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Abstract Background Cerebrospinal fluid (CSF) pleocytosis may be seen in asymptomatic HIV-infected individuals. This finding complicates interpretation of CSF abnormalities when such individuals are evaluated for other central nervous system infections. The goal of this study was to determine the relationship between CSF pleocytosis, central nervous system (CNS) antiretroviral penetration, adherence to antiretroviral medication regimens, neurological symptoms and performance on neuropsychological tests. Methods Clinically stable HIV-infected individuals at any peripheral blood CD4+ T cell count or any plasma viral load were asked to attend study visits at entry and every 6 months thereafter for at least one year. At each visit, they underwent a standardized neurological and medication history; neurological examination; a brief neuropsychological test battery: venipuncture; lumbar puncture; and assessment of medication adherence. Generalized estimating equations (GEE) were used to assess the relationships between CSF pleocytosis and other variables. Results CSF pleocytosis was independently and significantly related to lack of current antiretroviral use (OR 5.9, 95% CI 1.8–18.6, p = 0.003), CD4 count > 200/ul (OR 23.4, 95% CI 3.1–177.3, p = 0.002) and detectable plasma HIV RNA (OR 3.3, 95% CI 1.1–9.4, p = 0.03). At visits where antiretrovirals were used, and taking into account detectable plasma HIV RNA, an antiretroviral regimen that contained two or more agents with good CNS penetration conferred a trend toward lower odds of CSF pleocytosis (OR 0.45, 95% CI 0.18–1.12, p = 0.087). Conclusion CSF pleocytosis is a characteristic of HIV disease that varies significantly with easily identifiable clinical and laboratory features. Use of antiretroviral agents decreases the odds of pleocytosis. This association may be stronger when the regimen contains two or more agents with good CNS penetration.

The objective of this study was to evaluate potency and timing of trenbolone acetate ( TBA ) administration on live performance and carcass characteristics of beef × dairy steers. A total of 6,895 beef × dairy steers [initial body weight ( BW ) = 157 ± 5.2 kg] were allotted into 30 pens, with pen as the experimental unit. Each pen was randomly assigned one of three implant treatments: 1) Revalor-IS ( IS ) at d 0, IS at d 80, and Revalor-XS ( XS ) at d 160 ( IS/IS/XS ); 2) Ralgro at d 0, IS at d 80, and XS at d 160 ( Ral/IS/XS ); or 3) Encore at d 0 and XS at d 160 ( Enc/XS ). Steers were blocked by arrival date, each pen was terminally sorted in three ways at 257 ± 22 days on feed and harvested at 329 ± 25 days on feed. For live and carcass outcomes, fixed effect of implant treatment and random effect of block was evaluated. Data are reported on a deads and removals out basis. Removals, morbidity, and mortality were similar ( P  ≥ 0.45). Steers administered TBA prior to d 160 were 5.8 kg heavier ( P  = 0.03) than Enc/XS steers at d 160. Final BW was not different ( P  = 0.78). Early administration of a TBA-containing implant resulted in an increased prevalence of bullers [2.40%, 5.18%, 6.86% (for Enc/XS, Ral/IS/XS, and IS/IS/XS) respectively; P  < 0.01]. Dry matter intake ( DMI ) was 2.3% greater ( P  < 0.01) in steers administered Enc/XS compared to IS/IS/XS; however, DMI as a percentage of BW, average daily gain, and feed efficiency were not different ( P  ≥ 0.12). Dressing percentage, hot carcass weight, heavy carcass occurrence, Longissimus muscle area, and 12th rib fat thickness were similar among all steers ( P  ≥ 0.28). Marbling score tended to be greatest for Enc/XS and Ral/IS/XS ( P  = 0.09). Enc/XS graded a greater proportion of USDA Prime and fewer USDA Select carcasses than IS/IS/XS ( P  < 0.05). Enc/XS and Ral/IS/XS tended ( P  = 0.09) to have more USDA Yield Grade ( YG ) 1 carcasses. While delayed administration or decreased total potency of TBA-containing implants may decrease buller incidence and improve Quality Grade, few differences were observed in live or carcass outcomes., Competing Interests: Authors J. P. Hutcheson and L.-A. J. Walter are employees of Merck Animal Health., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Background: The influence of previous syphilis on the course of a subsequent episode is unknown., Methods: Individuals enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis were allowed to enroll in the study again with subsequent syphilis. For each participant, the index episode was defined as the most recent syphilis episode for which the study entry visit was performed within 30 days of the syphilis diagnosis date. Venipuncture and lumbar puncture (LP) were performed. Total number of syphilis episodes was determined by review of medical and public health records. T. pallidum DNA in blood and rRNA in CSF were detected by polymerase chain reaction (PCR) and reverse transcriptase PCR. Odds ratios (ORs) with 95% confidence intervals (95% CI) were determined by logistic regression., Results: 651 individuals had one (n = 482), two (n = 121) or three or more (n = 48) episodes of syphilis. The proportion of individuals whose index episode was early latent stage was significantly higher in those with ≥3 syphilis episodes; this relationship was reduced to a trend when rate of testing was taken into account. Adjusted odds (aOR) of detection of T. pallidum DNA in blood or rRNA in CSF at the index episode were significantly lower in those with previous syphilis (0.17 [95% CI, 0.09-0.31] and 0.15 [95% CI, 0.07-0.35]). The aOR for neurosyphilis at the index episode was also significantly lower in individuals with previous syphilis (0.54 [95% CI, 0.34-0.87])., Conclusions: Previous syphilis attenuates the manifestations of subsequent infection with T. pallidum., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Individuals with previous syphilis may experience cognitive impairment. The goal of this study was to determine if those at high risk for laboratory-defined neurosyphilis are cognitively impaired, and whether treatment based on cerebrospinal fluid (CSF) findings results in better outcomes., Methods: Participants had a new syphilis diagnosis, serum RPR titer ≥ 1:32 or peripheral blood CD4+ T cells ≤ 350/ul (in persons living with HIV) and did not endorse neurological symptoms. They underwent computerized cognitive assessment with the CogState. Thirty-two were randomized to either undergo lumbar puncture (LP) or to not undergo LP and 14 underwent LP; 64 were not randomized and 48 opted to undergo LP., Results: Demographics, cognitive complaints and cognitive impairment did not differ between randomized and nonrandomized participants. Two-thirds were cognitively impaired, and impairment was not more common in those with cognitive complaints. The adjusted odds of increased severity of impairment were 3.8 times greater in those with CSF pleocytosis compared to those without. Time to cognitive normalization, improvement or decline did not differ between those who did not undergo LP and those who underwent LP and whose treatment was based on CSF analysis. Taking into account pre-treatment cognitive impairment, the risk of cognitive decline was lower in those with CSF pleocytosis treated for neurosyphilis compared to those without CSF pleocytosis not treated for neurosyphilis, (HR 0.24 (95% CI 0.07-0.88], p = 0.03)., Conclusion: In individuals at high risk for laboratory-defined neurosyphilis, cognitive complaints are not a good indicator of cognitive impairment. Severity of cognitive impairment was greater in those with CSF pleocytosis. Identification and treatment of those with neurosyphilis may mitigate subsequent cognitive decline., Competing Interests: The authors have declared that no competing interests exist.

