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Objective: This study aimed to describe baseline characteristics of a cohort of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and determine if these correlate with disease severity and perinatal outcomes., Study Design: This was a retrospective cohort trial conducted at the University of Texas Medical Branch Galveston, Texas. All pregnant women presented to our medical center, who were screened and tested positive for SARS-CoV-2 virus, were included. We stratified our study population in three groups: asymptomatic, symptomatic not requiring oxygen therapy, and patients requiring oxygen support to maintain oxygen saturation >94%. Relevant population characteristics, laboratory data, and maternal and neonatal outcomes were abstracted. A p -value <0.05 was considered statistically significant., Results: Between March and July 2020, 91 women tested positive for SARS-CoV-2 upon admission to our labor and delivery unit. Among these, 61.5% were asymptomatic, 34.1% were symptomatic, and 4.4% required oxygen support. Our population was mainly Hispanic (80.2%), multiparous (76.9%), obese (70.3%), and with a median age of 27 years. Median gestational age at symptom onset or diagnosis was 36 weeks. Significant differences were found between gestational age and disease severity. Maternal characteristics including age, body mass index (BMI), and presence of comorbid conditions did not appear to influence severity of SARS-CoV-2 infection. Significant laboratory findings associated with increasing disease severity included decreasing hemoglobin and white blood cell count, lymphopenia, and increasing levels of inflammatory markers including CRP, ferritin, and procalcitonin. Maternal and neonatal outcomes did not differ among groups. No SARS-CoV-2 was detected by polymerase chain reaction testing in neonates of mothers with COVID-19., Conclusion: Pregnant patients with COVID-19 infection are predominantly asymptomatic. Patients appear to be at increased risk for more severe infection requiring oxygen support later in pregnancy., Key Points: · The majority of pregnant patients with COVID-19 are asymptomatic and <1 in 20 require oxygen support.. · Women in the later stages of pregnancy may be at increased risk for severe infection.. · Anemia, leukopenia, CRP, ferritin, and procalcitonin are associated with increasing severity.., Competing Interests: None declared., (Thieme. All rights reserved.)

Hydroxynorketamines (HNKs) are formed in vivo after ( R , S )-ketamine (ketamine) administration. The 12 HNK stereoisomers are distinguished by the position of cyclohexyl ring hydroxylation (at the 4, 5, or 6 position) and their unique stereochemistry at two stereocenters. Although HNKs were initially classified as inactive metabolites because of their lack of anesthetic effects, more recent studies have begun to reveal their biologic activities. In particular, ( 2R , 6R )- and ( 2S 6 )-HNK exert antidepressant-relevant behavioral and physiologic effects in preclinical models, which led to a rapid increase in studies seeking to clarify the mechanisms by which HNKs exert their pharmacological effects. To date, the majority of HNK research has focused on the actions of ( 2R , 6R )-HNK because of its robust behavioral actions in tests of antidepressant effectiveness and its limited adverse effects. This review describes HNK pharmacokinetics and pharmacodynamics, as well as the putative cellular, molecular, and synaptic mechanisms thought to underlie their behavioral effects, both following their metabolism from ketamine and after direct administration in preclinical studies. Converging preclinical evidence indicates that HNKs modulate glutamatergic neurotransmission and downstream signaling pathways in several brain regions, including the hippocampus and prefrontal cortex. Effects on other neurotransmitter systems, as well as possible effects on neurotrophic and inflammatory processes, and energy metabolism, are also discussed. Additionally, the behavioral effects of HNKs and possible therapeutic applications are described, including the treatment of unipolar and bipolar depression, post-traumatic stress disorder, chronic pain, neuroinflammation, and other anti-inflammatory and analgesic uses. SIGNIFICANCE STATEMENT: Preclinical studies indicate that hydroxynorketamines (HNKs) exert antidepressant-relevant behavioral actions and may also have analgesic, anti-inflammatory, and other physiological effects that are relevant for the treatment of a variety of human diseases. This review details the pharmacokinetics and pharmacodynamics of the HNKs, as well as their behavioral actions, putative mechanisms of action, and potential therapeutic applications., Competing Interests: The following authors declare competing financial interests: R.M. and C.A.Z. are listed as co-inventors on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydro- and hydroxylated metabolites of (R,S)-ketamine in the treatment of depression and neuropathic pain. P.Z., R.M., P.M., C.T., C.A.Z., and T.G. are listed as co-inventors on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. R.M., P.M., C.A.Z., and C.T. have assigned their patent rights to the United States government but will share a percentage of any royalties that may be received by the government. P.Z. and T.G. have assigned their patent rights to the University of Maryland Baltimore but will share a percentage of any royalties that may be received by the University of Maryland Baltimore. T.D.G. has received research funding from Allergan and Roche Pharmaceuticals and has served as a consultant for FSV7, LLC, during the preceding 3 years. All other authors declare no competing interests., (U.S. Government work not protected by U.S. copyright.)

Background: Although intravenous (IV) bisphosphonates are first-line medications for the management of hypercalcemia, studies examining their use in patients with preexisting renal dysfunction are limited., Objective: The objective of this study is to describe the safety and efficacy of pamidronate and zoledronic acid in the treatment of hypercalcemia in patients with baseline renal dysfunction., Methods: A retrospective analysis was conducted of IV pamidronate and zoledronic acid in adult patients with hypercalcemia and creatinine clearance (CrCl) <60 mL/min. The primary endpoint was incidence of all-grade serum creatinine (SCr) elevations. Secondary endpoints included refractory hypercalcemia, hypocalcemia, osteonecrosis of the jaw (ONJ), corrected serum calcium (CSC) decrease ≥1.0 mg/dL by day 7 of bisphosphonate administration, and normalization of CSC ≤10.5 mg/dL by days 10 and 30., Results: A total of 113 patients were included (n = 55 pamidronate, n = 58 zoledronic acid). The primary endpoint of all-grade SCr elevation occurred in 28 (24.8%) patients. Grades 3/4 SCr elevations occurred in 10.9% of patients treated with pamidronate and 1.7% of patients receiving zoledronic acid. Approximately 16% and 14% of patients developed grades 1 and 2 hypocalcemia, respectively, and there were no cases of ONJ. Overall, 64.6% of patients achieved normalization of CSC by day 10, and there were no statistical differences between bisphosphonate type and renal function., Conclusions and Relevance: The analysis suggests an association between IV bisphosphonates and increased rates of SCr elevations among patients with preexisting renal dysfunction. Future prospective studies are necessary to elucidate these findings.

The amount and distribution of water in nominally anhydrous minerals (NAMs) are usually determined by Fourier-transform infrared spectroscopy. This method is limited by the spot size of the beam to the study of samples with dimensions greater than a few micrometers. Here, we demonstrate the potential of using photoinduced force microscopy for the measurement of water in NAMs with samples sizes down to the nanometer scale with a study of water concentration across grain boundaries in forsterite. This development will enable the study of water speciation and diffusion in small-grained rock matrixes and allow a determination of the influence of nanoscale heterogeneity on the incorporation of water to NAMs.

The neurodevelopmental defects associated with ZIKV infections early in pregnancy are well documented, however the potential defects and long-term consequences associated with milder infections in late pregnancy and perinatal period are less well understood. To model these, we challenged 1 day old (P1) immunocompetent C57BL/6 mice with ZIKV. The animals developed a transient neurological syndrome including unsteady gait, kinetic tremors, severe ataxia and seizures 10-15 days post-infection (dpi) but symptoms subsided after a week, and most animals survived. Despite apparent recovery, MRI of convalescent mice show reduced cerebellar volume that correlates with altered coordination and motor function as well as hyperactivity and impulsivity. Persistent mRNA levels of pro-inflammatory genes including Cd80, Il-1α, and Ifn-γ together with Cd3, Cd8 and perforin (PrfA), suggested persistence of low-grade inflammation. Surprisingly, the brain parenchyma of convalescent mice harbor multiple small discrete foci with viral antigen, active apoptotic processes in neurons, and cellular infiltrates, surrounded by activated astrocytes and microglia as late as 1-year post-infection. Detection of negative-sense strand viral RNA and isolation of infectious virus derived from these convalescent mice by blinded passage in Vero cells confirmed long-term persistence of replicating ZIKV in CNS of convalescent mice. Although the infection appears to persist in defined reservoirs within CNS, the resulting inflammation could increase the risk of neurodegenerative disorders. This raises concern regarding possible long-term effects in asymptomatic children exposed to the virus and suggests that long-term neurological and behavioral monitoring as well as anti-viral treatment to clear virus from the CNS may be useful in patients exposed to ZIKV at an early age., Competing Interests: No authors have competing interests.

