Suprachiasmatic nucleus and vagus nerve trigger preovulatory LH and ovulation.
In the proestrus day, the neural and endocrine signals modulate ovarian function. This study shows vagus nerve plays a role in the multisynaptic pathways of communication between the suprachiasmatic nucleus and the ovaries where such neural information determines ovulation. The suprachiasmatic nucleus (SCN) regulates the activity of several peripheral organs through a parasympathetic-sympathetic pathway. Previously, we demonstrated that atropine (ATR) microinjection in the right SCN of rats during proestrus blocks ovulation. In the present study, we analysed whether the vagus nerve is one of the neural pathways by which the SCN regulates ovulation. For this, CIIZ-V strain cyclic rats on the day of proestrus were microinjected with a saline solution (vehicle) or ATR in the right or left SCN, which was followed by ventral laparotomy or ipsilateral vagotomy to the microinjection side. Some animal groups were sacrificed (i) on the same day of the surgery to measure oestradiol, progesterone and luteinizing hormone (LH) levels or (ii) at 24 h after surgery to evaluate ovulation. The left vagotomy in rats microinjected with ATR in the left SCN did not modify ovulation. In rats with ATR microinjection in the right SCN, the right vagotomy increased the levels of steroids and LH on the proestrus and ovulatory response. The present results suggest that the right vagus nerve plays a role in the multisynaptic pathways of communication between the SCN and the ovaries and indicate that such neural information participates in the regulation of the oestradiol and progesterone surge, which triggers the preovulatory peak of LH and determines ovulation.


[Ultrastructural morphometric changes in spiral ganglion cells of the rat after broad band noise (author's transl)].
The comparison of ultrastructural and ultrastructural-morphometric findings in spiral ganglion cells subsequent to broad noise with 105 dB SPL over a period of 40 min demonstrates that there are morphometric changes of the cytoarchitecture of granular ganglion cells even without evident ultrastructural changes. Morphometric analyses shows a significant extension of the volume proportion of mitochondria per unit volume cytoplasm. The volume and the surface of the rough endoplasmic reticulum, the volume of the free ribosomes and the average single volume of the nucleoli increase per granular ganglion cell. The physiologic significance of these changes is discussed. The results show that changes of the cytoarchitecture of granular spiral ganglion cells are earlier detected by morphometry than by ultrastructural description.


Data on cell survival, apoptosis, ceramide metabolism and oxidative stress in A-494 renal cell carcinoma cell line treated with hesperetin and hesperetin-7-O-acetate.
Ceramide pathway is a key regulator in cell proliferation and apoptosis and oxidative stress up-regulate ceramides. Acid ceramidase (ACDase), neutral sphingomyelinase (NSMase) and glucosylceramide synthase (GCS) are critical enzymatic systems in ceramide metabolism. Our data represent the comparative assessment of Hesperetin (Hst) and hesperetin-7-O-acetate (HTA) effects on A-494 renal carcinoma cells include cell survival, caspase-3 and 9 activities, total cellular ceramide and the activities of ACDase, NSMase, GCS and superoxide dismutase (SOD). Data reveals potentiating effects of both HTA and Hst on ceramide pathway and may offer a novel tool in human renal cell carcinoma therapy.


Robustness and efficiency of international pesticide trade networks subject to link removal strategies.
The international pesticide trade network (iPTN) is a key factor affecting global food production and food security. The trade relationship is a key component in iPTNs. In a complex international trade environment, we model the impacts of uncertain factors such as trade wars, economic blockades and local wars, as removing vital relationships in the trade network. There are many complex network studies on node centrality, but few on link centrality or link importance. We propose a new method for computing network link centrality. The main innovation of the method is in converting the original network into a dual graph, the nodes in the dual graph corresponding to the links of the original network. Through the dual graph, the node centrality indicators can measure the centrality of the links in the original network. We verify the effectiveness of the network link centrality indicator based on the dual graph in the iPTN, analyze the relationship between the existing network link centrality indicators and the indicator proposed in this paper, and compare their differences. It is found that the trade relationships with larger indicators (hub, outcloseness, outdegree) based on the dual graph have a greater impact on network efficiency than those based on the original pesticide trade networks.


Growth versus molting time of caterpillars as a function of temperature, nutrient concentration and the phenolic rutin.
A factorial experiment tested the effects of varying nutrient concentration (normal versus diluted), presence or absence of the phenolic allelochemical rutin and daytime temperature (20, 25 and 30° C) on growth, molting and food utilization efficiencies of tobacco hornworms (Manduca sexta). Two of the utilization efficiencies (approximate digestibility and efficiency of conversion of ingested food) were unaffected by temperature; the third one, efficiency of conversion of digested food, was affected by temperature but there was no consistent effect. Lower temperatures significantly increased the proportion of the stadium spent molting, with larvae at a daytime temperature of 20° C spending 9% more of the stadium in molting than larvae at 30° C. Growth time was not influenced by nutrient concentration. When temperature was low and rutin absent, molt time and the proportion of the stadium spent molting were affected by nutrient concentration. Addition of the phenolic rutin did not have an appreciable effect on growth time or digestive processes. However, it increased molting time by 7 to 14% and thus increased the duration of the stadium and reduced relative growth rate. These results indicate that the effect of food quality on growth rate is a function of the thermal conditions of insect herbivores. At cooler temperatures, a disproportionate increase in time spent molting, rather than altered food utilization efficiencies, contributed to lower growth rates. The consequences for larval growth of fluctuating temperatures due to diurnal cycles and the presence of predators forcing larvae into thermally suboptimal microhabitats are discussed.


Prediction and a stationary, structured visual background influence the dynamics of the smooth-pursuit offset in humans.
It is still not clear whether the transition from pursuit eye movements to fixation is mediated by the same system that initiates pursuit, or whether another system, a specialized fixation system, is responsible. To investigate this question we measured smooth-pursuit eye movements and smooth-pursuit termination in five normal subjects using both predictable and unpredictable step-ramp stimuli (velocities 10 degrees and 20 degrees/s) in front of a homogeneous and a structured visual background in order to compare the profile of eye velocity under these different conditions. With the predictable and/or structured visual background there was a gradual transition of eye velocity toward zero. In contrast, with the unpredictable stimulus in front of a homogeneous background, eye velocity during the offset was characterized by an overshoot (on the average, 2.2+/-1.0 degrees/s for 10 degrees/s ramps) before eye velocity settled at zero. Under this condition, steady-state velocity gain and the deceleration of the offset were significantly higher than during the other paradigm with the same target velocity. The latency of the pursuit offset was significantly shorter when a predictable stimulus was used. The duration of the offset did not depend on the experimental condition used. These findings imply that the pursuit onset and offset have some similarities and may be mediated by the same oculomotor system.


An integrated isothermal nucleic acid amplification test to detect HPV16 and HPV18 DNA in resource-limited settings.
High-risk human papillomavirus (HPV) DNA testing is widely acknowledged as the most sensitive cervical cancer screening method but has limited availability in resource-limited settings, where the burden of cervical cancer is highest. Recently, HPV DNA tests have been developed for use in resource-limited settings, but they remain too costly for widespread use and require instruments that are often limited to centralized laboratories. To help meet the global need for low-cost cervical cancer screening, we developed a prototype, sample-to-answer, point-of-care test for HPV16 and HPV18 DNA. Our test relies on isothermal DNA amplification and lateral flow detection, two technologies that reduce the need for complex instrumentation. We integrated all test components into a low-cost, manufacturable platform, and performance of the integrated test was evaluated with synthetic samples, provider-collected clinical samples in a high-resource setting in the United States, and self-collected clinical samples in a low-resource setting in Mozambique. We demonstrated a clinically relevant limit of detection of 1000 HPV16 or HPV18 DNA copies per test. The test requires six user steps, yields results in 45 min, and can be performed using a benchtop instrument and minicentrifuge by minimally trained personnel. The projected per-test cost is <$5, and the projected instrumentation cost is <$1000. These results show the feasibility of a sample-to-answer, point-of-care HPV DNA test. With the inclusion of other HPV types, this test has the potential to fill a critical gap for decentralized and globally accessible cervical cancer screening.


Distributed neurodynamic optimization for multi-energy management with time-varying external disturbances considering time-varying emission limitations and load demand in multi-microgrid.
An emerging time-varying distributed multi-energy management problem (MEMP) considering time-varying load and emission limitations for resisting time-varying external disturbances and communication time delays in the multi-microgrid (MMG) system is investigated. Each microgrid (MG) contains some smaller microgrids (SMGs), which are connected by energy routers (ERs) of the system and can monitor energy in real-time with each other. In addition, a time-varying multi-energy management optimization model (MEMOM) is proposed in this paper in order to minimize the total cost of the MEMP which considers environmental cost, renewable energy cost and fuel cost. Furthermore, time-varying distributed neurodynamic optimization algorithms are proposed for solving the above MEMP based on consensus theory and sliding mode control technique. Compared with the optimization algorithms which consist of symbolic functions proposed in traditional energy management problems, algorithms consisting of hyperbolic tangent functions proposed in this paper can effectively reduce the oscillation of the algorithms and improve the stability of algorithms. Furthermore, the algorithm can converge the optimal trajectory of optimization problems with time-varying external disturbances and communication time delays. Meanwhile, the stability and convergence of the algorithms are proved theoretically by constructing appropriate Lyapunov functions. Finally, the performance evaluation results of numerical simulations show that the proposed algorithms can efficiently handle energy trading under time-varying load and maintain excellent stability with time-varying external disturbances and communication time delays.


A practical guide to the development of microneedle systems - In clinical trials or on the market.
Microneedle systems are a rapidly growing and promising technology for delivery of drugs, such as vaccines, small molecules, or biologics and for aesthetic skin treatment in local clinics; however, they remain relatively new from a regulatory perspective. There are strong demands for established procedures, test requirements for approval, and recent trends that industries/researchers related to microneedle systems can refer to. Some microneedle systems are commercially available, many are currently undergoing clinical trials, and some are pending approval for commercialization. This review focuses on microneedle systems that are either on the market or in clinical trials, their applicability and characteristics, and the critical evaluation and test methods necessary for their development and approval.