Otosyphilis is a serious complication of syphilis.329 participants enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis underwent portable audiometry (250 Hz to 8000 Hz at 5-75 dB); it was repeated in 33 after otosyphilis treatment. Treponema pallidum spp pallidum ( T. pallidum ) DNA in blood was quantitated by polymerase chain reaction. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were determined by logistic, ordinal or Cox regression.166 (50.5%) had normal hearing; 15 (4.6%) had low frequency (LF) loss alone, 93 (28.3%) had high frequency (HF) loss alone, and 55 (16.7%) had both. Adjusted odds of any hearing loss were higher with detectable blood T. pallidum DNA (3.00 [1.58-5.69], p = 0.001), CSF pleocytosis (2.02 [1.12-3.66], p = 0.02), and older age (2.22 per 10-year increase, [1.70-2.91], p < 0.001). HRs of normalization of LF and HF loss were lower for older individuals (0.20 [0.07-0.63, p = 0.005] and 0.22 [0.05-0.94, p = 0.04]), and HRs for normalization of HF loss were lower for those with more severe loss (0.09 [0.02-0.43], p = 0.002), and in those with CSF pleocytosis (0.32 [0.11-0.96], p = 0.04).Older age and CSF pleocytosis increase the likelihood of otosyphilis and impair hearing recovery after otosyphilis treatment.

