Unusual sex chromosomal DSD in a domestic Shorthair cat with a 37,X/38,XY mosaic karyotype.

BACKGROUND: Sex chromosome abnormalities associated with disorders of sexual development (DSD) are rarely described in cats, mainly due to the lack of chromossome studies that precisely reveal the condition. Genetic approaches are therefore required in order to detect sex chromossomes abnormalities as variations in the number and structure of chromosomes, or the presence of a second cell line as mosaicim or chimerism. CASE PRESENTATION: A male Shorthair cryptorchid cat was presented with clinical signs of anorexia, tenesmus and hyperthermia. Ultrasonography revealed a fluid-filled structure, with approximately 1 cm in diameter, adjacent to the descending colon. Computed tomography evidenced a tubular structure, ventral to the descending colon and caudal to the bladder, which extended cranially, through two branches. Histopathological evaluation confirmed the presence of two atrophic uterine horns and one hypoplastic testicle with epididymis at the end of one of the uterine horns. The end of the other uterine horn was attached to a structure composed by a mass of adipocytes. Cytogenetic analysis revealed a mosaic 37,X/38,XY karyotype. The two cell lines were found in 15% and 85% of the lymphocytes, respectively. Genetic analysis confirmed the presence of SRY and ZFY genes in blood and hair bulbs, and revealed a marked reduction in SRY expression in the testicle. Additionally, this case presented exceptionally rare features, such as a Leydig' cell tumour and a chronic endometritis in both uterine horns. CONCLUSIONS: Complete imaging workup, cytogenetic analysis and SRY gene expression should be systematically realized, in order to properly classify disorders of sexual development (DSD) in cats.

Effect of a dairy farmworker stewardship training program on antimicrobial drug usage in dairy cows.

Antimicrobial use (AMU) is critical to preserving animal health and welfare. However, the development of antimicrobial resistance (AMR) represents a public health threat. Although most antimicrobials used on the farm require a veterinarian prescription, farmworkers make daily on-farm treatment decisions. Therefore, farmworker training is vital to promote responsible AMU. This research project aimed to evaluate the effect of farmworker antimicrobial stewardship (AMS) training on the quantity of AMU on dairy farms in Ohio and California. We hypothesized that farms receiving AMS training would have reduced AMU in dairy cattle compared with farms where training wasn't administered. We designed a quasiexperimental study with 18 conventional dairy farms enrolled in Ohio and California. Twelve farms received AMS training, and 6 farms did not. The AMS program included a 12-wk training focused on accurate identification of cows requiring antimicrobial treatment. We quantified AMU by collecting used drug containers, manually counted by researchers during farm visits. Treatment incidence (TI) was calculated using animal daily doses (ADD), and Poisson regression models were used to analyze the TI data. Disease incidence rate (DIR) in lactating cows was 2.2, 1.5, 1.0, 0.4, 0.3, 0.2, and 0.03/1,000 cow-days for mastitis, lameness, metritis, pneumonia, retained placenta, diarrheas, and other diseases (e.g., conjunctivitis, injuries), respectively. The highest TI by antimicrobial class (provided in ADD/1,000 cow-days) was cephalosporin (5.9), penicillin (5.2), tetracyclines (0.4), lincosamides (0.2), and sulfonamides (0.1). Among the trained farms using a within-treatment group analysis, no significant differences were observed in TI pre-intervention (10.9 ADD/1,000 cow-days) compared with TI postintervention (10.3 ADD/1,000 cow-days). Treatment incidence from the training group was 10.8 ADD/1,000 cow-days and although numerically lower, it was not significantly different compared with TI in the control groups at 13.9 ADD/1,000 cow-days (rate ratio = 0.77, CI = 0.25-2.38). Future research on AMS should incorporate farmworker training with social science approaches to overcome barriers and promote on-farm responsible use.

Assessment of runs of homozygosity, heterozygosity-rich regions and genomic inbreeding estimates in a subpopulation of Guzerá (Bos indicus) dual-purpose cattle.