Objective: To evaluate the effectiveness and safety of an intrauterine vacuum-induced hemorrhage-control device for postpartum hemorrhage treatment., Methods: A multicenter, prospective, single-arm treatment study of a novel intrauterine device that uses low-level vacuum to induce uterine myometrial contraction to achieve control of abnormal postpartum uterine bleeding and postpartum hemorrhage was undertaken at 12 centers in the United States. The primary effectiveness endpoint was the proportion of participants in whom use of the intrauterine vacuum-induced hemorrhage-control device controlled abnormal bleeding without requiring escalating interventions. The primary safety endpoint was the incidence, severity, and seriousness of device-related adverse events. Secondary outcomes included time to bleeding control, rate of transfusion, and device usability scored by each investigator using the device., Results: Of 107 participants enrolled with primary postpartum hemorrhage or abnormal postpartum uterine bleeding, 106 received any study treatment with the device connected to vacuum, and successful treatment was observed in 94% (100/106, 95% CI 88-98%) of these participants. In those 100 participants, definitive control of abnormal bleeding was reported in a median of 3 minutes (interquartile range 2.0-5.0) after connection to vacuum. Eight adverse events deemed possibly related to the device or procedure were reported, all of which were outlined as risks in the study and all of which resolved with treatment without serious clinical sequelae. Transfusion of 1-3 units of red blood cells was required in 35 participants, and five participants required 4 or more units of red blood cells. The majority of investigators reported the intrauterine vacuum-induced hemorrhage-control device as easy to use (98%) and would recommend it (97%)., Conclusion: Intrauterine vacuum-induced hemorrhage control may provide a new rapid and effective treatment option for abnormal postpartum uterine bleeding or postpartum hemorrhage, with the potential to prevent severe maternal morbidity and mortality., Funding Source: Alydia Health, Inc., Clinical Trial Registration: ClinicalTrials.gov, NCT02883673.

Unexplainable concrete softening below the water line has been observed by Sydney Water in their gravity sewer network, some of which is subjected to corrosion control methods using chemical ferrous chloride (FeCl 2 ) dosing of the wastewater. We applied a combination of physical and chemical tools to determine the properties of the top 20 mm of concrete cores recovered from sewer pipes. These techniques consist of neutron tomographic imaging, scanning electron microscopy, hardness mapping, and pH profiling. Concrete cores were collected from roof (crown), tidal (wall) and below flow regions of gravity sewer pipes of Sydney Water's wastewater system from locations that received no treatment as well as locations dosed with FeCl 2 . All samples showed a degree of softening of the surface exposed to the sewerage with an associated depletion in calcium concentration and reduced pH in the same regions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Prathapanius Viswajyothi & Clark, gen. nov. , is described and illustrated. The genus is placed in the chrysomelid section Diabroticites Chapuis (subtribe Diabroticina Chapuis, tribe Luperini Chapuis, subfamily Galerucinae Latreille). It is monobasic, containing Prathapanius fortis Viswajyothi & Clark, sp. nov. , from Ecuador. The new genus is briefly compared with Acalymma Barber, Isotes Weise, and Zischkaita Bechyné., (Keezhpattillam Viswajyothi, Shawn M. Clark.)

Background: The North Carolina Cancer Hospital at the University of North Carolina Medical Center serves patients with a variety of malignant conditions and discharges more than 130 patients each month. Processes to improve transitions of care prompted implementation of a first-cycle, pharmacist-led chemotherapy consultation service on the inpatient oncology units. This process provides education to improve patient engagement and activation. High patient activation has been associated with better patient outcomes; poor patient activation has been associated with increased health care costs., Objective: To determine the effect of pharmacist-led comprehensive chemotherapy consultation services on adherence to outpatient follow-up appointments within 30 days of discharge., Methods: This was a single-center, retrospective chart review. This study consisted of 2 groups: adult patients who received comprehensive consultation services between April 2017 and September 2017 and a 2:1 historical group of adult control patients randomly selected from a list of patients who received their first cycle of chemotherapy during a hospital admission between April 2014 and April 2017. The primary endpoint was the effect of comprehensive consultation services on adherence to outpatient follow-up appointments within 1 month after discharge., Results: Ninety-six patients were included in this study. The percentage of appointments attended was 98.0% for the intervention group and 92.3% for the control group ( P = 0.0018)., Conclusions: This study demonstrates that pharmacy consultation in the inpatient oncology setting is associated with improved adherence to outpatient appointments within 30 days of discharge. This represents the first published data on pharmacist interventions resulting in improved outpatient appointment adherence., Disclosures: Funding for this study was contributed by the Hematology/Oncology Pharmacy Association (HOPA). This publication was also supported by Grant Number UL1TR002489 from the National Center for Advancing Translational Sciences at the National Institutes of Health. Auten reports fees from PTCE and ASHP/ACCP, unrelated to this study. Clark reports consulting fees from Ellion Benson Research, unrelated to this study. The other authors do not have any conflicts of interest to report. This study was presented as a trainee poster on April 5, 2019, at the HOPA Ahead 15th Annual Conference in Fort Worth, TX.

The atomic structure of a germanium doped phosphorous selenide glass of composition Ge 2.8 P 57.7 Se 39.5 is determined as a function of pressure from ambient to 24 GPa using Monte-Carlo simulations constrained by high energy x-ray scattering data. The ambient pressure structure consists primarily of P 4 Se 3 molecules and planar edge shared phosphorus rings, reminiscent of those found in red phosphorous as well as a small fraction of locally clustered corner-sharing GeSe 4 tetrahedra. This low-density amorphous phase transforms into a high-density amorphous phase at ~6.3 GPa. The high-pressure phase is characterized by an extended network structure. The polyamorphic transformation between these two phases involves opening of the P 3 ring at the base of the P 4 Se 3 molecules and subsequent reaction with red phosphorus type moieties to produce a cross linked structure. The compression mechanism of the low-density phase involves increased molecular packing, whereas that of the high pressure phase involves an increase in the nearest-neighbor coordination number while the bond angle distributions broaden and shift to smaller angles. The entropy and volume changes associated with this polyamorphic transformation are positive and negative, respectively, and consequently the corresponding Clapeyron slope for this transition would be negative. This result has far reaching implications in our current understanding of the thermodynamics of polyamorphic transitions in glasses and glass-forming liquids.

Study Objective: To determine whether thiamine prophylaxis decreases the incidence of ifosfamide-induced encephalopathy in patients receiving ifosfamide for the treatment of lymphoma., Design: Retrospective, multi-center, cohort study., Patients: A total of 73 patients who received 187 total cycles of ifosfamide, carboplatin, and etoposide chemotherapy for the treatment of lymphoma were included in this study. Forty-four of these patients (114 cycles) were included in the no-thiamine group and 29 (65 cycles) in the thiamine group., Measurements and Main Results: The incidence of ifosfamide-induced encephalopathy was measured using the Common Terminology Criteria for Adverse Events and documentation in the patient chart. Regarding the primary endpoint of ifosfamide-induced encephalopathy, eight patients (18.2%) in the no-thiamine group and three patients (10.3%) in the thiamine group experienced an event ( p  = 0.5087). No patient experienced more than one neurotoxic event., Conclusion: There was no significant difference found in the incidence of ifosfamide-induced encephalopathy with the addition of thiamine prophylaxis in patients receiving ifosfamide, carboplatin, and etoposide-based chemotherapy regimens for lymphoma. Larger, prospective studies assessing the use of thiamine prophylaxis in this patient population are warranted to better assess its impact on the incidence of ifosfamide-induced encephalopathy.

Objective: To evaluate the effects of four different surgical interventions for stress urinary incontinence (SUI) on 2-year postoperative sexual function., Methods: This is a combined secondary analysis of SISTEr (Stress Incontinence Surgical Treatment Efficacy Trial) and TOMUS (Trial of Mid-Urethral Slings). Women in the original trials were randomized to receive surgical treatment for SUI with an autologous fascial sling or Burch colposuspension (SISTEr), or a retropubic or transobturator midurethral sling (TOMUS). Sexual function (assessed by the short version of the PISQ-12 [Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire]) was compared between groups at baseline, 12 and 24 months. Secondarily, the effects of subjective and objective surgical cure rates and the effect of concomitant surgical procedures on 24-month sexual function was explored., Results: Nine hundred twenty-four women were included in this study: 249 (26.9%) had an autologous fascial sling, 239 (25.9%) underwent Burch colposuspension, 216 (23.3%) had a retropubic midurethral sling placed, and 220 (23.8%) had transobturator midurethral sling placed. Baseline characteristics (including PISQ-12 scores) were similar between the four treatment arms, with notable exceptions including race-ethnicity, prolapse stage, concomitant surgery, and number of vaginal deliveries. After adjustment for differences between the groups, there was a clinically important improvement in PISQ-12 scores over the 24-month postoperative period for all treatment groups, with no significant differences attributed to the type of anti-incontinence procedure (baseline PISQ-12: 32.6, 33.1, 31.9, 31.4; 24-month PISQ-12: 37.7, 37.8, 36.9, 37.1, P<.01). There was no significant difference in mean PISQ-12 scores between 12 months and 24 months (12-month PISQ-12: 37.7, 37.8, 36.9, 37.1; 24 months as above, P=.97). Multivariable analysis showed independent associations between objective and subjective cure rates as well as concomitant procedures with a 24-month PISQ-12 score., Conclusion: Women undergoing anti-incontinence surgery show overall improvement in sexual function from baseline to 24 months postoperatively, without significant differences based on surgical procedure performed. The majority of this improvement occurs in the first 12 months and is maintained over 24 months.

