bluuebunny/crossref_metadata_2025 huggingface dataset:
PSXII-19 Urine Metabolomics Analysis Associated with Feed Efficiency on Crossbred Steers during the Growing and Finishing Period on Forage- and Concentrate- Based Diets
Authors: Artegoitia Virginia , Newman John , Lewis Ron , Foote Andrew P , Freetly Harvey C
Published: November 2020

A discovery project to identify non-invasive biomarkers that can detect subtle metabolic discrepancies for cattle feed efficiency was performed using untargeted and targeted urine metabolomics by ultra-performance liquid chromatography-mass spectrometry. Individual feed intake and body weight gain were measured in crossbred steers (n = 80) on a forage-based growing ration (stage-1) followed by a high-concentrate diet finishing ration (stage-2). Urine was collected on study days 0, 21, 42, 63, and 83 for each dietary stage. In total, 28 steers with the greatest and the least average daily-gain (ADG) within 0.32 SD of the mean of dry-matter-intake (DMI) were used. A principal component analysis of the untargeted metabolites fully segregated the highest-ADG and lowest-ADG animals, with overlap across diets (both stages). The urinary untargeted metabolites that segregated the ADG-groups (n = 199; P < 0.05), included steroid-hormones, bile-acids, alpha-linolenic acid metabolites, vitamin-B6, along with products of glycine, serine and threonine metabolism (metabolic pathway analysis: impact-value > 0.50; FDR < 0.10). Bile acids and steroids were then quantified in urine and their associations with animal performance and carcass composition evaluated by correlation and multiple logistic regression AUC-ROC curve analyses. In stage-1, urine concentration of cortisone was associated (P < 0.05) with ADG (r = -0.28), DMI (r = -0.40) and ribeye-area (r = -0.28); cortisol was associated with DMI (r = -0.32; P < 0.01) and testosterone was associated with ADG (r = -0.28; P < 0.01). The urine concentrations of 18 measured bile acids were negatively associated (P < 0.05) with DMI, and secondary bile acids were negatively associated (P < 0.01) with marbling and hot-carcass-weight. In stage-2, negative association between the bile acids glycocholic acid and deoxycholic acid with marbling and hot-carcass-weight were identified. Urine metabolomics provide new insight into the physiological mechanisms and potential biomarkers of cattle feed efficiency. USDA is an equal opportunity provider and employer.
PSXII-14 The influence of trace minerals source on copper, manganese, and zinc binding strength to rumen digesta in cattle fed a corn silage-based diet
Authors: Guimaraes Octavio , Loh Huey Yi , Thorndyke Meghan P , Tillquist Nicole M , Spears Jerry W , Engle Terry E
Published: November 2020

Twelve crossbred steers fitted with rumen cannulae were used to determine the influence of trace mineral (TM) source on relative binding strength of minerals in the ruminal insoluble digesta fraction (IDF). Steers (n = 4/treatment) were fed a corn silage-based diet containing no supplemental Cu, Mn, and Zn for 7d. On d 8, steers received a bolus dose (2 x NRC requirement) of the respective TM from sulfate (STM), organic (ORG; provided as Zn methionine, Mn methionine, and Cu lysine), or hydroxy TM (HTM; Micronutrients USA LLC) sources. Ruminal samples were obtained at 2 h intervals starting at -4 and ending at 24 h post dosing. Ruminal samples were centrifuged and supernatant and the IDF were collected and frozen separately. Binding strength of Cu, Mn, and Zn to the IDF was estimated at 0, 12, and 24 h using dialysis against 0.05 M Tris-EDTA. At 0 h pre-dosing, IDF concentrations of Cu, Mn, and Zn were similar across treatments. At 12 h post dosing Cu and Zn IDF concentrations were greater (P < 0.05) in HTM vs. STM and ORG supplemented steers, and Mn concentrations were greater (P < 0.05) in HTM and ORG vs. STM supplemented steers. At 24 h post dosing, IDF Zn concentrations were greater (P < 0.05) in HTM vs STM and ORG supplemented steers and Cu and Mn concentrations were similar across treatments. At 12 and 24 h post dosing the percent Cu and Zn released following dialysis was greater (P < 0.05) in HTM vs STM and ORG supplemented steers. The percent released of Cu, Mn, and Zn at 0 h, and Mn at 12 and 24 h were similar across treatments. Data indicate that a greater concentration of Cu and Zn from HTM is loosely bound to the ruminal IDF.
PSXII-7 Supplementing beef cattle finishing diets with ruminal protected live yeast affected fatty acid profiles in meat
Authors: Yang Wenzhu , He Maolong , Shen Yizhao , Ran Tao , Alzahal Ousama
Published: November 2020