Predator-based psychosocial stress animal model of PTSD: Preclinical assessment of traumatic stress at cognitive, hormonal, pharmacological, cardiovascular and epigenetic levels of analysis.
Research on post-traumatic stress disorder (PTSD) is faced with the challenge of understanding how a traumatic experience produces long-lasting detrimental effects on behavior and brain functioning, and more globally, how stress exacerbates somatic disorders, including cardiovascular disease. Moreover, the design of translational research needs to link animal models of PTSD to clinically relevant risk factors which address why only a subset of traumatized individuals develop persistent psychopathology. In this review, we have summarized our psychosocial stress rodent model of PTSD which is based on well-described PTSD-inducing risk factors, including a life-threatening experience, a sense of horror and uncontrollability, and insufficient social support. Specifically, our animal model of PTSD integrates acute episodes of inescapable exposure of immobilized rats to a predator with chronic daily social instability. This stress regimen produces PTSD-like effects in rats at behavioral, cognitive, physiological, pharmacological and epigenetic levels of analysis. We have discussed a recent extension of our animal model of PTSD in which stress exacerbated coronary pathology following an ischemic event, assessed in vitro. In addition, we have reviewed our research investigating pharmacological and non-pharmacological therapeutic strategies which may have value in clinical approaches toward the treatment of traumatized people. Overall, our translational approach bridges the gap between human and animal PTSD research to create a framework with which to enhance our understanding of the biological basis of trauma-induced pathology and to assess therapeutic approaches in the treatment of psychopathology.


Improvements in health care use associated with community coalitions: long-term results of the allies against asthma initiative.
We assessed changes in asthma-related health care use by low-income children in communities across the country where 6 Allies Against Asthma coalitions (Hampton Roads, VA; Washington, DC; Milwaukee, WI; King County/Seattle, WA; Long Beach, CA; and Philadelphia, PA) mobilized stakeholders to bring about policy changes conducive to asthma control. Allies intervention zip codes were matched with comparison communities by median household income, asthma prevalence, total population size, and race/ethnicity. Five years of data provided by the Center for Medicare and Medicaid Services on hospitalizations, emergency department (ED) use, and physician urgent care visits for children were analyzed. Intervention and comparison sites were compared with a stratified recurrent event analysis using a Cox proportional hazard model. In most of the assessment years, children in Allies communities were significantly less likely (P < .04) to have an asthma-related hospitalization, ED visit, or urgent care visit than children in comparison communities. During the entire period, children in Allies communities were significantly less likely (P < .02) to have such health care use. Mobilizing a diverse group of stakeholders, and focusing on policy and system changes generated significant reductions in health care use for asthma in vulnerable communities.


Gated cardiac tomography.
An ECG gated tomographic system is described and its application to routine diagnosis of cardiac wall dyskinesis discussed. The tomographic sections are gathered by a single section scanning system (Aberdeen Section Scanner). Technetium labelled red blood cells are used as the imaging agent. The time of the occurrence of the ECG R-wave is superimposed on the tomographic projection data stream and the gated images produced subsequently. The average patient study requires 15 min. Images at 8 phases of the cardiac cycle are generated at each of 5 levels, 16 mm apart, covering the length of the left ventricle. The images are stored as a three dimensional matrix and may be analysed in sections at any orientation. Fourier analysis of computer generated short axis sections are used to generate a set of coefficients describing the contraction of the left ventricle. The coefficients for each patient study are displayed as a series of two dimensional polar images, schematically displaying the spatial distribution of the coefficient over the left ventricle. These polar images are further analysed by comparison with distributions obtained from normal patient studies. The calculated deviations from the normal are then used to diagnose the magnitude and position of any dyskinesis. Initial results show that the tomographic system is capable of routinely detecting inferior cardiac wall dyskinesis, showing an advantage over non tomographic techniques.


Iron Overload or Oxidative Stress? Insight into a Mechanism of Early Cardiac Manifestations of Asymptomatic Hereditary Hemochromatosis Subjects with C282Y Homozygosity.
Hereditary hemochromatosis (HH) is a genetic disorder which affects the heart due to systemic iron overload and concomitant elevated oxidative stress. Increasing numbers of patients are diagnosed at an asymptomatic stage due to genetic testing. Subclinical abnormal left ventricular diastolic function (LVDF) and increased arrhythmias are noted in this population; however, the mechanism leading to these observances has not been well understood. In this study, we assessed the relationship between arrhythmia activity and biomarkers of oxidative stress and iron overload in order to elucidate the role of oxidative stress in this population since we observed a significant association with LVDF previously. A significant correlation between plasma malondialdehyde, a biomarker of oxidative stress, and supraventricular arrhythmia activity without a significant association with iron overload was identified (n = 22). Our findings further highlight a possible role of oxidative stress in early cardiac manifestations of HH. Further investigation is warranted to assess this role.


An FDA analysis of clinical hold deficiencies affecting investigational new drug applications for oncology products.
A systematic analysis of new commercial investigational new drug applications (IND) submitted to the FDA's Office of Hematology and Oncology Products (OHOP) in the Center for Drug Evaluation and Research was conducted to quantify the most common reasons INDs for oncology indications go on clinical hold. In OHOP, less than 10% of INDs went on hold or were withdrawn within the 30-day safety review period. Of INDs that were placed on hold, deficiencies were mainly clinical, followed by concerns related to pharmaceutical quality and nonclinical development. INDs were also characterized based on phase of development, product type, sponsors' regulatory experience, and occurrence of a pre-IND meeting. INDs that were placed on hold were mostly for first-in-human trials or submitted by sponsors with limited regulatory experience. INDs that went on hold or were safe-to-proceed had pre-IND meetings with comparable rates but sponsors with substantial experience appeared to benefit more from pre-IND meetings compared to those with limited experience. The time interval between the pre-IND meeting and the IND submission was longer for INDs that went on hold. To obtain useful FDA feedback on product development, it is essential to provide focused questions and supporting information in pre-IND meeting packages.


Hybrid treatment of a symptomatic popliteal pseudoaneurysm due to type-I endoleak after previous endovascular exclusion.
The development of endovascular repair of popliteal aneurysms has provided an alternative, minimally invasive way of treatment. We present a case of a late type-I endoleak, after previous exclusion of a popliteal pseudoaneurysm, leading to rupture and massive hematoma, which was excluded in a hybrid procedure. A 95-year-old woman presented with progressive swelling with skin ulceration and necrosis cranial to the medial side of her left knee. Four years earlier, a left popliteal pseudoaneurysm was excluded with a stent-graft. Rupture of the popliteal artery with massive hematoma was demonstrated by ultrasound examination and a spiral computed tomography scan, with high suspicion of a type-I endoleak. Endovascular repair of the endoleak with a polytetrafluoroethylene-covered stent-graft was followed by surgical resection of the damaged skin and evacuation of the hematoma. Type-I endoleaks after endovascular exclusion of popliteal pseudoaneurysms do occur and may lead to rupture. A symptomatic pseudoaneurysm may be successfully treated by a hybrid procedure.


Soil-transmitted helminthiasis in mainland China from 2016 to 2020: a population-based study.
Soil-transmitted helminthiasis is epidemic in China and many other countries of the world, and has caused substantial burdens to human health. We conducted successive national monitoring in China from 2016 to 2020 to analyze the prevalence, changing trends, and factors influencing soil-transmitted helminthiasis, which provided a reference for future control strategies. Soil-transmitted helminth monitoring was carried out in 31 provinces (autonomous regions or municipalities, herein after referred to as "provinces") throughout China. Each province determined the number and location of monitoring sites (counties), and a unified sampling method was employed. At least 1,000 subjects were investigated in each monitoring county. Stool samples were collected and the modified Kato-Katz thick smear method was employed for stool examination. Infection data and the details of factors influencing soil-transmitted helminthiasis from 2016 to 2020 were collected from national monitoring sites. Additional influencing factors such as environment, climate and human activities were obtained from authoritative websites. Prevalence of soil-transmitted helminths was presented by species, province, sex, and age group. ArcGIS software was used to conduct spatial autocorrelation and hotspot analysis on the infection data. A Poisson distribution model and SaTScan software were used to analyze the infection data with retrospective spatiotemporal scan statistics. A database was built by matching village-level infection rate data with influencing factors. Subsequently, machine learning methods, including a Linear Regression (LR), a Random Forest (RF), a Gradient Boosted Machine (GBM), and an Extreme gradient boosting (XGBOOST) model was applied to construct a model to analyze the main influencing factors of soil-transmitted helminthiasis. The infection rates of soil-transmitted helminths at national monitoring sites from 2016 to 2020 were 2.46% (6,456/262,380), 1.78% (5,293/297,078), 1.29% (4,200/326,207), 1.40% (5,959/424,766), and 0.84% (3,485/415,672), respectively. The infection rate of soil-transmitted helminths in 2020 decreased by 65.85% compared to that in 2016. From 2016 to 2020, the infection rate of soil-transmitted helminthiasis was relatively high in southern and southwestern China, including Hainan, Yunnan, Sichuan, Guizhou, and Chongqing. In general, the infection rate was higher in females than in males, with the highest rate in the population aged 60 years and above, and the lowest in children aged 0-6 years. Global autocorrelation and hotspot analyses revealed spatial aggregation in both the national and local distribution of soil-transmitted helminthiasis in China from 2016 to 2020. The hotspots were concentrated in southwestern China. The spatiotemporal scanning analysis revealed aggregation years from 2016 to 2017 located in southwestern China, including Yunnan, Sichuan, Chongqing, Guizhou and Guangxi. The RF model was the best fit model for the infection rate of soil-transmitted helminths in China. The top six influencing factors of this disease in the model were landform, barefoot farming, isothermality, temperature seasonality, year, and the coverage of sanitary toilets. The overall infection rate of soil-transmitted helminths in China showed a decreasing trend from 2016-2020 due to the implementation of control measures and the economic boom in China. However, there are still areas with high infection rates and the distribution of such areas exhibit spatiotemporal aggregation. As a strategic next step, control measures should be adjusted to local conditions based on the main influencing factors and the prevalence of different sites to aid in the control and elimination of soil-transmitted helminthiasis. This research was funded by the National Key Research and Development Program of China (Grant Nos. 2021YFC2300800 and 2021YFC2300804) and the National Natural Science Foundation of China (Grant No. 32161143036).


Low natural levels of Nosema ceranae in Apis mellifera queens.
Queens are the primary female reproductive individuals in honey bee colonies and, while they are generally free from Nosema ceranae infection, they are nevertheless susceptible. We sought to determine whether queens are naturally infected by N. ceranae, as these infections could be a factor in the rapid spread of this parasite. Queens were analyzed using real-time PCR and included larval queens, newly emerged, and older mated queens. Overall, we found that all tissues we examined were infected with N. ceranae at low levels but no samples were infected with Nosema apis. The infection of the ovaries and spermatheca suggests the possibility of vertical transmission of N. ceranae.


