Sex-Specific Skeletal Muscle Gene Expression Responses to Exercise Reveal Novel Direct Mediators of Insulin Sensitivity Change.

BACKGROUND: Understanding the causal pathways, systems, and mechanisms through which exercise impacts human health is complex. This study explores molecular signaling related to whole-body insulin sensitivity (Si) by examining changes in skeletal muscle gene expression. The analysis considers differences by biological sex, exercise amount, and exercise intensity to identify potential molecular targets for developing pharmacologic agents that replicate the health benefits of exercise. METHODS: The study involved 53 participants from the STRRIDE I and II trials who completed eight months of aerobic training. Skeletal muscle gene expression was measured using Affymetrix and Illumina technologies, while pre- and post-training Si was assessed via an intravenous glucose tolerance test. A novel gene discovery protocol, integrating three literature-derived and data-driven modeling strategies, was employed to identify causal pathways and direct causal factors based on differentially expressed transcripts associated with exercise intensity and amount. RESULTS: In women, the transcription factor targets identified were primarily influenced by exercise amount and were generally inhibitory. In contrast, in men, these targets were driven by exercise intensity and were generally activating. Transcription factors such as ATF1, CEBPA, BACH2, and STAT1 were commonly activating in both sexes. Specific transcriptional targets related to exercise-induced Si improvements included TACR3 and TMC7 for intensity-driven effects, and GRIN3B and EIF3B for amount-driven effects. Two key signaling pathways mediating aerobic exercise-induced Si improvements were identified: one centered on estrogen signaling and the other on phorbol ester (PKC) signaling, both converging on the epidermal growth factor receptor (EGFR) and other relevant targets. CONCLUSIONS: The signaling pathways mediating Si improvements from aerobic exercise differed by sex and were further distinguished by exercise intensity and amount. Transcriptional adaptations in skeletal muscle related to Si improvements appear to be causally linked to estrogen and PKC signaling, with EGFR and other identified targets emerging as potential skeletal muscle-specific drug targets to mimic the beneficial effects of exercise on Si.

Simulating Transplant Small-for-size Grafts Using Human Liver Monosegments: The Impact of Portal Perfusion Pressure.

Small-for-size-liver grafts (SFSG) in adult transplant recipients have elevated risk of graft failure, limiting its application in clinical liver transplantation. Relevant preclinical model of SFSG is lacking. Relevant to deceased-donor split liver transplant and living-donor liver transplant in adult recipients, in this study, we present our initial characterization of SFSG model using monosegments of a discarded human donor liver.

Sputum smear-positive, culture-negative state during anti-tuberculosis treatment in the MGIT liquid culture era.

The sputum smear-positive, culture-negative state poses a challenge for clinicians. Previous studies have shown that most samples with positive smears during the later stages of treatment are culture-negative. Earlier studies generally used solid culture media, which tend to be less sensitive than current liquid culture systems. We examined the smear-positive, culture-negative state in the era of MGIT™ 960™ liquid cultures. We found that the smear-positive, culture-negative state occurred less frequently with MGIT culture, and that the majority of the samples with late positive smears were culture-negative, regardless of media type.

Carotid artery ligation induced intimal thickening and proliferation is unaffected by ageing.

Following interventions to treat atherosclerosis, such as coronary artery bypass graft surgery, restenosis occurs in approximately 40% of patients. Identification of proteins regulating intimal thickening could represent targets to prevent restenosis. Our group previously demonstrated that in a murine model of vascular occlusion, Wnt4 protein expression and ß-catenin signalling was upregulated which promoted vascular smooth muscle cell (VSMC) proliferation and intimal thickening. In this study, the effect of age on VSMC proliferation, intimal hyperplasia and Wnt4 expression was investigated. In vitro proliferation of VSMCs isolated from young (2 month) or old (18-20 month) C57BL6/J mice was assessed by immunocytochemistry for EdU incorporation. As previously reported, 400 ng/mL recombinant Wnt4 protein increased proliferation of VSMCs from young mice. However, this response was absent in VSMCs from old mice. As our group previously reported reduced intimal hyperplasia in Wnt4+/- mice compared to wildtype controls, we hypothesised that impaired Wnt4 signalling with age may result in reduced neointimal formation. To investigate this, carotid artery ligation was performed in young and old mice and neointimal area was assessed 21 days later. Surprisingly, neointimal area and percentage lumen occlusion were not significantly affected by age. Furthermore, neointimal cell density and proliferation were also unchanged. These data suggest that although Wnt4-mediated proliferation was impaired with age in primary VSMCs, carotid artery ligation induced neointimal formation and proliferation were unchanged in old mice. These results imply that Wnt4-mediated proliferation is unaffected by age in vivo, suggesting that therapeutic Wnt4 inhibition could inhibit restenosis in patients of all ages.