Objectives: To determine if there is a difference in rates of surgical complications among patients who have reperitonealization of mesh versus no reperitonealization at time of sacrocolpopexy., Methods: This was a retrospective cohort study of all patients who underwent sacrocolpopexy at an academic medical center between 2008 and 2017. The medical record was reviewed for the operative method of sacrocolpopexy, concomitant surgeries, intraoperative or postoperative complications, and readmissions. Groups were compared on whether mesh was reperitonealized under pelvic peritoneum or not., Results: A total of 209 patients underwent sacrocolpopexy, with mesh reperitonealization performed in 115 (55%). Demographics were similar in both groups, except race/ethnicity and stage of prolapse. The majority (190 [91%]) of surgeries included concomitant procedures. A total of 18 intraoperative or postoperative complications (8.6%) were recorded. Relative risk of complication with mesh reperitonealization is 0.81 (95% confidence interval, 0.1-1.70). Complications for subjects without mesh reperitonealization included 4 cystostomies, 1 urethrotomy, 3 postoperative ileuses, and 1 small bowel obstruction. Among subjects with mesh reperitonealization, complications included 5 cystotomies, 2 proctotomies, 1 ureteral obstruction, and 1 small bowel obstruction. Rates of hospital readmission among both groups were not significantly different, with 3.2% of subjects without mesh reperitonealization versus 3.5% of mesh reperitonealization patients (P = 0.91) (relative risk, 1.09; 95% confidence interval, 0.38-2.56)., Conclusions: There is no significant difference in rates of complications or readmissions among patients with and without mesh reperitonealization at time of sacrocolpopexy. The only intraoperative complication solely attributed to mesh closure was a case with ureteral obstruction at time of reperitonealization.

Evidence suggests that substantial testosterone therapy is occurring without checking levels of testosterone, presumably based on the presence of symptoms alone. We sought to explore the relationship between total testosterone level and non-specific symptoms, metabolic abnormalities, and sexual dysfunction associated with hypogonadism. This cross-sectional study included 2994 generally healthy men aged 50-79 years examined at a preventive medicine clinic in Dallas, TX from January 2012 to March 2016. Symptoms of hypogonadism were assessed. Screening morning total testosterone levels were measured and categorized into low (<250 ng/dL), low normal (250-399 ng/dL), and normal (≥400 ng/dL). Multiple logistic regression models were used to test the associations between total testosterone and signs and symptoms of hypogonadism. When considering symptoms and signs of hypogonadism, only decreased libido (OR 1.31, 95% CI 1.00 to 1.70), fasting glucose ≥100 mg/dL (OR 1.47, CI 1.15 to 1.88), and hemoglobin A1c over 6% (OR 1.47, 95% CI 1.06 to 2.03) were associated with increased odds of low testosterone after adjustment for age, body mass index, and cardiorespiratory fitness. Testosterone levels were not associated with fatigue, depression, or erectile dysfunction in our study (p>0.6). In this preventive medicine cohort, symptoms commonly attributed to testosterone deficiency were not associated with low total testosterone levels., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Individuals who attempt to lose weight may struggle because they lack skills to address problematic eating behaviors. There are multiple programs that have taught patients some of these behavioral strategies; however, it is not clear which strategies patients find to be the most useful. The purpose of this study was to examine preliminary outcomes after completion of a six-week integrative group for weight management. Retrospective chart reviews were conducted of 51 patients who completed an integrative, psychological weight management group. Patients were mailed surveys 1-2 years after completion of the group assessing for current problematic eating behaviors (i.e. emotional eating and food addiction), satisfaction with treatment, and skills they continue to use. The majority of patients lost weight, were satisfied with the group, found the group to be helpful, and felt confident they could maintain behavior changes. The strategies patients most commonly continued to use post-group included mindful eating, keeping a food diary, carrying out an exercise plan, regular weigh-ins, and planning for social eating. The number of food addiction symptoms decreased from pre- to post-group. An integrative psychological weight management group may provide patients with skills and confidence to assist with managing problematic eating behaviors and weight loss.

Introduction: Addictive eating, a highly debated problematic eating behavior, may contribute to obesity and impede the success of individuals seeking bariatric surgery. The original Yale Food Addiction Scale (YFAS) was validated for use among patients who underwent bariatric surgery; however, the YFAS was revised to reflect changes in substance use criteria in the DSM-5. The purpose of this study was to validate the use of the revised measure, the YFAS 2.0, among patients pursuing bariatric surgery., Methods: A retrospective chart review was conducted of 314 patients who underwent pre-surgical psychological evaluation for bariatric surgery. Information gathered included symptoms of addictive eating (YFAS 2.0), emotional eating (Emotional Eating Scale; EES), and a history of substance use and binge eating., Results: In this sample, 27.3% met criteria for "food addiction" according to the YFAS 2.0. Of those, more than half met criteria for severe food addiction. The YFAS 2.0 was related to all factors of the EES: anger/frustration (p < .001); anxiety (p < .001); and depression (p < .001). There was no relationship between the YFAS 2.0 and a history of substance use. The YFAS 2.0 accounted for significant variance in history of binge eating after controlling for emotional eating (p < .001; Exp(B) = 1.30)., Conclusions: Results were similar to a prior validation of the YFAS among a bariatric population, and the updated YFAS 2.0 may be useful in assessing addictive eating among bariatric surgery candidates to further explore the concept of "food addiction."

The Principle-Based Integrative Therapy (PBIT) framework harnesses the principles of change underlying each theoretical model within integrative couple therapy treatments. PBIT has commonalities with other integrative approaches, and additional advantages stemming from its four tenets that guide therapists in combining strengths across models and overcoming each of their deficiencies. Tenet 1 advises that each model adds a core principle or mechanism of action that other models do not automatically address. Tenet 2 focuses on how techniques of one model may actualize the principles of other models. Tenet 3 ensures complementarity and a lack of conflict across principles. A case study and common case considerations are presented to illustrate how Tenets 1-3 can work in integrating Cognitive-Behavioral, Multicultural, and Emotionally Focused Therapy models in working with a couple. Finally, Tenet 4 advocates for the use of models and empirically supported principles that also have received empirical support with diverse populations. Prerequisites and training implications for PBIT, and future clinical and research directions to further the utility of PBIT are discussed., (© 2019 Family Process Institute.)

Hyperleukocytosis occurs in 15-20% of all newly diagnosed acute myeloid leukemia patients and requires emergent treatment with leukapheresis or hydroxyurea when accompanied by signs or symptoms of leukostasis. Currently, there is no standardized hydroxyurea dosing strategy, although usual dosing ranges from 50 to 150 mg/kg/day, and prescribing patterns vary significantly among oncologists and institutions. In addition to other hematologic and dermatologic toxicities, the use of hydroxyurea may be associated with significant mucositis and mucositis-related pain. The purpose of this study was to compare mucositis-related pain between two different hydroxyurea dosing strategies in patients who received hydroxyurea for cytoreduction during induction. A retrospective chart review of adult patients with acute myeloid leukemia treated with chemotherapy at UNC Medical Center from April 2014 to April 2016 who received at least one dose of hydroxyurea for cytoreduction was conducted. This study compared the safety and toxicity profiles of hydroxyurea in patients who received high-dose hydroxyurea (≥75 mg/kg/day) versus low-dose hydroxyurea (<75 mg/kg/day). Safety and toxicity were evaluated based on indicators of mucositis and cumulative intravenous narcotic requirements following induction chemotherapy. Data collection included baseline demographics, mucositis risk factors, baseline laboratory values, hydroxyurea dosing, mucositis indicators, and pain indicators. A total of 55 patients were included in the study, 21 patients (38.2%) received the high-dose hydroxyurea dosing strategy. The high-dose hydroxyurea dosing strategy had a significantly higher white blood cell count at diagnosis, increased duration of hydroxyurea, and received a higher cumulative dose of hydroxyurea. Additionally, the high-dose hydroxyurea dosing strategy patients were associated with significantly more grade 3 or 4 mucositis requiring a formulation change (0% versus 28.6%, p = 0.002) and significantly higher cumulative intravenous narcotic requirements during induction (p = 0.019). No significant differences in baseline demographics or mucositis risk factors between dosing strategies were identified. The high-dose hydroxyurea dosing strategy patients had a significant increase in cumulative intravenous narcotic requirements and formulation changes, both common interventions made for the treatment of mucositis. Additional studies are needed to further elucidate the safety and toxicity profiles of hydroxyurea dosing strategies and to explore the correlation between total cumulative hydroxyurea dose and total cumulative narcotic requirements.