For decades, inbreeding in cattle has been evaluated using pedigree information. Nowadays, inbreeding coefficients can be obtained using genomic information such as runs of homozygosity (ROH). The aims of this study were to quantify ROH and heterozygosity-rich regions (HRR) in a subpopulation of Guzerá dual-purpose cattle, to examine ROH and HRR islands, and to compare inbreeding coefficients obtained by ROH with alternative genomic inbreeding coefficients. A subpopulation of 1733 Guzerá animals genotyped for 50k SNPs was used to obtain the ROH and HRR segments. Inbreeding coefficients by ROH (FROH ), by genomic relationship matrix based on VanRaden's method 1 using reference allele frequency in the population (FGRM ), by genomic relationship matrix based on VanRaden's method 1 using allele frequency fixed in 0.5 (FGRM_0.5 ), and by the proportion of homozygous loci (FHOM ) were calculated. A total of 15,660 ROH were identified, and the chromosome with the highest number of ROH was BTA6. A total of 4843 HRRs were identified, and the chromosome with the highest number of HRRs was BTA23. No ROH and HRR islands were identified according to established criteria, but the regions closest to the definition of an island were examined from 64 to 67 Mb of BTA6, from 36 to 37 Mb of BTA2 and from 0.50 to 1.25 Mb of BTA23. The genes identified in ROH islands have previously been associated with dairy and beef traits, while genes identified on HRR islands have previously been associated with reproductive traits and disease resistance. FROH was equal to 0.095 ± 0.084, and its Spearman correlation with FGRM was low (0.44) and moderate-high with FHOM (0.79) and with FGRM_0.5 (0.80). The inbreeding coefficients determined by ROH were higher than other cattle breeds' and higher than pedigree-based inbreeding in the Guzerá breed obtained in previous studies. It is recommended that future studies investigate the effects of inbreeding determined by ROH on the traits under selection in the subpopulation studied.

Advancing the assessment of pacifier effects with a novel computational method.

BACKGROUND: Numerous studies have demonstrated a high likelihood of malocclusions resulting from non-nutritive sucking. Consequently, quantifying the impact of pacifiers can potentially aid in preventing the development or exacerbation of malocclusions and guide the design of improved performance pacifiers. METHODS: This work proposes and assesses a computational methodology that can effectively gather crucial information and provide more precise data regarding the consequences of non-nutritive pacifier sucking. The computational framework utilized is based on solids4Foam [1, 2], a collection of numerical solvers developed within the OpenFOAM® computational library [3]. The computational model focuses on the palate of a six-month-old baby and incorporates various components such as palate tissues, pacifier and tongue, and considers the negative intraoral pressure generated and the tongue displacement. Different models were tested, each offering varying levels of detail in representing the palate structure. These models range from a simplified approach, with one tissue, to a more intricate representation, involving up to five different tissues, offering a more comprehensive palate model compared to existing literature. RESULTS: The analysis of results involved examining the distribution of stress on the palate surface, as well as the displacement and forces exerted on the dental crowns. By comparing the obtained results, it was possible to evaluate the precision of the approaches previously described in the literature. The findings revealed that the predictions were less accurate when using the simplified model with a single tissue for the palate, which is the most common approach proposed in the literature. In contrast, the results demonstrated that the palate model with the most intricate structure, incorporating five different tissues, yielded distinct outcomes compared to all other combinations. CONCLUSIONS: The computational methodology proposed, employing the most detailed palate model, has demonstrated its effectiveness and necessity in obtaining accurate data on the impact of non-nutritive sucking habits, which are recognized as a primary contributor to the development of dental malocclusions. In the future, this approach could be extended to conduct similar studies encompassing diverse pacifier designs, sizes, and age groups. This would foster the design of innovative pacifiers that mitigate the adverse effects of non-nutritive sucking on orofacial structures.

Cystic ovarian disease in dairy cattle: Diagnostic accuracy when using B-mode and color Doppler ultrasound.

