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Anisotropy of biological tissues is a low-frequency phenomenon that is associated with the function and structure of cell membranes. Imaging of anisotropic conductivity has potential for the analysis of interactions between electromagnetic fields and biological systems, such as the prediction of current pathways in electrical stimulation therapy. To improve application to the clinical environment, precise approaches are required to understand the exact responses inside the human body subjected to the stimulated currents. In this study, we experimentally evaluate the anisotropic conductivity tensor distribution of canine brain tissues, using a recently developed diffusion tensor-magnetic resonance electrical impedance tomography method. At low frequency, electrical conductivity of the biological tissues can be expressed as a product of the mobility and concentration of ions in the extracellular space. From diffusion tensor images of the brain, we can obtain directional information on diffusive movements of water molecules, which correspond to the mobility of ions. The position dependent scale factor, which provides information on ion concentration, was successfully calculated from the magnetic flux density, to obtain the equivalent conductivity tensor. By combining the information from both techniques, we can finally reconstruct the anisotropic conductivity tensor images of brain tissues. The reconstructed conductivity images better demonstrate the enhanced signal intensity in strongly anisotropic brain regions, compared with those resulting from previous methods using a global scale factor.

Nature Communications 8: Article number: 14433 (2017) Published online 14 February 2017; Updated 20 April 2018 In this Article, a subset of the H3K27ac ChIP-seq data (15 benign meningiomas and 2 dura samples (Sample IDs: MN-297, MN-288, MN-292, MN-163, MN-1037, MN-105, MN-201, MN-249, MN-191, MN-1066, MN-169, MN-291, MN-24, MN-79, MN-1044, CONTROL1, CONTROL2) was reported previously in a publication by the corresponding author1.

Electromagnetic fields provide fundamental data for the imaging of electrical tissue properties, such as conductivity and permittivity, in recent magnetic resonance (MR)-based tissue property mapping. The induced voltage, current density, and magnetic flux density caused by externally injected current are critical factors for determining the image quality of electrical tissue conductivity. As a useful tool to identify bio-electromagnetic phenomena, precise approaches are required to understand the exact responses inside the human body subject to an injected currents. In this study, we provide the numerical simulation results of electromagnetic field mapping of brain tissues using a MR-based conductivity imaging method. First, we implemented a realistic three-dimensional human anisotropic head model using high-resolution anatomical and diffusion tensor MR images. The voltage, current density, and magnetic flux density of brain tissues were imaged by injecting 1 mA of current through pairs of electrodes on the surface of our head model. The current density map of anisotropic brain tissues was calculated from the measured magnetic flux density based on the linear relationship between the water diffusion tensor and the electrical conductivity tensor. Comparing the current density to the previous isotropic model, the anisotropic model clearly showed the differences between the brain tissues. This originates from the enhanced signals by the inherent conductivity contrast as well as the actual tissue condition resulting from the injected currents.

Nature Communications 8: Article number:14385 (2017); Published: 9 February 2017; Updated: 1 June 2017 In the original version of Supplementary Data 1 associated with this Article, the list of predicted enhancer-associated insertions was inadvertently truncated. The HTML has now been updated to include the correct version of the Supplementary Data 1.

A continuous Nondestructive monitoring method is required to apply proper feedback controls during tissue regeneration. Conductivity is one of valuable information to assess the physiological function and structural formation of regenerated tissues or cultured cells. However, conductivity imaging methods suffered from inherited ill-posed characteristics in image reconstruction, unknown boundary geometry, uncertainty in electrode position, and systematic artifacts. In order to overcome the limitation of microscopic electrical impedance tomography (micro-EIT), we applied a 3D-specific container with a fixed boundary geometry and electrode configuration to maximize the performance of Graz consensus reconstruction algorithm for EIT (GREIT). The separation of driving and sensing electrodes allows us to simplify the hardware complexity and obtain higher measurement accuracy from a large number of small sensing electrodes. We investigated the applicability of the GREIT to 3D micro-EIT images via numerical simulations and large-scale phantom experiments. We could reconstruct multiple objects regardless of the location. The resolution was 5 mm3 with 30 dB SNR and the position error was less than 2.54 mm. This shows that the new micro-EIT system integrated with GREIT is robust with the intended resolution. With further refinement and scaling down to a microscale container, it may be a continuous nondestructive monitoring tool for tissue engineering applications.