Defining the optimal dose of rifapentine for pulmonary tuberculosis: Exposure-response relations from two phase II clinical trials.

Rifapentine is a highly active antituberculosis antibiotic with treatment-shortening potential; however, exposure-response relations and the dose needed for maximal bactericidal activity have not been established. We used pharmacokinetic/pharmacodynamic data from 657 adults with pulmonary tuberculosis participating in treatment trials to compare rifapentine (n = 405) with rifampin (n = 252) as part of intensive-phase therapy. Population pharmacokinetic/pharmacodynamic analyses were performed with nonlinear mixed-effects modeling. Time to stable culture conversion of sputum to negative was determined in cultures obtained over 4 months of therapy. Rifapentine exposures were lower in participants who were coinfected with human immunodeficiency virus, black, male, or fasting when taking drug. Rifapentine exposure, large lung cavity size, and geographic region were independently associated with time to culture conversion in liquid media. Maximal treatment efficacy is likely achieved with rifapentine at 1,200 mg daily. Patients with large lung cavities appear less responsive to treatment, even at high rifapentine doses.

Review: Effects of Ractopamine Hydrochloride (Paylean) on welfare indicators for market weight pigs.

This review summarizes the effects of ractopamine hydrochloride (RAC) dose (5, 7.5, 10, and 20 mg/kg) on market weight pig welfare indicators. Ractopamine hydrochloride (trade name Paylean) is a ß-adrenergic agonist that was initially approved in the U.S. in 1999 at doses of 5 to 20 mg/kg to improve feed efficiency and carcass leanness. However, anecdotal reports suggested that RAC increased the rate of non-ambulatory (fatigued and injured) pigs at U.S. packing plants. This led to the addition of a caution statement to the Paylean label, and a series of research studies investigating the effects of RAC on pig welfare. Early research indicated that: (1) regardless of RAC administration, fatigued (non-ambulatory, non-injured) pigs are in a state of metabolic acidosis; (2) aggressive handling increases stress responsiveness at 20 mg/kg RAC, while 5 mg/kg reduces stress responsiveness to aggressive handling. Given this information, dosage range for Paylean was changed in 2006 to 5 to 10 mg/kg in market weight pigs. Subsequent research on RAC demonstrated that: (1) RAC has minimal effects on mortality, lameness, and home pen behavior; (2) RAC fed pigs demonstrated inconsistent prevalence and intensity of aggressive behaviors; (3) RAC fed pigs may be more difficult to handle at doses above 5 mg/kg; and (4) RAC fed pigs may have increased stress responsiveness and higher rates of non-ambulatory pigs when subjected to aggressive handling, especially when 20 mg/kg of RAC is fed.

Reader variability and validation of the Timika X-ray score during treatment of pulmonary tuberculosis.