Background: Individuals with previous syphilis may be more likely to be asymptomatic when they are reinfected with Treponema pallidum., Methods: Individuals enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis were allowed to enroll in the study again with subsequent syphilis. For each participant, the index episode was defined as the most recent syphilis episode for which the study entry visit was performed within 30 days of the syphilis diagnosis date. Venipuncture and lumbar puncture were performed. The total number of syphilis episodes was determined by review of medical and public health records. Treponema pallidum DNA in blood and rRNA in CSF were detected using polymerase chain reaction (PCR) and reverse transcriptase PCR. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined using logistic regression., Results: 701 individuals had 1 (n = 478), 2 (n = 155), or ≥3 (n = 68) episodes of syphilis. The proportion of individuals whose index episode was asymptomatic significantly increased with increased number of syphilis episodes (P < .001). This difference was not explained by frequency of serological tests. Adjusted ORs (aORs) of detection of T. pallidum DNA in blood or rRNA in CSF at the index episode were significantly lower in those with previous syphilis (0.13; 95% CI, .08-.23, and 0.06, 95% CI, .02-.17). The aOR of neurosyphilis at the index episode was also significantly lower in individuals with previous syphilis (0.43; 95% CI, .27-.68)., Conclusions: Previous syphilis attenuates clinical and laboratory manifestations of infection with T. pallidum., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Data comparing neurosyphilis treatment regimens are limited., Methods: Participants were enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis that was conducted at the University of Washington between April 2003 to May 2014. They were diagnosed with syphilis and referred by their providers due to concerns for neurosyphilis. We evaluated 150 people with CSF abnormalities who were treated with either intravenous aqueous penicillin G (PenG) or intramuscular aqueous procaine penicillin G plus oral probenecid (APPG-P). An abnormal CSF diagnosis was defined as a white blood cell (WBC) count >20/µL, a CSF protein reading >50 mg/dL, or a reactive CSF-Venereal Disease Research Laboratory test (VDRL). Hazard ratios for normalization of CSF or serum measures were determined using Cox regression., Results: In individuals treated with either PenG or APPG-P, CSF WBCs and CSF-VDRL reactivity normalized within 12 months after treatment, while protein normalized more slowly and less completely. There was no relationship between treatment regimen or human immunodeficiency virus (HIV) status and likelihood of normalization of any measure. Among those living with HIV, CSF WBC counts and CSF-VDRL reactivity were more likely to normalize in those treated with antiretrovirals. Unexpectedly, CSF WBCs were more likely to normalize in those with low CD4+ T cell counts. When neurosyphilis was more stringently defined as a reactive CSF-VDRL, the relationship with the CD4+ T cell count remained unchanged., Conclusions: In the current antiretroviral treatment era, neurosyphilis treatment outcomes are not different for PenG and APPG-P, regardless of HIV status. The relationship between the normalization of CSF WBC counts and CD4+ T cell counts may indicate continued imprecision in neurosyphilis diagnostic criteria, due to HIV-related CSF pleocytosis., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Mild-to-moderate bone pain is the most commonly reported adverse event associated with pegfilgrastim., Aims: To investigate the effect of bone pain education on pegfilgrastim-related bone pain in patients with breast cancer receiving chemotherapy and pegfilgrastim., Design: Randomized, single-blind study., Settings: Forty-eight community oncology clinics throughout the United States., Participants: Three hundred women ≥18 years of age with newly diagnosed stage I -III breast cancer, who were planning ≥4 cycles of neoadjuvant or adjuvant chemotherapy with pegfilgrastim support starting in cycle 1., Methods: Patients were randomized 1:1 to view a general education DVD on chemotherapy side effects (GE-DVD) or a DVD on bone pain following chemotherapy and pegfilgrastim (BP-DVD). Patients recorded severity of bone pain on a scale of 0-10, location of pain, and use of bone pain medications (i.e., analgesics, antihistamines, and nonsteroidal anti-inflammatory drugs) for 5 days, beginning on the day of pegfilgrastim administration, in each of the first four chemotherapy cycles., Results: Patient-reported maximum bone pain was similar in the two groups (GE-DVD vs BP-DVD: cycle 1, 3.2 vs. 3.5, p = .3479; across all cycles, 4.1 vs. 4.6, p = .2196). Other measures of bone pain were also similar between the groups. Bone pain was highest in cycle 1 but decreased and then remained stable in subsequent cycles. Bone pain medication use was similar in both groups and was highest in cycle 1., Conclusions: The bone pain-specific education evaluated here did not improve perceptions of bone pain reported in this patient population., (Copyright © 2018 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Purpose: Mild-to-moderate bone pain is a commonly reported adverse event (AE) associated with pegfilgrastim. We evaluated the effect of prophylactic naproxen or loratadine vs no prophylactic treatment on pegfilgrastim-associated bone pain., Methods: In this open-label study (NCT01712009), women ≥ 18 years of age with newly diagnosed stage I-III breast cancer and an ECOG performance status ≤ 2 who were planning ≥ 4 cycles of adjuvant or neoadjuvant chemotherapy with pegfilgrastim support starting in cycle 1 were randomized 1:1:1 to receive naproxen, loratadine, or no treatment to prevent pegfilgrastim-associated bone pain. The primary endpoint was all-grade bone pain in cycle 1 from AE reporting. Secondary endpoints included bone pain in cycles 2-4 and across all cycles from AE reporting and patient-reported bone pain by cycle and across all cycles., Results: Six hundred patients were enrolled. Most patients (83.0%) were white, and mean (SD) age was 54.2 (11.1) years. The percentage of patients with all-grade bone pain in cycle 1 from AE reporting in the naproxen, loratadine, and no prophylaxis groups was 40.3, 42.5, and 46.6%, respectively; differences between the treatment groups were not statistically significant. Maximum, mean, and area under the curve for patient-reported bone pain were consistently lower in the naproxen and loratadine groups than in the no prophylaxis group; some of these differences were significant. Loratadine was associated with fewer treatment-related AEs and discontinuations than naproxen., Conclusions: Given its tolerability, its ease of administration, and its potential benefit, treatment with loratadine should be considered to help prevent bone pain in patients receiving chemotherapy and pegfilgrastim., Clinical Trial Registration: ClinicalTrials.gov ; NCT01712009.