Abstract: Background: Hepatic ischemia/reperfusion (HI/R) injury is a common pathologic process caused by many clinical settings, such as liver resection, liver transplantation, hypovolemic shock, and trauma. The use of ambroxol, which acts as a mucolytic agent, provides antioxidant and anti-inflammatory effects. Methods: A rat model of HI/R was induced by clamping the hepatic artery, the hepatoportal vein, and the bile duct with a vascular clamp for 30 minutes followed by reperfusion for 6 hours under anesthesia. The sham group underwent laparotomy without hepatic ischemia. The ambroxol group was injected into the tail vein in the ambroxol group 5 minutes before HI/R at one dose of 20 mg/kg, 80 mg/kg, or 140 mg/kg. The control group underwent the same procedure as the ambroxol group but with administration of physiological saline. Liver injury was evaluated by biochemical and histopathological examinations. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed in serum samples. Superoxide dismutase (SOD), catalase (CAT), malondiadehyde (MDA), and glutathione (GSH) were spectrophotometrically measured. Furthermore, caspase-3, Bcl-2 and Bax expression as well as the level of c-Jun N-terminal kinases (JNK) we estimated activation. Results: Wistar rats that received 20, 80 mg or 140 mg of ambroxol displayed reduced HI/R injury compared with controls. Use of ambroxol reduced the histologic injury and significantly decreased serum ALT and AST levels. In addition, ambroxol enhanced the activity of hepatic tissue SOD and CAT, increasing GSH but decreasing MDA tissue contents. In the ambroxol group, Bcl-2 expression was increased and Bax and caspase-3 decreased compared with the controls. Furthermore, ambroxol reduced levels of phosphorylated JNK (P < .05). Conclusion: These results indicated that ambroxol attenuated rat HI/R through upregulation of intracellular antioxidant and anti-apoptotic signaling pathways. [Copyright &y& Elsevier]

The antioxidant and lysosomotropic properties of a fluorescent analogue of propranolol, 9-amino-acridine-propranolol (9-AAP) were compared to those of propranolol. Using isolated microsomal membranes exposed to a superoxide and hydroxyl radical generating system, 9-AAP was found to be at least 10-fold more potent than propranolol (and about 50% as potent as vitamin E) in inhibiting lipid peroxidation. In cultured endothelial cells, 9-AAP afforded moderate protective effect against acute loss of glutathione but potent cytoprotective activity against free radical-mediated loss of viability/survival. Intracellular localization of 9-AAP was examined by fluorescent microscopy and compared with two known fluorescent lysosomal markers: acridine orange and Lysosensor. All three agents appeared to localize to similar peri-nuclear vesicles, presumably lysosomes or pre-lysosomes. Lysosensor fluorescence was not observable in the presence of 9-AAP, foreclosing the possibility of a direct dual labeling experiment. We employed the pH sensitivity of acridine orange to determine if it labels the same vesicles as 9-AAP. When the endothelial cells were preloaded with acridine orange, washed and resuspended in buffer containing 9-AAP, the dark orange-labeled vesicles observed with acridine orange alone became increasingly lighter with time. Since the fluorescence of acridine orange is altered by pH change, this spectral shift in fluorescence emission is consistent with the indication that added propranolol (or the analog) leads to lysosomal alkalization. In conclusion, 9-AAP is both a strong antioxidant and a lysosomotropic agent that is remarkably insensitive to photobleaching . These properties may contribute to the enhanced endothelial cytoprotective effects against free radical-induced injury. [ABSTRACT FROM AUTHOR]

The gene expression programs that define the identity of each cell are controlled by master transcription factors (TFs) that bind cell-type-specific enhancers, as well as signaling factors, which bring extracellular stimuli to these enhancers. Recent studies have revealed that master TFs form phase-separated condensates with the Mediator coactivator at super-enhancers. Here, we present evidence that signaling factors for the WNT, TGF-β, and JAK/STAT pathways use their intrinsically disordered regions (IDRs) to enter and concentrate in Mediator condensates at super-enhancers. We show that the WNT coactivator β-catenin interacts both with components of condensates and DNA-binding factors to selectively occupy super-enhancer-associated genes. We propose that the cell-type specificity of the response to signaling is mediated in part by the IDRs of the signaling factors, which cause these factors to partition into condensates established by the master TFs and Mediator at genes with prominent roles in cell identity. • Signaling factors incorporate into Mediator condensates at super-enhancers • β-Catenin IDRs are required for both phase separation and target gene activation • Both condensate interactions and TF interactions contribute to β-catenin localization Zamudio et al. demonstrate that components of the WNT, TGF-β, and JAK/STAT signaling pathways use their intrinsically disordered regions to condense with Mediator and to target specific genes. These findings provide a model for how context-dependent transcriptional responses can be achieved in cell signaling. [ABSTRACT FROM AUTHOR]