SETTING: Chest radiographs (CXRs) are widely used for diagnosing pulmonary TB and assessing response to therapy. The Timika X-ray score has been proposed as a tool for measuring disease severity and predicting treatment outcome. OBJECTIVE: To evaluate inter- and intra-reader agreement of Timika scores and assess the ability of the score to predict microbiologic outcome at 2 months. DESIGN: Analytical validation study. Disease severity was measured by two readers using pretreatment radiographs and follow-up films taken at 2, 6 and 12 months after the start of treatment among 110 human immunodeficiency virus negative adults with pulmonary TB. One fourth of the films were reread to assess intra-reader agreement. RESULTS: The two-component Timika score had high inter- and intra-reader agreement (intraclass correlation (ICC)inter = 75%, ICCintra > 0.81). Baseline Timika score was associated with positive month 2 smear (P = 0.0004) and culture status (P = 0.03). The average Timika score declined significantly over the course of successful treatment. CONCLUSION: The Timika score showed good inter- and intra-reader agreement and a significant association with microbiological outcomes after 2 months of treatment. The results of this study strengthen the evidence supporting the use of the Timika score for measuring disease severity on CXR.

Genetic parameters estimated at receiving for circulating cortisol, immunoglobulin G, interleukin 8, and incidence of bovine respiratory disease in feedlot beef steers.

Bovine respiratory disease complex (i.e., shipping fever and bacterial bronchopneumonia) is a multifaceted respiratory illness influenced by numerous environmental factors and microorganisms. Bovine respiratory disease (BRD) is just one component of BRD complex. Because BRD is moderately heritable, it may be possible to reduce the incidence of BRD through genetic selection. The objectives of this study were to determine the heritability and associative genetic relationships among immune system traits (i.e., cortisol, total IgG, IgG isotypes, and IL-8) in cattle monitored for BRD incidence. At an average of 83 d after weaning (219 d age and mean = 221.7 kg [SD 4.34]), crossbred steer calves ( = 2,869) were received at a commercial feedlot in southeastern Colorado over a 2-yr period. At receiving, jugular blood samples were collected at 212 (yr 1) and 226 d (yr 2) of age for immune trait analyses. The BRD phenotype was defined as a binomial variable (0 = no and 1 = yes) and compared with immune system traits measured at receiving (prior to illness onset). An animal identified as BRD positive exhibited ≥ 2 clinical signs (i.e., eye or nasal discharge, cough, lethargy, rapid breathing, acute interstitial pneumonia, or acute upper respiratory syndrome and/or a rectal temperature > 39.7°C). Heritability and genetic correlation estimates for categorical variable BRD, cortisol, IgG, IgG1, IgG2, and IL-8 were estimated from a sire model using ASREML. Heritability estimates were low to moderate for BRD (0.17 ± 0.08), cortisol (0.13 ± 0.05), IgG (0.15 ± 0.05), IgG1 (0.11 ± 0.05), IgG2 (0.24 ± 0.06), and IL-8 (0.30 ± 0.06). A moderate negative genetic correlation was determined between BRD and cortisol ( = -0.19 ± 0.32). Moderate positive correlations were found between BRD with IgG (0.42 ± 0.28), IgG1 (0.36 ± 0.32), and IL-8 ( = 0.26 ± 0.26). Variation in the BRD phenotype and immune system traits suggested herd health improvement may be achieved through genetic selection.

Exploiting Chromatin Biology to Understand Immunology.

The activation of immune responses relies on variations of a common rule where immune cells that are able to sense infections produce one set of cytokines to induce lymphocytes to produce another set of cytokines, which in turn activate the appropriate effector responses. This multitiered immune response is in fact a remarkable showcase of different ways the same genome can be used to facilitate cellular communications. Here, we review next-generation sequencing methods enabling us to map the differential usage of our genome in primary immune cells.

Wider stall space affects behavior, lesion scores, and productivity of gestating sows.