Background: Individuals infected with human immunodeficiency virus (HIV) who have previously had syphilis may have cognitive impairment. We tested the hypothesis that neurosyphilis causes cognitive impairment in HIV by amplifying HIV-related central nervous system (CNS) inflammation., Methods: HIV-infected participants enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis underwent the mental alternation test (MAT), venipuncture, and lumbar puncture. CSF concentrations of chemokine (C-X-C motif) ligand 10 (CXCL10), chemokine (C-C motif) ligand 2 (CCL2), and neurofilament light (NFL) were determined by commercial assays. The proportion of peripheral blood mononuclear cells (PBMCs) and of CSF white blood cells (WBCs) that were activated monocytes (CD14+CD16+) was determined by flow cytometry. Neurosyphilis was defined as detection of Treponema pallidum 16S RNA in CSF or CSF white blood cells (WBCs) >20/uL or a reactive CSF-Venereal Disease Research Laboratory (VDRL) test; uncomplicated syphilis was defined as undetectable CSF T. pallidum, CSF WBCs ≤5/uL and nonreactive CSF-VDRL. MAT <18 was considered low., Results: Median proportion of PBMCs that were activated monocytes (16.6 vs. 5.3), and median CSF CXCL10 (10658 vs. 2530 units), CCL2 (519 vs. 337 units) and HIV RNA (727 vs. 50 c/mL) were higher in neurosyphilis than in uncomplicated syphilis (P ≤ .001 for all comparisons). Neurosyphilis was not related to low MAT scores. Participants with low MAT scores had higher median CSF CXCL10 (10299 vs. 3650 units, P = .008) and CCL2 (519 vs. 365 units, P = .04) concentrations than those with high MAT scores., Conclusions: Neurosyphilis may augment HIV-associated CNS inflammation, but it does not explain cognitive impairment in HIV-infected individuals with syphilis., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Holstein steers raised for beef production consistently have a higher prevalence and more severe form of liver abscesses than cattle of beef breeds. A study was conducted to compare bacterial flora of liver abscesses collected from multiple abattoirs from 4 groups of cattle, arranged in a 2 × 2 factorial design, consisting of crossbred cattle and Holstein steers, and each group fed a finishing diet supplemented with or without tylosin. A total of 383 liver abscess samples, consisting of 94 and 81 from crossbred cattle and 89 and 119 from Holstein steers fed finishing diets with or without tylosin, respectively, were subjected for anaerobic and aerobic bacterial isolations. The minimum inhibitory concentrations (MIC) of tylosin to the predominant bacterial species were determined. The likelihood chi-square test was performed to assess unadjusted differences in bacterial prevalence proportions between the 2 types of cattle (crossbred and Holstein steers) and feed type (tylosin or no tylosin). There was no interaction between cattle type and tylosin inclusion on the prevalence of any of the bacterial species isolated. Liver abscesses from Holstein steers yielded a higher total number of isolates compared to liver abscesses from crossbred cattle (1060 vs. 788). subsp. was isolated from all abscesses. The prevalence of subsp. was 19.1% and was not affected by the cattle type or tylosin. The prevalence of was higher ( < 0.01) in crossbred cattle (73.7%) compared to Holstein steers (29.8%). Also, the prevalence of was higher in abscesses from tylosin-fed (66.1%) cattle than no tylosin-fed cattle (35%). The overall prevalence of was 25.3% and was similar ( = 0.58) between cattle type, but the prevalence was lower ( < 0.01) in tylosin-fed (16.9%) compared to no tylosin-fed group (33%). Mean MIC of tylosin for and were similar across both cattle types and tylosin inclusion. Although bacterial flora of liver abscesses from Holstein steers appeared to be more diverse than that of crossbred cattle, there was no difference in the prevalence of the and and in fact, prevalence of was higher in crossbred than Holstein steers. Therefore, the difference in bacterial flora is not the likely reason for higher prevalence and severity of liver abscesses in Holstein steers than crossbred beef cattle.

Limited data suggest that the cerebrospinal fluid Treponema pallidum particle agglutination assay (CSF-TPPA) is sensitive and a CSF Treponema pallidum hemagglutination assay (CSF-TPHA) titer of ≥1:640 is specific for neurosyphilis diagnosis. CSF-TPPA reactivity and titer were determined for a convenience sample of 191 CSF samples from individuals enrolled in a study of CSF abnormalities in syphilis (training data set). The sensitivity of a reactive test and the specificity for reactivity at serial higher CSF dilutions were determined. Subsequently, CSF-TPPA reactivity at a 1:640 dilution was determined for all available samples from study participants enrolled after the last training sample was collected (validation data set, n = 380). Neurosyphilis was defined as (i) a reactive CSF Venereal Disease Research Laboratory test (CSF-VDRL), (ii) detection of T. pallidum in CSF by reverse transcriptase PCR, or (iii) new vision loss or hearing loss. In the training data set, the diagnostic sensitivities of a reactive CSF fluorescent treponemal antibody absorption test (CSF-FTA-ABS) and a reactive CSF-TPPA did not differ significantly (67 to 98% versus 76 to 95%). The specificity of a CSF-TPPA titer of ≥1:640 was significantly higher than that of lower dilutions and was not significantly different from that of CSF-VDRL. In the validation data set, the diagnostic specificity of a CSF-TPPA titer of ≥1:640 was high and did not differ significantly from that of CSF-VDRL (93 to 94% versus 90 to 91%). Ten CSF samples with a nonreactive CSF-VDRL had a CSF-TPPA titer of ≥1:640. If a CSF-TPPA titer of ≥1:640 was used in addition to a reactive CSF-VDRL, the number of neurosyphilis diagnoses would have increased from 47 to 57 (21.3%). A CSF-TPPA titer cutoff of ≥1:640 may be useful in identifying patients with neurosyphilis when CSF-VDRL is nonreactive., (Copyright © 2017 American Society for Microbiology.)

Bovine respiratory disease (BRD) is responsible for the majority of morbidity, mortality, and production losses occurring in feedlots. This experiment evaluated the effects of BRD incidence on subsequent finishing performance, efficiency, carcass characteristics, and lung scores of steers. Crossbred steers (n = 516) were monitored daily for clinical signs of BRD (BRD attributed morbidity and mortality were 66.5 and 13.2%, respectively). A subset of calves (n = 174) were grouped by the number of times treated for BRD (BRDX) and randomly allocated to finishing pens. The BRDX experimental groups included never treated for BRD (0X; 8 pens) and treated 1 time (1X; 8 pens), 2 times (2X; 8 pens), or 3 or 4 times (3/4X; 8 pens). Arrival BW was not different among BRDX groups ( P = 0.17); however, BRDX during the receiving period decreased performance, resulting in BW of 324, 316, 285, and 260 kg for 0X, 1X, 2X, and 3/4X, respectively, at the start of finishing ( P < 0.001). Ultrasound estimates, BW, and visual appraisal were used to target a common body composition (average days on feed = 182). With increasing BRDX, days on feed increased linearly ( P = 0.002), whereas HCW, DP, rib eye area, QG, and unconsolidated lungs decreased linearly ( P ≤ 0.03). These results suggest that with additional days on feed, calves treated multiple times for BRD are able to reach similar compositional endpoints as their untreated cohorts; however, it may not be possible for these calves to reach the same QG and carcass yield., (© 2017 American Registry of Professional Animal Scientists.)