Background: Hypertension (HTN) accounts for one in five deaths of American women. Major societies worldwide aim to make evidence-based recommendations for HTN management. Sex- or gender-based differences exist in epidemiology and management of HTN; in this study, we aimed to assess sex- and gender-based language in major society guidelines. Materials and Methods: We reviewed HTN guidelines from four societies: the American College of Cardiology (ACC), the American College of Emergency Physicians (ACEP), the European Society of Cardiology (ESC), and the Eighth Joint National Committee (JNC8). We quantified the sex- and gender-based medicine (SGBM) content by word count in each guideline as well as identified the gender of guideline authors. Results: Two of the four HTN guidelines (ACC, ESC) included SGBM content. Of these two guidelines, there were variations in the quantity and depth of content coverage. Pregnancy had the highest word count found in both guidelines (422 words in ACC and 1,523 words in ESC), which represented 2.45% and 3.04% of the total words in each guideline, respectively. There was minimal coverage, if any, of any other life periods. The number of women authors did not impact the SGBM content within a given guideline. Conclusions: Current HTN management guidelines do not provide optimal guidance on sex- and gender-based differences. Inclusion of sex, gender identity, hormone therapy, pregnancy and lactation status, menopause, and advanced age in future research will be critical to bridge the current evidence gap. Guideline writing committees should include diverse perspectives, including cisgender and transgender persons from diverse racial and ethnic backgrounds.

In this retrospective cohort study of patients presenting to a national direct-to-consumer medical practice, we found that provider geographic location is a stronger driver of antibiotic prescribing than patient location. Physicians in the Northeast and South are significantly more likely than physicians in the West to prescribe antibiotics for upper respiratory infection and bronchitis.

Objective: To assess the effectiveness of telemedicine video visits in the management of hypertensive patients at home during the first year of the COVID-19 pandemic., Methods: A quantitative analysis was performed of all home video visits coded with a diagnosis of essential hypertension during the first 12 months of the COVID-19 pandemic (March 2020 through February 2021). A total of 10,634 patients with 16,194 hypertension visits were present in our national telemedicine practice database during this time. Among this population, a total of 569 patients who had 1785 hypertension visits met the criteria of having 2 or more blood pressure (BP) readings, with the last BP reading occurring in the report period. We analyzed baseline characteristics and BP trends of these 569 patients during the study period. Voluntarily submitted patient satisfaction ratings, which were systematically requested at the end of each visit, were also analyzed., Results: The mean age of the patients in this study cohort of 569 patients was 43.9 years, and 48.3% (275) were women. More than 62% (355) of the patients had an initial systolic BP (SBP) above 140 mm Hg, and 25.3% (144) had an initial SBP of greater than 160 mm Hg. The average number of visits during the study period was 3.1 visits per patient; an average of 6.4 BP measurements per patient were available. During the study period, 77% (438) of the patients experienced an improvement in either SBP or diastolic BP (DBP), with mean reductions of -9.7 mm Hg and -6.8 mm Hg in SBP and DBP, respectively. A total of 416 patients in the cohort started with a BP above 140/90 mm Hg. For this subset of patients, 55.7% (232) achieved a BP of 140/90 mm Hg or lower by the end of the study period, and the average reductions in SBP and DBP were -17.9 mm Hg and -12.8 mm Hg, respectively, which corresponded to improvements of 11.2% and 12.4%. These improvements did not vary significantly when patients were stratified by age, sex, or geographic region of residence (rural vs urban/suburban). Voluntarily submitted patient surveys indicated a high degree of patient satisfaction, with a mean satisfaction score of 4.94 (5-point scale)., Conclusion: Clinician-patient relationships established in a video-first telemedicine model were broadly effective for addressing suboptimally controlled hypertension. Patient satisfaction with these visits was high., (© 2021 The Authors.)

Background: Sex and gender, two important factors affecting health care, should be routinely taken into consideration in clinical practice. Members of the Sex and Gender Health Collaborative Scholarship Committee reviewed clinical guidelines published by the American College of Cardiology (ACC) from 2008 to 2018 to determine if the number of women authors on the writing committee influenced the presence of sex- and gender-specific content and recommendations in each guideline. Methods: We reviewed 33 ACC clinical guidelines from 2008 to 2018 and determined the number of women authors on the writing committee for each guideline. We then reviewed each guideline to identify specific content on sex and/or gender differences as it pertained to the guideline's subject cardiac condition. Results: The median proportion of women authors among the 33 ACC guidelines was 22.2% (interquartile range 4.4-81.1). Only two guidelines (6%) had writing committees with >50% women authors. Overall, 25 of 33 guidelines (75.8%) contained sex and gender content; however, the depth and detail of the sex and gender content varied widely among guidelines. The proportion of women authors was not associated with the presence of sex- and gender-specific content. Conclusions: Our findings demonstrate continued gender disparities in authorship, and changes should be made to increase the inclusion of women in clinical practice guideline writing committees. We propose selecting a sex and gender champion for guideline writing committees and/or including a specific section on sex- and gender-related content in each guideline to ensure inclusion of sex- and gender-specific recommendations in clinical guidelines.