Introduction: Although behavioral health treatment can improve distress and pain functioning for patients with chronic pain, few who are referred by their primary care physician will see a behavioral health specialist. Given the benefits of integrating behavioral health into primary care, this may be an avenue for delivering a psychological intervention for chronic pain. The purpose of this study was to optimize a psychological intervention for patients with chronic pain to be delivered in primary care, utilizing the perspectives of providers and patients., Method: Psychologists (n = 9), primary care providers (n = 9), and patients with chronic pain (n = 9) participated in separate focus groups. Participants reviewed the proposed 4-session intervention, provided feedback prompted by a set of open-ended questions, and completed a survey., Results: Statements from focus groups were transcribed and coded into 2 thematic categories: (a) content of the intervention and (b) logistics and design. Participants believed that offering a brief, behavioral intervention for chronic pain in a primary care clinic was feasible and useful. All providers (100%) agreed or strongly agreed that they would refer a patient to this intervention, and 100% of patients agreed or strongly agreed that they would participate., Discussion: Feedback solicited from the focus groups led to alterations to the treatment manual, such as adding a fifth session, using different psychological strategies, and logistical changes in delivery (i.e., meeting biweekly and intervisit contacts). The modified version of this intervention will be evaluated with a pilot randomized controlled clinical trial. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background: Healthcare systems and policy makers worldwide are demonstrating interest in shared decision making, which requires patient activation. Patient activation can be measured using a validated tool called the patient activation measure-10. First cycle comprehensive chemotherapy consultation services (3CS) is provided by an oncology pharmacy team member during a patient encounter at the beginning of the patient's treatment for cancer., Methods: This was a single center, prospective, non-randomized, observational clinical study in patients with cancer who required a new chemotherapy plan. A baseline patient activation measure-10 survey was administered and a pharmacy team member met with the patient to complete the first cycle 3CS encounter. Within two business days of that encounter, a second patient activation measure-10 survey was administered, and thus, patients served as their own control., Results: Forty-nine patients who met the inclusion criteria were enrolled, of which 36 completed the study. Mean patient activation measure-10 scores measured at baseline and two business days after the 3CS encounter were significantly different (68.5 ± SD 14.7 vs. 75.0 ± SD 14.3, p = 0.001). This difference persisted when evaluated by gender (female: 70.0 ± SD 14.8 vs. 81.6 ± SD 10.5, p = 0.001; male: 66.1 ± SD 14.8 vs. 70.8 ± SD 14.7, p = 0.022)., Conclusion: This study demonstrates that cancer patients had significantly increased patient activation scores after engagement in a 3CS encounter provided by an oncology pharmacy team. Further studies are needed to verify these data in a larger population, different healthcare settings, and to evaluate for patients who have solid tumor malignancies.

A feature extraction methodology based on lamb waves is developed for the non-invasive detection and prediction of the gap in concrete-metal composite structures, such as concrete-filled steel tubes. A popular feature extraction method, partial least squares regression, is utilised to predict the gaps. The data is collected using the piezoelectric transducers attached to the external surface of the metal of the composite structure. A piezoelectric actuator generates a sine burst signal, which propagates along the metal and is received by a piezoelectric sensor. The partial least squares regression is performed on the raw sensor signal to extract features and to determine the relationship between the signal and the gap size, which is then used to predict the gaps. The applicability of the developed system is tested on two concrete-metal composite specimens. The first specimen consisted of an aluminium plate and the second specimen consisted of a steel plate. This technique is able to detect and predict gaps as low as 0.1 mm. The results demonstrate the applicability of this technique for the gap and debonding detection in concrete-filled steel tubes, which are critical in determining the degree of composite action between concrete and metal.

Maternal immune activation (MIA) with the viral mimic poly I:C provides an established rodent model for studying schizophrenia (SZ) and other human neurodevelopmental disorders. Postnatal infections are additional risk factors in SZ and may cumulatively contribute to the emergence of pathophysiology. Underlying mechanisms may involve metabolites of the kynurenine pathway (KP) of tryptophan degradation, which is readily induced by inflammatory stimuli. Here we compared the expression of selected cytokines and KP enzymes, and the levels of selected KP metabolites, in the brain of MIA offspring following a second, acute immune challenge with lipopolysaccharides (LPS) on postnatal day (PND) 35 (adolescence) or PND 60 (early adulthood). Assessed in adolescence, MIA did not alter the expression of pro-inflammatory cytokines (except TNF-α) or KP metabolite levels compared to controls, but substantially reduced the expression of the anti-inflammatory cytokines IL-4 and IL-10 and influenced the expression of two of the four KP enzymes examined (IDO1 and TDO2). LPS treatment caused distinct changes in the expression of pro- and anti-inflammatory cytokines, as well as KP enzymes in MIA offspring, but had no effect on KP metabolites compared to control rats. Several of these effects were blunted in MIA offspring receiving LPS on PND 60. Notably, LPS caused a significant reduction in brain kynurenine levels in these animals. Of relevance for SZ-related hypotheses, these results indicate that MIA leads to an increasingly defective, rather than an overactive, immune regulation of cerebral KP metabolism during the postnatal period., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Leaf beetles (Chrysomelidae: Coleoptera) constitute a highly diverse family of phytophagous insects with high ecological relevance, due to their host plant specificity and their close association to vegetation variables. Therefore, secondary succession and seasonal changes after loss of vegetal cover will have a significant influence on their community patterns. Accordingly, responses of leaf beetles to such environmental heterogeneity make them a suitable taxon for monitoring disturbance, which is more important for endangered habitats such as the low thorn forests (LTF) in northeastern Mexico. We conducted a study in a LTF fragment in order to assess the effects of secondary succession and seasonality on leaf beetle communities, as well as to quantify the importance of Chrysomelidae as an indicator taxon. Landsat scenes were used for delimiting a successional gradient, in which four succession categories were selected: four years, 17 years, and 31 years since loss of vegetal cover, and conserved areas. Eight plots of 100 m 2 were randomly delimited in each category; plots were sampled monthly, using an entomological sweep net, from May 2016 to April 2017. In total, 384 samples were collected by the end of study, from which 6978 specimens, six subfamilies, 57 genera, and 85 species were obtained. Species richness was higher in early succession areas. Abundance declined significantly from early successional to conserved areas, but the conserved areas had the higher diversity. Furthermore, differences in abundance were significant between rainy and dry seasons in areas of four, 17, and 31 years of succession, but not in conserved areas; also, all categories had a similar abundance during the dry season. Intermediate (17 and 31 years) and conserved areas differed in the season of higher diversity. Regarding inventory completeness, it was close to or above 70 % for all comparisons, although it was very low for the 17-year category during the rainy season. Faunistic similarity was higher between intermediate categories. A total of 24 species had a significant indicator value. Effects of succession time and seasonality on leaf beetle communities are here quantified for first time in LTF forests. Influences of environmental heterogeneity and intermediate disturbance are discussed as main drivers of the results obtained. Several leaf beetle species are proposed that could be useful for monitoring succession time and secondary LTF vegetation in northeastern Mexico. However, studies must be replicated at other regions, in order to obtain a better characterization of disturbance influence on leaf beetles.

Background and Objective: Cytochrome P450 (CYP) 2C9 catalyzes the biotransformation of indomethacin to its inactive metabolite O-desmethylindomethacin (DMI). The aim of this work was to determine the effect of CYP2C9 polymorphisms on indomethacin metabolism in pregnant women., Methods: Plasma concentrations of indomethacin and DMI at steady state were analyzed with a validated LC-MS/MS method. DNA was isolated from subject blood and buccal smear samples. Subjects were grouped by genotype for comparisons of pharmacokinetic parameters., Results: For subjects with the *1/*2 genotype, the mean steady-state apparent oral clearance (CL/F ss ) of indomethacin was 13.5 ± 7.7 L/h (n = 4) and the mean metabolic ratio (AUC DMI /AUC indomethacin ) was 0.291 ± 0.133. For subjects with the *1/*1 genotype, these values were 12.4 ± 2.7 L/h and 0.221 ± 0.078, respectively (n = 14). Of note, we identified one subject who was a carrier of both the *3 and *4 alleles, resulting in an amino acid change (I359P) which has not been reported previously. This subject had a metabolic ratio of 0.390 and a CL/F ss of indomethacin (24.3 L/h) that was nearly double the wild-type clearance., Conclusion: Although our results are limited by sample size and are not statistically significant, these data suggest that certain genetic polymorphisms of CYP2C9 may lead to an increased metabolic ratio and an increase in the clearance of indomethacin. More data are needed to assess the impact of CYP2C9 genotype on the effectiveness of indomethacin as a tocolytic agent.

