Mortality impact of further delays in active targeted antibiotic therapy in bacteraemic patients that did not receive initial active empiric treatment: results from the prospective, multicentre cohort PROBAC.

OBJECTIVES: The early initiation of the empirical antibiotic treatment and its impact on mortality in patients with bacteraemia has been extensively studied. However, information on the impact of precocity of the targeted antibiotic treatment is scarce. We aimed to study the impact of further delay in active antibiotic therapy on 30-day mortality among patients with bloodstream infection (BSI) who had not received appropriate empirical therapy. DESIGN: We worked with PROBAC cohort (prospective and compound by patients from 26 different Spanish hospitals). We selected a total of 1703 patients, who survived to day 2 without having received any active antibiotic therapy against the causative pathogen. RESULTS: The 30-day mortality was 14% (238 patients). The adjusted odds of mortality increased for every day of delay, from 1.53 (95% CI 1.13-2.08) for day 3 or after to 11.38 (95% CI 7.95-16.38) for day 6 or after. CONCLUSIONS: We concluded that among patients who had not received active treatment within the first two days of blood culture collection, additional delays in active targeted therapy were associated with increased mortality. These results emphasize the importance of active interventions in the management of patients with bloodstream infections.

Chronic Cough and Cerebellar Ataxia With Neuropathy and Bilateral Vestibular Areflexia Syndrome (CANVAS): Screening for Mutations in Replication Factor C Subunit 1 (RFC1).

INTRODUCTION: A common complaint in patients is chronic cough (CC), which may be refractory (RCC) or unexplained (UCC). Recent studies point, as a possible cause of CC, to the hereditary cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS), with an estimated carrier prevalence of 1 in 20000. AIM: In patients with CC, determine the prevalence of the biallelic (AAGGG)exp mutation in replication factor C subunit 1 (RFC1) responsible for CANVAS, test the usefulness of the Rydel-Seiffer fork test, and evaluate patient quality of life (QoL). METHODS: Clinical and functional data were collected for the 33 included patients undergoing CC studies in our specialized unit. Performed were an etiological study of CC following European Respiratory Society recommendations, a genetic study of RFC1 mutations, and Rydel-Seiffer fork testing to detect possible peripheral vibratory sensitivity impairment. Administered to evaluate QoL were 4 questionnaires. RESULTS: Prevalence of biallelic (AAGGG)exp in RFC1 was 6.1% (n=2) overall, increasing to 7.1% in the RCC subgroup, and to 33.3% in the Rydel-Seiffer fork altered results subgroup. Prevalence of monoallelic (AAGGG)exp in RFC1 was 18.2% (n=6) overall, rising to 50.0% (n=2) in the UCC subgroup. CONCLUSION: Genetic screening for (AAGGG)exp in RFC1, and also use of the Rydel-Seiffer fork test, should be considered in specialized CC consultations for patients with RCC and UCC. Detecting possible CANVAS symptoms in CC studies would identify candidates for early genetic screening, of interest in reducing the disease burden for patients and health systems alike.

Salmonella Bacteremia in Spanish Pediatric Emergency Departments: Uncommon But Not Mild.

BACKGROUND: Salmonella spp. is an uncommon microorganism in bloodstream infections among pediatric patients in our setting, although in developing countries it is the most common causative organism in blood cultures. METHODS: We describe the children presenting to pediatric emergency departments and diagnosed with Salmonella bacteremia (SB) and identify clinical and laboratory predictors of poor outcome (ie, complications, sequelae and death) by bivariate analysis. We performed an observational study and subanalysis of a multicenter prospective registry, including patients <18 years of age with a positive blood culture obtained at any of the 22 participating Spanish pediatric emergency departments between 2011 and 2016. We considered young age, chronic diseases, immunosuppressive treatment and intestinal flora disruption as risk factors for SB. RESULTS: Of the 55 patients with SB (3.2% of registered bacteremia), 32 (58.2%) had no risk factors for SB, 42 (76.3%) had a normal pediatric assessment triangle and 45 (81.8%) an associated gastrointestinal infection (acute gastroenteritis or enteric fever). Nine (16.4%) had a poor outcome, including 1 death (1.8%). A poor outcome was more common in patients with an abnormal pediatric assessment triangle [odds ratio (OR): 51.6; 95% confidence interval (CI): 9.2-289.5], an altered physical examination (OR: 15.2; 95% CI: 4.4-58.8) and elevated C-reactive protein (OR: 1.01; 95% CI: 1.005-1.03). CONCLUSIONS: Most SBs were related to a gastrointestinal infection. One in 6 children had a poor outcome; abnormal pediatric assessment triangle on arrival (25% of patients) was the main risk factor identified.