Fatty acid (FA) composition in beef is related to beef quality and human health. It was recently reported that feeding active dried yeast (ADY) in finishing bull altered some FA of longissimus muscle. The objective was to evaluate the effects of adding ruminally protected versus non-protected ADY on FA profiles of the pars costalis diaphragmatis (PCD) muscle of beef cattle. Seventy-five Angus steers (initial BW 448 kg) were assigned to a randomized complete block design with five treatments: control (no additives), antibiotics (ANT, 330 mg monensin + 110 mg tylosin/d), ADY (1.5 g/d), encapsulated ADY (EDY, 3 g/d) and combination of ADY and EDY (MDY). The encapsulated ADY consisted of 1.5 g ADY and 2 g capsule. Antibiotics, ADY and EDY were top-dressed to a diet containing 10% barley silage and 90% barley concentrate (DM basis). The PCD samples were collected from cattle at slaughter. Intakes (g/d) of total FA (144), saturated FA (SFA; 41), monounsaturated FA (MUFA, 16) and polyunsaturated FA (PUFA, 87) were not different among treatments. Proportion of SFA (49.0%) and MUFA (48.2%) in PCD did not differ among treatments, whereas the proportion of PUFA was greater (P < 0.05) with EDY (3.0%) and MDY (3.0%) than control (2.4%). The proportion of n-3 FA also tended (P < 0.06) to be greater with EDY (0.49%) and MDY (0.50%) than control (0.41%) and ADY (0.41%). Steers fed EDY and MDY enhanced (P < 0.05) the proportion of linoleic acid (LA n-6) and decosapentaenoic acid (DPA n-3) compared with control. These results indicated that feeding EDY and MDY increased amounts of PUFA, FA n-3, LA n-6 and DPA n-3. Inclusion of encapsulated yeasts to diet might increase the amount of bioactive yeasts reached intestines and result in better utilization of PUFA from the digesta and increase the accumulation in the intramuscular fat.
PSXII-17 Trace minerals source influences the performance of Nellore cattle in the growing phase during the transition between dry to rainy season in Brazil
Authors: Cidrini Iorrano A , Lage Josiane F , Ferreira Igor , Oliveira Karla , Prados Laura F , Siqueira Gustavo R , Resende Flávio D
Published: November 2020

The relative bioavailability of trace minerals may vary between the sources and impact the animal performance. The study was carried out to evaluate the effect of TM source (Cu and Zn) on the liver concentration and performance of Nellore cattle supplemented in the growing phase during the transition between dry to rainy season. A hundred and twenty Nellore young bulls (BW = 349.72 ± 24 kg; 24 months), blocked by BW, were assigned randomly to twelve paddocks (six paddocks/treatment and 10 animals/paddock). Animals grazing Urochloa brizantha cv. Marandu and supplemented at 5 g/kg BW with soybean meal, corn and mineral mix (250 g/kg of CP and 650 g/kg de NDT, natural matter basis). Supplements consisted of 40 mg Cu and 148 mg Zn/kg DM from either inorganic TM (ITM) or hydroxy TM (HTM) Intellibond® sources. Liver samples were collected at the beginning and end of the study (three animals per paddock). Animals were weighed at each period (30 days) during three periods. Period was used as a REPEATED measurement for BW and values of initial BW as independent covariates for all variables. Paddock was considered experimental unit. Data were analyzed by ANOVA using PROC MIXED, SAS 9.4. The animals supplemented with HTM had higher (+0.037 kg/day) general ADG (day 0 to 90; P = 0.012), with 0.469 and 0.506 kg/day to ITM and HTM, respectively. Final BW (day 90) from animals fed HTM was 5.13 kg higher than ITM (391.97 vs. 397.11 kg BW; P = 0.030). No differences were found in the liver concentrations of Cu and Zn between ITM or HTM (P ≥ 0.288). Cu and Zn from HTM improve the performance of animals supplemented in pasture compared to ITM sources.
PSX-16 Genome-wide association studies for growth and carcass traits in Russian sheep
Authors: Deniskova Tatiana Evgenievna , Petrov Sergey N , Sermyagin Alexander A , Fornara Margaret S , Dotsev Arsen V , Reyer Henry , Wimmers Klaus , Bagirov Vugar A , Brem Gottfried , Zinovieva Natalia A
Published: November 2020

Breeding fast-growing sheep with good carcass traits is beneficial for lamb producers. However, genomic selection for relevant traits is still lagging in Russian sheep industry. In this regard, detection of the QTLs and candidate genes specific for local sheep is of great scientific and practical interest in Russia. In our research, we aimed to perform GWAS for growth and carcass traits in the QTL-mapping sheep population obtained from crossing slow- and fast-growing breeds. Backcrosses from (Katahdin× Romanov) × Romanov mapping population were genotyped with Ovine Infinium HD SNP BeadChip (Illumina, USA). Quality control in PLINK v.1.9 resulted in 459,868 SNPs which were used for GWAS. Threshold p-value for Bonferroni genome-wide significance was estimated as p = 1.09х10–7. The Manhattan plots were visualized in R package qqman. The measurements included body weight (BW), chest depth (CD), chest width (CW), and width at the iliac tubercle (WT) were recorded at the age of 6, 42 and 180 days. Significant SNPs including oar3_OAR7_44462236 (p = 8.40E-07), oar3_OAR7_44496608 (p = 8.40E-07) and oar3_OAR7_44975375 (p = 8.60E-07) were associated with WT at age of 180 days (13.31±0.23 cm). In addition, genomic regions located on chromosome 7 (44462236 – 44975375) and chromosome 2 (148067154 – 148077728) contained SNPs associated with CD at age of 180 days (21.42±0.39 cm) as well as with WT at age of 180 days. One SNPs (oar3_OAR4_4568047) on chromosome 4 and four SNPs on chromosome 7 (oar3_OAR7_44462236, oar3_OAR7_44496608, oar3_OAR7_44975375, and oar3_OAR7_45012432) were associated with BW at age of 180 days (22.61± 0.89 cm). The genes identified by GWAS were annotated. There were candidates responsible for bone metabolism, prenatal growth, skeletal muscle growth, related to meat quality and involved in carbohydrate and lipid metabolism. The reported study was funded by RFBR, project No. 17-29-08015.
PSX-23 Predicting feedstuff associative effects in goats
Authors: Tsukahara Yoko , Puchala Ryszard , Goetsch Arthur L
Published: November 2020