Research has indicated that trace mineral (TM) supplementation may alter immune function and reduce morbidity associated with bovine respiratory disease. The objective of this experiment was to determine the influence of dietary Cu, Mn, and Zn supplementation on the performance, clinical signs, and TM balance of calves following a bovine viral diarrhea virus (BVDV) and (MH) combination respiratory pathogen challenge. Steers ( = 16; 225 ± 20 kg BW) from a single ranch were processed, weaned, and randomly pairwise assigned to either the TM-supplemented (MIN) or the control (CON) experimental treatments. The MIN calves received an additional 150 mg of Cu, 130 mg of Mn, and 320 mg of Zn daily and the CON calves received the basal diet with no additional Cu, Mn, or Zn supplementation. The basal diet contained sufficient Mn and Zn but inadequate Cu based on published nutrient requirements. After 46 d on the experimental treatments, all calves were naturally exposed to a heifer persistently infected with BVDV type 1b for 4 d and then subsequently intratracheally challenged with MH. Data were analyzed using the GLIMMIX procedure of SAS with sampling time serving as a repeated measure and calf serving as the experimental unit. The respiratory challenge was validated via increased BVDV type 1b antibody concentrations, MH whole cell and leukotoxin antibody concentrations, rectal temperatures (TEMP), and subjective clinical severity scores (CS). Calf performance ( ≥ 0.48) was not affected by TM supplementation. Mineral supplementation also did not impact the CS or TEMP of calves ( ≥ 0.53). There was a treatment × time ( < 0.001) interaction observed for liver Cu concentrations. The concentrations of Cu, Mn, Zn, and Fe within the liver; Cu, Mn, and Zn within the muscle; and Cu, Zn, and Fe within the serum were all impacted by time ( ≤ 0.03). Calves receiving the MIN treatment had greater ( < 0.01) liver Cu and Mn concentrations compared with CON calves. In contrast, serum Cu and Fe concentrations were increased ( ≤ 0.05) in CON calves compared with MIN calves. Mineral supplementation did not impact TM concentrations within the muscle ( ≥ 0.38). The supplementation of Cu, Mn, and Zn can improve the Cu and Mn status within the liver and serum of calves in response to a BVDV and MH challenge. When Cu is supplemented to calves receiving a marginally Cu-deficient diet, Cu status within the body is significantly improved.

Ancillary therapy (ANC) is commonly provided in conjunction with an antimicrobial when treating calves for suspected bovine respiratory disease (BRD) in an attempt to improve the response to a suspected BRD challenge. The first experiment evaluated the effects of 3 ANC in combination with an antimicrobial in high-risk calves treated for BRD during a 56-d receiving period. Newly received crossbred steers (n = 516; initial BW = 217 ± 20 kg) were monitored by trained personnel for clinical signs of BRD. Calves that met antimicrobial treatment criteria (n = 320) were then randomly assigned to experimental ANC treatment (80 steers/experimental ANC treatment): intravenous flunixin meglumine injection (NSAID), intranasal viral vaccination (VACC), intramuscular vitamin C injection (VITC), or no ANC (NOAC). Animal served as the experimental unit for all variables except DMI and G:F (pen served as the experimental unit for DMI and G:F). Within calves treated 3 times for BRD, those receiving NOAC had lower (P < 0.01) clinical severity scores (severity scores ranged from 0 to 4 on the basis of observed clinical signs and severity) and heavier (P = 0.01) BW than those receiving NSAID, VACC, or VITC at the time of third treatment. Between the second and third BRD treatments, calves receiving NOAC had decreased (P < 0.01) daily BW loss (−0.13 kg ADG) compared with those receiving NSAID, VACC, or VITC (−1.30, −1.90, and −1.41 kg ADG, respectively). There were no differences in rectal temperature, combined mortalities and removals, or overall performance among the experimental ANC treatments. Overall, morbidity and mortality attributed to BRD across treatments were 66.5% and 13.2%, respectively. After the receiving period, a subset of calves (n = 126) were allocated to finishing pens to evaluate the effects ANC administration on finishing performance, carcass characteristics, and lung scores at harvest. Ultrasound estimates, BW, and visual appraisal were used to target a common physiological end point for each pen of calves. There were no differences among the experimental ANC observed during the finishing period (P ≥ 0.11). In summary, the use of NSAID, VACC, and VITC do not appear to positively impact clinical health and could potentially be detrimental to performance during the receiving period in high-risk calves receiving antimicrobial treatment for suspected BRD.