Limited space allowance within the standard gestation stall is an important welfare concern because it restricts the ability of the sow to make postural adjustments and hinders her ability to perform natural behaviors. Therefore, we evaluated the impacts of increasing stall space and/or providing sows the freedom to access a small pen area on sow well-being using multiple welfare metrics. A total of 96 primi- and multiparous crossbred sows were randomly assigned in groups of 4 sows/treatment across 8 replicates to 1 of 3 stall treatments (TRT): standard stall (CTL; dimensions: 61 by 216 cm), width-adjustable stall (flex stall [FLX]; dimensions: adjustable width of 56 to 79 cm by 216 cm), or an individual walk-in/lock-in stall with access to a small communal open-pen area at the rear of the stall (free-access stall [FAS]; dimensions: 69 by 226 cm). Lesion scores, behavior, and immune and productivity traits were measured at various gestational days throughout the study. Total lesion scores were greatest for sows in FAS and least for sows in FLX ( < 0.001). Higher-parity sows in FAS had the most severe lesion scores (TRT × parity, < 0.0001) and scores were greatest at all gestational days (TRT × day, < 0.05). Regardless of parity, sows in FLX had the least severe scores ( < 0.0001). As pregnancy progressed, lesion scores increased among sows in CTL ( < 0.05). Sow BW and backfat (BF) were greater for sows in FLX and FAS ( < 0.05), and BCS and BF were greater for parity 1 and 2 sows in FAS than the same parity sows in CTL (TRT × parity, < 0.05). Duration and frequency of some postural behaviors and sham chew behavior were affected by TRT ( < 0.05) and time of day (TRT × day, < 0.05). These data indicate that adequate stall space, especially late in gestation, may improve the well-being of higher-parity and heavier-bodied gestating sows as assessed by changes in postural behaviors, lesion severity scores, and other sow traits. Moreover, compromised welfare measures found among sows in various stall environments may be partly attributed to the specific constraints of each stall system such as restricted stall space in CTL, insufficient floor space in the open-pen area of the FAS system, and gate design of the FLX (e.g., direction of bars and feeder space). These results also indicate that parity and gestational day are additional factors that may exacerbate the effects of restricted stall space or insufficient pen space, further compromising sow well-being.

Serum biomarkers of treatment response within a randomized clinical trial for pulmonary tuberculosis.

RATIONALE: Biomarkers for monitoring response to anti-tuberculosis treatment are needed. We explored immune markers previously published as having predictive capability for 8 week culture status in 39 adults enrolled in a clinical trial in Kampala, Uganda. METHODS: We consecutively selected 20 HIV-negative pulmonary TB subjects with positive cultures, and 19 subjects with negative cultures at the end of intensive phase therapy. At baseline and after 8 weeks, serum was assayed for nine cytokines and soluble cytokine receptors using multiplexed platforms or ELISA. We evaluated their association with week 8 culture status first using single-variable logistic models, then using cross-validated estimates of the C-statistic, a measure of discrimination, of candidate models including 2 or 3 analytes in addition to age. RESULTS: All but one analyte decreased from baseline to week 8 (all p < 0.01). Individual biomarkers were not associated with 8 week culture status. Logistic models including increasing age, higher baseline soluble tumor necrosis factor receptor alpha 1 (sTNF-R1), and higher week 8 C-reactive protein (CRP) concentration classified subjects by culture status with up to 85% accuracy and acceptable discrimination (cross-validated C-statistic 0.76) and calibration (Hosmer-Lemeshow P > 0.2). CONCLUSION: Exploratory post-hoc models including sTNF-R1, CRP, and age, classified 8 week culture status with promising accuracy.

Platinum coat color in red fox (Vulpes vulpes) is caused by a mutation in an autosomal copy of KIT.

The red fox (Vulpes vulpes) demonstrates a variety of coat colors including platinum, a common phenotype maintained in farm-bred fox populations. Foxes heterozygous for the platinum allele have a light silver coat and extensive white spotting, whereas homozygosity is embryonic lethal. Two KIT transcripts were identified in skin cDNA from platinum foxes. The long transcript was identical to the KIT transcript of silver foxes, whereas the short transcript, which lacks exon 17, was specific to platinum. The KIT gene has several copies in the fox genome: an autosomal copy on chromosome 2 and additional copies on the B chromosomes. To identify the platinum-specific KIT sequence, the genomes of one platinum and one silver fox were sequenced. A single nucleotide polymorphism (SNP) was identified at the first nucleotide of KIT intron 17 in the platinum fox. In platinum foxes, the A allele of the SNP disrupts the donor splice site and causes exon 17, which is part of a segment that encodes a conserved tyrosine kinase domain, to be skipped. Complete cosegregation of the A allele with the platinum phenotype was confirmed by linkage mapping (LOD 25.59). All genotyped farm-bred platinum foxes from Russia and the US were heterozygous for the SNP (A/G), whereas foxes with different coat colors were homozygous for the G allele. Identification of the platinum mutation suggests that other fox white-spotting phenotypes, which are allelic to platinum, would also be caused by mutations in the KIT gene.