The objective was to develop means of predicting effects of supplementation on forage and total ME intake in goats. A database of treatment mean observations from the literature currently has 529 individual animal observations with ad libitum intake from 24 studies. Essential data were supplement and forage OM digestibility without supplementation or sufficient information for estimation, total diet OM digestibility, forage and supplement CP concentration and OM intake, and BW. Intake of ME was assumed 15.104 MJ/kg digested OM. For observations with supplementation, forage ME intake was the difference between total and supplement ME intake. The original database had 134 observations, although 24 were omitted because of questionable values and(or) unlikely estimates. Forage averaged 9.4 MJ/kg DM of ME (SD=1.77, 4.6–12.6), 59.1% OM digestibility without supplementation (SD=8.67, 42.9–77.1; AOMDIGFOR), and 8.1% CP (SD=3.72, 2.1–17.1) (PTCPFOR), and supplement was 12.3 MJ/kg ME (SD=1.38, 7.1–15.1) and 28.4% CP (SD=41.5, 0–288). Forage ME intake (MEIMBWFOR, kJ/kg BW0.75) was regressed against supplement ME intake (MEIMBWSUP, kJ/kg BW0.75), with inclusion of other variables tested. The equation explaining most variation (R2=0.77) was 155.9 ± 135.75 – (0.5403±0.04381 × MEIMBWSUP) – (41.0063±20.71841 × PTCPFOR) + (5.3497±2.31608 × AOMDIGFOR) + (0.74056±0.345002 × PTCPFOR × AOMDIGFOR), with P values of 0.253, < 0.001, 0.050, 0.023, and 0.034, respectively. The mean difference between observed and predicted MEIMBWFOR (379±15.0 and 382±12.8, respectively) was -3±7.4, with minimum and maximum values of -181 and 167, respectively. The equation for the regression of residual MEIMBWFOR (observed – predicted) against predicted values was -10±22.3 + (0.018±0.0553 × predicted MEIMBWFOR), with the intercept and slope not different from 0 (P = 0.670 and 0.739, respectively). Equations describing associative effects can be used to predict the quantity of a particular supplement with a given forage necessary to meet nutrient requirements of goats in specific production settings.
PSX-7 Effect of varying levels of hempseed meal supplementation on animal performance, rumen fermentation, and blood metabolites of growing meat goats
Authors: Abrahamsen Frank W , Gurung Nar , Abdela Woubit , Reddy Gopal , Mullenix Kim
Published: November 2020

Hempseed meal (HSM) is a byproduct of hemp oil production and is high in crude protein, fiber, and fat, making it a potential feedstuff for ruminants. The objective of this study was to evaluate the effect of HSM supplementation on growth performance, rumen fermentation and blood chemistry profile of growing meat goats. Forty castrated, Boer cross goats were randomly assigned to one of the four treatments (n = 10): control, 10%, 20%, and 30% HSM supplementation. Data collected over a period of a 60-day feeding trial were analyzed utilizing the mixed model analysis function of SYSTAT, version 13. The result revealed total live weight gain decreased with the increasing levels of HSM supplementation 10.75, 9.53, 8.48, and 7.80 kg, for 0, 10, 20, and 30%, respectively. Average daily gain followed the same trend 0.179, 0.159, 0.141, and 0.13 kg, with a significant difference (P < 0.05) observed between the control and 30 % supplementation. Conversely, feed to gain ratio increased with the increasing levels of supplementation 9.0, 10.2, 11.9, 12.2, likewise a significant difference was observed (P < 0.05) between the control and 30% supplementation. Acetic, propionic, butyric, valeric, iso-valeric, and iso-butyric acid concentrations as well as the total VFA concentration decreased significantly (P < 0.05) with the increasing level of supplementation. Acetic to propionic acid ratios increased with increasing level of supplementation 3.43, 4.36, 4.52, and 4.59, significant differences (P < 0.05) were observed between control-20% and 30% HSM group. Serum glucose concentration decreased with an increasing rate of HSM supplementation while BUN concentration increased with no significant differences. These findings provide new insights into the feeding value of HSM for meat goats; however, further research needs to be conducted to determine the optimal level of supplementation.
PSX-2 Antioxidant system characteristics in Saanen goats depending on lactation period
Authors: Kurilova Anastasiia A , Bakhta Alesya A , Karpenko Larisa Y , Plemyashov Kirill , Kozitcyna Anna I , Balykina Anna B , Enukashvili Abram I , Polistovskaia Polina A , Ershova Olga N , Dushenina Olga A
Published: November 2020