Risk factors for early and late mortality after thoracic endovascular aortic repair.
The risk factors associated with death after thoracic endovascular aortic repair are poorly understood. The aim of this study is to analyze the risk factors associated with early and late mortality after thoracic endovascular aortic repair. A total of 153 patients underwent 184 thoracic endovascular aortic repairs between 1998 and 2005. Prospectively collected data were entered into statistical software. Univariate and multivariate analyses were performed. The underlying pathologies included descending thoracic aortic aneurysm (n = 91), acute type B aortic dissection (n = 25), chronic type B aortic dissection (n = 42), aortic transection (n = 12), and penetrating aortic ulcer (n = 14). Thoracic endovascular aortic repair was technically successful in all but 3 patients. Another 3 patients required an open repair within the first month. Early and late mortality rates were 9.8% (n = 18) and 19% (n = 35) in a 16-month average period of follow-up, respectively. Type I procedural endoleak was the only significant predictor of early death in the multivariate model (P = .0036; odds ratio: 8.4; 95% confidence interval: 1.6-43.9). Multivariate Cox regression revealed chronic obstructive pulmonary disease (P = .024; odds ratio: 3.8; 95% confidence interval: 1.2-12.1), postoperative myocardial infarction (P = .0053; odds ratio: 9.7; 95% confidence interval: 2.0-48.4), and acute renal failure (P = .0006; odds ratio: 22.8; 95% confidence interval: 3.8-137.6) to be independent risk factors for late mortality. Procedural type I endoleak is an independent risk factor of early mortality after thoracic endovascular aortic repair. Chronic obstructive pulmonary disease, postoperative myocardial infarction, and acute renal failure are predictors of late death in the multivariate analysis.


Synthesis and Activity of 6″-Deoxy-6″-thio-α-GalCer and Peptide Conjugates.
A major challenge in the development of highly defined synthetic vaccines is the codelivery of vaccine components (i.e., antigen and adjuvant) to secondary lymphoid tissue to induce optimal immune responses. This problem can be addressed by synthesizing vaccines that comprise peptide antigens covalently attached to glycolipid adjuvants through biologically cleavable linkers. Toward this, a strategy utilizing previously unreported 6″-deoxy-6″-thio analogues of α-GalCer that can undergo chemoselective conjugation with peptide antigens is described. Administration of these conjugate vaccines leads to enhanced priming of antigen specific T cells. This simple vaccine design is broadly applicable to multiple disease indications such as cancer and infectious disease.


Lipoamide dehydrogenase in cultured human skin fibroblasts.
Lipoamide dehydrogenase was identified in cultured skin fibroblasts of normal individuals and patients with Friedreich's ataxia. The optimum conditions for its assay were defined. Data disclosed a normal range of 36--122 mumol/min/mg protein in control fibroblasts and 61--112 mumol/min/mg protein in patients fibroblasts. Numerous precautions should be taken in handling fibroblast cultures for lipoamide dehydrogenase determination.


Complete heart block following TAVR: blocking the way forward?
This study demonstrated an increasing rate in complete heart block (CHB) and permanent pacemaker (PPM) after trans-catheter aortic valve replacement (TAVR). The development of CHB was associated with increased in-hospital mortality, prolonged length of stay and augmented hospitalization cost. Pre-existing RBBB was the strongest independent risk factor for subsequent development of CHB after TAVR.


Multiple mode coupling in Cy3 molecules by impulsive coherent vibrational spectroscopy using a few-cycle laser pulse.
Multiple vibrational mode coupling that induces the missing mode effect and Duschinsky rotation on the potential energy surface of the S(1) state in the Cy3 molecule was clarified by real-time ultrafast spectroscopy with a few-cycle laser pulse. The contributions of homogeneous and inhomogeneous dephasing to the total dephasing time were found to be 55% and 45%, respectively.


Racial Identity and Mental Well-Being: The Experience of African American Medical Students, A Report from the Medical Student CHANGE Study.
Diversification of the physician workforce continues to be a national priority; however, a paucity of knowledge about the medical school experience for African American medical students limits our ability to achieve this goal. Previous studies document that African American medical students are at greater risk for depression and anxiety. This study moves beyond these findings to explore the role of racial identity (the extent to which a person normatively defines her/himself with regard to race) and its relationship to well-being for African American medical students in their first year of training. This study used baseline data from the Medical Student Cognitive Habits and Growth Evaluation (CHANGE) Study; a large national longitudinal cohort study of 4732 medical students at 49 medical schools in the US racial identity for African American students (n = 301) was assessed using the centrality sub-scale of the Multidimensional Inventory of Black Identity. Generalized linear regression models with a Poisson regression family distribution were used to estimate the relative risks of depression, anxiety, and perceived stress. First year African American medical students who had lower levels of racial identity were less likely to experience depressive and anxiety symptoms in their first year of medical school. After controlling for other important social predictors of poor mental health (gender and SES), this finding remained significant. Results increase knowledge about the role of race as a core part of an individual's self-concept. These findings provide new insight into the relationship between racial identity and psychological distress, particularly with respect to a group of high-achieving young adults.


Unveiling potentially convergent key events related to adverse outcome pathways induced by silver nanoparticles via cross-species omics-scale analysis.
The adverse effects of silver nanoparticles (AgNPs) have been studied in various models. However, there has been discordance between molecular responses across the literature, attributed to methodological biases and the physicochemical variability of AgNPs. In this study, a gene pathway meta-analysis was conducted to identify convergent and divergent key events (KEs) associated with AgNPs and explore common patterns of these KEs across species. We performed a cross-species analysis of transcriptomic data from multiple studies involving various AgNPs exposure. Pathway enrichment analysis revealed a set of pathways linked to oxidative stress, apoptosis, and metabolite and lipid metabolism, which are considered potentially conserved KEs across species. Subsequently, experiments confirmed that oxidative stress responses could be early KEs in both Caenorhabditis elegans and HepG2 cells. Moreover, AgNPs preferentially impaired the mitochondria, as evidenced by mitochondrial fragmentation and dysfunction. Furthermore, disruption of amino acids, nucleotides, sulfur compounds, glycerolipids, and glycerophospholipids metabolism were in good agreement with gene pathway shreds of evidence. Our findings imply that, although there may be organism-specific responses, potentially conserved events could exist regardless of species and physicochemical factors. These results provide valuable insights into the development of adverse outcome pathways of AgNPs across species and the regulatory toxicity of AgNPs.


Factors affecting the use of long term and permanent contraceptive methods: a Facebook-focused cross-sectional study.
In the Muslim world, the use and acceptance of long-term and permanent contraceptives were limited. Our aim was to investigate those limiting factors so we can help making these methods widely available and acceptable to the society. There were 1365 women from Facebook groups in the period 08/10/2020-8/11/2020. Participants were married women, living in Jordan. This was a cross-sectional study. Statistical Package for Social Sciences (SPSS), version 16, software was used for statistical analysis (Chicago, Illinois, USA). Among participants, 22.3% had never used any contraceptives. Non-hormonal IUCD was the most commonly used method. There was a statistically significant association between the use of hormonal IUCD and women's age, marriage duration, education and number of children (p < 0.0001). Tubal ligation was adopted by only 44 (3.22%) participants. 19.68% of participants declined tubal ligation merely due to religious issues. Women who completed only high school level of education underwent tubal ligation significantly more than those with university (Bachelor) and post-university (Master or PhD) degrees (p < 0.0001 and 0.026, respectively). Only 1.83% of women's partners underwent vasectomy, the majority of these vasectomies (72.0%) were done because of the need for lifelong contraception. Around 17% of women's partners had poor knowledge about vasectomy. Further, women's employment status (housewives or full-time employees) was found to be the only variable that affected acceptance of vasectomy (p = 0.0047). Women endured a heavy burden of contraception. Cultural and religious taboos influenced tubal ligation. Vasectomy was still very rarely adopted by men due to the lack of knowledge about the procedure. Our results raised the need for further dissemination of contraception knowledge and counselling through the primary care and maternity centers, mosques and media in official, comprehensive and integrated programs. Future research is needed in the field of permanent contraceptive methods.


Electroacupuncture enhances cell proliferation and neuronal differentiation in young rat brains.
To investigate the effect of electroacupuncture on cell proliferation and differentiation in young rat hippocampus, postnatal day-14 rats were assigned randomly to control, ketamine anesthesia, nonacupoint, or acupoint electroacupuncture groups. Electroacupuncture was applied at bilateral acupoints (Quchi, Waiguan, Huantiao, and Zusanli) 30 min daily for 7 successive days. The proliferation and neuronal differentiation of proliferated surviving cells in the dentate gyrus were evaluated at 4 weeks after last stimulation. The stimulatory effect of electroacupuncture on cell proliferation had a long-lasting effect, as indicated by the increased phosphor-histone H3-positive cells. The number of proliferated and survival cells, indicated by BrdU labeling, was highest in the electroacupuncture group. The number of newly differentiated neurons, as indicated by BrdU/NeuN double labeling, was significantly higher in the electroacupuncture group than in any of the other groups. This finding provides a theoretical basis for the clinical application of acupuncture to cerebral injury rehabilitation in children.


Clinical utility of right ventricular fractional area change in preterm infants.
Right ventricular fractional area change (RV FAC) is a novel non-invasive quantitative measure of RV function. Reference values of RV FAC and RV end systolic and diastolic areas (RVEDA, RVESA) have recently been established in preterm infants, but their role as marker to assess the efficacy of patient management strategies in the first week of life is largely unknown. The aims of this study were to assess the relationship between RV FAC and gestational age/birthweight, assess the RV FAC on day one of age to predict the later evolution of peri/intraventricular haemorrhage (P/IVH), and assess the influence of a persistent patent ductus arteriosus (PDA) on RV FAC during the first week of age. Preterm infants <29 weeks gestation underwent echocardiography assessments on days 1, 2 and 5-7. RVEDA and RVESA were traced in the RV-focused apical four-chamber view, and RV FAC was calculated using the formula [(RVEDA-RVESA)÷(RVEDA)] × 100. PDA treatment was not carried out during the study period. A cranial ultrasound was carried out on all infants on Days 5-7 of age. P/IVH was defined as IVH grades II to IV. One hundred and one infants with a mean gestation of 26.5 (1.4) weeks and a birthweight of 983 (240) grams were enrolled in the study. There was no relationship between RV FAC and birthweight (r=-0.02, p=0.86) but there was a negative correlation between RV FAC and echo-measured SVR (r=-0.57, p<0.001). On Day 1, RV FAC was lower in infants who developed P/IVH (24% [18-34] vs. 31% [25-40], p=0.04). On Days 5-7 infants with a PDA had a lower RV FAC compared with those without [42 (7) vs. 49 (9) %, p<0.001]. RV FAC may be a useful addition to the haemodynamic assessment of preterm infants during the first week of age.