Differences in clinical outcomes of bloodstream infections caused by Klebsiella aerogenes, Klebsiella pneumoniae and Enterobacter cloacae: a multicentre cohort study.

BACKGROUND: Klebsiella aerogenes has been reclassified from Enterobacter to Klebsiella genus due to its phenotypic and genotypic similarities with Klebsiella pneumoniae. It is unclear if clinical outcomes are also more similar. This study aims to assess clinical outcomes of bloodstreams infections (BSI) caused by K. aerogenes, K. pneumoniae and Enterobacter cloacae, through secondary data analysis, nested in PRO-BAC cohort study. METHODS: Hospitalized patients between October 2016 and March 2017 with monomicrobial BSI due to K. aerogenes, K. pneumoniae or E. cloacae were included. Primary outcome was a composite clinical outcome including all-cause mortality or recurrence until 30 days follow-up. Secondary outcomes were fever ≥ 72 h, persistent bacteraemia, and secondary device infection. Multilevel mixed-effect Poisson regression was used to estimate the association between microorganisms and outcome. RESULTS: Overall, 29 K. aerogenes, 77 E. cloacae and 337 K. pneumoniae BSI episodes were included. Mortality or recurrence was less frequent in K. aerogenes (6.9%) than in E. cloacae (20.8%) or K. pneumoniae (19.0%), but statistical difference was not observed (rate ratio (RR) 0.35, 95% CI 0.08 to 1.55; RR 0.42, 95% CI 0.10 to 1.71, respectively). Fever ≥ 72 h and device infection were more common in K. aerogenes group. In the multivariate analysis, adjusted for confounders (age, sex, BSI source, hospital ward, Charlson score and active antibiotic therapy), the estimates and direction of effect were similar to crude results. CONCLUSIONS: Results suggest that BSI caused by K. aerogenes may have a better prognosis than E. cloacae or K. pneumoniae BSI.

Pegvisomant or pasirotide in PRL and GH co-secreting vs GH-secreting Pit-NETs.

AIM: To evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH/PRL-Pit-NET) and compare to those caused by a GH-Pit-NET. METHODS: A multicenter retrospective study of patients with acromegaly on treatment with pasireotide or pegvisomant. Patients were classified in two groups: GH/PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC; and GH-Pit-NETs when the previously mentioned criteria were not met. RESULTS: A total of 28 cases with GH/PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH/PRL-Pit-NETs presented at a younger age, caused hypopituitarism and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide neither with pegvisomant were observed between GH/PRL-Pit-NETs and GH-Pit-NETs. All GH/PRL-Pit-NET cases treated with pasireotide (n=6) and 82.6% (n=19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH/PRL-Pit-NETs (84.9% vs. 66.7%, P=0.178). CONCLUSION: Despite the more aggressive behavior of GH/PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide is observed between both groups, and both drugs are effective treatments to control IGF-1 and PRL hypersecretion in these tumors.

Predictors of cardiovascular risk in familial hypercholesterolemia.

PURPOSE OF REVIEW: Familial Hypercholesterolemia is associated with an increased risk of cardiovascular disease. The current international guidelines of the main scientific societies consider that all people with familial hypercholesterolemia have a high or very high cardiovascular risk. However, the occurrence of atherosclerotic cardiovascular disease is very heterogeneous in this population. Stratifying risk within people with familial hypercholesterolemia is essential to identify individuals who require intensive cholesterol-lowering therapies. RECENT FINDINGS: In the last year, several studies have been published focusing on the contribution of diabetes to familial hypercholesterolemia, the role of stroke, as a manifestation of atherosclerotic disease, and the external validation of the SAFEHEART risk equation in the English population diagnosed with Familial Hypercholesterolemia. SUMMARY: It is necessary the development of a tool that allows us to identify, in a simple, reproducible, and universal way, patients who may have a high risk of suffering a cardiovascular event and who are susceptible to more intensive treatments to reduce cholesterol levels.