Dairy goats require attention and high-quality feeding during the lactation due to metabolism intensity. The metabolic rate during different lactation periods in order to better understanding production physiology in Saanen goats is the case of interest. The aim of this research was to evaluate antioxidant system characteristics in Saanen goats depending on lactation period. The experiment was conducted in the north-western region of Russian Federation, in the laboratory of the biochemistry and physiology department, FSBEI of Higher Education «SPbSAVM». The experimental group included 30 Saanen goats, 2nd–3rd lactations, selected using matched pairs method. The blood samples were taken 3 times: at the start of the lactation (2 days after parturition), at peak lactation performance (45 days after parturition) and before the interlactation period (4 months after parturition). Control group included 30 non-lactating Saanen goats, same age. The blood samples in control group animal were taken once. The blood levels of lipid peroxygenation markers (malondialdehyde, dienketone and conjugated dienes) and superoxide dismutase and catalase activity were assessed by standard methods. Results presented as mean±standard error of the mean. Student’s t-test was used after proving normal distribution. Level of significance is labeled as P < 0.05. The results are displayed in table 1 and 2. After analyzing the received data of antioxidant system characteristics the free radical oxidation highest intensity were revealed at the start of the lactation and at peak lactation performance, which indicates the development of oxidative stress in this periods. Also antioxidant enzymes’ activity was reduced during the peak lactation performance and remained at the control group level at the start of the lactation. This indicates free radical oxidation processes decompensation during the peak lactation performance. Thus, due to the development of decompensated oxidative stress in high milk producing ability animals during peak lactation, exogenous use of anti-oxidants is recommended.
PSIV-31 Do community-engaged learning courses benefit the equine student over a traditional laboratory setting?
Authors: Walters Avery , Cagle-Holtcamp Katie , Nicodemus Molly , Evans Holly , Lee Samantha , Gilmore Alicia
Published: November 2020

Vocational training is essential in developing both the skills and confidence to perform these activities within a profession. This type of training can be achieved through a traditional laboratory setting or within a laboratory centered around community engagement activities. While the benefits of both types of pedagogical strategies have been documented, comparison of these approaches to teaching in the equine environment is limited, and yet, development of skills and confidence is essential to the equine student as they step into the equine industry. Therefore, the objective of the study was to compare development of students’ confidence levels and skills through a traditional equine laboratory-setting to that of a community-engaged pedagogy. The study was conducted over the fall semester. A survey instrument was given at the beginning (pre-) and end (post-) of each semester for a weekly 2-hour traditional equine laboratory (TL; n = 36) and an equine course with a weekly 2-hour equine community engagement activity (CE; n = 47). Students in both course types completed a total of 30 hours handling horses during the semester. The survey consisted of 18 questions evaluating the student’s confidence in their perceived equine horsemanship skills. Students ranked their confidence from 1–5 with 5 indicating higher confidence. A skill assessment was completed by course instructors in conjunction with the students’ self-evaluation surveys. The skill assessment consisted of 10 questions with instructors ranking skills from 1–4 with 4 indicating higher skill level. Paired samples t-tests showed significant differences by the end of the semester in the skill assessment scores for both the TL and CE courses (P < 0.01) and in the student-perceived confidence levels for the CE course (P < 0.01). Although results indicate that both pedagogical strategies can be beneficial in equine skill development, community-engaged learning courses can provide a more effective approach to improving confidence in equine students.
PSI-30 Evaluation of urine estrone sulfate (P-Test) in beef cattle as an alternative pregnancy detection method
Authors: Hooten Bailey , Runyan Cheyenne , Roper David , Smith William B , Dias Nicholas W , Mercadante Vitor R G
Published: November 2020

Pregnancy detection in cattle can be expensive and labor intensive to producers. A simple, cost-efficient method of determining early pregnancy, chute side, is lacking within the industry. This study tested various proven pregnancy detection methods against an alternative method. Pregnancy was assessed by ultrasonography, blood serum pregnancy-specific protein B (PSPB), and urine estrone sulfate (“P-Test”). A fixed timed AI (FTAI) protocol was conducted on 14 predominantly British cattle housed at Tarleton State University in Stephenville, TX. Cows were synchronized using the co-synch plus 7 day CIDR protocol, with PGF injection of d 7. Heifers were synchronized similarly with the exception of GnRH injection on d 1. Estrotech patch scores (1 – 4, 1 showing little signs of estrus to 4 presenting signs of estrus) were utilized to indicate estrus activity prior to FTAI (21.4% vs. 78.6% females scored 1 vs. 4, respectively). FTAI was performed on protocol d 10 along with a 2mL injection of GnRH. Serum for PSPB analysis was collected at d 30 and 60 post insemination, while urine was sampled on d 60. Overall 53.8% (ultrasonography) and 71.4% (PSPB) of cattle were determined to be pregnant at d 30 post FTAI. Chi squared analysis proved that PSPB and ultrasound were similar at detecting pregnancy (P = 0.04). At d 60 “P-Test” color varied indicating differing levels of estrone sulfate. A t-test revealed increased PSPB from d 30–60 post FTAI (P < 0.0001); however, “P-Test” could not predict similar results (P = 0.655). Data suggest the “P-Test” is not a consistent method to diagnose early pregnancy. Future studies may be warranted to investigate a more desirable time point for utilizing the chute side “P-Test” as a reliable method to determine pregnancy.
Development of a rule-based system to enhance the data consistency and usability of COBie datasheets☆
Authors: Kumar Vishal , Teo Ai Lin Evelyn
Published: November 2020

Building information modeling (BIM) for facilities management (FM) has been gaining considerable attention. Construction operations building information exchange (COBie) datasheets are conceptualized as an electronic format of data for FM handover extracted from the BIM model and supplemented with information from other sources. To build an efficient COBie datasheet, it is advocated to build and verify data at all stages of design and construction, commonly known as data drops. Nevertheless, data consistency verification is a difficult task pertaining to COBie's complex structure and data representation. This study aims to understand the challenges associated with the COBie datasheet verification and consistency checking process, especially during data drop stages, and develop a solution to mitigate these challenges. The study uses a combined methodology of design thinking and waterfall model from the software development process. The outcome of the research study manifests in a prototype application. The prototype application can help in verifying COBie datasheet consistency during data drop stages. Additionally, this study proposes a new dimension to utilize the COBie datasheet to track various asset-related changes in a project by comparing COBie datasheets and visualizing this data in a visually interactive manner using a property graph model.
Is salvage radiotherapy optimal to patients with occult cervical cancer undergoing inadvertent simple hysterectomy? A propensity score-matched analysis of a nationwide clinical oncology database
Authors: Wang Yanhong , Ouyang Yi , Su Jingjing , Xiao Lihua , Bai Zhigang , Cai Qunrong , Cao Xinping
Published: November 2020

Objective

We used National Cancer Institute’s Surveillance, Epidemiology and End Result database to assess the role of salvage radiotherapy for women with unanticipated cervical cancer after simple hysterectomy.