Background: Antibiotics prescribed for acute respiratory tract infections in the telemedicine setting are often unwarranted., Objective: We hypothesized that education plus individualized feedback, compared with education alone, would significantly reduce antibiotic prescription rates for upper respiratory infections, bronchitis, sinusitis, and pharyngitis in a telemedicine setting., Design: Two-arm, parallel-group randomized controlled trial conducted at a telemedicine practice from January 1, 2018, to November 30, 2018., Participants: Clinicians employed at the practice on or after January 1, 2017 (n = 45)., Interventions: The control group received education (treatment guideline presentation and online course) in April 2018. The intervention group received education plus individualized feedback via an online dashboard with monthly rates of personal and practice-wide antibiotic prescription rates starting May 2018., Main Measures: Antibiotic prescription for any visit with at least one target condition: upper respiratory tract infection, bronchitis, sinusitis, and pharyngitis., Key Results: Baseline antibiotic prescription rates in control and intervention groups across conditions were as follows: upper respiratory infection (URI): 626/3410 (18.4%), 413/2752 (15.0%), bronchitis: 689/1471 (46.8%), 742/1162 (64.0%), sinusitis: 5154/6131 (84.1%), 4250/4876 (87.2%), pharyngitis: 2308/2838 (81.3%), 1593/2126 (74.9%). Antibiotic prescriptions for all conditions decreased in the post-intervention period compared with those in the pre-intervention period, for both control and intervention groups. Reduction of antibiotic prescriptions for URI and bronchitis was greater for the group receiving education plus individualized feedback compared with that for the group receiving education alone (interaction term ratio 0.60, 95% CI 0.47 to 0.77 for URI; and interaction term ratio 0.42, 95% CI 0.32 to 0.55 for bronchitis), but not sinusitis and pharyngitis., Conclusion: Education plus individualized feedback in a telemedicine practice significantly decreased antibiotic prescription rates for upper respiratory tract infections and bronchitis, compared with education alone. Future studies should focus on tailoring antibiotic stewardship programs based on underlying conditions, and the maintenance of early reductions in antibiotic prescription.

Background: The COVID-19 pandemic has led to an increase in the use of and demand for telehealth services., Objective: Here, we describe the utilization of telehealth services provided by Doctor On Demand, Inc., a well-known telehealth company in the United States, before and during the COVID-19 pandemic. We also explore how the number of virtual visits, reasons for visits, and patients served changed over time., Methods: We reported data as a percentage change from the baseline week during 2 distinct time periods: February-June 2019 and February-June 2020 based on 4 categories of visits: respiratory illness, unscheduled behavioral health, scheduled behavioral health, and chronic illness., Results: In 2020, the total visit volume increased considerably from March through April 7, 2020 (59% above the baseline) and then declined through the week of June 2 (15% above the baseline). Visits for respiratory illnesses increased through the week of March 24 (30% above the baseline) and then steadily declined through the week of June 2 (65% below the baseline). Higher relative increases were observed for unscheduled behavioral health and chronic illness visits through April (109% and 131% above the baseline, respectively) before a decline through the week of June 2 (69% and 37% above the baseline, respectively). Increases in visit volume among rural residents were slightly higher than those among urban residents (peak at 64% vs 58% above the baseline, respectively)., Conclusions: Although this telehealth service provider observed a substantial increase in the volume of visits during the COVID-19 pandemic, it is interesting to note that this growth was not fueled by COVID-19 concerns but by visits for behavioral health and chronic illness. Telehealth services may play a role as a "safety valve" for patients who have difficulty accessing care during a public health emergency., (©Lori Uscher-Pines, James Thompson, Prentiss Taylor, Kristin Dean, Tony Yuan, Ian Tong, Ateev Mehrotra. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 15.12.2020.)