Codeine-induced hyperalgesia and allodynia: investigating the role of glial activation.

Chronic morphine therapy has been associated with paradoxically increased pain. Codeine is a widely used opioid, which is metabolized to morphine to elicit analgesia. Prolonged morphine exposure exacerbates pain by activating the innate immune toll-like receptor-4 (TLR4) in the central nervous system. In silico docking simulations indicate codeine also docks to MD2, an accessory protein for TLR4, suggesting potential to induce TLR4-dependent pain facilitation. We hypothesized codeine would cause TLR4-dependent hyperalgesia/allodynia that is disparate from its opioid receptor-dependent analgesic rank potency. Hyperalgesia and allodynia were assessed using hotplate and von Frey tests at days 0, 3 and 5 in mice receiving intraperitoneal equimolar codeine (21 mg kg(-1)), morphine (20 mg kg(-1)) or saline, twice daily. This experiment was repeated in animals with prior partial nerve injury and in TLR4 null mutant mice. Interventions with interleukin-1 receptor antagonist (IL-1RA) and glial-attenuating drug ibudilast were assessed. Analyses of glial activation markers (glial fibrillary acid protein and CD11b) in neuronal tissue were conducted at the completion of behavioural testing. Despite providing less acute analgesia (P=0.006), codeine induced similar hotplate hyperalgesia to equimolar morphine vs saline (-9.5 s, P<0.01 and -7.3 s, P<0.01, respectively), suggesting codeine does not rely upon conversion to morphine to increase pain sensitivity. This highlights the potential non-opioid receptor-dependent nature of codeine-enhanced pain sensitivity-although the involvement of other codeine metabolites cannot be ruled out. IL-1RA reversed codeine-induced hyperalgesia (P<0.001) and allodynia (P<0.001), and TLR4 knock-out protected against codeine-induced changes in pain sensitivity. Glial attenuation with ibudilast reversed codeine-induced allodynia (P<0.001), and thus could be investigated further as potential treatment for codeine-induced pain enhancement.

Space allowance and high fiber diet impact performance and behavior of group-kept gestating sows.

Identifying and optimizing housing and management systems that improve the well-being of the gestating sow is essential to sustaining animal agriculture. Therefore, the impact of 2 floor-space allowances and a high-fiber gestation diet on dry group-housed sows were evaluated using multiple measures of well-being. Groups of 10 multiparous sows/pen (n = 221) were assigned randomly to treatments in a 2 × 2 factorial arrangement to either a corn-soybean meal diet (CTL) or corn-soybean meal diet supplemented with soybean hulls and wheat middlings (FBR), and floor-space allowance of either 1.7 or 2.3 m(2)/sow. Sow BW, backfat (BF), and body condition score (BCS) were all recorded on d 34, 65, 90, and 110 of gestation, whereas skin lesions were scored on d 34, every 2 d for the first 2-wk postmixing, and then biweekly throughout gestation. Blood sample was collected only on d 34 for cortisol (baseline), and samples were collected on d 90 of gestation for other measures including cortisol. Behavior was registered on multiple days throughout gestation. Sows fed FBR and kept at 1.7 m(2) produced heavier litter and weaning weights and greater number of piglets born alive, compared to sows fed FBR but kept at 2.3 m(2) of floor space (diet × floor space, P ≤ 0.04). Sows fed FBR and kept at 1.7 m(2) performed fewer oral-nasal-facial and sham-chew behaviors than sows fed CTL and kept at the same floor space (diet × floor space, P ≤ 0.044). Sows kept at 1.7 m(2) of floor space had a greater (P < 0.05) total lesion severity score than sows kept at 2.3 m(2)/sow, and vulva lesion scores were more (P < 0.02) severe among CTL-fed sows than FBR-fed sows. Parities 2 and 3 sows fed FBR and kept at 1.7 m(2) of floor space were heavier (P < 0.001) than sows fed the same diet but kept at 2.3 m(2). These results indicate that keeping small groups of pregnant sows at a minimum floor-space allowance of 1.7 m(2)/sow and floor feeding these sows a high-fiber diet can improve short-term sow well-being.