Psychological stress is known to have profound effects on immune function and to promote inflammatory conditions. Elevated circulating levels of cytokines associated with stress are known to increase the risk to several diseases, but little is known about this mechanism. This study assessed the role of T cells on cytokine levels after exposure to stress in the learned helplessness paradigm. Adoptive transfer of CD4 + T cells into Rag2 -/- mice did not change cytokine levels to stress while CD8 + T cells resulted in an increase in TNF-α, IL-6 and IFN-γ in stressed Rag2 -/- mice. Moreover, depletion of CD8 + T cells in WT mice abolished these cytokine responses to stress. Corticosterone and behavioral stress responsiveness was impaired in Rag2 -/- mice reconstituted with CD8 + T cells. Notably, depletion of these cells in WT mice had no effect on behavior or corticosterone levels. Exposure to stress did not change the expression of canonical markers of T cell activation including CD62L and CD44 or modified intracellular cytokine content, suggesting that they are not the main producers of circulating cytokines in response to stress. These results show that CD8 + T cells promote TNF-α, IL-6 and IFN-γ responses to stress, possibly by stimulating non-lymphoid cells., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Currently, exogenous hormone replacement is used in many men with hypogonadism without clear organic cause. This study examines the contribution of modifiable health behaviors, i.e., physical activity and weight control, to the maintenance of testosterone levels with aging., Methods: In a cross-sectional study of 2994 healthy men aged 50-79 years examined at a preventive medicine clinic from January 2012 to March 2016, screening morning total testosterone levels were measured and categorized as low (<250 ng/dL), low normal (250-399 ng/dL), and normal (>400 ng/dL). Cardiorespiratory fitness (fitness) was estimated from a maximal exercise treadmill test. Multiple logistic regression models were used to test the associations between low testosterone levels and age, body mass index (BMI), and fitness., Findings: Mean testosterone levels were in the normal range for each age group (50-59, 60-69, and 70-79). There was a similar prevalence of low testosterone in each age group (11·3%, 10%, and 10·5%, respectively). The prevalence of low testosterone was positively associated with BMI and negatively associated with fitness but was not associated with age., Interpretation: This study found no evidence that low testosterone is an inevitable consequence of aging. Maintenance of healthy weight and fitness may help maintain normal testosterone levels., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Research has shown that inflammatory processes affect brain function and behavior through several neuroimmune pathways. However, high order brain functions affected by inflammation largely remain to be defined. Resting state functional connectivity of synchronized oscillatory activity is a valid approach to understand network processing and high order brain function under different experimental conditions. In the present study multi-electrode EEG recording in awake, freely moving rats was used to study resting state connectivity after administration of lipopolysaccharides (LPS). Male Wistar rats were implanted with 10 cortical surface electrodes and administered with LPS (2 mg/kg) and monitored for symptoms of sickness at 3, 6 and 24 h. Resting state connectivity and power were computed at baseline, 6 and 24 h. Three prominent connectivity bands were identified using a method resistant to spurious correlation: alpha (5-15 Hz), beta-gamma (20-80 Hz), and high frequency oscillation (150-200 Hz). The most prominent connectivity band, alpha, was strongly reduced 6 h after LPS administration, and returned to baseline at 24 h. Beta-gamma connectivity was also reduced at 6 h and remained reduced at 24 h. Interestingly, high frequency oscillation connectivity remained unchanged at 6 h and was impaired 24 h after LPS challenge. Expected elevations in delta and theta power were observed at 6 h after LPS administration, when behavioral symptoms of sickness were maximal. Notably, gamma and high frequency power were reduced 6 h after LPS and returned to baseline by 24 h, when the effects on connectivity were more evident. Finally, increases in cross-frequency coupling elicited by LPS were detected at 6 h for theta-gamma and at 24 h for theta-high frequency oscillations. These studies show that LPS challenge profoundly affects EEG connectivity across all identified bands in a time-dependent manner indicating that inflammatory processes disrupt both bottom-up and top-down communication across the cortex during the peak and resolution of inflammation., Competing Interests: The authors have declared that no competing interests exist.

Accumulating evidence has shown that lymphocytes modulate behaviour and cognition by direct interactions with the central nervous system. Studies have shown that reconstitution by adoptive transfer of lymphocytes from wild type into immune-deficient mice restores a number of neurobehavioural deficits observed in these models. Moreover, it has been shown that these effects are mostly mediated by T lymphocytes. Studies of adoptive transfer thus far have employed adult mice, but whether lymphocytes may also modulate behaviour during development remains unknown. In this study, neonate lymphocyte-deficient Rag2 -/- mice were reconstituted within 48 hours after birth with lymphoid cells from transgenic donors expressing green fluorescent protein, allowing for their identification in various tissues in recipient mice while retaining all functional aspects. Adolescent Rag2 -/- and reconstituted Rag2 -/- along with C57BL/6J wild-type mice underwent a series of behavioural tests, including open field, social interaction and sucrose preference tests. At 12 weeks, they were evaluated in the Morris water maze (MWM). Reconstituted mice showed changes in almost all aspects of behaviour that were assessed, with a remarkable complete rescue of impaired social behaviour displayed by adolescent Rag2 -/- mice. Consistent with previous reports in adult mice, neonatal reconstitution in Rag2 -/- mice restored spatial memory in the MWM. The presence of donor lymphocytes in the brain of neonatally reconstituted Rag2 -/- mice was confirmed at various developmental points. These findings provide evidence that lymphocytes colonize the brain during post-natal development and modulate behaviour across the lifespan supporting a role for adaptive immunity during brain maturation., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Chronic pain impacts individuals with pain as well as their loved ones. Yet, there has been little attention to the social context in individual psychological treatment approaches to chronic pain management. With this need in mind, we developed a couple-based treatment, "Mindful Living and Relating," aimed at alleviating pain and suffering by promoting couples' psychological and relational flexibility skills. Currently, there is no integrative treatment that fully harnesses the power of the couple, treating both the individual with chronic pain and the spouse as two individuals who are each in need of developing greater psychological and relational flexibility to improve their own and their partners' health. Mindfulness, acceptance, and values-based action exercises were used to promote psychological flexibility. The intervention also targets relational flexibility, which we define as the ability to interact with one's partner, fully attending to the present moment, and responding empathically in a way that serves one's own and one's partner's values. To this end, the intervention also included exercises aimed at applying psychological flexibility skills to social interactions as well as emotional disclosure and empathic responding exercises to enhance relational flexibility. The case presented demonstrates that healthy coping with pain and stress may be most successful and sustainable when one is involved in a supportive relationship with someone who also practices psychological flexibility skills and when both partners use relational flexibility skills during their interactions.

Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, acts as an endogenous antagonist of alpha7 nicotinic and NMDA receptors and is implicated in a number of neurophysiological and neuropathological processes including cognition and neurodegenerative events. Therefore, kynurenine aminotransferase II (KAT II/AADAT), the enzyme responsible for the formation of the majority of neuroactive kynurenic acid in the brain, has prompted significant interest. Using immunohistochemistry, this enzyme was localized primarily in astrocytes throughout the adult rat brain, but detailed neuroanatomical studies are lacking. Here, we employed quantitative in situ hybridization to analyze the relative expression of KAT II mRNA in the brain of rats under normal conditions and 6 h after the administration of lipopolysaccharides (LPSs). Specific hybridization signals for KAT II were detected, with the highest expression in the subventricular zone (SVZ), the rostral migratory stream and the floor of the third ventricle followed by the corpus callosum and the hippocampus. This pattern of mRNA expression was paralleled by differential protein expression, determined by serial dilutions of antibodies (up to 1:1 million), and was confirmed to be primarily astrocytic in nature. The mRNA signal in the SVZ and the hippocampus was substantially increased by the LPS treatment without detectable changes elsewhere. These results demonstrate that KAT II is expressed in the rat brain in a region-specific manner and that gene expression is sensitive to inflammatory processes. This suggests an unrecognized role for kynurenic acid in the brain's germinal zones., (Published by Elsevier Ltd.)