The objectives of this study were to examine the effects of feedlot production systems with and without the use of a β-adrenergic agonist compared to an all-natural production program on feedlot performance and carcass characteristics. Crossbred beef steers ( = 336; initial BW = 379 ± 8 kg) were randomized to 1 of 3 treatments in a randomized complete block design (RCBD; 14 steers/pen; 8 pens/treatment). Treatments consisted of an all-natural treatment (NAT), a conventional treatment (CONV), and a conventional treatment with a β-agonist (CONV-Z). All treatments were fed the same basal diet with NAT cattle receiving no growth promoting technologies. The CONV and CONV-Z cattle were implanted with 40 mg of estradiol and 200 mg of trenbolone acetate (TBA) on d 0 and were fed 33 and 9 mg/kg of monensin and tylosin daily, respectively. The CONV-Z cattle were fed zilpaterol hydrochloride (ZH) at 6.76 mg/kg (90% DM basis) for the last 20 days on feed (DOF) There was no effect of treatment on DMI ( = 0.83); however, CONV-Z steers gained 3.8% faster (1.64 vs. 1.58 kg/d; < 0.01) and were 5.3% more efficient (0.160 vs. 0.152; < 0.01) than CONV steers, and CONV steers gained 32.8% faster (1.58 vs. 1.19 kg/d; < 0.01) and were 26.7% more efficient (0.152 vs. 0.120; < 0.01) than NAT steers. There was a 35.7% improvement in estimated carcass gain (1.29 vs. 0.95 kg/d; < 0.01) and a 32.6% improvement in carcass efficiency (0.126 vs. 0.095; < 0.01) for CONV-Z steers compared to NAT steers. Hot carcass weight was increased by 8 kg for CONV-Z steers compared to CONV steers (394 vs. 386 kg; = 0.05) and 46 kg compared to NAT steers (394 vs. 348 kg; < 0.01). Longissimus muscle area was increased by 3.6 cm for CONV-Z steers compared to CONV steers (92.29 vs. 88.67 cm; = 0.02) and 12.1 cm for CONV-Z steers compared to NAT steers (92.29 vs. 80.16 cm; < 0.01), resulting in a 9.6% unit increase in USDA yield grade (YG) 1 (15.14 vs. 5.52%; < 0.05) and a 21.6% unit reduction in USDA YG 3 for CONV-Z steers compared to CONV steers (30.70 vs. 52.32%; < 0.05). The CONV-Z steers had a lower marbling score compared to the other treatments (432; 0.01), resulting in an 11.7% unit increase (20.70 vs. 9.03%; < 0.05) in USDA Select carcasses compared to CONV steers. The results of this experiment show that CONV-Z and CONV production results in a significant improvement in feedlot performance and USDA YG compared to NAT.

Implantation of anabolic steroids to increase growth rate in beef cattle impacts adrenal glucocorticoid production. The mechanism by which combination androgen and estrogen implants reduce cortisol biosynthesis in heifers is not clear. The objective of this study was to identify whether pituitary or adrenal gene expression and liver enzyme activity may contribute to altered serum cortisol concentrations in heifers receiving a combination implant. On d 0 of a 122-d finishing phase, 187 predominantly Angus heifers (361 kg) approximately 14 months old were randomly assigned to one of three implant groups: (1) non-implanted control, (2) implanted at the beginning of the finishing phase (d 0; early implant) with a combination implant (200mg TBA+20mg E2; Revalor 200®), and (3) implanted during the late stage of the finishing phase (d 56; late implant) with Revalor 200®. At d 56, body weight (BW) was greater (P<0.0001) for the early implanted heifers (456 ± 1.9 kg) compared to 437 and 435 (± 1.8) kg for control and late implanted heifers, respectively. Final BW (d 122) was similar between both implanted groups and heavier than non-implanted controls (P<0.0001). Serum cortisol was similar among groups at d 0 (P=0.86) however, by d 28 heifers receiving the combination implant had reduced (P<0.05) serum cortisol concentrations (31.2 ng/mL) compared to controls (49.4 ng/mL) and late (48.2 ng/mL) groups. On d 84 cortisol was similar (P=0.75) among implanted heifers and was less (P<0.01) than non-implanted heifers. Expression of pituitary and adrenal genes involved in glucocorticoid synthesis was evaluated at d 28/29 or 84/85; however, despite decreased serum cortisol in implanted heifers, no change in mRNA expression was demonstrated. Liver CYP3A enzyme activity at d 28/29 was decreased 59% in early implanted heifers compared to control heifers (P=0.01). Additionally, at d 84/85 AKR1C activity was greatest (P=0.01) in control heifers compared to both implanted groups. Data suggest that components of hypothalamic-pituitary-adrenal axis are influenced by exposure to exogenous hormones and this should be recognized when considering cortisol levels as a marker for stress response., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The objective of this study was to evaluate conventional (CONV) and natural (NAT) beef production systems from annual pasture through finishing through grazing. Beef steers (n=180, initial BW=250±19 kg) were assigned randomly to 2 treatments in the pasture phase. Steers were implanted with 40 mg of trenbolone acetate (TBA), 8 mg estradiol, and 29 mg tylosin tartrate (CONV), or received no implant (NAT). Steers on the 2 treatments grazed wheat or cereal rye for 109 d. Conventional steers had an 18.5% improvement in ADG (1.22 vs. 1.03 kg/d, P<0.01) and a heavier final BW (385 vs. 366 kg, P<0.01) compared with NAT steers. Following the pasture phase, steers (n=160 steers, 5 steers/pen, 8 pens/treatment) were assigned to a 2×2 factorial in the feedlot phase. Production system (NAT vs. CONV) was maintained from the pasture phase, and the second factor was 7 vs. 12% low-quality roughage (DM basis, LOW vs. HIGH). During finishing, CONV steers were given 120 mg of TBA and 24 mg estradiol at processing, fed monensin and tylosin, and fed zilpaterol hydrochloride for the last 20 d of the experiment. There were no program×roughage level interactions (P>0.07). The CONV steers ate 6.9% more feed (11.8 vs. 11.0 kg/d, P<0.01), gained 28.4% faster (1.90 vs. 1.48 kg/d, P<0.01), and were 24.2% more efficient (0.164 vs. 0.132, P<0.01) compared with NAT steers. The LOW steers had greater G:F (0.153 vs. 0.144, P<0.01) compared with HIGH steers. There was a 28.3% improvement in estimated carcass weight gain (1.36 vs. 1.06 kg/d), 18.6% improvement in carcass efficiency (0.115 vs. 0.097, P<0.01), and 21.6% improvement (1.52 vs. 1.25 Mcal/kg, P<0.01) in calculated dietary NEg for CONV compared with NAT steers. Hot carcass weight was increased by 62 kg (424 vs. 362 kg, P<0.01) and LM area was increased by 16.9 cm2 (100.9 vs. 84.0 cm2, P<0.01), decreasing USDA yield grade (YG, 3.09 vs. 3.54, P<0.01) for CONV steers compared with NAT steers. Natural steers had a greater percentage of carcasses in the upper 2/3 of USDA Choice grade (48.7 vs. 18.7%, P<0.01), a greater percentage of YG 4 and 5 carcasses (25.4 vs. 9.3%, P<0.01), and a greater percentage of abscessed livers (39.6 vs. 10.5%, P<0.01) compared with CONV steers. The results show that CONV production results in more rapid and efficient production that resulted in heavier carcasses with superior YG and desirable quality grades with both roughage levels.