Differences between rural and urban residence in the detection and treatment of perinatal mood and anxiety disorders.

BACKGROUND: Perinatal mood and anxiety disorders are common, serious complications of pregnancy. Disparities exist by race and income in the prevalence and treatment of these conditions, and overall treatment rates remain low. Outside of pregnancy, a small body of literature suggests that rural residency may contribute to higher rates of depression for those who identify as women. However, among more diverse populations, evidence suggests urban residency may be associated with higher rates of depression among women of color. It is not known whether these trends hold for mood and anxiety disorders during pregnancy and postpartum. OBJECTIVE: We examined differences in the detection and treatment of perinatal mood and anxiety disorders by rural and urban residents and assessed if the observed differences varied by maternal race or ethnicity. STUDY DESIGN: We conducted a cross-sectional study using linked Medicaid claims and birth certificate records from Oregon and South Carolina from 2016 to 2020. We identified perinatal mood and anxiety disorder diagnoses during the perinatal period (pregnancy and within 60 days postpartum) using International Classification of Disease 10th edition codes and enumerated receipt of pharmacotherapy and psychotherapy treatment using Medicaid claims. We used logistic regression models controlling for relevant clinical and sociodemographic characteristics to estimate associations between rural residence and mood disorder detection and treatment. RESULTS: Among the 185,809 births in our sample, 27% of births (n=50,820) were to people who lived in rural areas and 73% (n=134,989) to those in urban areas. The prevalence of any perinatal mood and anxiety disorders diagnosis was higher for urban residents (19.5%) than for rural residents (18.0%; P<.001). Overall treatment rates were low among people with a perinatal mood and anxiety disorder (42% [n=14,789]). In our adjusted models, those living in urban areas had higher odds of a perinatal mood and anxiety disorder diagnosis (adjusted odds ratio, 1.059 [95% confidence interval, 1.059-1.059], P<.001). We found a significant interaction between maternal race and rurality (P<.001). When we stratified by race, we found that among those who identified as Black, the odds of a perinatal mood and anxiety disorder diagnosis were increased for urban residents (odds ratio, 1.188 [95% confidence interval, 1.188-1.188]), whereas among those who identified as White, there were no such increased odds (odds ratio, 1.027 [95% confidence interval, 0.843-1.252]). CONCLUSION: We saw small but meaningful differences between rural and urban residents in perinatal mood and anxiety disorder diagnosis rates. We detected an interaction between race and rural vs urban maternal residence that impacted the observed differences. By elucidating the intersection between race and other sociodemographic factors, we hope more targeted and meaningful investments can be made in the communities most in need.

Combining melatonin with dexmedetomidine improves anesthesia in rats.

Melatonin (ML) and dexmedetomidine (DM) are used separately as anesthetic premedication or as an anesthetic in humans and laboratory animals. In this study, we aimed to investigate the anesthetic properties of both drugs combined. The anesthetic effects of several combinations of ML (50 and 100 mg/kg) and DM (50 and 100 µg/kg) were evaluated in rats by observing behavioral manifestations and recording the duration and depth of anesthesia. Five anesthetic intervals were established according to the loss and recovery of reflexes. While each individual drug did not induce an appropriate anesthetic effect at the tested doses, ML50 + DM100, ML100 + DM50 and ML100 + DM100 combinations resulted in surgical anesthesia intervals of 60 to 360 min. Together, our results point that the use of ML allows to decrease the dose of DM, reducing the unwanted anesthetic effects of this α2-agonist.

Effectiveness of Combined First-Line Medical Treatment in Acromegaly with Prolactin Co-secretion.