Methods

Patients with non-metastatic cervical cancer and meeting inclusion criteria were divided into three groups based on treatment strategy: simple hysterectomy, salvage radiotherapy after hysterectomy and radical surgery. Parallel propensity score-matched datasets were established for salvage radiotherapy group vs. simple hysterectomy group (matching ratio 1: 1), and salvage radiotherapy group vs. radical surgery group (matching ratio 1:2). The primary endpoint was the overall survival advantage of salvage radiotherapy over simple hysterectomy or radical surgery within the propensity score-matched datasets.

Results

In total, 2682 patients were recruited: 647 in the simple hysterectomy group, 564 in the salvage radiotherapy group and 1471 in the radical surgery group. Age, race, histology, grade, FIGO stage, insured and marital status and chemotherapy were comprised in propensity score-matched. Matching resulted in two comparison groups with neglectable differences in most variables, except for black race, FIGO stage III and chemotherapy in first matching. In the matched analysis for salvage radiotherapy vs. simple hysterectomy, the median follow-up time was 39 versus 32 months. In the matched analysis for salvage radiotherapy vs. radical surgery, the median follow-up time was 39 and 41 months, respectively. Salvage radiotherapy (HR 0.53, P = 0.046) significantly improved overall survival compared with simple hysterectomy, while salvage radiotherapy cannot achieve similar overall survival to radical surgery (HR 1.317, P = 0.045).

Conclusions

This is the largest study of the effect of salvage radiotherapy on overall survival in patients with unanticipated cervical cancer. Salvage radiotherapy can improve overall survival compared with hysterectomy alone, while cannot achieve comparable survival to radical surgery.
Protein phosphatase NtPP2C2b and MAP kinase NtMPK4 act in concert to modulate nicotine biosynthesis
Authors: Liu Xiaoyu , Singh Sanjay Kumar , Patra Barunava , Liu Yongliang , Wang Bingwu , Wang Jinsheng , Pattanaik Sitakanta , Yuan Ling
Published: November 2020

Protein phosphatases (PPs) and protein kinases (PKs) regulate numerous developmental, defense, and phytohormone signaling processes in plants. However, the underlying regulatory mechanism governing biosynthesis of specialized metabolites, such as alkaloids, by the combined effects of PPs and PKs, is insufficiently understood. Here, we report the characterization of a group B protein phosphatase type 2C, NtPP2C2b, that likely acts upstream of the NICOTINE2 locus APETALA 2/Ethylene Response Factors (AP2/ERFs), to regulate nicotine biosynthesis in tobacco. Similar to the nicotine pathway genes, NtPP2C2b is highly expressed in roots and induced by jasmonic acid (JA). Overexpression of NtPP2C2b in transgenic hairy roots or stable transgenic tobacco plants repressed nicotine pathway gene expression and reduced nicotine accumulation. Additionally, transient overexpression of NtPP2C2b, together with the NtERF221, repressed transactivation of the quinolinate phosphoribosyltransferase promoter in tobacco cells. We further demonstrate that the JA-responsive tobacco mitogen-activated protein kinase (MAPK) 4 interacts with NtPP2C2b in yeast and plant cells. Conditional overexpression of NtMPK4 in tobacco hairy roots up-regulated nicotine pathway gene expression and increased nicotine accumulation. Our findings suggest that a previously uncharacterized PP-PK module acts to modulate alkaloid biosynthesis, highlighting the importance of post-translational control in the biosynthesis of specialized plant metabolites.
Miniature inverted repeat transposable elements cis-regulate circular RNA expression and promote ethylene biosynthesis, reducing heat tolerance in Populus tomentosa
Authors: Song Yuepeng , Bu Chenhao , Chen Panfei , Liu Peng , Zhang Deqiang
Published: November 2020

Transposable elements (TEs) and their reverse complementary sequence pairs (RCPs) are enriched around loci that produce circular RNAs (circRNAs) in plants. However, the function of these TE–RCP pairs in modulating circRNA expression remains elusive. Here, we identified 4609 circRNAs in poplar (Populus tomentosa) and showed that miniature inverted repeat transposable elements (MITEs)–RCPs were enriched in circRNA flanking regions. Moreover, we used expression quantitative trait nucleotide (eQTN) mapping to decipher the cis-regulatory role of MITEs. eQTN results showed that 14 single-nucleotide polymorphisms (SNPs) were significantly associated with Circ_0000408 and Circ_0003418 levels and the lead associated SNPs were located in MITE–RCP regions, indicating that MITE–RCP sequence variations affect exon circularization. Overexpression and knockdown analysis showed that Circ_0003418 positively modulated its parental gene, which encodes the RING-type E3 ligase XBAT32, and specifically increased the expression of the PtoXBAT32.5 transcript variant, which lacks the E3 ubiquitin ligase domain. Under heat stress, PtoXBAT32.5 expression was induced with up-regulation of Circ_0003418, resulting in increased production of ethylene and peroxidation of membrane lipids. Our findings thus reveal the cis-regulatory mechanism by which a MITE–RCP pair affects circRNA abundance in poplar and indicate that Circ_0003418 is a negative regulator of poplar heat tolerance via the ubiquitin-mediated protein modification pathway.
Postoperative Septic Shock
Authors: Littlejohn James E.
Published: November 2020