Background  Massive transfusion protocols (MTPs) have been examined in trauma. The exact ratio of packed red blood cells (PRBC) to other blood replacement components in hemostatic resuscitation in obstetrics has not been well defined. Objective  The objective of this study was to evaluate hemostatic resuscitation in peripartum hysterectomy comparing pre- and postinstitution of a MTP. Study Design  We conducted a retrospective, descriptive study of women undergoing peripartum hysterectomies from January 2002 to January 2015 who received ≥ 4 units of PRBC. Individuals were grouped into either a pre-MTP institution group or a post-MTP institution group. The post-MTP group was subdivided into those who had the protocol activated (MTP) versus not activated (no MTP). Primary outcomes were estimated blood loss (EBL) and need for blood product replacement. The secondary outcome was a composite of maternal morbidity, including need for mechanical ventilation, venous thromboembolism, pulmonary edema, acute kidney injury, and postpartum infection. A Mann-Whitney U test was used to compare continuous variables, and a chi-squared test was used for categorical variables with significance of p  < 0.05. Results  Of the 165 women who had a peripartum hysterectomy during the study period, 62 received four units or more of PRBC. No significant differences were noted in EBL or blood product replacement between the pre-MTP ( n  = 39) and post-MTP ( n  = 23) groups. Similarly, the MTP ( n  = 6) and no MTP ( n  = 17) subgroups showed no significant difference between EBL and overall blood product replacement. Significant differences were seen in transfusion of individual blood products, such as fresh frozen plasma (FFP) (MTP = 4, no MTP = 2; p  = 0.02) and platelets (plts) (MTP = 6, no MTP = 0; p  = 0.03). The use of high ratio replacement therapy for both plasma and plts was more common in the MTP group (FFP/PRBC ratio [MTP = 0.5, no MTP = 0.3; p  = 0.02]; plts/PRBC ratio [MTP = 0.7, no MTP = 0; p  = 0.03]). There were no differences in the secondary outcome between pre- and post-MTP or MTP and no MTP. Conclusion  Initiation of the MTP did result in an increase in transfusion of FFP and plts intraoperatively. At our institution, the MTP is underutilized, but it appears that providers are more cognizant of the use of high transfusion ratios., Competing Interests: Conflict of Interest: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The stem cells that safeguard synovial joints in adulthood are undefined. Studies on mesenchymal stromal/stem cells (MSCs) have mainly focused on bone marrow. Here we show that lineage tracing of Gdf5-expressing joint interzone cells identifies in adult mouse synovium an MSC population largely negative for the skeletal stem cell markers Nestin-GFP, Leptin receptor and Gremlin1. Following cartilage injury, Gdf5-lineage cells underpin synovial hyperplasia through proliferation, are recruited to a Nestin-GFP high perivascular population, and contribute to cartilage repair. The transcriptional co-factor Yap is upregulated after injury, and its conditional ablation in Gdf5-lineage cells prevents synovial lining hyperplasia and decreases contribution of Gdf5-lineage cells to cartilage repair. Cultured Gdf5-lineage cells exhibit progenitor activity for stable chondrocytes and are able to self-organize three-dimensionally to form a synovial lining-like layer. Finally, human synovial MSCs transduced with Bmp7 display morphogenetic properties by patterning a joint-like organ in vivo. Our findings further the understanding of the skeletal stem/progenitor cells in adult life.

Background: Bupropion is used to treat depression during pregnancy. However, its usefulness as a smoking cessation aid for pregnant women is not fully known., Objective: The objective of the study was to evaluate the preliminary efficacy of bupropion sustained release for smoking cessation during pregnancy., Study Design: We conducted a randomized, prospective, double-blind, placebo-controlled, pilot trial. Pregnant women who smoked daily received individualized behavior counseling and were randomly assigned to a 12 week, twice-a-day treatment with 150 mg bupropion sustained release or placebo. The primary study objectives were to determine whether bupropion sustained release reduces nicotine withdrawal symptoms on the quit date and during the treatment period compared with placebo and whether it increases 7 day point prevalence abstinence at the end of the treatment period and at the end of pregnancy., Results: Subjects in the bupropion (n = 30) and placebo (n = 35) groups were comparable in age, smoking history, number of daily smoked cigarettes, and nicotine dependence. After controlling for maternal age and race, bupropion sustained release reduced cigarette cravings (1.5 ± 1.1 vs 2.1 ± 1.2, P = .02) and total nicotine withdrawal symptoms (3.8 ± 4.3 vs 5.4 ± 5.1, P = .028) during the treatment period. Administration of bupropion sustained release reduced tobacco exposure, as determined by levels of carbon monoxide in exhaled air (7.4 ± 6.4 vs 9.1 ± 5.8, P = .053) and concentrations of cotinine in urine (348 ± 384 ng/mL vs 831 ± 727 ng/mL, P = .007) and increased overall abstinence rates during treatment (19% vs 2%, P = .003). However, there was no significant difference in 7 day point prevalence abstinence rates between the 2 groups at the end of medication treatment (17% vs 3%, P = .087) and at the end of pregnancy (10% vs 3%, P = .328)., Conclusion: Individual smoking cessation counseling along with the twice-daily use of 150 mg bupropion sustained release increased smoking cessation rates and reduced cravings and total nicotine withdrawal symptoms during the treatment period. However, there was no significant difference in abstinence rates between groups at the end of medication treatment and at the end of pregnancy, likely because of the small sample size. A larger study is needed to confirm these findings and to examine the potential benefit/ risk ratio of bupropion sustained release for smoking cessation during pregnancy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Incongruence of pain severity ratings among people experiencing pain and their observers has been linked to psychological distress. Previous studies have measured pain rating congruence through static self-report, involving a single rating of pain; however, this method does not capture changes in ratings over time. The present study examined the extent to which partners were congruent on multiple ratings of a participants' pain severity during the cold pressor task. Furthermore, 2 components of pain anxiety-pain catastrophizing and perceived threat-were examined as predictors of pain congruence. Undergraduate couples in a romantic relationship (N = 127 dyads) participated in this study. Both partners completed measures of pain catastrophizing and perceived threat before randomization to their cold pressor participant or observer roles. Participants and observers rated the participant's pain in writing several times over the course of the task. On average, observers rated participants' pain as less severe than participants' rated their own pain. In addition, congruence between partners increased over time because of observers' ratings becoming more similar to participant's ratings. Finally, pain catastrophizing and perceived threat independently and jointly influenced the degree to which partners similarly rated the participant's pain., Perspective: This article presents a novel application of the cold pressor task to show that pain rating congruence among romantic partners changes over time. These findings indicate that pain congruence is not static and is subject to pain anxiety in both partners., (Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Background: We provide volume II of a distributional atlas of aquatic insects for the eastern USA state of Ohio. This treatment of stoneflies (Plecoptera) is companion to Armitage et al. (2011) on caddisflies (Trichoptera). We build on a recent analysis of Ohio stonefly diversity patterns based on large drainages (DeWalt et al. 2012), but add 3717 new records to the data set. We base most analyses on the United States Geological Survey Hierarchical Unit Code eight (HUC8) drainage scale. In addition to distributional maps for each species, we provide analyses of species richness versus HUC8 drainage area and the number of unique locations in a HUC8 drainage, species richness versus Ohio counties, analyze adult presence phenology throughout the year, and demonstrate stream size range affiliation for each species., New Information: This work is based on a total of 7797 specimen records gathered from 21 regional museums, agency data, personal collections, and from the literature Table 1. To our knowledge this is the largest stonefly data set available for a similarly sized geopolitical area anywhere in the world. These data are made available as a Darwin Core Archive supported by the Pensoft Integrated Publishing Toolkit (DeWalt et al. 2016b). All known published papers reporting stoneflies from Ohio are detailed in Suppl. material 1. We recovered 102 species from Ohio, including all nine Nearctic families Table 2​. Two species were removed from the DeWalt et al. (2012) list and two new state records added. Perlidae (32 spp.) was most speciose, compared to the low diversity Pteronarcyidae (2 spp.) and Peltoperlidae (1 sp.). The richest HUC8 drainages occurred in northeastern, south-central, and southern regions of the state where drainages were heavily forested, had the highest slopes, and were contained within or adjacent to the unglaciated Allegheny and Appalachian Plateaus. Species poor drainages occurred mainly in the northwestern region where Wisconsinan aged lake plains climaxed to an expansive wooded wetland, the Black Swamp. The unglaciated Lower Scioto drainage (72 spp.) in south-central Ohio supported the greatest species richness. There was no relationship between species richness and HUC8 drainage size, but the number of unique locations in a drainage strongly related to species richness. All Ohio counties were represented in the data set with Hocking County (59 spp.) of the Lower Scioto drainage being the richest and most heavily sampled. Adult presence phenology was influenced by phylogenetic relationships such that the superfamily Nemouroidea (Capniidae, Leuctridae, Nemouridae, and Taeniopterygidae) generally emerged in winter and spring while the superfamilies Pteronarcyoidea (Pteronarcyidae, Peltoperlidae) and Perloidea (Chloroperlidae, Perlidae, Perlodidae) emerged later, some species continuing emergence through summer months. Species often occupied specific stream size ranges, while others were generalists. Two species once histrorically abundant in the western Lake Erie Bass Islands no longer reside there. Each of the 102 species is discussed in detail, including several that require additional collecting efforts to confirm their identities, presence, and distribution in Ohio.