Autoantibodies against central nervous system antigens in a subset of B cell-dominant multiple sclerosis patients.
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), with characteristic inflammatory lesions and demyelination. The clinical benefit of cell-depleting therapies targeting CD20 has emphasized the role of B cells and autoantibodies in MS pathogenesis. We previously introduced an enzyme-linked immunospot spot (ELISpot)-based assay to measure CNS antigen-specific B cells in the blood of MS patients and demonstrated its usefulness as a predictive biomarker for disease activity in measuring the successful outcome of disease-modifying therapies (DMTs). Here we used a planar protein array to investigate CNS-reactive antibodies in the serum of MS patients as well as in B cell culture supernatants after polyclonal stimulation. Anti-CNS antibody reactivity was evident in the sera of the MS cohort, and the antibodies bound a heterogeneous set of molecules, including myelin, axonal cytoskeleton, and ion channel antigens, in individual patients. Immunoglobulin reactivity in supernatants of stimulated B cells was directed against a broad range of CNS antigens. A group of MS patients with a highly active B cell component was identified by the ELISpot assay. Those antibody reactivities remained stable over time. These assays with protein arrays identify MS patients with a highly active B cell population with antibodies directed against a swathe of CNS proteins.


Twelve-lead electrocardiographic characteristics of the aortic cusp region guided by intracardiac echocardiography and electroanatomic mapping.
The most common site of origin of idiopathic ventricular tachycardia (VT) is the right ventricular outflow tract. Idiopathic VT also can arise from the left ventricular outflow tract and the surrounding structures. Morphologic descriptions of 12-lead ECG characteristics of the aortic cusp region are limited. The purpose of this study was to define unique ECG characteristics of the aortic cusp region by performing a systematic analysis of pacemapping of this region in patients with structurally normal hearts. A combination of electroanatomic mapping, intracardiac echocardiography, and fluoroscopic guidance was used to study a total of 30 patients with structurally normal hearts undergoing left-sided ablation procedures. Each of the aortic valve cusps and the aortomitral continuity were paced at threshold and analyzed offline to determine unique ECG characteristics. Pacing from the left coronary cusp typically produced a multiphasic QRS morphology consistent with an M or W pattern in lead V(1) with a precordial transition (R>S) no later than V(2). Pacing from the right coronary cusp typically resulted in a left bundle-type pattern with a broad small R wave in V(2) and a precordial transition generally at V(3). Pacing from the aortomitral continuity resulted in a qR pattern that was not observed anywhere else in the left ventricular outflow tract. When comparing the right coronary cusp and left coronary cusp, the precordial transition was earlier in the left coronary cusp than in the right coronary cusp. Pacing the noncoronary cusp uniformly resulted in atrial capture. When considering ablation of idiopathic VT, the aortic cusps and aortomitral continuity must be considered as possible foci. The 12-lead ECG, a readily and easily obtainable source of information, has useful characteristics for differentiating VTs arising from the cusp region.


Catabolism of fibrinogen in pregnant rabbits before and after delivery.
16 non-pregnant female and 19 pregnant rabbits were injected with purified rabbit 125I-fibrinogen in order to study the catabolism of fibrinogen before and after delivery. The half-life time (T 1/2) of the clottable 125I-radioactivity in pregnant rabbits during the last third of gestation was 27.3 +/- 5.3 hr in comparison to 54.4 +/- 3.7 hr in non-pregnant rabbits. After delivery, T 1/2 returned to normal values of 47.9 +/- 10.9 hr. The fractional catabolic rate (FCR) of the clotabble 125I-radioactivity was 67.1% X d-1 +/- 8.6 before and 41.6% X d-1 after delivery whereas FCR in non-pregnant rabbits amounted to 44.7% X d-1 +/- 4.8. These figures demonstrate a pronounced increase in fibrinogen catabolism during the last third of gestation in pregnant rabbits and a normalization immediately after delivery. Although in pregnant rabbits the elimination of fibrinogen from the circulating blood was pronouncedly increased, the plasma fibrinogen concentration did not change. Only after delivery did the fibrinogen concentration increase when the fibrinogen catabolism had already normalized.


Thyroid gland invasion in advanced laryngeal and hypopharyngeal carcinoma.
To assess the rate of thyroid gland invasion and the need for thyroidectomy in advanced laryngeal and hypopharyngeal carcinomas that require total laryngectomy. Between 1994 and 2001, 129 total laryngectomy with ipsilateral hemithyroidectomy and 14 total laryngopharyngectomy with total thyroidectomy operations were performed for primary squamous cell carcinoma of the larynx and hypopharynx. In the surgical specimens of the patients, the presence of tumor invasion to the thyroid cartilage and thyroid gland was evaluated retrospectively by light microscopic examination. None of the laryngeal carcinoma patients had thyroid gland invasion whereas eight (57%) hypopharyngeal carcinoma patients had thyroid gland invasion. Twenty patients (16%) had evidence for thyroid cartilage invasion in the laryngeal carcinoma group. There were only three cases (21%) with thyroid cartilage invasion in the hypopharyngeal carcinoma patients. There may be no need for performing thyroidectomy in all total laryngectomy cases. We recommend thyroidectomy during total laryngectomy in laryngeal carcinoma cases with subglottic extension and advanced hypopharyngeal tumors. Except for these two conditions, the assessment of extralaryngeal extension and thyroid gland invasion will guide whether thyroidectomy should be performed or not.


On the existence of 'L-alanine cadmium bromide'.
It is argued that the recently reported nonlinear optical crystal L-alanine cadmium bromide, grown by slow solvent evaporation method at room temperature [P. Ilayabarathi, J. Chandrasekaran, Spectrochim. Acta 96A (2012) 684-689] is the well-known L-alanine crystal. The isolation of L-alanine crystal is explained due to fractional crystallization.


Complete Response to Bicalutamide Withdrawal Prolonged for Almost 2 Years in Patients With Metastatic Prostate Cancer.
This is the first case report describing a complete response to bicalutamide withdrawal that lasted for almost 2 years in a patient with metastatic prostate cancer. An 80-year-old man who had prostate-specific antigen (PSA) level elevation (168.1 ng/mL) visited our hospital in February 2010. Bone scintigraphy showed pelvic metastases. We started hormonal therapy with leuprorelin and bicalutamide. The PSA concentration decreased to <0.1 ng/mL but started increasing again and reached 1.64 ng/mL in October 2012, at which time bicalutamide administration was discontinued. The PSA concentration decreased again and has remained below the limit of sensitivity for almost 2 years.


Are they necessary? Preventive therapies for post-stroke depression: A meta-analysis of RCTs.
To explore the necessity and feasibility of early anti-depressive therapies in acute stroke patients, we conducted a meta-analysis of currently available randomized control studies (RCTs). Literature search in six databases was done with keywords of cerebrovascular accident, depression and prevention. Only RCTs that met the inclusion criteria were enrolled for further analysis. Twelve eligible studies were included in this meta-analysis. Prophylactic anti-depressive therapies following acute stroke were shown to reduce the incidence of depression in the patients (RR = =0.33, 95% CI: 0.25 to 0.43, p < 0.001), improve symptoms of depression (WMD: 5.73, 95% CI: 4.18 to 7.29, p < 0.001), improve motor function (WMD: 12.56, 95%CI: 9.07 to 16.04, p < 0.001) and neurological function (WMD: 1.13, 95%CI: 0.57 to 1.69, p < 0.001). However, anti-depressive therapies showed no effects on mortality (RR = 1.63, 95%CI: 0.55 to 4.85, p = 0.377) and adverse events incidence (RR = 0.93, 95%CI: 0.53 to 1.64, p = 0.806). Anti-depressive therapies following acute stroke is effective thus deserves to be advocated.


Herpes simplex virus alters Alzheimer's disease biomarkers - A hypothesis paper.
Human herpes simplex virus 1 (HSV1) is discussed to induce amyloid-β (Aβ) accumulation and neurofibrillary tangles of hyperphosphorylated tau (pTau) in Alzheimer's disease (AD) in cell culture and animal models. Aβ appears to be virostatic. We investigated the association between intrathecal antibodies against HSV or cytomegalovirus (CMV) and cerebrospinal fluid (CSF) AD biomarkers. Aβ42 /Aβ40 ratio, pTau, and tTau were measured in CSF of 117 patients with early AD positive for amyloid pathology (A+) and 30 healthy controls (A-). CSF-to-serum anti-HSV1/2-IgG antibody indices (AI-IgGHSV1/2 ) and CMV (AI-IgGCMV ) were determined by enzyme-linked immunosorbent assay (ELISA). Exclusively in HSV1-seropositive AD, pTau was positively and significantly predicted by AI-IgGHSV1/2 and negatively by the Aβ42 /Aβ40 ratio in both univariate and multivariate regression analyses. Furthermore, a significant and negative interaction between the AI-IgGHSV1/2 and Aβ42 /Aβ40 ratio on pTau was found. The results support the hypothesis that HSV infection contributes to AD. HSV antibody index is positively associated with tau pathology in patients with AD. HSV antibody index is negatively associated with cerebral FDG metabolism. Amyloid modulates the association of HSV antibody index with CSF-pTau. HSV in AD offers a pathophysiological model connecting tau and amyloid.


A note on the haematophagous nature of poultry shaft louse, Menopon gallinae (Amblycera: Phthiraptera).
An analysis of the crop contents of the poultry shaft louse, Menopon gallina indicates that 67 % of adult males and 72 % of the adult females examined carried red content compatible to host blood, along with feather barbules. The percentage of nymphal instars carrying red content in the crop was quite low. On the basis of crop contents the louse does not seem to harbor any triturating agent and is also not involved in cannibalism or predation. SEM studies on the ventral side of head do not indicate the presence of any pointed structure which can be used to pierce the skin.


Losartan, an antagonist of AT1 receptor for angiotensin II, attenuates lipopolysaccharide-induced acute lung injury in rat.
Angiotensin II (Ang II) plays an important role in inflammatory process. Acute lung injury (ALI), an inflammatory disorder of the lung, is commonly associated with endotoxemia; however, the mechanism that endotoxin (lipopolysaccharide, LPS) induces the inflammatory response in ALI is not well defined. Here, we showed, in LPS-induced ALI rat model, that Ang II and Ang II type 1 (AT(1)) receptor were significantly increased in lung tissues, compared with those in controls. Meanwhile, nuclear factor (NF)-kappaB-DNA-binding activity, tumor necrosis factor (TNF)-alpha mRNA, and pneumocytic apoptosis were significantly increased. Moreover, pretreatment of rats with losartan, an antagonist of AT(1) receptor for Ang II, improved the inflammation, reduced the elevation of Ang II and AT(1) receptor, and inhibited NF-kappaB-DNA-binding activity, expression of TNF-alpha mRNA, and pneumocytic apoptosis. The data indicate that Ang II may mediate the inflammatory process in LPS-induced ALI through AT(1) receptor, which can be blocked by losartan.