Inflammation caused by bovine respiratory disease (BRD) continues to be one of the greatest challenges facing beef cattle producers and feedlot managers. Inflammation decreases DMI, ADG, and G:F in feedlot calves, decreasing growth rate and increasing days on feed, which results in economic losses during the feeding period. During the past decade, marketing of feedlot animals has changed from selling cattle on a live basis to a grid-based marketing system. When cattle are marketed on a live basis, the economic effects of BRD stop at increased health cost and decreased feedlot performance, carcass weight, and death loss. However, when cattle are marketed in a grid-based system, inflammation has the potential to also affect carcass cutability and quality. The effects of inflammation on feedlot cattle in regards to performance are well understood; however, specific effects on cattle growth and ultimately carcass merit are not as well described. Recent studies in feedlot cattle have indicated that the incidence of BRD decreases both HCW and marbling; however, mechanisms are not understood. Research in other species has demonstrated that during the acute phase response, pro-inflammatory cytokines promote skeletal muscle catabolism to supply AA and energy substrates for immune tissues. Further, during this early immune response, the liver changes its metabolic priorities to the production of acute phase proteins for use in host defense. Together these dramatic shifts in systemic metabolism may explain the detrimental effects on performance and carcass traits commonly associated with BRD in feedlot calves. Moreover, recent studies relative to human health have revealed complex multilevel interactions between the metabolic and immune systems, and highlighted inflammation as being a significant contributor to major metabolic diseases. The objective of this paper is to review data to help explain the economical and physiological effects of inflammation on cattle growth and carcass merit.

Background: Success of neurosyphilis treatment is defined by normalization of cerebrospinal fluid (CSF) and clinical abnormalities. The goal of this study was to determine whether normalization of serum rapid plasma reagin (RPR) titer could accurately predict treatment success., Methods: One hundred ten patients who were enrolled in a longitudinal study of CSF abnormalities in syphilis had asymptomatic syphilitic meningitis, symptomatic syphilitic meningitis, or syphilitic eye disease and were treated for neurosyphilis. At 4, 7, and 13 months after treatment, serum RPR titer and CSF and clinical abnormalities were analyzed for normalization. Odds ratios for normalization of each CSF and clinical abnormality when serum RPR titer had normalized and the positive predictive value of normalization of serum RPR titer for normalization of CSF and clinical abnormalities were determined., Results: Serum RPR titer had normalized in 63 patients (57%) by 4 months after treatment, in 94 (85%) by 7 months, and in 97 (88%) by 13 months. Except for CSF protein concentration, normalization of serum RPR titer predicted normalization of other CSF and clinical abnormalities in >80% of patients at 4 months, >85% at 7 months, and >90% at 13 months. The odds of normalization of CSF and clinical abnormalities were 28-57-fold higher when serum RPR titer had normalized, compared with when it had not. Normalization of serum RPR titer was consistently less accurate in predicting treatment success in human immunodeficiency virus-infected patients who were not receiving antiretroviral therapy, compared with those who were receiving such therapy., Conclusions: In most instances, normalization of serum RPR titer correctly predicts success of treatment of neurosyphilis, and follow-up lumbar puncture can be avoided.

To identify factors that affect normalization of laboratory measures after treatment for neurosyphilis, 59 subjects with neurosyphilis underwent repeated lumbar punctures and venipunctures after completion of therapy. The median duration of follow-up was 6.9 months. Stepwise Cox regression models were used to determine the influence of clinical and laboratory features on normalization of cerebrospinal fluid (CSF), white blood cells (WBCs), CSF protein concentration, CSF Venereal Disease Research Laboratory (VDRL) reactivity, and serum rapid plasma reagin (RPR) titer. Human immunodeficiency virus (HIV)-infected subjects were 2.5 times less likely to normalize CSF-VDRL reactivity than were HIV-uninfected subjects. HIV-infected subjects with peripheral blood CD4+ T cell counts of < or =200 cells/ mu L were 3.7 times less likely to normalize CSF-VDRL reactivity than were those with CD4+ T cell counts of >200 cells/ mu L. CSF WBC count and serum RPR reactivity were more likely to normalize but CSF-VDRL reactivity was less likely to normalize with higher baseline values. Future studies should address whether more intensive therapy for neurosyphilis is warranted in HIV-infected individuals.