This chapter discusses postoperative sepsis, which is a severe systemic inflammatory response to an infection. Sepsis is particularly difficult to diagnose in the early postoperative period because the systemic inflammatory response syndrome (SIRS) from cardiac surgery alone can mimic the early symptoms. Organ dysfunction identified using the Sequential Organ Failure Assessment (SOFA) score has been replacing the SIRS criteria as a more sensitive means by which to identify physiologic effects of infection. Evidence from studies using the SOFA-guided definition supports the use of the Sepsis-3 criteria for early identification and treatment of patients who are at high risk of adverse outcomes from sepsis and septic shock. The chapter also explores the role of biomarkers to expedite diagnosis and management of infections and/or sepsis. Procalcitonin levels are a biomarker that shows promise in predicting bacteremia, as well as lending clinical support to wean antibiotic duration in certain circumstances. The chapter then details the treatment for sepsis and septic shock. The first objective is to identify possible causes of infection and accomplish source control. Once sepsis has been identified, early resuscitation interventions are pivotal to reduce morbidity and mortality.
“I hear there is a new medicine that means I don’t need to take so many pills?”
Authors: Newman Gretchen Snoeyenbos , Wood Brian R.
Published: November 2020

Judging potential benefits versus risks of an antiretroviral therapy (ART) regimen switch or update has become a mainstay of HIV clinical medicine. A regimen switch for a person with HIV who has long-standing viral suppression may minimize toxicity and maximize quality of life but requires shared decision-making and a careful preswitch evaluation. All regimen changes should be preceded by a review of the complete ART history and resistance profile, evaluation for hepatitis B co-infection, and potential drug-drug interactions or drug-food requirements, as well as contingency planning in case of unforeseen side effects or logistical issues. These steps ensure a successful ART regimen switch.
“I’m not that good with taking pills every day”
Authors: Max Blake
Published: November 2020

The treatment goal of antiretroviral therapy is to achieve and maintain an undetectable viral load. Patients on antiretroviral therapy who do not achieve this goal can develop drug resistance to one or more drugs in the regimen. Poor medication adherence is the most likely reason for virologic failure and the development of drug resistance. Development of new drugs and clinical availability of HIV resistance tests has given providers more options for treatment-experienced patients with extensive drug resistance. Evaluating patients with extensive drug resistance requires knowledge of previous antiretroviral drug regimens, previous drug resistance tests, and interpretation of those tests. Managing treatment-experienced patients can be complex and may require consultation with an HIV expert.
“My doctor changed my HIV medications, and now my hepatitis B is back”
Authors: Meisner Jessica A. , Jain Mamta K.
Published: November 2020

This chapter reviews the evaluation and management of a patient with HIV and hepatitis B virus (HBV) co-infection who has an acute rise in liver function tests (LFTs) after a change in his HIV regimen. Abnormal LFTs in a patient with HIV require a thorough workup, including review of medications, history, laboratory evaluation, and often an ultrasound. It describes the reasoning for being placed on active agents for both HIV and HBV. It recommends the use of a tenofovir-containing backbone in antiretroviral therapy (ART) and avoidance of lamivudine monotherapy. A change in ART that does not cover HBV could precipitate HBV rebound and a rise in LFTs.
“My baby has a fever”
Authors: Aziz Mariam
Published: November 2020

HIV infection should be considered in any infant with recurrent illness, developmental delay, or failure to thrive who is high risk, that is, born to a mother with HIV who did not receive intrapartum or antepartum antiretroviral therapy, mothers who received only intrapartum antiretroviral therapy, mothers who received antiretroviral therapy but did not experience virologic suppression at the time of delivery, or mothers who had HIV seroconversion during pregnancy. In these patients, Pneumocystis jirovecii pneumonia prophylaxis should be considered starting at 4–6 weeks of age, and PJP should be considered in the differential diagnosis of infants with HIV with hypoxia and respiratory distress. Diagnosis of HIV infection is made using HIV-1 RNA or HIV DNA polymerase chain reaction testing rather than HIV antibody testing because of the presence of maternal antibodies in this age. There are unique issues related to adherence and the treatment of HIV in growing and immunologically immature children.
“I’ve been rashed and confused”: Part 1
Authors: Barker David E.
Published: November 2020

Patients with advanced immunosuppression from AIDS can have a wide variety of causes of diminished alertness (delirium). Diagnostic considerations include results from neuroimaging to rule-out space occupying lesions and permit CSF examination. Presence or absence of other imaging findings especially on MRI of white matter changes, enhancement, or ventriculitis. Serologic testing can be helpful especially in excluding neurosyphilis and cryptococcal disease. Presence of findings outside the CNS (e.g. the lungs, bone marrow, or eyes) can also provide important clues.
“Doc, I think I have a hemorrhoid”
Authors: Dunlevy Hillary
Published: November 2020