Objective: Using an animal model of preeclampsia induced by overexpression of soluble fms-like tyrosine kinase 1 (sFlt-1), we previously showed that pravastatin prevents the development of a preeclampsia phenotype. Our objective is to determine whether pravastatin treatment may be explained by its effects on apoptotic/survival pathways in the placenta., Methods: Pregnant CD1 mice at day 8 of gestation (length of gestation 19 days) were randomly allocated to injection via tail vein with either adenovirus carrying sFlt-1 or adenovirus carrying the murine immunoglobulin G2α Fc fragment (mFc virus control group). Mice from the sFlt group were randomly assigned to receive pravastatin (5 mg/kg/d) in their drinking water from day 9 until killing (sFlt-1 + Pravastatin) or water (sFlt-1). The mFc control received water only. Mice were killed on day 18, and the placentas were collected. Protein mitogen-activated protein kinase (MAPK) pathway substrates were assayed using Bioplex Multiplex Immunoassay (Bio-Rad, Hercules, California). Data are reported as mean  ±  standard error of the mean or median (interquartile range) when appropriate. One-way analysis of variance followed by post hoc analysis was performed. Two-sided P value < .05 was considered statistically significant., Results: The sFlt-1 + Pravastatin mice had significantly higher placental protein concentrations of prosurvival/ antiapoptotic factors (activating transcription factor 2, pp38, phosphorylated c-jun N-terminal kinase, and phosphorylated extracellular signal-regulated kinase) and of heat-shock protein 27 and signal transducer and activator of transcription 3, 2 factors crucial for embryonic and placental development during oxidative stress, compared to sFlt-1 mice (P  <  .05) and similar to the mFc control group. No differences were noted in substrates of the proapoptotic pp53 pathway., Conclusion: Pravastatin ability to prevent preeclampsia phenotype may be mediated through pleiotropic mechanisms involving a prosurvival/ antiapoptotic MAPK pathway in the placenta. Our results further support continued research in the role for statins in the prevention of preeclampsia., (© The Author(s) 2016.)

Bupropion sustained release is used to promote smoking cessation in males and nonpregnant females. However, its efficacy as a smoking cessation aid during pregnancy is not reported. The pregnancy-associated changes in maternal physiology may alter the pharmacokinetics and pharmacodynamics of bupropion and consequently its efficacy in pregnant smokers. Therefore, the aims of this study were to determine the steady-state pharmacokinetics of bupropion during pregnancy and the effect of functional genetic variants of CYP2B6 and CYP2C19 on bupropion pharmacokinetics in pregnant women. Plasma and urine concentrations of bupropion and its metabolites hydroxybupropion (OHBUP), threohydrobupropion, and erythrohydrobupropion were determined by liquid chromatography-mass spectrometry. Subjects were genotyped for five nonsynonymous single-nucleotide polymorphisms that result in seven CYP2B6 alleles, namely *2, *3, *4, *5, *6, *7, and *9, and for CYP2C19 variants *2, *3, and *17 The present study reports that the isoform-specific effect of pregnancy on bupropion-metabolizing enzymes along with the increase of renal elimination of the drug could collectively result in a slight decrease in exposure to bupropion in pregnancy. In contrast, pregnancy-induced increase in CYP2B6-catalyzed bupropion hydroxylation did not impact the plasma levels of OHBUP, probably due to a higher rate of OHBUP glucuronidation, and renal elimination associated with pregnancy. Therefore, exposure to OHBUP, a pharmacologically active metabolite of the bupropion, appears to be similar to that of the nonpregnant state. The predicted metabolic phenotypes of CYP2B6*6 and variant alleles of CYP2C19 in pregnancy are similar to those in the nonpregnant state., (Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.)

Abscisic acid (ABA) is a well-characterized plant hormone, known to mediate developmental aspects as well as both abiotic and biotic stress responses. Notably, the exogenous application of ABA has recently been shown to increase susceptibility to the fungal pathogen Fusarium graminearum, the causative agent of Fusarium head blight (FHB) in wheat and other cereals. However roles and mechanisms associated with ABA's modulation of pathogen responses remain enigmatic. Here the identification of putative ABA receptors from available genomic databases for Triticum aestivum (bread wheat) and Brachypodium distachyon (a model cereal) are reported. A number of these were cloned for recombinant expression and their functionality as ABA receptors confirmed by in vitro assays against protein phosphatases Type 2Cs. Ligand selectivity profiling of one of the wheat receptors (Ta&#95;PYL2DS&#95;FL) highlighted unique activities compared to Arabidopsis AtPYL5. Mutagenic analysis showed Ta&#95;PYL2DS&#95;FL amino acid D180 as being a critical contributor to this selectivity. Subsequently, a virus induced gene silencing (VIGS) approach was used to knockdown wheat Ta&#95;PYL4AS&#95;A (and similar) in planta, yielding plants with increased early stage resistance to FHB progression and decreased mycotoxin accumulation. Together these results confirm the existence of a family of ABA receptors in wheat and Brachypodium and present insight into factors modulating receptor function at the molecular level. That knockdown of Ta&#95;PYL4AS&#95;A (and similar) leads to early stage FHB resistance highlights novel targets for investigation in the future development of disease resistant crops., Competing Interests: Marci Surpin is employed by Valent Biosciences Corporation. The other authors confirm that no competing interests exist. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Background: Topical therapy is an important alternative to systemic antibacterial therapy for treatment of canine superficial pyoderma in light of the emergence of multidrug-resistant staphylococci. Chlorhexidine is widely used in shampoo products alone or in combination with miconazole or tromethamine-ethylenediaminetetraacetic acid (trisEDTA). Comparisons of these combinations have not been made., Hypothesis/objectives: To determine minimum inhibitory concentrations (MICs) of combinations of chlorhexidine/miconazole and chlorhexidine/trisEDTA in vitro in a collection of Staphylococcus pseudintermedius (SP) from northern (NUK) and southeastern (SEUK) United Kingdom (UK) sources., Methods: MICs of chlorhexidine, miconazole, trisEDTA and combinations of chlorhexidine/miconazole (1:1) or chlorhexidine/trisEDTA (80:16:1 and 80:5:1) were determined for 196 canine SP isolates from NUK [49 meticillin-resistant (MRSP), 50 meticillin-susceptible (MSSP)] and fom SEUK (48 MRSP, 49 MSSP) using agar dilution., Results: TrisEDTA alone did not inhibit growth. Chlorhexidine/miconazole MICs (median = 0.5 mg/L) were lower than those of either drug alone (P < 0.05) and lower than chlorhexidine/trisEDTA MICs (median = 1 mg/L; P < 0.0005) in each bacterial type and from both regions, except for miconazole in NUK MSSP. An additive interaction was noted between chlorhexidine and miconazole or trisEDTA (80:16:1 ratio) in 79 and 43 isolates, respectively, whereas antagonism between chlorhexidine and trisEDTA was noted for three isolates. NUK isolates were more susceptible than SEUK isolates (P < 0.05), except MRSP exposed to chlorhexidine and the chlorhexidine/trisEDTA (80:16:1) combination., Conclusions and Clinical Importance: These low MICs are likely to be exceeded by topical therapy. Evaluation of the mechanisms by which chlorhexidine combinations interact to reduce MICs is warranted, in view of increasing concerns of biocide tolerance in staphylococci., (© 2016 ESVD and ACVD.)

The concept of the brain as an immune privileged organ is rapidly evolving in light of new findings outlining the sophisticated relationship between the central nervous and the immune systems. The role of T cells in brain development and function, as well as modulation of behavior has been demonstrated by an increasing number of studies. Moreover, recent studies have redefined the existence of a brain lymphatic system and the presence of T cells in specific brain structures, such as the meninges and choroid plexus. Nevertheless, much information is needed to further the understanding of brain T cells and their relationship with the central nervous system under non-inflammatory conditions. In the present study we employed the Rag2(-/-) mouse model of lymphocyte deficiency and reconstitution by adoptive transfer to study the temporal and anatomical expansion of T cells in the brain under homeostatic conditions. Lymphopenic Rag2(-/-) mice were reconstituted with 10 million lymphoid cells and studied at one, two and four weeks after transfer. Moreover, lymphoid cells and purified CD4(+) and CD8(+) T cells from transgenic GFP expressing mice were used to define the neuroanatomical localization of transferred cells. T cell numbers were very low in the brain of reconstituted mice up to one week after transfer and significantly increased by 2weeks, reaching wild type values at 4weeks after transfer. CD4(+) T cells were the most abundant lymphocyte subtype found in the brain followed by CD8(+) T cells and lastly B cells. Furthermore, proliferation studies showed that CD4(+) T cells expand more rapidly than CD8(+) T cells. Lymphoid cells localize abundantly in meningeal structures, choroid plexus, and circumventricular organs. Lymphocytes were also found in vascular and perivascular spaces and in the brain parenchyma across several regions of the brain, in particular in structures rich in white matter content. These results provide proof of concept that the brain meningeal system, as well as vascular and perivascular spaces, are homing sites of lymphocytes and suggest the possibility of a brain specific T cell subtype., (Published by Elsevier Inc.)