Objective: To define clinical and laboratory features that identify patients with neurosyphilis., Methods: Subjects (n=326) with syphilis but no previous neurosyphilis who met 1993 Centers for Disease Control and Prevention criteria for lumbar puncture underwent standardized history, neurological examination, venipuncture, and lumbar puncture. Neurosyphilis was defined as a cerebrospinal fluid (CSF) white blood cell count >20 cells/ microL or reactive CSF Venereal Disease Research Laboratory (VDRL) test result., Results: Sixty-five subjects (20.1%) had neurosyphilis. Early syphilis increased the odds of neurosyphilis in univariate but not multivariate analyses. In multivariate analyses, serum rapid plasma reagin (RPR) titer > or =1 : 32 increased the odds of neurosyphilis 10.85-fold in human immunodeficiency virus (HIV)-uninfected subjects and 5.98-fold in HIV-infected subjects. A peripheral blood CD4+ T cell count < or =350 cells/ microL conferred 3.10-fold increased odds of neurosyphilis in HIV-infected subjects. Similar results were obtained when neurosyphilis was more stringently defined as a reactive CSF VDRL test result., Conclusion: Serum RPR titer helps predict the likelihood of neurosyphilis. HIV-induced immune impairment may increase the risk of neurosyphilis.

The hyperlocomotion induced by the noncompetitive NMDA antagonist MK-801 (0.3 mg/kg SC) in mice was attenuated by the nonselective 5-HT2 antagonist ritanserin (0.12 and 0.25 mg/kg SC) and by the 5-HT2A selective antagonist MDL100907 (0.05 and 0.1 mg/kg SC). SB242084 (0.25-1.0 mg/kg), a selective 5-HT(2C) antagonist, had no effect on MK-801-induced hyperactivity. These same doses of ritanserin and MDL100907 reduced the hyperactivity induced by cocaine (10 mg/ kg). Amphetamine (2.5 mg/kg SC) induced hyperlocomotion that was also attenuated by ritanserin (0.064).25 mg/kg SC). The hyperlocomotion induced by the D1 agonist C-APB (1.0 mg/kg) is not altered by pretreatment with ritanserin or MDL100907. This suggests that compounds that increase locomotor activity via indirectly increasing dopaminergic activity (either by increased release or blockade of reuptake) require the activation of a 5-HT2A receptor. Activity of compounds that act directly at the postsynaptic dopamine receptors such as C-APB is not dependent on such a mechanism. This suggests a selective involvement of 5-HT2A receptors but not 5-HT2c receptors in the mediation of the behavioral effects of compounds that increase synaptic concentration of dopamine but not directly acting agonists. This implies that the 5-HT2A receptors modulate elevation of extracellular dopamine, not the postsynaptic sensitivity of dopamine neurons.

To identify neurological abnormalities in HIV infection, 159 HIV-seropositive men without AIDS and 76 seronegative controls underwent standardized general and neurological examinations, lumbar puncture (LP), neuropsychological (NP) assessment, and brain magnetic resonance (MR) imaging. History, physical, and laboratory evaluations were repeated every six months. NP tests (all subjects) and MR imaging (seropositives only) was repeated every 6-12 months; LP (seropositives only) was repeated yearly. Mean follow-up was 24.6 months. Neurological abnormalities, most related to hearing, were seen in 60 (38.2%) of 157 seropositives and 23 (30.3%) of 76 controls at baseline (p = NS). During follow-up, 43 (31.6%) of 136 seropositives had persistent hearing abnormalities compared to 9 (14.1%) of 64 seronegatives (p = 0.008). Seven HIV-seropositives developed peripheral neuropathy; this was more common among those with hearing abnormalities (p = 0.03). HIV-seropositives performed less well on NP tests than controls, but overall performance did not decline. Worsening brain atrophy by MR imaging or cerebrospinal fluid abnormalities are more common in HIV-seropositives than seronegatives and may share a common mechanism with peripheral neuropathy. Further study is needed to determine whether these abnormalities portend more serious neurological disease.

We analyzed demographic and behavioral risk factors for HIV seropositivity using data from 3601 clients of the main HIV counseling and testing clinic for high-risk people in Seattle, Washington, USA. Clients with lower income were found to be more likely to be HIV seropositive, before and after controlling for other demographic and risk factors with logistic regression. This result supports the hypothesis that the impoverished are at increased risk for HIV infection due to the physical and social circumstances in which their poverty places them. These may include poor access to risk-reduction information and less support for implementation of risk-reduction strategies.

Nucleotide sequence variation in mitochondrial DNA isolated from human leukemic cells has been analyzed by recombinant DNA techniques. Three hundred eighty-seven independent recombinant DNA clones, each containing one of three defined segments of mitochondrial DNA isolated from the neoplastic cells of four leukemic patients, were analyzed. Partial nucleotide sequence determination of the 387 clones yielded a total of 81.7 kilobases of nucleotide sequence information. The only evidence of within-individual nucleotide sequence divergence consisted of three clones containing deletions of one or two nucleotides in one mitochondrial DNA region. These clones were three of 113 independent clones isolated from a patient with acute lymphocytic leukemia. The low level of nucleotide sequence divergence in the mitochondrial DNA population of neoplastic cells from individual leukemic patients suggests that a mechanism or mechanisms exist that limit the development of nucleotide sequence divergence in mammalian mitochondrial DNA. The results further suggest that this mechanism does not appear to be abrogated by neoplastic transformation in leukemic patients.

The last decade has witnessed increasing application of human cytogenetic technology to prenatal chromosome analysis. However, unlike the rather uniform peripheral blood T-lymphocyte system which has provided most of our experience in human cytogenetics, long-term amniotic-fluid cell cultures display extreme cellular heterogeneity and disproportionate growth of certain cell types as a consequence of clonal amplification. When they enter cell culture, many of these cells are approaching the terminal stages of their respective, life spans and may have accumulated chromosomal aberrations. Concern about the possibility of true fetal mosaicism seems warranted chiefly in situations were multiple colonies display potentially viable aberrations. Clonal analysis, preferably of multiple clonal types, and attention to details of clonal morphology are likely to minimize diagnostic errors and undue apprehension resulting from mosaicism in amniotic-fluid cell cultures.