In February 2020, CDC issued guidance advising persons and health care providers in areas affected by the coronavirus disease 2019 (COVID-19) pandemic to adopt social distancing practices, specifically recommending that health care facilities and providers offer clinical services through virtual means such as telehealth.* Telehealth is the use of two-way telecommunications technologies to provide clinical health care through a variety of remote methods. † To examine changes in the frequency of use of telehealth services during the early pandemic period, CDC analyzed deidentified encounter (i.e., visit) data from four of the largest U.S. telehealth providers that offer services in all states. § Trends in telehealth encounters during January-March 2020 (surveillance weeks 1-13) were compared with encounters occurring during the same weeks in 2019. During the first quarter of 2020, the number of telehealth visits increased by 50%, compared with the same period in 2019, with a 154% increase in visits noted in surveillance week 13 in 2020, compared with the same period in 2019. During January-March 2020, most encounters were from patients seeking care for conditions other than COVID-19. However, the proportion of COVID-19-related encounters significantly increased (from 5.5% to 16.2%; p<0.05) during the last 3 weeks of March 2020 (surveillance weeks 11-13). This marked shift in practice patterns has implications for immediate response efforts and longer-term population health. Continuing telehealth policy changes and regulatory waivers might provide increased access to acute, chronic, primary, and specialty care during and after the pandemic., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Peter Antall reports that he is President and Chief Medical Officer of Amwell Medical Group and on the advisory board of Chatbot Company; Bridget McCabe reports personal fees from Teladoc Health, Inc., as the Medical Director, Clinical Quality/Clinical Informatics; Ian Tong reports personal fees from Doctor On Demand, Inc, as the Chief Medical Officer; and Cynthia Zelis reports personal fees from MDLIVE, Inc., as the Chief Medical Officer. No other potential conflicts of interest were disclosed.

Objectives: To understand the interpersonal and communication behaviors that are perceived positively by patients in a video encounter and whether patient-centered relationships can be established virtually., Patients and Methods: A qualitative analysis of patient visit feedback was performed to build consensus around exemplary interpersonal and communication practices during a virtual urgent care visit. Voluntarily submitted patient comments associated with a 5-star review after a visit were randomly selected from more than 49,000 comments in an 11-month period, from January 1, 2016, through November 30, 2016. Researchers used a consensus-based, widely used health care communications framework as a sensitizing scaffold to develop a preliminary set of codes., Results: More than 30% of the comments coded were classified as Building Rapport. The next most frequently assigned code was Shares Information/Provides Guidance. Among codable comments, the third most frequently assigned code was Elicits Information. Provided Treatment accounted for only 2% of comments., Conclusion: These results suggest that patients who are satisfied with telemedicine encounters appreciate their relational experiences with the clinician and overall user experience, including access and convenience. Highly satisfied patients who interacted with providers on this platform commented on key aspects of medical communication, particularly skills that demonstrate patient-centered relationship building. This supports the notion that clinician-patient relationships can be established in a video-first model, without a previous in-person encounter, and that positive ratings do not seem to be focused solely on prescription receipt., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

Background Reducing pregnancy risk requires a multidimensional approach to sexual and reproductive health product development. The purpose of this analysis is to identify, compare, and contrast women's pre-use beliefs and attitudes about three different forms of contraceptives: intravaginal rings; spermicide in conjunction with condoms; and oral contraceptive pills - and explore how those attitudes and beliefs, along with actual method-use experience, may affect potential choices in contraceptive method moving forward. The relationship of beliefs and attitudes to their risk-benefit calculations when using these methods was also considered.?, Methods: Women used one or more contraceptive methods, each for 3-6 months. Qualitative data from individual in-depth interviews completed after each 3-month use period were analysed using a summary matrix framework. Data were extracted and summarised into themes. Each woman's experiences were compared among the methods she used; comparisons were also made across participants., Results: The data consist of 33 90-120 min in-depth qualitative interviews from 16 women aged 20-34 years, in which they discussed various elements of their method use experience. One prominent theme was identified: the influence of attitudes and beliefs on the risk-benefit calculus. There were six key elements within the theme: pregnancy prevention; dosing and the potential for user error; side-effects; familiarity; disclosure; and sexual partnerships., Conclusions: Women weighed perceived risks and benefits in their decision-making and, ultimately, their contraception choices. Understanding women's beliefs and attitudes that contribute to a calculation of risk-benefit can inform the development of sexual and reproductive health products.

Objective: To elucidate the effects of the intravaginal ring, oral contraceptive pill (OCP), and spermicide plus condom on women's sexual experiences through an in-depth understanding of the physical characteristics of these contraceptive methods., Methods: We conducted qualitative in-depth interviews with women (aged 18-45 years) who used up to three contraceptive methods (intravaginal ring, OCP, and spermicide plus condom). Women completed in-depth interviews after each 3-month use period. We used a summarized matrix framework and thematic content analysis to explore how each method affected participants' sexual experiences., Results: Sixteen women completed interviews, yielding 33 transcripts. Women reported physical effects on their sexual experiences while using the intravaginal ring and spermicide plus condom. The OCP was often discussed as lacking these physical effects. Discussion themes included product administration (eg, navigating intravaginal ring removal) and physical product awareness (eg, spermicide as a lubricant). From these experiences, women often altered and individualized their use and subsequent opinions of the contraceptive method., Conclusion: The range of contraceptive effects on women's sexual experiences shape their use and opinions of the product, leading to either increased motivation and consistent use or poor adherence and discontinuation. Awareness of these individualized experiences can help providers better understand and guide their patients towards successful contraceptive use.