Altered circadian rhythm of melatonin concentrations in hypocretin-deficient men.
Hypocretin deficiency causes narcolepsy. It is unknown whether melatonin secretion is affected in this sleep disorder. Therefore, in both narcolepsy patients and matched controls, the authors measured plasma melatonin levels hourly for 24 h before and after 5 days of sodium oxybate (SXB) administration. Although mean melatonin concentrations were similar between patients and controls, in narcoleptics the percentage of 24-h melatonin secreted during the daytime was significantly higher, and melatonin secretion exhibited a weaker coupling to sleep. SXB did not affect melatonin secretion. These findings suggest that hypocretin deficiency might disturb both the circadian control of melatonin release and its temporal association with sleep.


Uric acid activates extracellular signal-regulated kinases and thereafter endothelin-1 expression in rat cardiac fibroblasts.
The association between hyperuricemia and cardiovascular diseases has long been recognized. Elevated levels of uric acid may have a causal role in hypertension and cardiovascular diseases. However, the direct effect of uric acid on cardiac cells remains unclear. Therefore, this study was aimed to examine the effect of uric acid in rat cardiac fibroblasts and to identify the putative underlying signaling pathways. Cultured rat cardiac fibroblasts were stimulated with uric acid; cell proliferation and endothelin-1 (ET-1) gene expression were examined. The effect of uric acid on NADPH oxidase activity, reactive oxygen species (ROS) formation, and extracellular signal-regulated kinases (ERK) phosphorylation were tested to elucidate the intracellular mechanism of uric acid in ET-1 gene expression. Uric acid-increased cell proliferation and ET-1 gene expression. Uric acid also increased NADPH oxidase activity, ROS formation, ERK phosphorylation, and activator protein-1 (AP-1)-mediated reporter activity. Antioxidants suppressed uric acid-induced ET-1 gene expression, and ERK phosphorylation, and AP-1 reporter activities. Mutational analysis of the ET-1 gene promoter showed that AP-1 binding site was an important cis-element in uric acid-induced ET-1 gene expression. These results suggest that uric acid-induced ET-1 gene expression, partially by the activation of ERK pathway via ROS generation in cardiac fibroblasts.


Transcriptome profiling analysis of uterus during chicken laying periods.
The avian eggshell is formed in the uterus. Changes in uterine function may have a significant effect on eggshell quality. To identify the vital genes impacting uterine functional maintenance in the chicken, uteri in three different periods (22W, 31W, 51W) were selected for RNA sequencing and bioinformatics analysis. In our study, 520, 706 and 736 differentially expressed genes (DEGs) were respectively detected in the W31 vs W22 group, W51 vs W31 group and W51 vs W22 group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated DEGs were enriched in the extracellular matrix, extracellular region part, extracellular region, extracellular matrix structural constituent, ECM receptor interaction, collagen-containing extracellular matrix and collagen trimer in the uterus (P < 0.05). Protein-protein interaction analysis revealed that FN1, LOX, THBS2, COL1A1, COL1A2, COL5A1, COL5A2, POSTN, MMP13, VANGL2, RAD54B, SPP1, SDC1, BTC, ANGPTL3 might be key candidate genes for uterine functional maintenance in chicken. This study discovered dominant genes and pathways which enhanced our knowledge of chicken uterine functional maintenance.


Rikkunshito increases appetite by enhancing gastrointestinal and incretin hormone levels in patients who underwent pylorus-preserving pancreaticoduodenectomy: A retrospective study.
Rikkunshito (TJ-43) relieves gastrointestinal disturbance by increases in the levels of acylated ghrelin. To investigate the effects of TJ-43 in patients undergoing pancreatic surgery. Forty-one patients undergoing pylorus-preserving pancreaticoduodenectomy (PpPD) were divided into two groups; patients took daily doses of TJ-43 after surgery or after postoperative day (POD) 21. The plasma levels of acylated and desacylated ghrelin, cholecystokinin (CCK), peptide YY (PYY), gastric inhibitory peptide (GIP), and active glucagon-like peptide (GLP)-1 were evaluated. Oral calorie intake was assessed at POD 21 in both groups. The primary endpoint of this study was the total food intake after PpPD. The levels of acylated ghrelin were significantly greater in patients treated with TJ-43 than those in patients without TJ-43 administration at POD 21, and oral intake was significantly increased in patients treated with TJ-43. The CCK and PYY levels were significantly greater in patients treated with TJ-43 than those in patients without TJ-43 treatment. Furthermore, the GIP and active GLP-1 levels increased and values at POD 21 were significantly greater in patients treated with TJ-43 than those in patients without TJ-43 administration. Insulin secretion tended to increase in patients treated with TJ-43. TJ-43 may have advantages for oral food intake in patients in the early phase after pancreatic surgery. Further investigation is needed to clarify the effects of TJ-43 on incretin hormones.


Climate Change and Its Lexicon: An Analytical and Critical View.
Climate change is an overwhelming issue today, but sociology has yet to fully engage with its hermeneutical and political aspects. The article tackles this limitation and thus the lexicon of climate change, proposing an integrated framework that brings its principal concepts and notions together. In particular, it singles out hazard, risk and threat, vulnerability and resilience, adaptation, mitigation and precaution, Anthropocene and Capitalocene, nature and society. Although some authors have stressed the political aspects underlying these concepts and notions, and the IPCC itself has incipiently recognised this issue, the parameters of the debate remain conspicuously narrow. The article therefore proposes to engage it in direct and strong political terms, countering the partly successful operation of depoliticisation that such concepts and notions undergo. While the article concentrates on discursive aspects, it eventually points to the role of agents and power within the UN system concerning the articulation of this lexicon.


miR-150-Based RNA Interference Attenuates Tubulointerstitial Fibrosis through the SOCS1/JAK/STAT Pathway In Vivo and In Vitro.
We investigated whether microRNA-150 (miR-150)-based RNA interference (RNAi) ameliorates tubular injury and tubulointerstitial fibrosis. Mice injected with folic acid developed tubulointerstitial fibrosis at day 30. miR-150 levels were increased at day 7 and peaked at day 30. At day 30, protein levels of α-smooth muscle actin, fibronectin (FN), and collagen 1 (COL-1) were increased, while suppressor of cytokine signal 1 (SOCS1) was decreased. Kidneys manifested increased macrophage numbers and increased expression of potential mediators: interferon-γ, interleukin-6, and tumor necrosis factor-α. Locked nucleic acid-anti-miR-150, started prior to or after tubular injury and administered twice weekly for 4 weeks, reversed renal inflammation and fibrosis. In HK-2 cells, co-culture with macrophages increased miR-150 expression and decreased SOCS1. Janus kinase (JAK) and signal transducer and activators of transcription (STAT) pathway-related proteins p-JAK1, p-JAK2, p-STAT1, p-STAT3, and pro-fibrotic genes encoding α-smooth muscle actin, FN, and COL-1 were all upregulated. The miR-150 antagonist reversed these transcriptional changes. Lastly, in renal biopsies from patients with chronic interstitial fibrosis, renal miR-150, and pro-fibrotic gene expression and macrophage numbers were increased, while SOCS1 expression was decreased. In conclusion, miR-150-based RNAi is as a potential novel therapeutic agent for tubulointerstitial fibrosis, suppressing the SOCS1/JAK/STAT pathway and reducing macrophage influx.


Diagnostic progression to bipolar disorder in 17,285 adolescents and young adults with attention deficit hyperactivity disorder: A longitudinal follow-up study.
We investigated the diagnostic progression to bipolar disorder (BD) among adolescents and young adults with attention-deficit/hyperactivity disorder (ADHD). Using the Taiwan National Health Insurance Research Database, we enrolled adolescents and young adults aged 10-29 years with ADHD between January 1, 2001, and December 31, 2010, who were followed up until December 31, 2011, to determine progression to BD. Cox regression analysis was used to examine candidate risk and protective factors. At the 11-year follow-up, the progression rate from ADHD to BD was 5.12%. Of the participants who progressed, 62.16% (322/518) progressed within the first 3 years. Risk factors for progression were as follows: older age (hazard ratio [HR], 1.058; 95% confidence interval [CI], 1.033-1.084), comorbidity with autistic spectrum disorder (HR, 1.839; 95% CI, 1.415-2.391), disruptive behavior disorder (HR, 1.434; 95% CI, 1.132-1.816), intelligence disability (HR, 1.744; 95% CI, 1.399-2.176), depressive disorder (HR, 1.978; 95% CI, 1.577-2.482), alcohol use disorder (HR, 1.705; 95% CI, 1.057-2.751), cluster A (HR, 2.508; 95% CI, 1.167-5.391) or B (HR, 2.718; 95% CI, 1.974-3.741) personality disorder, and a family history of BD (HR, 2.618; 95% CI, 1.823-3.758) Identified protective factors were male sex (HR, 0.771; 95% CI, 0.630-0.943) and cluster C personality disorder (HR, 0.278; 95% CI, 0.086-0.898). The study demonstrated the specific risk and protective factors for BD progression among adolescents and young adults with ADHD. It is important for clinician and mental health care providers to recognize identified factors to focus on early detection and prompt intervention.


Chromosome size and number polymorphisms in Leishmania infantum suggest amplification/deletion and possible genetic exchange.
We have studied the molecular karyotypes of 21 strains and 14 clones of Leishmania infantum using pulsed field gel electrophoresis (PFGE). We detected a high degree of polymorphism within this species, with 'strain-specific' patterns for most isolates, even within a restricted endemic area. Variations relate to both the size of chromosomes (270-2600 kb) and their number, which can vary from 24 to 31 between closely related isolates. This polymorphism does not correlate with isoenzyme analysis. Small size variations between homologous chromosomes of different strains are suggestive of DNA amplification/deletion events. Strains are also shown to be multiclonal, with slight differences between most clones, but with a predominant clone concealing the others in PFGE analysis. The analysis of these data leads to the hypothesis of occasional genetic exchange by nuclear fusion in Leishmania, as recently shown in the related protozoan Trypanosoma brucei.