Comparison of time to positive and colony counting in an early bactericidal activity study of anti-tuberculosis treatment.

SETTING: Patients with smear-positive, newly diagnosed pulmonary tuberculosis (TB) presenting to the out-patient TB clinic in Kampala, Uganda. OBJECTIVE: To compare colony-forming unit (cfu) counting and time to positive (TTP) in Mycobacteria Growth Indicator Tube (MGIT) culture as measures of early bactericidal activity (EBA). DESIGN: Patients were enrolled in an EBA feasibility study of standard TB chemotherapy. Sixteen-hour overnight sputum collections were obtained before and on days 2, 4, 7, 10, 12 and 14 of treatment for quantitative culture on selective Middlebrook 7H11 agar media and TTP in the MGIT liquid culture system. RESULTS: Log cfu and TTP were correlated over all time points (r(s) = -0.71, P < 0.001). Within-subject (day to day) variation as a percentage of total variation was very similar between the two measures: 25.7% for cfu and 25% for TTP. Mean EBA 0-14, 0-2 and 2-14 measured by TTP were similar to those previously reported. CONCLUSION: TTP measured by an automated, standardized, commercially available culture system correlates with cfu determinations. EBA measured by TTP provides similar information to cfu counting, and is reproducible across sites and in different patient populations. These findings support replacing cfu counting with TTP as the primary measurement in EBA studies.

Relapse more common than reinfection in recurrent tuberculosis 1-2 years post treatment in urban Uganda.

OBJECTIVE: To determine the proportion of recurrent tuberculosis (TB) due to relapse with the patient's initial strain or reinfection with a new strain of Mycobacterium tuberculosis 1-2 years after anti-tuberculosis treatment in Uganda, a sub-Saharan TB-endemic country. DESIGN: Records of patients with culture-confirmed TB who completed treatment at an urban Ugandan clinic were reviewed. Restriction fragment length polymorphism (RFLP) patterns were used to determine relapse or reinfection. Associations between human immunodeficiency virus (HIV) positivity and type of TB recurrence were determined. RESULTS: Of 1701 patients cured of their initial TB episode with a median follow-up of 1.24 years, 171 (10%) had TB recurrence (8.4 per 100 person-years). Rate and risk factors for recurrence were similar to other studies from sub-Saharan Africa. Insertion sequence (IS) 6110-based RFLP of paired isolates from 98 recurrences identified 80 relapses and 18 reinfections. Relapses among HIV-positive and -negative patients were respectively 79% and 85% of recurrences. CONCLUSIONS: Relapse was more common and presented earlier than reinfection in both HIV-positive and -negative TB patients 1-2 years after completing treatment. These findings impact both the choice of retreatment drug regimen, as relapsing patients are at higher risk for acquired drug resistance, and clinical trials of new TB regimens with relapse as clinical endpoint.

Anti-tuberculosis treatment outcomes in HIV-infected adults exposed to isoniazid preventive therapy in Botswana.

SETTING: Eight public health clinics in Gaborone and Francistown, Botswana. OBJECTIVES: To describe the characteristics and outcomes of incident tuberculosis (TB) cases in human immunodeficiency virus (HIV) infected adults exposed to isoniazid preventive therapy (IPT) with access to antiretroviral and anti-tuberculosis treatment. DESIGN: In 1995 HIV-infected adults, TB disease was excluded before commencing IPT. During and after receipt of 6 or 36 months of IPT, symptomatic participants were evaluated using chest radiographs, sputum microscopy, cultures and drug susceptibility testing (DST). Incident TB cases received ≥6 months of anti-tuberculosis treatment. RESULTS: Seventy-five incident TB cases were identified among 619 symptomatic participants. The median duration of IPT in these cases was 6 months (range 1-35), and the median time to initiation of anti-tuberculosis treatment was 12 months after IPT cessation. Antiretroviral therapy (ART) was initiated before anti-tuberculosis treatment in 37 cases. Culture was positive in 43/58 (74%) TB cultures. DST was available for 38 cases, of which six (16%) were resistant to isoniazid (INH); 67/75 (89%) cases, including four with INH-monoresistant TB, completed anti-tuberculosis treatment or were cured. CONCLUSIONS: With prompt initiation of anti-tuberculosis treatment and access to ART, excellent outcomes were achieved in a public health setting in HIV-infected adults who developed TB disease.