Objective: Pregnancy and the obesity epidemic impacting women of reproductive age appear to predispose women to obstructive sleep apnea (OSA) in pregnancy. The aim of this study is to examine the association between OSA and adverse maternal outcomes in a national cohort., Methods: The National Perinatal Information Center in the US was used to identify women with a delivery discharge diagnosis of OSA from 2010 to 2014. We used the International Classification of Diseases, ninth Revision to classify OSA diagnosis and maternal outcomes., Measurements: The sample consisted of 1,577,632 gravidas with a rate of OSA of 0.12% (N = 1963). There was a significant association between OSA and preeclampsia (adjusted odds ratio (aOR) 2.22, 95% confidence interval (CI) 1.94-2.54), eclampsia (aOR 2.95, 1.08-8.02), and gestational diabetes (aOR 1.51, 1.34-1.72) after adjusting for a comprehensive list of covariates which includes maternal obesity. OSA status was also associated with a 2.5-3.5-fold increase in risk of severe complications such as cardiomyopathy, congestive heart failure, and hysterectomy. Length of hospital stay was significantly longer (5.1 + 5.6 vs 3.0 + 3.0 days, p < 0.001) and odds of an admission to an intensive care unit higher (aOR 2.74, 2.36-3.18) in women with OSA., Conclusions: Compared to pregnant women without OSA, pregnant women with OSA have a significantly higher risk of pregnancy-specific complications such as gestational hypertensive conditions and gestational diabetes, and rare medical and surgical complications such as cardiomyopathy, pulmonary edema, congestive heart failure, and hysterectomy. OSA diagnosis was also associated with a longer hospital stay and significantly increased odds for admission to the intensive care unit., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Restless legs syndrome (RLS) is a commonly occurring neurologic disorder that affects up to one third of women during pregnancy. RLS has been associated with increased sympathetic tone in the nonpregnant population. We examined whether a RLS surrogate is associated with a higher prevalence of pregnancy and neonatal outcomes., Methods: Data were analyzed from a cross-sectional survey of 1000 women interviewed soon after delivery by using an RLS surrogate question. Women were asked how frequently (0 = none, 1 = rarely [<1 time/week], 2 = sometimes [1-2 times/week], 3 = frequently [3-4 times/week], and 4 = always [5-7 times/week]) they had "experienced jumpy or jerky leg movements" in the last 3 months of pregnancy. Clinical charts were reviewed to obtain relevant demographic and clinical data, including the presence of gestational hypertensive disorders and neonatal outcomes at birth. Subjects who "always" experienced RLS were compared with subjects experiencing symptoms less frequently or not at all with respect to prevalence of gestational hypertensive disorder., Findings: The mean ([SD]) age, prepregnancy body mass index (BMI), and BMI at delivery were 29.0 (6.1) years, 26.1 (6.2) kg/m(2), and 32.0 (6.3) kg/m(2), respectively. The overall prevalence of the RLS surrogate (jumpy or jerky leg movements) was 35.5% with the following distribution on a Likert scale: score 1 = 6.4%; score 2 = 10.2%; score 3 = 8.1%; and score 4 = 10.8%. Chronic hypertension was present in 2.1%, pregnancy-induced hypertension in 9.5%, and preeclampsia in 4.5% of respondents. Subjects who reported "always" having sensations of jumpy or jerky legs were more likely to have gestational hypertensive disorders compared with those who reported less frequent occurrence of the symptoms. Adjusted odds ratios were 3.74 (95% CI, 1.31-10.72; P = 0.014) for chronic hypertension; 1.26 (95% CI, 0.65-2.46; P = 0.487) for pregnancy-induced hypertension; and 2.15 (95% CI, 0.97-4.75; P = 0.060) for preeclampsia. There was a significant association between leg movement score and neonatal birth weight (coefficient, -149.5 g [95% CI, -276.9 to -22.5]; P = 0.005) and gestational age at birth (-0.7 week [95% CI, -1.1 to -0.2]; P = 0.021) that persisted after adjusting for preeclampsia, diabetes, and smoking., Implications: A higher frequency of jumpy or jerky leg symptoms, a proxy for RLS during pregnancy, was associated with a higher likelihood of gestational hypertensive disorders and neonatal outcomes such as gestational age at birth and birth weight. These findings may affect RLS treatment decisions during pregnancy., (Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.)