Susceptible and Protective Associations of HLA Alleles and Haplotypes with Cervical Cancer in South India.
Human leukocyte antigen (HLA) genes have been implicated in cervical cancer in several populations. To study the predispositions of HLA alleles/haplotypes with cervical cancer. Clinically diagnosed and PAP smear confirmed cervical cancer patients (n 48) and age matched controls (n 47) were genotyped for HLA-A,-B,-DRB1* and DQB1* alleles by PCR-SSP methods. The frequencies of alleles DRB1*04 (OR=2.57), DRB1*15 (OR=2.04), DQB1*0301 (OR=4.91), DQB1*0601 (OR=2.21), B*15 (OR=13.03) and B*07 (OR=6.23) were higher in cervical cancer patients than in the controls. The frequencies of alleles DRB1*10 (OR=0.22) and B*35 (OR=0.19) were decreased. Strong disease associations were observed for haplotypes DRB1*15-DQB1*0601 (OR=6.56; < 3.5.10-4), DRB1*14-DQB1*0501 (OR=6.51; <0.039) and A*11-B*07 (OR=3.95; <0.005). The reduced frequencies of haplotypes DRB1*10-DQB1*0501 (OR=0.45), A*03-B*35 (OR=0.25) and A*11-B*35 (OR= 0.06) among patients suggested a protective association. HLA-C* typing of 8 patients who possessed a unique three locus haplotype 'A*11-B*07-DRB1*04' (8/48; 16.66%; OR=6.51; <0.039) revealed the presence of a four locus haplotype 'A*11-B*07-C*01-DRB1*04' in patients (4/8; 50%). Amino acid variation analysis of susceptible allele DQB1*0601 suggested 'tyrosine' at positions β9 and β37 and tyrosine-non-tyrosine genotype combination increased the risk of cervical cancer. Strong susceptible associations were documented for HLA alleles B*15, B*07, DRB1*04, DRB1*15, DQB1*0301, DQB1*0601 and haplotypes DRB1*15-DQB1*0601 and DRB1*14-DQB1*0501. Further, protective associations were evidenced for alleles B*35 and DRB1*10 and haplotypes A*11-B*35 and DRB1*10-DQB1*0501 with cervical cancer in South India.


Evaluating Movement of Patients With Carbapenem-resistant Enterobacteriaceae Infections in the Greater Atlanta Metropolitan Area Using Social Network Analysis.
Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent threat with potential for rapid spread. We evaluated the role of Medicare patient movement between facilities to model the spread of CRE within a region. Through population-based CRE surveillance in the 8-county Atlanta (GA) metropolitan area, all Escherichia coli, Enterobacter spp., or Klebsiella spp. resistant to ≥1 carbapenem were reported from residents. CRE was attributed to a facility based on timing of culture and facility exposures. Centrality metrics were calculated from 2016 Medicare data and compared to CRE-transfer derived centrality metrics by Spearman correlation. During 2016, 283 incident CRE cases with concurrent or prior year facility stays were identified; cases were attributed mostly to acute care hospitals (ACHs; 141, 50%) and skilled nursing facilities (SNFs; 113, 40%), and less frequently to long-term acute care hospitals (LTACHs; 29, 10%). Attribution was widespread, originating at 17 of 20 ACHs (85%), 7 of 8 (88%) LTACHs, but only 35 of 65 (54%) SNFs. Betweenness of Medicare patient transfers strongly correlated with betweenness of CRE case-transfer data in ACHs (r = 0.75; P < .01) and LTACHs (r = 0.77; P = .03), but not in SNFs (r = 0.02; P = 0.85). We noted 6 SNFs with high CRE-derived betweenness but low Medicare-derived betweenness. CRE infections originate from almost all ACHs and half of SNFs. We identified a subset of SNFs central to the CRE transfer network but not the Medicare transfer network; other factors may explain CRE patient movement in these facilities.


Fractionation of ovalbumin glycopeptide AC-C by high-pressure liquid chromatography. Determination of structure by 1H-NMR spectroscopy.
We describe for the first time a method for the separation of intact ovalbumin glycopeptides by high-pressure liquid chromatography (HPLC). The separation was achieved using two reverse-phase columns connected in series and eluting with an isocratic solvent system at acid pH containing 1-hexane sulfonate. Ovalbumin glycopeptide fraction AC-C has been separated into at least four distinct glycopeptides. High resolution 1H-NMR spectroscopy has confirmed the reported structure of the two major species. We also extend our structural studies to the two other glycopeptides and establish the structure of a previously unreported ovalbumin glycopeptide, Man3GalGlcNAcAsn.


Diagnosis of the intraductal component of invasive breast cancer: assessment with mammography and sonography.
The aim of this study was to investigate mammographic and sonographic features and their sensitivities for depiction of the intraductal component associated with invasive ductal carcinoma (IDC). During a 1-year period, 132 patients with IDC underwent surgical treatment. All patients underwent mammography and high-resolution sonography, and the findings were reported according to the American College of Radiology's Breast Imaging Reporting and Data System lexicon. Tumors were classified as "pure IDC" and "IDC with an intraductal component" by histopathologic evaluation. We compared mammographic and sonographic features between the above 2 groups and attempted to correlate them with histopathologic findings. We also investigated separate and combined sensitivities, specificities, and accuracies of both mammography and breast sonography for showing intraductal components. Finally, imaging measurements were compared with pathologic measurements. One hundred four (79%) of the 132 IDCs contained an intraductal component. Patients with IDC with an intraductal component showed calcifications on mammography and showed an echogenic halo, duct dilatation, calcifications, and increased vascularity in surrounding tissue on sonography more frequently than patients with pure IDC. The sensitivities of mammography, sonography, and their combined assessment for detection of an intraductal component were 55%, 80%, and 86%, respectively. The combined assessment (r = 0.90) measured the extent of the tumor more accurately than mammography (r = 0.71) or sonography (r = 0.79) separately. Combined assessment with mammography and sonography offers more accurate information for the presence of an intraductal component and the extent of a tumor than each separate assessment.


Reducing arsenic and groundwater contaminants down to safe level for drinking purposes via Fe3+-attached hybrid column.
Monitoring of groundwater is fundamentally important due to it has emerged as a major source of drinking water and also used for irrigation purposes in many places in the world. Arsenic contamination in surface water and groundwater resources is a major concern due to its presence at high concentration and associated adverse health effects. Thus, the remediation of As in water resources, alongside other chemical species including fluoride, lithium, vanadium aluminium and nitrate is necessary. We have designed a hybrid [polyethyleneimine (PEI)-supported Fe3+-attached poly-(HEMA-co-GMA)] column for the reduction of arsenic (III and V) and other groundwater chemicals from natural groundwater as a potential contribution to water resource management. Swelling behaviour and scanning electron microscopy (SEM) were performed for the characterization of hybrid material. For the optimization of experimental conditions, the effects of pH and initial arsenic concentrations on adsorption were studied using arsenic solutions. Maximum adsorption capacity in equilibrium was 11.44 and 5.79 mg/g polymer for As(III) and As(V), respectively at pH 7. The reduction of metalloids and other subsurface chemicals were carried out with natural groundwater samples obtained from local sources. The mean concentrations of arsenic were recorded between 44.96 and 219.04 μg/L and of which 71.3-95.4 % (0.32-1.22 mg/g) were removed. The average removals were determined as F-1 50-86%, Li+ 43.2-99.7%, Al+3 83.8-91.4%, NO3- 48.4-72.2% and V 91.3-95.7. Chemical-loaded hybrid columns were regenerated successfully 15 times with only a loss of 5% in adsorption capacity by 0.01 M NaCl- treatment for potential adaptation into water industry. No pre-oxidation of As species was performed for the treatment of ground water samples prior to the hybrid column testing.


Pelvic irradiation for stage II ovarian carcinoma.
Over a 20-year period, 34 patients with FIGO stage II ovarian carcinoma were treated with postoperative pelvic irradiation at the University of Michigan. Complications of radiation treatment were minimal. The overall actuarial disease-free 5-year survival was 53%. This was not significantly different for substages IIA, IIB, or IIC. Patients with well-differentiated tumors had a significantly better survival than patients with moderate or poorly differentiated tumors (P less than 0.05). The implications for managing stage II ovarian carcinoma are discussed.


Transcription of subtelomere tandemly repetitive DNA in chicken embryogenesis.
Transcription of tandemly repetitive DNA in embryogenesis seems to be of special interest due to a crucial role of non-coding RNAs in many aspects of development. However, only a few data are available on tandem repeats transcription at subtelomere regions of chromosomes during vertebrate embryogenesis. To reduce this gap, we examined stage and tissue-specific pattern of subtelomeric PO41 (pattern of 41 bp) tandem repeat transcription during embryogenesis of chicken (Gallus gallus domesticus). Using whole-mount RNA fluorescent in situ hybridization and reverse transcription PCR with specific primers, we demonstrated that both strands of PO41 repeat are transcribed at each of the studied stages of chicken embryo development: from 7-8 HH to 20 HH stages. Subtelomere-derived transcripts localize in the nuclei of all cell types and throughout the all embryonic bodies: head, somites, tail, wings and buds. In embryo-dividing cells and cultured embryonic fibroblasts, PO41 RNAs envelop terminal regions of chromosomes. PO41-containing RNAs are predominantly single-stranded and can be polyadenylated, indicating appearance of non-nascent form of subtelomeric transcripts. PO41 repeat RNAs represent a rare example of ubiquitously transcribed non-coding RNAs, such as Xist/XIST RNA or telomere repeat-containing RNA. Distribution of PO41 repeat transcripts at different stages of embryo development and among cell types has extremely uniform pattern, indicating on possible universal functions of PO41 non-coding RNAs.


Preliminary evaluation of the reliability and validity of the Shame and Stigma Scale in head and neck cancer.
Facial disfigurement from head and neck cancer can lead to the development of shame and a perception of stigma. We sought to develop the Shame and Stigma Scale (SSS) to measure this. Items were administered to 104 patients with squamous cell carcinoma of the oral cavity, together with measures of quality of life and adaptation. Exploratory factor analysis and item response theory (IRT) models assessed its psychometric properties. A 20-item SSS had a Cronbach's alpha of 0.94 and 4 factors: shame with appearance, sense of stigma, regret, and speech/social concerns. These factors show satisfactory internal validity, convergent validity with the Functional Assessment of Cancer Therapy-General (FACT-G) and Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N), Demoralization Scale and Patient Health Questionnaire (PHQ) Depression, and divergent validity with the Social Desirability Scale. The items displayed desirable properties in factor-specific (IRT) models. Further validation studies are worthwhile to confirm this factor structure, reliability, and validity, and generalizability to all head and neck cancers.


New Prognostic and Predictive Markers in Cancer Progression.
Biomarkers are a critical medical need for oncologists to predict and detect disease and to determine the best course of action for cancer patient care [...].