Smoking and 2-month culture conversion during anti-tuberculosis treatment.

OBJECTIVE: To investigate risk factors for delayed sputum culture conversion to negative during anti-tuberculosis treatment, with an emphasis on smoking. DESIGN: Nested case-control study of adults with non-cavitary, culture-confirmed pulmonary tuberculosis (TB) participating in an anti-tuberculosis treatment trial in Brazil. A case of delayed culture conversion was a patient who remained culture-positive after 2 months of treatment. Odds ratios with 95% confidence intervals were calculated. RESULTS: Fifty-three cases and 240 control patients were analyzed. Smokers had three-fold greater odds of remaining culture-positive after 2 months of treatment (P = 0.007) than non-smokers, while smokers and ex-smokers who smoked >20 cigarettes a day had two-fold greater odds of remaining culture-positive after 2 months of treatment (P = 0.045). CONCLUSION: Cigarette smoking adversely affects culture conversion during anti-tuberculosis treatment. Support for smoking cessation should be considered to improve outcomes in TB control programs.

Effect of variability in lighting and temperature environments for mature gilts housed in gestation crates on measures of reproduction and animal well-being.

The effects of room temperature and light intensity before breeding and into early gestation were evaluated on the reproductive performance and well-being of gilts housed individually in crates. In eight replicates, estrus was synchronized in mature gilts (n = 198) and after last feeding of Matrix were randomly assigned to a room temperature of 15°C (COLD), 21°C (NEUTRAL), or 30°C (HOT) and a light intensity of 11 (DIM) or 433 (BRIGHT) lx. Estrous detection was performed daily and gilts inseminated twice. Blood samples were collected before and after breeding for determination of immune measures and cortisol concentrations. Gilt ADFI, BW, and body temperature were measured. On d 30 postbreeding, gilts were slaughtered to recover reproductive tracts to evaluate pregnancy and litter characteristics. There were no temperature × light intensity interactions for any response variable. Reproductive measures of follicle development, expression of estrus, ovulation rate, pregnancy rate (83.2%), litter size (14.3 ± 0.5), and fetal measures were not affected by temperature or lighting (P > 0.10). Gilts in COLD (37.6°C) had a lower (P < 0.05) rectal temperature than those in NEUTRAL (38.2°C) and HOT (38.6 ± 0.04°C). Both BW gain and final BW were greater (P < 0.0001) for gilts kept in HOT than those in NEUTRAL or COLD environments. Cortisol was greater (P < 0.01) for gilts kept in COLD compared with those kept in the HOT room. Gilts housed in the HOT environment made more postural changes (P < 0.05) than did those kept in either COLD or NEUTRAL temperatures. Gilts kept in the HOT temperature spent more total time lying and more time lying ventrally compared with those gilts housed in the NEUTRAL or COLD rooms. Total white blood cells and the percentage of neutrophils as well as neutrophil-to-lymphocyte ratio were all influenced (P < 0.05) by temperature but there was no effect (P > 0.10) of light or interaction with temperature on other immune cells or measures. These results indicate that temperatures in the range of 15 to 30°C or light intensity at 11 to 433 lx do not impact reproduction during the follicular phase and into early gestation for mature gilts housed in gestation crates. However, room temperature does impact physiological, behavioral, and immune responses of mature gilts and should be considered as a potential factor that may influence gilt well-being during the first 30 d postbreeding.