Ras/Raf/MEK/ERK singal transduction plays an important role in cell proliferation, differentiation, apoptosis, metastasis and metabolism. This investigation focused on this signal pathway and chose farnesyl transferase (FTase) as the main target and Raf-1 kinase as the second target. A lot of compounds were selected to construct the pharmacophore models of farnesyl transferase inhibitors (FTIs) and Raf-1 kinase inhibitors by using computer-aided drug design (CADD). The pharmacophore of FTIs is constituted by a hydrogen bonding acceptor, an aromatic ring, a positive ionizable and two hydrophobic regions; the pharmacophore of Raf-1 kinase is constituted by a hydrogen donor, a hydrogen acceptor, a hydrophobic regions and an aromatic ring. There are some similarities between the two pharmacophores. After analysis of the constructions of these two pharmacophores, some new aminomethylbenzoic acid derivatives with good forecasting activity against both of FTase and Raf-1 kinase were designed with these new pharmacophore models.

Surfactant wastewater is usually difficult to treat due to its toxicity and poor biodegradability. A separate physico-chemical or biochemical treatment method achieves a satisfactory effect with difficulty. In this study, treatment of the wastewater collected from a daily chemical plant by the combination processes of Fe/C internal electrolysis and biological contact oxidation was investigated. For the internal electrolysis process, the optimal conditions were: pH = 4-5, Fe/C = (10-15):1, air-water ratio = (10-20):1 and hydraulic retention time (HRT)= 2 h. For the biological contact oxidation process, the optimal conditions were: HRT = 12 h, DO = 4.0-5.0 mg/L. Treated by the above combined processes, the effluent could meet the I-grade criteria specified in Integrated Wastewater Discharge Standard of China (GB 8978-1996). The results provide valuable information for full-scale linear alkylbenzene sulfonate wastewater treatment.

Background: Physicians require communications training to improve effective and compassionate care. Clinicians discuss challenging communication issues in existing hospital "Schwartz Rounds.", Aims: To improve communication skills, the Warren Alpert Medical School of Brown University designed "Schwartz Communication Sessions" for the mandatory 2-year pre-clerkship Doctoring course. Alongside learning interviewing, physical examination, and professionalism skills, the new Schwartz curriculum provides medical students with the rationale and proficiency for effective communication with patients, families and the healthcare team., Methods: First-year students experience a graduated curriculum of three sessions on themes such as empathy and professionalism using innovative methods. Sessions highlight cases and videos depicting successful and ineffective interactions, large and small group discussions, role play and skills practice, guest patient presentations, and multi-disciplinary panels. The second-year students' session focuses on communications with challenging patients., Results: Students and faculty rate the sessions highly on effectiveness of enhancing communication skills, gaining perspective in healthcare communication, and appreciating the complexities of healthcare situations. Expansion of the program using case-based sessions for clerkship students is planned for a continuous and graduated experience., Conclusions: Integrating a pre-clerkship communications curriculum may help improve future physicians' interactions with patients and families. Implications of this curriculum for medical education are discussed.

Objective: To investigate the feasibility of one-stage phallic reconstruction with the extended pudendal-thigh flap (EPTF) to achieve a higher survival rate, shorter surgical cycle, and more experimental evidence for the clinical application of the technique., Methods: We equally randomized 36 healthy adult New Zealand rabbits to an experimental and a control group to receive one-stage phallic reconstruction, the former with EPTF (pudendal-thigh flap + thigh cutaneous branches of the superficial external pudendal artery, PTF + TCB), the urethra reconstructed with the TCB flap, and the latter with bilateral pudendal-thigh flaps., Results: The survival rate of the reconstructed phallus was 83.33% (15/18) and the urine leakage was 55.56% (10/18) in the experimental group, as compared with 38.89% (7/18) and 72.22% (13/18) in the controls., Conclusion: One-stage phallic reconstruction with EPTF, with its higher survival rate and shorter surgical cycle, is a desirable substitute for phallic reconstruction with bilateral pudendal-thigh flaps.

The high water content of municipal solid waste (MSW) will reduce the efficiency of mechanical sorting, consequently unfavorable for beneficial utilization. In this study, a combined hydrolytic-aerobic biodrying technology was introduced to remove water from MSW. The total water removals were proved to depend on the ventilation frequency and the temporal span in the hydrolytic stage. The ventilation frequency of 6 times/d was preferable in the hydrolytic stage. The hydrolytic span should not be prolonged more than 4 d. At this optimal scenario, the final water content was 50.5% reduced from the initial water content of 72.0%, presenting a high water removal efficiency up to 78.5%. A positive correlation was observed between the organics losses and the water losses in both hydrolytic and aerobic stages (R = 0.944, p < 0.01). The evolutions of extracellular enzyme activities were shown to be consistent with the organics losses.