Identification and characterization of cytochrome P450 CYP77A59 of loquat (Rhaphiolepis bibas) responsible for biosynthesis of phenylacetonitrile, a floral nitrile compound.
Cytochrome P450 CYP77A59 is responsible for the biosynthesis of phenylacetonitrile in loquat flowers. Flowers of some plants emit volatile nitrile compounds, but the biosynthesis of these compounds is unclear. Loquat (Rhaphiolepis bibas) flowers emit characteristic N-containing volatiles, such as phenylacetonitrile (PAN), (E/Z)-phenylacetaldoxime (PAOx), and (2-nitroethyl)benzene (NEB). These volatiles likely play a defense role against pathogens and insects. PAN and NEB are commonly biosynthesized from L-phenylalanine via (E/Z)-PAOx. Two cytochrome P450s-CYP79D80 and "promiscuous fatty acid ω-hydroxylase" CYP94A90, which catalyze the formation of (E/Z)-PAOx from L-phenylalanine and NEB from (E/Z)-PAOx, respectively-are involved in NEB biosynthesis. However, the enzymes catalyzing the formation of PAN from (E/Z)-PAOx in loquat have not been identified. In this study, we aimed to identify candidate cytochrome P450s catalyzing PAN formation in loquat flowers. Yeast whole-cell biocatalyst assays showed that among nine candidate cytochrome P450s, CYP77A58 and CYP77A59 produced PAN from (E/Z)-PAOx. CYP77As catalyzed the dehydration of aldoximes, which is atypical of cytochrome P450; the reaction was NADPH-dependent, with an optimum temperature and pH of 40 °C and 8.0, respectively. CYP77As acted on (E/Z)-PAOx, (E/Z)-4-hydroxyphenylacetaldoxime, and (E/Z)-indole-3-acetaldoxime. Previously characterized CYP77As are known to hydroxylate fatty acids; loquat CYP77As did not act on tested fatty acids. We observed higher expression of CYP77A59 in flowers than in buds; expression of CYP77A58 was remarkably reduced in the flowers. Because the flowers, but not buds, emit PAN, CYP77A59 is likely responsible for the biosynthesis of PAN in loquat flowers. This study will help us understand the biosynthesis of floral nitrile compounds.


Heteroplasmic Mutant Load Differences in Mitochondrial DNA-Associated Leigh Syndrome.
Mitochondrial DNA (mtDNA)-associated Leigh syndrome is influenced by mutant pathogenicity and corresponding heteroplasmic loads; however, the manner in which heteroplasmic mutant load affects patient phenotypes and the relationship between mutant types and heteroplasmic mutant loads remain unknown. We aimed to investigate the distribution of the mutant load of different mtDNA mutations in a single-center cohort. We used next-generation sequencing to confirm mtDNA mutations in 31 patients with Leigh syndrome. Subsequently, we counted the number of mtDNA reads to quantitatively analyze the heteroplasmic mutant load and categorize the patients according to the mtDNA mutations they harbored. Confirmed cases of mtDNA-associated Leigh syndrome were classified according to the mutations observed in six genes and 10 nucleotides. Of the 31 patients with Leigh syndrome, 27 harbored known pathogenic mutations. We discovered that MT-ATP6 was the most commonly mutated gene (n = 13 patients), followed by MT-ND3 (n = 7) and MT-ND5 (n = 4). MT-ATP6 had a significantly higher mutant load than MT-ND3 and MT-ND5 (P < 0.001, each). By contrast, MT-ND5 had a significantly lower mutant load than MT-ND3 (P = 0.007). Notably, the mutation loads varied significantly among patients carrying the MT-ATP6, MT-ND3, and MT-ND5 mutations. Our study illustrated the heteroplasmic diversity and phenotypic expression threshold of mutated mitochondrial genes in mtDNA-associated Leigh syndrome. The results provide promising insights into the genotype-phenotype correlation in mtDNA-associated Leigh syndrome that are expected to guide the development of tailored treatments for Leigh syndrome.


Serological Proteome Analysis (SERPA) as a tool for the identification of new candidate autoantigens in type 1 diabetes.
Type 1 diabetes (T1D) is an autoimmune disease characterized by the presence of circulating autoantibodies directed against proteins of islet beta-cell. Autoantibody testing is used for diagnostic purposes; however, up to 2-5% of patients who are clinically diagnosed with T1D are found negative for known antibodies, suggesting that the T1D autoantigen panel is incomplete. With the aim of identifying new T1D autoantigen(s), we used sera from subjects clinically diagnosed with T1D, but who tested negative for the four T1D autoantibodies currently used in clinical practice and for genes responsible for sporadic cases of diabetes. Sera from these patients were challenged by Western blot against the proteome from human pancreatic beta-cells resolved by 2DE. Eleven proteins were identified by MS. A radiobinding assay (RBA) was developed to test the reactivity to Rab GDP dissociation inhibitor beta (GDIβ) of T1D sera using an independent method. Depending on the construct used (open reading frame or COOH-terminus) 22% to 32% of fifty T1D sera showed increased binding to GDIβ by RBA. In addition, 15% of patients with celiac disease had raised binding to the COOH-terminus GDIβ. These results indicate that immunoproteomics is a feasible strategy for the identification of candidate T1D autoantigens. Several approaches have been previously used to look for new type 1 diabetes autoantigens. With the present work we show that carefully selected sera from rare patients with diabetes both negative for the 5 autoantibodies currently used in clinical practice and for genes responsible for sporadic cases of diabetes, may be exploited in experiments utilizing human pancreatic islets extracts as a target for SERPA to identify novel candidate T1D autoantigens.


[Effect of N-ethyl-N-(4-pyridylmethyl)tropamide (Mydriaticum Roche) on the results of the Schirmer test].
Deficient lacrimal secretion as a consequence of systemic drug therapy has been reported after the use of phenothiazines, antihistaminics, psychotropic drugs, anesthetics, diuretics, beta-blocking agents, ganglion blockers etc. But topical application of beta-blocking eye drops may also decrease tear production. The study reported here proves that tear production is also decreased if one drop of "Mydriaticum Roche" eye drops is applied. This effect was observed especially in patients who had "normal basic tear production" prior to treatment; however, "Mydriaticum Roche" did not cause a further decrease in tear production during Schirmer's test when the basic tear secretion level was already very low. Therefore, in order to avoid "false positive" results Schirmer's test should always be performed before instillation of atropine-active eye drops such as "Mydriaticum Roche".


Depression of lymphocyte responses to mitogens in mangabeys with disseminated experimental leprosy.
Mononuclear cells from mangabey monkeys with disseminated experimental leprosy had increasingly severe depression of blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen as the disease progressed. Blastogenic responses were not depressed in cells from mangabeys with more localized disease. Blastogenic responses of cells from normal mangabeys appeared to vary with a circannual rhythm. The demonstration of significant negative correlations between the blastogenic responses to mitogens and the percentages of OKT8+ cells suggested that the mangabey OKT8+ subset may contain cells with suppressor function. The depressed responses to mitogens by cells from monkeys with disseminated experimental leprosy were associated with relatively high percentages of OKT8+ cells. Polyclonal immunoglobulin plaque-forming cell responses to pokeweed mitogen were depressed in cells from experimentally infected mangabeys. The results indicated that defects in immune regulation may occur in experimental leprosy in mangabeys, similar in some respects to the defects that have been reported in human leprosy.


The innate immune cell response to bacterial infection in larval zebrafish is light-regulated.
The circadian clock, which evolved to help organisms harmonize physiological responses to external conditions (such as the light/dark cycle, LD), is emerging as an important regulator of the immune response to infection. Gaining a complete understanding of how the circadian clock influences the immune cell response requires animal models that permit direct observation of these processes within an intact host. Here, we investigated the use of larval zebrafish, a powerful live imaging system, as a new model to study the impact of a fundamental zeitgeber, light, on the innate immune cell response to infection. Larvae infected during the light phase of the LD cycle and in constant light condition (LL) demonstrated enhanced survival and bacterial clearance when compared with larvae infected during the dark phase of the LD cycle and in constant dark condition (DD). This increased survival was associated with elevated expression of the zebrafish orthologues of the mammalian pro-inflammatory cytokine genes, Tumour necrosis factor-α, Interleukin-8 and Interferon-γ, and increased neutrophil and macrophage recruitment. This study demonstrates for the first time that the larval zebrafish innate immune response to infection is enhanced during light exposure, suggesting that, similar to mammalian systems, the larval zebrafish response to infection is light-regulated.


Informed Consent Challenges in Frail, Delirious, Demented, and Do-Not-Resuscitate Adult Patients.
Without informed consent, any invasive procedure becomes an assault. The prevailing legal and ethical standard is that the physician has a fiduciary duty to give enough information to the patient so that a reasonable person can make an informed decision to accept or refuse the proposed treatment. The patient's frailty, delirium and/or dementia, and end-of-life concerns and expectations can make informed consent a difficult task. This review examines informed consent requirements for adults and provides communication tools to enable shared decision making while engendering patient-physician trust.


Norovirus GII.2[P16] strain in Shenzhen, China: a retrospective study.
Norovirus (NoV) is the main cause of non-bacterial acute gastroenteritis (AGE) outbreaks worldwide. From September 2015 through August 2018, 203 NoV outbreaks involving 2500 cases were reported to the Shenzhen Center for Disease Control and Prevention. Faecal specimens for 203 outbreaks were collected and epidemiological data were obtained through the AGE outbreak surveillance system in Shenzhen. Genotypes were determined by sequencing analysis. To gain a better understanding of the evolutionary characteristics of NoV in Shenzhen, molecular evolution and mutations were evaluated based on time-scale evolutionary phylogeny and amino acid mutations. A total of nine districts reported NoV outbreaks and the reported NoV outbreaks peaked from November to March. Among the 203 NoV outbreaks, 150 were sequenced successfully. Most of these outbreaks were associated with the NoV GII.2[P16] strain (45.3%, 92/203) and occurred in school settings (91.6%, 186/203). The evolutionary rates of the RdRp region and the VP1 sequence were 2.1 × 10-3 (95% HPD interval, 1.7 × 10-3-2.5 × 10-3) substitutions/site/year and 2.7 × 10-3 (95% HPD interval, 2.4 × 10-3-3.1 × 10-3) substitutions/site/year, respectively. The common ancestors of the GII.2[P16] strain from Shenzhen and GII.4 Sydney 2012[P16] diverged from 2011 to 2012. The common ancestors of the GII.2[P16] strain from Shenzhen and previous GII.2[P16] (2010-2012) diverged from 2003 to 2004. The results of amino acid mutations showed 6 amino acid substitutions (*77E, R750K, P845Q, H1310Y, K1546Q, T1549A) were found only in GII.4 Sydney 2012[P16] and the GII.2[P16] recombinant strain. This study illustrates the molecular epidemiological patterns in Shenzhen, China, from September 2015 to August 2018 and provides evidence that the epidemic trend of GII.2[P16] recombinant strain had weakened and the non-structural proteins of the recombinant strain might have played a more significant role than VP1.