OBJECTIVE: To compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary adenoma (GH-PA) and those with GH and prolactin co-secreting PA (GH&PRL-PA). DESIGN: Retrospective multicentric study of acromegaly patients followed from 2003 to 2023 in 33 tertiary Spanish hospitals with at least six months of first-line medical treatment. METHODS: Baseline characteristics, first-line medical treatment strategies, and outcomes were analysed. We employed a multiple logistic regression full model to estimate the impact of some baseline characteristics on disease control after each treatment modality. RESULTS: Of the 144 patients included, 72.9% had a GH-PA, and 27.1% had a GH&PRL-PA. Patients with GH&PRL-PA were younger (43.9 ± 15.0 vs. 51.9 ± 12.7 years; p < 0.01) and harboring more frequently macroadenomas (89.7% vs. 72.1%, p = 0.03). First generation somatostatin receptor ligand (fgSRL) as monotherapy was given to 106 (73.6%) and a combination treatment with fgSRL and cabergoline in the remaining 38 (26.4%). Patients with GH&PRL-PA received more frequently a combination therapy (56.4% vs. 15.2%; p < 0.01). After 6 months of treatment, in the group of patients under fgSRL as monotherapy, those patients with GH&PRL-PA had worse control compared to GH-PAs (29.4% vs. 55.1%, p = 0.04). However, these differences in the rate of disease control between both groups disappeared when both received combination treatment with fgSRL and cabergoline. CONCLUSION: In GH&PRL-PA the biochemical control achieved with fgSRL as monotherapy is substantially worse than in patients harboring GH-PA, supporting the inclusion of cabergoline as first line medical treatment in combination with fgSRLs in these subgroups of patients.

Availability of Mifepristone and Misoprostol in Oregon Pharmacies: A Comparison by Rural and Urban Status.

OBJECTIVES: To evaluate the availability of mifepristone and misoprostol at pharmacies in a state with protective abortion legislation and variation in access by rurality. STUDY DESIGN: Using a secret shopper survey, researchers attempted to contact all community pharmacies in Oregon and evaluate their mifepristone and misoprostol provision. RESULTS: Among the 444 pharmacies surveyed, mifepristone was planned at 19.2%. Misoprostol was available at 77.5%, but stocking issues and medication ordering impact access, without significant difference by rurality. CONCLUSIONS: Pharmacy engagement and support is key to increasing access to these essential medicines, which may be improved through education and referral programs.

Human vs machine: identifying ChatGPT-generated abstracts in Gynecology and Urogynecology.

BACKGROUND: ChatGPT, a publicly available artificial intelligence large language model, has allowed for sophisticated artificial intelligence technology on demand. Indeed, use of ChatGPT has already begun to make its way into medical research. However, the medical community has yet to understand the capabilities and ethical considerations of artificial intelligence within this context, and unknowns exist regarding ChatGPT's writing abilities, accuracy, and implications for authorship. OBJECTIVE: We hypothesize that human reviewers and artificial intelligence detection software differ in their ability to correctly identify original published abstracts and artificial intelligence-written abstracts in the subjects of Gynecology and Urogynecology. We also suspect that concrete differences in writing errors, readability, and perceived writing quality exist between original and artificial intelligence-generated text. STUDY DESIGN: Twenty-five articles published in high-impact medical journals and a collection of Gynecology and Urogynecology journals were selected. ChatGPT was prompted to write 25 corresponding artificial intelligence-generated abstracts, providing the abstract title, journal-dictated abstract requirements, and select original results. The original and artificial intelligence-generated abstracts were reviewed by blinded Gynecology and Urogynecology faculty and fellows to identify the writing as original or artificial intelligence-generated. All abstracts were analyzed by publicly available artificial intelligence detection software GPTZero, Originality, and Copyleaks, and were assessed for writing errors and quality by artificial intelligence writing assistant Grammarly. RESULTS: A total of 157 reviews of 25 original and 25 artificial intelligence-generated abstracts were conducted by 26 faculty and 4 fellows; 57% of original abstracts and 42.3% of artificial intelligence-generated abstracts were correctly identified, yielding an average accuracy of 49.7% across all abstracts. All 3 artificial intelligence detectors rated the original abstracts as less likely to be artificial intelligence-written than the ChatGPT-generated abstracts (GPTZero, 5.8% vs 73.3%; P<.001; Originality, 10.9% vs 98.1%; P<.001; Copyleaks, 18.6% vs 58.2%; P<.001). The performance of the 3 artificial intelligence detection software differed when analyzing all abstracts (P=.03), original abstracts (P<.001), and artificial intelligence-generated abstracts (P<.001). Grammarly text analysis identified more writing issues and correctness errors in original than in artificial intelligence abstracts, including lower Grammarly score reflective of poorer writing quality (82.3 vs 88.1; P=.006), more total writing issues (19.2 vs 12.8; P<.001), critical issues (5.4 vs 1.3; P<.001), confusing words (0.8 vs 0.1; P=.006), misspelled words (1.7 vs 0.6; P=.02), incorrect determiner use (1.2 vs 0.2; P=.002), and comma misuse (0.3 vs 0.0; P=.005). CONCLUSION: Human reviewers are unable to detect the subtle differences between human and ChatGPT-generated scientific writing because of artificial intelligence's ability to generate tremendously realistic text. Artificial intelligence detection software improves the identification of artificial intelligence-generated writing, but still lacks complete accuracy and requires programmatic improvements to achieve optimal detection. Given that reviewers and editors may be unable to reliably detect artificial intelligence-generated texts, clear guidelines for reporting artificial intelligence use by authors and implementing artificial intelligence detection software in the review process will need to be established as artificial intelligence chatbots gain more widespread use.

