpha-tocopherol, .013 mg tau-tocopherol, and 25.464 microg selenium. The nutrient content values did not differ (P > .05) among the cuts of meat. Cuts from individual bulls were different (P < .05) with regard to alpha- and tau-tocopherols, selenium, and vitamin A but not with regard to thiamin, vitamin B6, and vitamin B12. Nutrient concentrations, with the exception of one nutrient, of five bison from the same producer were similar. Great variation was observed between the alpha- and tau-tocopherols, selenium, and vitamin A contents among bison bulls but not among cuts of meat.


Inhibiting autophagy reduces retinal degeneration caused by protein misfolding.
Mutations in the genes necessary for the structure and function of vertebrate photoreceptor cells are associated with multiple forms of inherited retinal degeneration. Mutations in the gene encoding RHO (rhodopsin) are a common cause of autosomal dominant retinitis pigmentosa (adRP), with the Pro23His variant of RHO resulting in a misfolded protein that activates endoplasmic reticulum stress and the unfolded protein response. Stimulating macroautophagy/autophagy has been proposed as a strategy for clearing misfolded RHO and reducing photoreceptor death. We found that retinas from mice heterozygous for the gene encoding the RHOP23H variant (hereafter called P23H) exhibited elevated levels of autophagy flux, and that pharmacological stimulation of autophagy accelerated retinal degeneration. In contrast, reducing autophagy flux pharmacologically or by rod-specific deletion of the autophagy-activating gene Atg5, improved photoreceptor structure and function. Furthermore, proteasome levels and activity were reduced in the P23H retina, and increased when Atg5 was deleted. Our findings suggest that autophagy contributes to photoreceptor cell death in P23H mice, and that decreasing autophagy shifts the degradation of misfolded RHO protein to the proteasome and is protective. These observations suggest that modulating the flux of misfolded proteins from autophagy to the proteasome may represent an important therapeutic strategy for reducing proteotoxicity in adRP and other diseases caused by protein folding defects.


Biomarkers Associated with Cognitive Impairment in Treated Cancer Patients: Potential Predisposition and Risk Factors.
Purpose: Cognitive impairment in cancer patients induced, at least in part, by treatment are frequently observed and likely have negative impacts on patient quality of life. Such cognitive dysfunctions can affect attention, executive functions, and memory and processing speed, can persist after treatment, and their exact causes remain unclear. The aim of this review was to create an inventory and analysis of clinical studies evaluating biological markers and risk factors for cognitive decline in cancer patients before, during, or after therapy. The ultimate objectives were to identify robust markers and to determine what further research is required to develop original biological markers to enable prevention or adapted treatment management of patients at risk. Method: This review was guided by the PRISMA statement and included a search strategy focused on three components: "cognition disorders," "predictive factors"/"biological markers," and "neoplasms," searched in PubMed since 2005, with exclusion criteria concerning brain tumors, brain therapy, and imaging or animal studies. Results: Twenty-three studies meeting the criteria were analyzed. Potential associations/correlations were identified between cognitive impairments and specific circulating factors, cerebral spinal fluid constituents, and genetic polymorphisms at baseline, during, and at the end of treatment in cancer populations. The most significant results were associations between cognitive dysfunctions and genetic polymorphisms, including APOE-4 and COMT-Val; increased plasma levels of the pro-inflammatory cytokine, IL-6; anemia; and hemoglobin levels during chemotherapy. Plasma levels of specific hormones of the hypothalamo-pituitary-adrenal axis are also modified by treatment. Discussion: It is recognized in the field of cancer cognition that cancer and comorbidities, as well as chemotherapy and hormone therapy, can cause persistent cognitive dysfunction. A number of biological circulating factors and genetic polymorphisms, can predispose to the development of cognitive disorders. However, many predictive factors remain unproven and discordant findings are frequently reported, warranting additional clinical and preclinical longitudinal cohort studies, with goals of better characterization of potential biomarkers and identification of patient populations at risk and/or particularly deleterious treatments. Research should focus on prevention and personalized cancer management, to improve the daily lives, autonomy, and return to work of patients.