Purpose: To explore the best approach to identify and adjust for confounders in epidemiologic practice., Methods: In the Port Pirie cohort study, the selection of covariates was based on both a priori and an empirical consideration. In an assessment of the relationship between exposure to environmental lead and child development, change-in-estimate (CE) and significance testing (ST) criteria were compared in identifying potential confounders. The Pearson correlation coefficients were used to evaluate the potential for collinearity between pairs of major quantitative covariates. In multivariate analyses, the effects of confounding factors were assessed with multiple linear regression models., Results: The nature and number of covariates selected varied with different confounder selection criteria and different cutoffs. Four covariates (i.e., quality of home environment, socioeconomic status (SES), maternal intelligence, and parental smoking behaviour) met the conventional CE criterion (> or =10%), whereas 14 variables met the ST criterion (p < or = 0.25). However, the magnitude of the relationship between blood lead concentration and children's IQ differed slightly after adjustment for confounding, using either the CE (partial regression coefficient: -4.4; 95% confidence interval (CI): -0.5 to -8.3) or ST criterion (-4.3; 95% CI: -0.2 to -8.4)., Conclusions: Identification and selection of confounding factors need to be viewed cautiously in epidemiologic studies. Either the CE (e.g., > or = 10%) or ST (e.g., p < or = 0.25) criterion may be implemented in identification of a potential confounder if a study sample is sufficiently large, and both the methods are subject to arbitrariness of selecting a cut-off point. In this study, the CE criterion (i.e., > or = 10%) appears to be more stringent than the ST method (i.e., p < or = 0.25) in the identification of confounders. However, the ST rule cannot be used to determine the trueness of confounding because it cannot reflect the causal relationship between the confounder and outcome. This study shows the complexities one can expect to encounter in the identification of and adjustment for confounders.

Intercellular adhesion molecule-2 (ICAM-2), a cell surface glycoprotein, is a second counter-receptor for lymphocyte function-associated Ag-1 (LFA-1). We report here the isolation and characterization of the cDNA and the gene that encode murine ICAM-2 (Accession numbers X65493 and X65490, respectively). The deduced sequence of the cDNA has 60% amino acid identity with its human counterpart and has the same expression pattern in cells and tissues. Furthermore, COS cells transfected with mouse ICAM-2 complementary and genomic DNA bind to purified human LFA-1, demonstrating the conservation of the function of ICAM-2 as a ligand for LFA-1 and conservation across species of sequences that are critical for binding to human LFA-1. COS cells transfected with the ICAM-2 cDNA do not react with mAb PA3, previously suggested to define ICAM-2 in the mouse. The mouse ICAM-2 gene was isolated and its structural organization determined. The gene is present in a single copy in the mouse genome and contains four exons spanning about 5.0 kb of DNA. The exon/intron architecture correlates to the structural domains of the protein and resembles that of other Ig superfamily members. The gene for ICAM-2, which is constitutively expressed in endothelial cells, has several conserved sequence motifs in its promoter region, including a direct repeat, and lacks transcription factor-binding sites present in the ICAM-1 gene, which is inducible in endothelial cells.

The dha regulon in Klebsiella pneumoniae enables the organism to grow anaerobically on glycerol and produce 1,3-propanediol (1,3-PD). Escherichia coli, which does not have a dha system, is unable to grow anaerobically on glycerol without an exogenous electron acceptor and does not produce 1,3-PD. A genomic library of K. pneumoniae ATCC 25955 constructed in E. coli AG1 was enriched for the ability to grow anaerobically on glycerol and dihydroxyacetone and was screened for the production of 1,3-PD. The cosmid pTC1 (42.5 kb total with an 18.2-kb major insert) was isolated from a 1,3-PD-producing strain of E. coli and found to possess enzymatic activities associated with four genes of the dha regulon: glycerol dehydratase (dhaB), 1,3-PD oxidoreductase (dhaT), glycerol dehydrogenase (dhaD), and dihydroxyacetone kinase (dhaK). All four activities were inducible by the presence of glycerol. When E. coli AG1/pTC1 was grown on complex medium plus glycerol, the yield of 1,3-PD from glycerol was 0.46 mol/mol. The major fermentation by-products were formate, acetate, and D-lactate. 1,3-PD is an intermediate in organic synthesis and polymer production. The 1,3-PD fermentation provides a useful model system for studying the interaction of a biochemical pathway in a foreign host and for developing strategies for metabolic pathway engineering.

Our study of 20 patients correlates the clinical picture of each patient with the pathology of synovial tissue obtained at the time of revision arthroplasty. While 12 patients had rheumatoid arthritis and 8 had osteoarthritis, the histopathology was identical. Additionally, while 15 of the 20 had an etiology for the revision, 5 patients were revised for pain alone with no explanation other than the synovitis. The characteristic histologic findings included lining cell hyperplasia, vascular congestion, giant cells, brightly birefringent high density polyethylene chards and cysts that represented ghosts of methyl methacrylate debris.