Headache and Other Factors Modifying Cerebrospinal Fluid Opening Pressure in Pediatric Patients.

Cerebrospinal fluid opening pressure values are associated with various neurologic diseases; however, numerous factors can modify this measurement. This study aims to describe factors related to modifications in opening pressure measurements in pediatric patients. Methods: A retrospective analysis of lumbar punctures in pediatric patients conducted by the neuropediatrics group with institutional standardization. Bivariate and linear regression analyses were performed to determine the association between opening pressure and variables included in the study. Results: 544 events, median age 107 months, median opening pressure 19.7 cm H2O. Bivariate analysis found no association with medication use; anesthetics that increased opening pressure were remifentanil (P = .02) and propofol (P = .05), along with a positive linear correlation between opening pressure and age (P < .0001). Multiple linear regression analysis revealed that age, BMI, male gender, and remifentanil use were associated with an increase in opening pressure, whereas corticosteroid withdrawal was associated with a reduction in opening pressure. There is an interaction between age and headache, with an association with increased opening pressure up to around 140 months. Conclusion: This study identifies factors associated with changes in opening pressure, crucial for estimating normal opening pressure values in children. Headaches, anesthetic use, and corticosteroid withdrawal are confirmed as significant factors.

Phase I Trial of SPECT-Guided Liver-Directed Radiotherapy for Patients with Low Functional Liver Volume.

BACKGROUND: Traditional constraints specify that 700 cc of liver should be spared a hepatotoxic dose when delivering liver-directed radiotherapy to reduce the risk of inducing liver failure. We investigated the role of single photon emission computed tomography (SPECT) to identify and preferentially avoid functional liver during liver-directed radiation treatment planning in patients with preserved liver function but limited functional liver volume after receiving prior hepatotoxic chemotherapy or surgical resection. METHODS: This phase I trial with a 3 + 3 design evaluated the safety of liver-directed radiotherapy using escalating functional liver radiation dose constraints in patients with liver metastases. Dose limiting toxicities (DLTs) were assessed 6-8 weeks and 6 months after completing radiotherapy. RESULTS: All twelve patients had colorectal liver metastases and received prior hepatotoxic chemotherapy. Eight patients underwent prior liver resection. Median computed tomography (CT) anatomical non-tumor liver volume was 1,584 cc (range 764-2,699 cc). Median SPECT functional liver volume was 1,117 cc (range 570-1,928cc). Median non-target CT and SPECT liver volumes below the volumetric dose constraint were 997 cc (range 544-1,576 cc) and 684 cc (range 429-1,244 cc), respectively. The prescription dose was 67.5-75 Gy in 15 fractions or 75-100 Gy in 25 fractions. No DLTs were observed during follow-up. One-year in-field control was 57%. One-year overall survival was 73%. CONCLUSION: Liver-directed radiotherapy can be safely delivered to high doses when incorporating functional SPECT into the radiation treatment planning process which may enable sparing of lower volumes of liver than traditionally accepted in patients with preserved liver function. TRIAL REGISTRATION: NCT02626312.

Impact of the Dobbs decision on abortion services from a large tertiary center in Oregon.