Background: Bupropion is used for treatment of depression during pregnancy. However, its use as a smoking cessation aid for pregnant women is currently under evaluation., Objective: The aim of this opportunistic study was to investigate the transfer of bupropion and its major pharmacologically active metabolites, hydroxybupropion and threohydrobupropion, across the placenta in vivo. In addition, the concentrations of the drug and its metabolites were determined in the amniotic fluid., Study Design: The following samples were collected at deliveries from 22 women taking bupropion: maternal blood (n = 22), umbilical cord venous blood (n = 22), and amniotic fluid (n = 9). The concentrations of the drug and its metabolites in blood plasma and amniotic fluid were determined by means of liquid chromatography-mass spectrometry. Placental passage was calculated as a ratio of umbilical cord venous plasma to maternal plasma concentrations., Results: The levels of hydroxybupropion and threohydrobupropion in umbilical cord venous plasma were invariably lower than their corresponding concentrations in maternal plasma. The concentrations of bupropion in umbilical cord plasma were lower than in maternal plasma in the majority of the maternal-cord blood pairs. The median values of the umbilical cord venous plasma to maternal plasma ratios were: bupropion, 0.53 (interquartile range 0.35, n = 18), hydroxybupropion, 0.21 (interquartile range 0.12, n = 18), and threohydrobupropion, 0.61 (interquartile range 0.11, n = 21). In umbilical cord venous plasma, the median concentration of bupropion was 5.3 ng/mL; hydroxybupropion, 103.6 ng/mL; and threohydrobupropion, 59.6 ng/mL. Bupropion and its metabolites were detectable in the amniotic fluid but the concentrations of threohydrobupropion were higher than those in the corresponding umbilical cord venous plasma., Conclusion: Bupropion and its active metabolites cross the placenta to the fetal circulation. The concentrations of hydroxybupropion and threohydrobupropion in umbilical cord venous plasma were higher than bupropion concentrations suggesting a higher fetal exposure to the metabolites than the parent drug. The higher levels of threohydrobupropion in the amniotic fluid than those in umbilical cord venous plasma suggest that enzymes involved in the metabolism of bupropion to threohydrobupropion are most likely active in the fetus. The biological consequences of fetal exposure to maternally administered bupropion and/or its active metabolites via placental transfer and recirculation of the amniotic fluid are yet to be determined., (Copyright © 2016. Published by Elsevier Inc.)

Background: Neuroinflammatory processes are increasingly believed to participate in the pathophysiology of a number of major psychiatric diseases, including depression. Immune activation stimulates the conversion of the amino acid tryptophan to kynurenine, leading to the formation of neuroactive metabolites, such as quinolinic acid and kynurenic acid. These compounds affect glutamatergic neurotransmission, which plays a prominent role in depressive pathology. Increased tryptophan degradation along the kynurenine pathway (KP) has been proposed to contribute to disease etiology., Methods: We used postmortem brain tissue from the ventrolateral prefrontal cortex (VLPFC) to assess tissue levels of tryptophan and KP metabolites, the expression of several KP enzymes and a series of cytokines as well as tissue pathology, including microglial activation. Tissue samples came from nonpsychiatric controls ( n = 36) and individuals with depressive disorder not otherwise specified (DD-NOS, n = 45) who died of natural causes, homicide, accident, or suicide., Results: We found a reduction in the enzymatic conversion of tryptophan to kynurenine, determined using the kynurenine:tryptophan ratio, and reduced messenger RNA expression of the enzymes indoleamine-2,3-dioxygenase 1 and 2 and tryptophan-2,3-dioxygenase in depressed individuals irrespective of the cause of death. These findings correlated with reductions in the expression of several cytokines, including interferon-γ and tumour necrosis factor-α. Notably, quinolinic acid levels were also lower in depressed individuals than controls., Limitations: Information on the use of antidepressants and other psychotropic medications was insufficient for statistical comparisons., Conclusion: Contrary to expectations, the present results indicate that depression, in the absence of medical illness or an overt inflammatory process, is associated with compromised, rather than increased, KP metabolism in the VLPFC.

The study of biodiversity of Chrysomelidae in Mexico and its variation within ecological gradients has increased recently, although important areas in the country remain to be explored. We conducted a faunistic inventory and analyzed the elevational and temporal variation of leaf beetle communities in the Sierra de San Carlos, in the state of Tamaulipas, in northeastern Mexico. This is an area with high to extreme priority for conservation, and due to its insular geographical position and to the vegetational communities present, it must be considered as a sky island. We selected seven sample sites distributed in different elevations within three localities, and comprising different vegetational communities. At each site, we randomly delimited 12 sample plots of 400 m(2) where sampling was conducted by entomological sweep netting and collecting directly by hand. Sampling was conducted monthly at each plot, for a total of 1,008 samples between February 2013 and January 2014. By the end of the study, we had obtained a total of 3,081 specimens belonging to six subfamilies, 65 genera, and 113 species, with Trichaltica scabricula (Crotch, 1873) being recorded for first time in Mexico. Species richness was less than the values observed at other studies conducted in the same region, which is attributed to differences in the number of plant species and to the insular location of Sierra de San Carlos; however, the higher diversity values suggest a higher quality of natural resources and vegetational communities. No consistent pattern of leaf beetle communities was correlated with elevation, although higher values of species richness and diversity were obtained at the highest elevation site. The seasonal gradient showed that the rainy season is most favorable for leaf beetle communities. We found that species composition was different between sites and months, and also that there exists a significant association between the abundance obtained at each site and particular months. These results highlight the importance of different microhabitats for species distribution, and suggest that each species of Chrysomelidae has a differential response to environmental factors that vary within the elevational gradient and according to seasons. Also, we confirm and emphasize the important status of Sierra de San Carlos as a key natural area for biological conservation.

Systematic correlation in alkaline-earth carbonate compounds between the deviation of the CO3 units from the perfect D3h symmetry and their (13)C nuclear magnetic resonance (NMR) chemical shift anisotropy (CSA) parameters is established. The (13)C NMR CSA parameters of amorphous calcium carbonate (ACC) are measured using two-dimensional (13)C phase adjusted spinning sidebands (PASS) NMR spectroscopy and are analyzed on the basis of this correlation. The results indicate a distortion of the CO3 units in ACC in the form of an in-plane displacement of the C atom away from the centroid of the O3 triangle, resulting from hydrogen bonding with the surrounding H2O molecules, without significant out-of-plane displacement. Similar distortion for all C atoms in the structure of ACC suggests a uniform spatial disposition of H2O molecules around the CO3 units forming a hydrogen-bonded amorphous network. This amorphous network is stabilized against crystallization by steric frustration, while additives such as Mg presumably provide further stabilization by increasing the energy of dehydration.

Background: Acid suppressive therapy (AST)-namely, proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs)-is routinely prescribed to hospitalized patients for stress ulcer prophylaxis (SUP)., Objective: To identify the incidence of and indications for AST use in the hematology/oncology population as well as to identify the occurrence of the following PPI-associated adverse events: pneumonia and Clostridium difficile-associated diarrhea (CDAD)., Methods: A retrospective chart review was conducted on adult hematology/oncology patients admitted to any oncology service for ≥48 hours from October 1, 2014, to December 31, 2014., Results: Of the 298 patients who met the inclusion criteria, 73% (n = 218) received an AST during admission. The most common indication for an AST was SUP (63%). The incidence of hospital-acquired pneumonia (HAP) was 10%, 0%, and 4% in patients who received a PPI, H2RA, and no AST, respectively (14/142 vs 0/70 vs 3/80; odds ratio [OR] for PPI vs no AST = 2.68; 95% CI = 0.75-9.63). The incidence of CDAD was 3%, 1.3%, and 1.2% in patients who received a PPI, H2RA, and no AST, respectively (4/142 vs 1/70 vs 1/80; OR for PPI vs H2RA = 1.92; 95% CI = 0.21-17.47)., Conclusion: This is the first study to describe the incidence of and indications for AST use in the hospitalized hematology/oncology population. There was a high occurrence of AST use, particularly PPIs, in these patients at our institution. Additionally, there was a trend toward an increased risk of HAP and CDAD in patients who received AST during admission., (© The Author(s) 2016.)

Purpose: To assess the impact of single-dose fosaprepitant on nausea and emesis after BEAM and high-dose melphalan conditioning regimens for autologous hematopoietic stem cell transplantation., Methods: In a single-center cohort study patients receiving melphalan containing hematopoietic stem cell transplantation regimens who received a one-time dose of 150 mg IV fosaprepitant (n = 56) were compared to a historical control (n = 70)., Results: The primary endpoint of no emesis from melphalan administration through five days afterward was 80% for the fosaprepitant group versus 66% in the control group (p = 0.068). Addition of fosaprepitant demonstrated significant improvement in emetic episodes per patient during the entire assessment period (p = 0.011) and days 1-5 after melphalan (p = 0.045). Fosaprepitant resulted in no substantial nausea during the entire assessment period in 37% of high-dose melphalan patients and 57% of BEAM patients., Conclusions: Further studies are suggested to investigate the optimal number and timing of doses of fosaprepitant in this setting., (© The Author(s) 2015.)