Development of a Behavior Change Intervention to Improve Sexual Health Service Use Among University Undergraduate Students: Mixed Methods Study Protocol.
University students are at risk for acquiring sexually transmitted infections and suffering other negative health outcomes. Sexual health services offer preventive and treatment interventions that aim to reduce these infections and associated health consequences. However, university students often delay or avoid seeking sexual health services. An in-depth understanding of the factors that influence student use of sexual health services is needed to underpin effective sexual health interventions. In this study, we aim to design a behavior change intervention to address university undergraduate students' use of sexual health services at two universities in Nova Scotia, Canada. This mixed methods study consists of three phases that follow a systematic approach to intervention design outlined in the Behaviour Change Wheel. In Phase 1, we examine patterns of sexual health service use among university students in Nova Scotia, Canada, using an existing dataset. In Phase 2, we identify the perceived barriers and enablers to students' use of sexual health services. This will include focus groups with university undergraduate students, health care providers, and university administrators using a semistructured guide, informed by the Capability, Opportunity, Motivation-Behaviour Model and Theoretical Domains Framework. In Phase 3, we identify behavior change techniques and intervention components to develop a theory-based intervention to improve students' use of sexual health services. This study will be completed in March 2018. Results from each phase and the finalized intervention design will be reported in 2018. Previous intervention research to improve university students' use of sexual health services lacks a theoretical assessment of barriers. This study will employ a mixed methods research design to examine university students' use of sexual health service and apply behavior change theory to design a theory- and evidence-based sexual health service intervention. Our approach will provide a comprehensive foundation to co-design a theory-based intervention with service users, health care providers, and administrators to improve sexual health service use among university students and ultimately improve their overall health and well-being.


Osseointegration of total hip arthroplasties: studies in humans and animals.
Total hip replacement is a successful, time-proven surgical procedure for reconstruction of the arthritic hip joint. The state of the bone-implant interface is crucial to the long-term integration and durability of hip replacements whether cemented or cementless. This review summarizes current clinical implant retrieval and animal research in hip-joint reconstruction. Future research must attempt to extend the longevity of hip replacements to avoid complex revision surgery.


An anatomical study on the arteries to the left adrenal gland of sheep and goat.
The arteries supplying the left adrenal gland were determined in 12 mature sheep and goats of both sexes and different breeds. The adrenal branches arose from the first and second lumbal arteries in both species but in one goat they originated from the first lumbal artery while in another from the last intercostal artery. The cranial adrenal branches arose from the celiac artery in 8 sheep, both from the celiac and cranial mesenteric arteries in 3 sheep and from the common celiacomesenteric trunk in 1 sheep. In all goats the cranial adrenal branches originated from the cranial mesenteric artery. The caudal adrenal branches arose singly from the renal artery in all sheep and goats. In both species any branch from the aorta or caudal phrenic arteries to the adrenal gland was not seen.


Adjuvant immunotherapy in patients with renal cell carcinoma and urothelial carcinoma: A systematic review and network meta-analysis.
Adjuvant immune checkpoint inhibitor therapies have radically altered the treatment landscape for renal cell carcinoma and urothelial carcinoma. However, studies have reported negative data regarding adjuvant immune checkpoint inhibitor therapies. Thus, this study aimed to assess the role of adjuvant immune checkpoint inhibitor therapy for both renal cell carcinoma and urothelial carcinoma. A systematic review and network meta-analysis were conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Multiple databases were searched for articles published as of February 2023. Studies were deemed eligible if they evaluated disease-free survival in patients with renal cell carcinoma and urothelial carcinoma receiving adjuvant immune checkpoint inhibitor therapy. Five studies met the inclusion criteria. In a network meta-analysis, pembrolizumab was shown to be the most effective regimen for patients with renal cell carcinoma, whereas nivolumab was found to be the most effective regimen for patients with urothelial carcinoma. Additionally, these results were consistently observed in a sub-analysis of the T stage. The present analysis provides findings that support the usefulness of adjuvant nivolumab therapy in urothelial carcinoma and adjuvant pembrolizumab therapy in renal cell carcinoma, in agreement with the currently available guidelines. However, the caveat is that the randomized controlled trials included in this analysis differed in important respects despite being similar in study design. Therefore, with these differences in mind, care needs to be taken when selecting patients for these immune checkpoint inhibitor therapies to maximize their benefits.