Human papillomavirus (HPV) is a pervasive infection worldwide, with high rates of infection in people living with HIV. HPV lesions range from benign condyloma to precancerous and cancerous lesions in sites of anogenital and oropharyngeal HPV infection. The most effective prevention of infection, condylomas, precancerous lesions, and malignancy is through HPV vaccination, with recently expanded indications for 9-valent HPV vaccination up to age 45. Multiple modalities exist for treatment of anogenital condyloma, with high recurrence rates for most. For millions of people living with HIV, screening for premalignant lesions has been found to prevent HPV-related cervical cancer. Anal Papanicolaou testing and high-resolution anoscopy with biopsy are effective at identifying precancerous lesions. Treatment is available but has high rates of recurrence of HPV-related lesions. Studies are underway to help create guidelines for anal HPV lesion screening and cancer prevention.
“I feel fine. Do I really need to take a cholesterol pill?”
Authors: Nishtala Arvind , Feinstein Matthew J.
Published: November 2020

With widespread antiretroviral therapy (ART) accessibility and uptake, HIV has transitioned in many ways to a chronic condition marked by heightened risks of non-communicable diseases. Several clinical and epidemiological studies over the past two decades have demonstrated elevated risks for cardiovascular diseases (CVDs) among people with HIV. These risks appear to be particularly elevated among people with histories of long periods of uncontrolled viremia and CD4 lymphopenia, and dovetail with traditional risk factors (such as smoking) that are common among people with HIV. This chapter presents a discussion of the evolving epidemiology, clinical manifestations, and putative mechanisms of CVDs among people with HIV.
“I want to stop using drugs. What should I do next?”
Authors: Elion Rick
Published: November 2020

The care of individuals living with HIV who inject drugs involves a unique subset of patients. People who inject drugs have become a key driver of new cases in the United States as the opiate epidemic has impacted such a large group of the population. The proliferation of oral narcotics prompted increased use of injectable opiates as the sale of oral medications became both more expensive and difficult. This epidemic has been confluent with the development of addiction, which can be very hard to treat, as well as the impact of adherence of active addiction on antiretroviral therapy medications. The challenge to the clinician caring for people who inject drugs is to become fluent in the treatment of HIV, hepatitis C virus, and hepatitis B virus, the psychosocial skills of dealing with addiction, and opiate substitution therapy. The chapter outlines approaches to care for this population that can assist with these clinical challenges as the actual selection of medications will not be unique for this population. Therefore, different approaches are being learned, not different sets of medications (except for opiate substitution treatment).
“What shots do I need?”
Authors: Hadjivassiliou Giorgos , Overton Edgar T.
Published: November 2020

This chapter reviews the current recommendations for adult persons living with HIV (PLWH) in the United States regarding vaccine-preventable diseases. In clinical practice, PLWH should be offered annual influenza vaccine; a combination of tetanus, diphtheria, and pertussis vaccine; depending on previous vaccination, pneumococcal vaccine, meningococcal conjugate vaccine, and hepatitis A and hepatitis B vaccines. Human papilloma virus vaccine can be given in PLWH up until the age of 26. Live vaccines, including the measles-mumps-rubella vaccine and varicella vaccine, can be given in those individuals who have CD4 cell counts of greater than 200 cells/mm3 and did not receive these vaccines during childhood. Some expert panels endorse recombinant zoster vaccination in PLWH at least 50 years old, although there is no current official recommendation from the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices. The chapter covers routine vaccinations for PLWH.
The Evolution of Benzodiazepine Receptor Agonists
Authors: Hansen Jamie L. , Atkinson Timothy J.
Published: November 2020

Benzodiazepines have been touted as safer alternatives to their barbiturate predecessor since their arrival on the market in 1960. Their proposed improved safety is based on their reported reduced drug interactions, lower abuse potential, and decreased respiratory depression. Benzodiazepines bind to the GABAA receptor and positively modulate GABAergic transmission and hyperpolarization of neuronal membranes. Individual agents are utilized differently depending on their varying degrees of hypnotic, anxiolytic, antiepileptic, muscle relaxant, and amnestic properties. Benzodiazepines are frequently classified by their half-life (t½), a key pharmacokinetic parameter that dictates the agents’ ability to precipitate dangerous withdrawals. The majority of benzodiazepines undergo phase I hepatic metabolism via cytochrome p450 that introduce the potential for drug interactions. Following hepatic metabolism, almost all agents within this drug class have active metabolites that have extended half-lives beyond that of the parent drug that prolong the duration of activity. Urine drug screens are an essential component of medication monitoring and require a foundational understanding of the parent drug, its metabolites, and what the available immunoassay is designed to detect. A similar drug class that is frequently grouped with benzodiazepines are Z-drugs. These agents were developed in attempt to create a sleep aid that lacked the undesirable qualities of benzos with an improved safety profile. Z-drugs share the common characteristic of being short-acting in nature and are proposed to cause less disruption in the normal sleep cycle than benzodiazepines.
Benzodiazepine Therapy
Authors: Guina Jeffrey , Merrill Brian , LeQuang Jo Ann
Published: November 2020

Benzodiazepines are some of the most commonly prescribed medications worldwide. When used appropriately for the right condition, patient, dose, and duration, these drugs can provide rapid relief of the symptoms of anxiety and insomnia for some patients, but they are also linked to a variety of adverse effects (whether used long-term, short-term, or as needed). Many patients are prescribed, and take, benzodiazepines long-term without ever receiving evidence-based first-line treatments such as psychotherapy, relaxation techniques, sleep hygiene education, or serotonergic agents. This chapter discusses the risks and benefits of, and alternatives to, benzodiazepines. The evidence-based indications and contraindications are discussed, as are putative biopsychosocial bases for effectiveness, ineffectiveness, and harm. The known potential adverse effects and drug-drug interactions are summarized. Finally, alternative fast-acting/acute and chronic treatments for anxiety and/or insomnia are discussed. Response to treatment—whether benzodiazepines, other pharmacological agents, or psychotherapy—must be assessed.
Use of Benzodiazepines and Z-Drugs in the Geriatric Population
Authors: Kitzen Jan M.
Published: November 2020