OBJECTIVE: Evaluate the impact of the Dobbs vs Jackson decision on abortion volume and patient characteristics in Oregon, a state with no legal restrictions on abortion, at a single tertiary care hospital. METHODS: Electronic health records from patients who received an abortion at Oregon's largest tertiary health center were utilized comparing the year before and after Dobbs. RESULTS: Monthly average abortions increased from 57.8 pre-Dobbs to 77.1 post-Dobbs (p=0.001). This trend was associated with an increased proportion of out-of-state patients (14.3% vs 9.5%, p=0.004) presenting with gestational duration ≥ 26 weeks (23.6% vs 3.7% in-state, p<0.001). CONCLUSIONS: The Dobbs decision resulted in increased utilization of hospital-based abortion care in a protective state, characterized by a greater prevalence of patients traveling from out-of-state and presenting at later gestational durations. These trends reflect the critical role of protective states in preserving access to abortion care.

The Perceived Quality of Life of Older People in Spain Who Care for Grandchildren and Related Variables: A Mixed Methods Study.

Grandparental care of grandchildren is a prevalent social phenomenon. This study explores the perceptions of health-related quality of life of grandparents caring for their grandchildren. A mixed methods design was developed. In the first phase, participants were interviewed using a baseline questionnaire. The second phase consisted of focus groups with 19 of the 100 participants in the quantitative phase. The scores obtained from the quantitative analysis are in line with the qualitative data; they reflect that grandparent carers who are more involved in the care of their grandchildren have more symptoms of depression and stress and have poorer perceptions of physical health-related quality of life. What may at first appear to be a positive aspect, keeping grandparent carers active, can become negative when it comes to shared care and when the grandparents' willingness to provide care is abused.

Analysis of the Prognostic Factors That Influence the Outcome of Periapical Surgery, including Biomimetic Membranes for Tissue Regeneration: A Review.

The objective of this study was to analyze the prognostic factors that influence the outcome of periapical surgery. A systematic search of the literature was carried out using PubMed and Scopus databases between January 2000 and December 2023 with no language limitations. The PICO question of the present systematic review was: What prognostic factors may influence the outcome of periapical surgery? The most relevant randomized controlled clinical trials (RCTs), prospective clinical trials, retrospective studies, and meta-analyses (n = 44) were selected from 134 articles. The reviewed literature evidenced that bone-lesion healing could significantly be improved by the absence of deep periodontal pockets (>4 mm), localization in anterior teeth, the absence of pain and/or preoperative symptoms, a size of bone lesion < 5 mm, the use of ultrasound, the correct placement of retrograde filling material, and the use of different biomimetic membranes for guided tissue regeneration (GTR). Some preoperative and intraoperative factors could significantly improve the prognosis of periapical surgery. However, these results were not conclusive, and further high-quality research is required.

An Algoclay-Based Decontaminant Decreases Exposure to Aflatoxin B1, Ochratoxin A, and Deoxynivalenol in a Toxicokinetic Model, as well as Supports Intestinal Morphology, and Decreases Liver Oxidative Stress in Broiler Chickens Fed a Diet Naturally Contaminated with Deoxynivalenol.

The aims of this study were (i) to determine the effect of an algoclay-based decontaminant on the oral availability of three mycotoxins (deoxynivalenol; DON, ochratoxin A; OTA, and aflatoxin B1; AFB1) using an oral bolus model and (ii) to determine the effect of this decontaminant on the performance, intestinal morphology, liver oxidative stress, and metabolism, in broiler chickens fed a diet naturally contaminated with DON. In experiment 1, sixteen 27-day-old male chickens (approximately 1.6 kg body weight; BW) were fasted for 12 h and then given a bolus containing either the mycotoxins (0.5 mg DON/kg BW, 0.25 mg OTA/kg BW, and 2.0 mg AFB1/kg BW) alone (n = 8) or combined with the decontaminant (2.5 g decontaminant/kg feed; circa 240 mg/kg BW) (n = 8). Blood samples were taken between 0 h (before bolus administration) and 24 h post-administration for DON-3-sulphate, OTA, and AFB1 quantification in plasma. The algoclay decontaminant decreased the relative oral bioavailability of DON (39.9%), OTA (44.3%), and AFB1 (64.1%). In experiment 2, one-day-old male Ross broilers (n = 600) were divided into three treatments with ten replicates. Each replicate was a pen with 20 birds. The broiler chickens were fed a control diet with negligible levels of DON (0.19-0.25 mg/kg) or diets naturally contaminated with moderate levels of DON (2.60-2.91 mg/kg), either supplemented or not with an algoclay-based decontaminant (2 g/kg diet). Jejunum villus damage was observed on day 28, followed by villus shortening on d37 in broiler chickens fed the DON-contaminated diet. This negative effect was not observed when the DON-contaminated diet was supplemented with the algoclay-based decontaminant. On d37, the mRNA expression of glutathione synthetase was significantly increased in the liver of broiler chickens fed the DON-contaminated diet. However, its expression was similar to the control when the birds were fed the DON-contaminated diet supplemented with the algoclay-based decontaminant. In conclusion, the algoclay-based decontaminant reduced the systemic exposure of broiler chickens to DON, OTA, and AFB1 in a single oral bolus model. This can be attributed to the binding of the mycotoxins in the gastrointestinal tract. Moreover, dietary contamination with DON at levels between 2.69 and 2.91 mg/kg did not impair production performance but had a negative impact on broiler chicken intestinal morphology and the liver redox system. When the algoclay-based decontaminant was added to the diet, the harm caused by DON was no longer observed. This correlates with the results obtained in the toxicokinetic assay and can be attributed to a decreased absorption of DON.