The use of carbon 11-labeled acetate for assessment of aerobic metabolism.
Carbon 11-labeled acetate has been validated as a tracer of citric acid flux and indirectly of oxidative metabolism. 11C-labeled acetate is predominantly metabolized to 11C-labeled carbon dioxide, which clears from the heart. The myocardial 11CO2 efflux rate that can be estimated by dynamic positron emission tomographic imaging closely correlates with myocardial oxygen consumption over a wide range of flow, substrate use, and metabolic conditions. 11C-labeled acetate clearance rates are indirect indexes of oxidative metabolism. To provide absolute mass fluxes, the 11C-labeled acetate approach would require biochemical validation and configuration of a tracer kinetic model. Clinically, estimates of myocardial oxygen consumption appear to be useful in assessing tissue viability, as shown in patients after acute myocardial infarction or with chronic coronary artery disease. In non-coronary artery disease, 11C-labeled acetate may provide measurement of cardiac efficiency and be useful for monitoring therapy.


Human basement membrane collagen (type IV). The amino acid sequence of the alpha 2(IV) chain and its comparison with the alpha 1(IV) chain reveals deletions in the alpha 1(IV) chain.
The cDNA and protein sequences of the N-terminal 60% of the alpha 2(IV) chain of human basement membrane collagen have been determined. By repeated primer extension with synthetic oligodeoxynucleotides and mRNA from either HT1080 cells or human placenta overlapping clones were obtained which cover 3414 bp. The derived protein sequence allows for the first time a comparison and alignment of both alpha chains of type IV collagen from the N terminus. This alignment reveals an additional 43 amino acid residues in the alpha 2(IV) chain as compared to the alpha 1(IV) chain. 21 of these additional residues form a disulfide-bridged loop within the triple helix which is unique among all known collagens.


Effect of antimicrobial treatments applied individually and in combination on the growth of Listeria monocytogenes in Queso Fresco at 3 different temperatures.
Queso fresco (QF), a fresh soft cheese, is one of the most popular Hispanic cheeses in the United States and is frequently associated with Listeria monocytogenes outbreaks. Listeria monocytogenes can grow and thrive at room temperature as well as refrigeration temperatures. A combination of antimicrobial agents provides a larger spectrum of listeriostatic and listeriocidal activity resulting in a more effective approach toward the control of L. monocytogenes. In this study, we evaluated the efficacy of 3 Food and Drug Administration-approved generally recognized as safe (GRAS) antimicrobials, nisin (NIS), lauric arginate ethyl ester (LAE), and ε-polylysine (EPL), and the endolysin PlyP100 individually and in combination for control of L. monocytogenes in QF at 4°C, 7°C, and 10°C. Additionally, growth curves of L. monocytogenes were obtained in BHI broth and QF at these temperatures. In order for an antimicrobial to be considered a postlethality treatment for L. monocytogenes, it should not allow an increase of more than 2-log over the product's shelf life. Three treatments, PlyP100, PlyP100 + NIS, and EPL + LAE, effectively kept the pathogen below the 2 log growth threshold at 4°C. However, at 7°C and 10°C, none of the antimicrobial treatments could inhibit L. monocytogenes growth (i.e., <2 log). Overall, our results suggest the importance of considering the effect of cold storage temperatures above 4°C on the antilisterial efficacy of antimicrobial treatments in QF.


Nr5a2 heterozygosity sensitises to, and cooperates with, inflammation in KRas(G12V)-driven pancreatic tumourigenesis.
Nr5a2 participates in biliary acid metabolism and is a major regulator of the pancreatic exocrine programme. Single nucleotide polymorphisms in the vicinity of NR5A2 are associated with the risk of pancreatic ductal adenocarcinoma (PDAC). To determine the role of Nr5a2 in pancreatic homeostasis, damage-induced regeneration and mutant KRas-driven pancreatic tumourigenesis. Nr5a2+/- and KRas(G12V);Ptf1a-Cre;Nr5a2+/- mice were used to investigate whether a full dose of Nr5a2 is required for normal pancreas development, recovery from caerulein-induced pancreatitis, and protection from tumour development. Adult Nr5a2+/- mice did not display histological abnormalities in the pancreas but showed a more severe acute pancreatitis, increased acino-ductal metaplasia and impaired recovery from damage. This was accompanied by increased myeloid cell infiltration and proinflammatory cytokine gene expression, and hyperactivation of nuclear factor κb and signal transducer and activator of transcription 3 signalling pathways. Induction of multiple episodes of acute pancreatitis was associated with more severe damage and delayed regeneration. Inactivation of one Nr5a2 allele selectively in pancreatic epithelial cells was sufficient to cause impaired recovery from pancreatitis. In comparison with Nr5a2+/+ mice, KRas(G12V);Ptf1a(Cre/+);Nr5a2+/- mice showed a non-statistically significant increase in the area affected by preneoplastic lesions. However, a single episode of acute pancreatitis cooperated with loss of one Nr5a2 allele to accelerate KRas(G12V)-driven development of preneoplastic lesions. A full Nr5a2 dose is required to restore pancreatic homeostasis upon damage and to suppress the KRas(G12V)-driven mouse pancreatic intraepithelial neoplasia progression, indicating that Nr5a2 is a novel pancreatic tumour suppressor. Nr5a2 could contribute to PDAC through a role in the recovery from pancreatitis-induced damage.


Use of skin and oral cancer examinations in the United States, 1998.
Findings from previous surveys suggest low utilization of oral cancer examinations, even though this examination is noninvasive. The purpose of this analysis is to compare the use of an oral cancer examination (OCE) and a skin cancer examination (SCE) in the past 12 months within the United States. Both exams are noninvasive and include a visual component. Weighted data from the Adult Prevention Supplement of the 1998 National Health Interview Survey (NHIS) for adults 40 years of age or older were analyzed using SAS and SUDAAN. A ratio compared the percentage reporting an OCE (%OCE) with the percentage reporting a SCE (%SCE). The percentage having an OCE in the past year (13.8%) was very similar to the percentage having a SCE (13.5%) during that same period. With increasing age group, the %OCE/%SCE ratio varied inversely from 1.60 (C.I. 1.42-1.78) among persons 40-49 years to 0.62 (C.I. 0.55-0.69) among persons 70+ years. The ratio was similar in whites and blacks, males and females, and Hispanics and non-Hispanics. There was a positive gradient in the ratio by education and family income. Overall, less than 15% of the population is receiving either of these examinations, although the American Cancer Society recommends both of them on an annual basis for individuals 40 years of age and older. To increase detection of these cancers at early stages, extensive educational and media campaigns for the public and providers identifying risk factors and the availability of and the need for these examinations are required.


Bicarbonate-Mediated CO2 Formation on Both Sides of Photosystem II.
The effect of bicarbonate (HCO3-) on photosystem II (PSII) activity was discovered in the 1950s, but only recently have its molecular mechanisms begun to be clarified. Two chemical mechanisms have been proposed. One is for the electron-donor side, in which mobile HCO3- enhances and possibly regulates water oxidation by acting as proton acceptor, after which it dissociates into CO2 and H2O. The other is for the electron-acceptor side, in which (i) reduction of the QA quinone leads to the release of HCO3- from its binding site on the non-heme iron and (ii) the Em potential of the QA/QA•- couple increases when HCO3- dissociates. This suggested a protective/regulatory role of HCO3- as it is known that increasing the Em of QA decreases the extent of back-reaction-associated photodamage. Here we demonstrate, using plant thylakoids, that time-resolved membrane-inlet mass spectrometry together with 13C isotope labeling of HCO3- allows donor- and acceptor-side formation of CO2 by PSII to be demonstrated and distinguished, which opens the door for future studies of the importance of both mechanisms under in vivo conditions.


[The rate of formation of necrotic focus and the severity of clinical picture in the acute period of myocardial infarction].
The relationship between necrotic focus characteristics (weight and rate of necrotization) and the clinical pattern of myocardial infarction was examined. Necrosis weight was shown to have no significant effect on the course of myocardial infarction, while maximum necrotization rate was found to be a valuable predictive factor: the higher the necrotization rate, the higher the risk of fatal outcome and various complications. Prognosis, based on necrotization rate and patient's age, can be made, using an equation, derived for early prediction of myocardial infarction outcome.


Digital Image Correlation Compatible Mechanoluminescent Skin for Structural Health Monitoring.
Monitoring structural health using mechanoluminescent (ML) effects is widely considered as a potential full-field and direct visualizing optical method with high spatial and temporal resolution and simple setup in a noncontact manner. The challenges and uncertainties in the mapping of ML field to effective strain field, however, tend to limit significant commercial ML applications for structural health monitoring systems. Here, however, quantification problems are resolved using the digital image correlation (DIC) method. Specifically, an image containing mechanically induced photon information is processed using a DIC algorithm to measure the strain field components, which enables the establishment of a calibration curve when the ML field is mapped onto the effective strain field using pixel level information. The results show a linear relationship between effective strain and ML intensity despite the plastic flow in ML skin. Furthermore, the calibration curve allows for easy conversion of ML field to effective-strain field at the crack-tip plastic zone of the alloy structure, retaining its spatial resolution. The compatibility of ML skin with the DIC algorithm not only enables the quantification of the ML effects of several organic/inorganic ML materials, but may also be useful in elucidating the fundamentals of the trap-controlled mechanism.


Association between ambient air pollutant interaction with kidney function in a large Taiwanese population study.
The associations and interactions between kidney function and other air pollutants remain poorly defined. Therefore, the aim of this study was to evaluate associations among air pollutants, including particulate matter (PM) with a diameter ≤ 2.5 μm (PM2.5), PM10 (PM with a diameter ≤ 10 μm), carbon monoxide (CO), nitrogen oxide (NO), nitrogen oxides (NOx), sulfur dioxide (SO2), and ozone (O3) with kidney function, and explore interactions among these air pollutants on kidney function. We used the Taiwan Air Quality Monitoring and Taiwan Biobank databases to derive data on community-dwelling individuals in Taiwan and daily air pollution levels, respectively. We enrolled 26,032 participants. Multivariable analysis showed that high levels of PM2.5, PM10, O3 (all p < 0.001), and SO2 (p = 0.001) and low levels of CO, NO (both p < 0.001), and NOx (p = 0.047) were significantly correlated with low estimated glomerular filtration rate (eGFR). With regard to negative effects, the interactions between PM2.5 and PM10 (p < 0.001), PM2.5 and PM10 (p < 0.001), PM2.5 and SO2, PM10 and O3 (both p = 0.025), PM10 and SO2 (p = 0.001), and O3 and SO2 (p < 0.001) on eGFR were significantly negatively. High PM10, PM2.5, O3, and SO2 were associated with a low eGFR, whereas high CO, NO, and NOx were associated with a high eGFR. Furthermore, negative interactions between PM2.5 and PM10, O3 and SO2, PM10 and O3, PM2.5 and SO2, and PM10 and SO2 on eGFR were observed. The findings of this study have important implications for public health and environmental policy. Specifically, the results of this study may be useful in individuals and organizations to take action to reduce air pollution and promote public health.