The benzodiazepine (BZD) class of drugs has proven to be a useful addition to therapeutic management of anxiety and sleep disorders in the adult population. However, after many years of experience with BZDs in elderly patients (≥65 years), a large body of evidence indicates that BZDs are no longer recommended for use in this segment of the population, except under special conditions. Several aging-related changes in physiology such as decreases in renal and hepatic function, altered central nervous system function and changes in body composition can lead to impaired excretion of drug, higher plasma levels and accumulation of these drugs in the body. Side effects such as sedation, dizziness, cognitive impairment, and diminished control of gait and balance functions place the elderly at greater risk of various adverse events, especially falls and fractures, compared to younger adults. Another class of drugs, known as Z-drugs is structurally dissimilar from the BZDs but able to bind to GABAA, receptors making them useful for management of insomnia. These drugs have also been found to pose significant hazards to the elderly and are also not recommended for use in elderly patients. Both of these classes of drugs are currently included in the AGS Beers Criteria® of potentially inappropriate medications for use in the elderly. Alternative pharmacologic approaches to managing these conditions include use of either serotonin-norepinephrine reuptake inhibitors or buspirone for anxiety and the use of either low doses of doxepin, melatonin, or the melatonin agonist ramelteon for management of insomnia. Cognitive behavioral therapy and other relaxation techniques offer non-pharmacologic approaches to managing these conditions, thereby decreasing the need for prescribing BZDs or Z-drugs in the elderly.
Benzodiazepine Receptors in the Periphery
Authors: Raffa Robert B.
Published: November 2020

The benzodiazepines are almost universally thought to produce one and only one pharmacologic effect: positive allosteric modulation of GABAA receptors located in the brain. This results in an increased Cl−ion influx, greater negative transmembrane potential difference, and neurons that are less likely to fire in response to anxiety-producing stimulation. Unfortunately, the simplicity and success of this mono-target belief has distracted researchers and clinicians from studying and appreciating their other pharmacology. A glaring example is the general lack of awareness of the peripheral benzodiazepine receptor. The peripheral benzodiazepine receptor alters mitochondrial function (energy supply), cholesterol transport, and immune function. A patient who is on long-term benzodiazepine therapy (or withdrawing from them) will have these sites affected, just as are the sites located in the brain. One can easily imagine that the adverse effects associated with the peripheral sites would be fundamental, varied, and potentially profound—involving lack of energy, altered cholesterol metabolism, and aberrant immune function.
Drug Withdrawal
Authors: Koob George F.
Published: November 2020

Drug withdrawal has long been considered a key symptom in the diagnosis of alcohol and substance use disorders. In this chapter, it is also conceptualized as a major motivational factor that drives compulsive drug taking. Drawing from the negative emotional components of withdrawal, termed hyperkatifeia (i.e., the negative emotional and motivational signs of withdrawal), the hypothesis here is that withdrawal sets up another major source of reinforcement—namely, negative reinforcement—for drug seeking in substance use disorders. From the perspective of the hyperkatifeia phenotype, withdrawal then returns to being a key part of moderate to severe alcohol and substance use disorders to become the primary factor that motivates sustained drug seeking. Such hyperkatifeia is mediated by a multidetermined neurocircuitry that compromises within-system neurochemical systems that are involved in the rewarding effects of drugs and promotes the activation of pro-stress neuromodulators that combine with a weakening or inadequate anti-stress response. Altogether, these neurocircuitry, neurochemical, and molecular changes lead to a negative emotional state (hyperkatifeia) that sets up an allostatic hedonic load that drives negative reinforcement. Under this framework, strong multidetermined buffers, if activated and sufficient to allow the reward and pro-stress systems to recover, may help return the organism to homeostasis.
Chemical, biological, radiological, and nuclear incidents
Authors: Greaves Ian , Porter Keith
Published: November 2020

A chemical, biological, radiological, or nuclear (CBRN) incident may occur as the result of an accident or specific act of terrorism. Events such as the Chernobyl nuclear incident in Ukraine, the Sarin gas release on the underground system in Tokyo, the anthrax releases in the US, and the Salisbury Novichok attack, highlight the necessity for a structured multi-agency and multi-disciplinary response of which medical support is an essential component. This chapter covers the mode of presentation, and then focuses on each type in turn. Scene safety, triage, and information gathering are described. For chemical incidents, decontamination and specific antidotes are also included. Characteristics of biological agents are defined, and methods of managing a radiation and nuclear incident are specifically covered, including managing the patient.
The Y dwarf population with HST: unlocking the secrets of our coolest neighbours – I. Overview and first astrometric results
Authors: Fontanive C , Bedin L R , Bardalez Gagliuffi D C
Published: November 2020

In this paper, we present our project that aims at determining accurate distances and proper motions for the Y brown dwarf population using the Hubble Space Telescope. We validate the program with our first results, using a single new epoch of observations of the Y0pec dwarf WISE J163940.83−684738.6. These new data allowed us to refine its proper motion and improve the accuracy of its parallax by a factor of three compared to previous determinations, now constrained to ϖ = 211.11 ± 0.56 mas. This newly derived absolute parallax corresponds to a distance of 4.737 ± 0.013 pc, an exquisite and unprecedented precision for faint ultracool Y dwarfs.