Quantification of ovine gammaherpesvirus 2 in clinical cases of cattle with sheep-associated malignant catarrhal fever.

Ovine gammaherpesvirus 2 (OvGHV2) produces sheep-associated malignant catarrhal fever (SA-MCF), a frequently lethal, lymphoproliferative disease that is characterized by widespread vascular lesions. Most studies that evaluated the viral load in tissues of animals with SA-MCF were done in the Northern Hemisphere, with scant information from the Southern part of the globe. This study investigated the viral load of OvGHV2 in the tissues of cattle and an underdeveloped fetus with SA-MCF from three distinct biomes of Brazil. All animals had clinical and histopathological manifestations consistent with SA-MCF. Molecular testing identified the OvGHV2 tegument protein and glycoprotein B genes in the tissues of all animals and the fetus. Viral quantification based on the DNA polymerase gene detected elevated loads of OvGHV2 in tissues with histopathological evidence of SA-MCF and organs with unknown histological data, except for the tissues of the fetus, where the viral load was comparatively reduced. The viral loads detected in multiple organs of cattle from this study with SA-MCF are consistent with those identified in different animal species from the USA and Europe. The detection of a low viral load of OvGHV2 in fetal tissue confirmed transplacental dissemination since elevated viral loads were detected in multiple tissues of the cow with SA-MCF. Furthermore, the elevated viral loads detected in the pulmonary tissues of cattle with interstitial pneumonia indicate that OvGHV2 is an inductor of pulmonary disease in cattle.

Chromosomal Damage, Chromosome Instability, and Polymorphisms in GSTP1 and XRCC1 as Biomarkers of Effect and Susceptibility in Farmers Exposed to Pesticides.

In the department of Boyacá, Colombia, agriculture stands as one of the primary economic activities. However, the escalating utilization of pesticides within this sector has sparked concern regarding its potential correlation with elevated risks of genotoxicity, chromosomal alterations, and carcinogenesis. Furthermore, pesticides have been associated with a broad spectrum of genetic polymorphisms that impact pivotal genes involved in pesticide metabolism and DNA repair, among other processes. Nonetheless, our understanding of the genotoxic effects of pesticides on the chromosomes (as biomarkers of effect) in exposed farmers and the impact of genetic polymorphisms (as susceptibility biomarkers) on the increased risk of chromosomal damage is still limited. The aim of our study was to evaluate chromosomal alterations, chromosomal instability, and clonal heterogeneity, as well as the presence of polymorphic variants in the GSTP1 and XRCC1 genes, in peripheral blood samples of farmers occupationally exposed to pesticides in Aquitania, Colombia, and in an unexposed control group. Our results showed statistically significant differences in the frequency of numerical chromosomal alterations, chromosomal instability, and clonal heterogeneity levels between the exposed and unexposed groups. In addition, we also found a higher frequency of chromosomal instability and clonal heterogeneity in exposed individuals carrying the heterozygous GSTP1 AG and XRCC1 (exon 10) GA genotypes. The evaluation of chromosomal alterations and chromosomal instability resulting from pesticide exposure, combined with the identification of polymorphic variants in the GSTP1 and XRCC1 genes, and further research involving a larger group of individuals exposed to pesticides could enable the identification of effect and susceptibility biomarkers. Such markers could prove valuable for monitoring individuals occupationally exposed to pesticides.