The most frequently reported definition of cystic ovarian disease in cattle is an abnormally persistent follicle (>7 to 10 d) with a diameter >25 mm. Discrimination between luteal and follicular ovarian cystic structures has traditionally been conducted by measuring the rim width of luteal tissue. The most common practice used in the field for diagnosis of cystic ovarian disease is examination by rectal palpation with or without the use of a B-mode ultrasound. Color Doppler ultrasound technology allows assessment of blood flow area measurements in the ovary, which has been proposed as a potential indirect measure for plasma progesterone (P4) concentrations. The objective of this study was to compare the diagnostic accuracy of differentiating luteal structures from follicular ovarian cysts using measures collected with B-mode and color Doppler transrectal ultrasonography. The definition of an ovarian cyst was a follicle greater than 20 mm in diameter in the absence of a corpus luteum that persisted for at least 10 d. A 3-mm luteal rim width was used to differentiate follicular and luteal cysts. A total of 36 cows were enrolled in the study during routine herd reproductive examination visits, with 26 and 10 having follicular and luteal cysts, respectively. Cows enrolled in the study were examined using a Mini-ExaPad mini ultrasound with color Doppler capabilities (IMV Imaging Ltd.). Blood samples were collected from each cow to measure P4 serum concentrations. History and signalment of each cow, including days in milk, lactation, times bred, days since last heat, milk composition, and somatic cell counts, were retrieved from an online database (DairyComp 305, Valley Agricultural Software). The accuracy of diagnosing follicular from luteal cysts based on luteal rim thickness was analyzed by receiver operating characteristic (ROC) curve using P4 as the gold standard, where P4 concentrations exceeding 1 ng/mL was defined as luteal, and all other structures with less P4 were considered follicular. Luteal rim and blood flow area were selected for further analysis because they presented the best ROC curves for differentiating cystic ovarian structures, with areas under the curve of 0.80 and 0.76, respectively. Luteal rim width of 3 mm was used as the cutoff standard in the study, resulting in sensitivity and specificity of 50% and 86%, respectively. Blood flow area of 0.19 cm2 was used as the cutoff standard in the study, resulting in sensitivity and specificity of 79% and 86%, respectively. When combining the use of luteal rim width and blood flow area to differentiate cystic ovarian structures, a parallel approach resulted in sensitivity and specificity of 73% and 93%, respectively, whereas an in-series approach resulted in sensitivity and specificity of 35% and 100%, respectively. In conclusion, the use of color Doppler ultrasonography when discriminating between luteal and follicular ovarian cysts in dairy cattle resulted in higher diagnostic accuracy compared with using B-mode ultrasonography alone.

Characterization of a DRC1 null variant associated with primary ciliary dyskinesia and female infertility.

PROPOSE: We here present a female case with primary ciliary dyskinesia (PCD) and infertility. In this report, we also present the evaluation of the patient family, including her twin sister, also with PCD and infertility. METHODS: Confirmation of the PCD clinical diagnosis was performed through assessment of cilia motility, by high-speed video microscopy (HSVM), axoneme ultrastructure, by transmission electron microscopy (TEM), and genetic characterization, by whole-exome sequence (WES). Gene expression studies used qPCR for mRNA expression and immunofluorescence to determine cell protein localization. RESULTS: We identified a homozygous nonsense variant in the DRC1 gene (NM 145038.5:c.352C>T (p.Gln118Ter)) in the female patient with PCD and infertility that fit the model of autosomal recessive genetic transmission. This variant eventually results in a dyskinetic ciliary beat with a lower frequency and a partial lack of both dynein arms as revealed by TEM analysis. Moreover, this variant implies a decrease in the expression of DRC1 mRNA and protein. Additionally, expression analysis suggested that DRC1 may interact with other DRC elements. CONCLUSIONS: Our findings suggest that the DRC1 null variant leads to PCD associated with infertility, likely caused by defects in axoneme from Fallopian tube cilia. Overall, our outcomes contribute to a better understanding of the genetic factors involved in the pathophysiology of PCD and infertility, and they highlight the interaction of different genes in the patient phenotype, which should be investigated further because it may explain the high heterogeneity observed in PCD patients.

A non-coding RNA balancing act: miR-346-induced DNA damage is limited by the long non-coding RNA NORAD in prostate cancer.

BACKGROUND: miR-346 was identified as an activator of Androgen Receptor (AR) signalling that associates with DNA damage response (DDR)-linked transcripts in prostate cancer (PC). We sought to delineate the impact of miR-346 on DNA damage, and its potential as a therapeutic agent. METHODS: RNA-IP, RNA-seq, RNA-ISH, DNA fibre assays, in vivo xenograft studies and bioinformatics approaches were used alongside a novel method for amplification-free, single nucleotide-resolution genome-wide mapping of DNA breaks (INDUCE-seq). RESULTS: miR-346 induces rapid and extensive DNA damage in PC cells - the first report of microRNA-induced DNA damage. Mechanistically, this is achieved through transcriptional hyperactivation, R-loop formation and replication stress, leading to checkpoint activation and cell cycle arrest. miR-346 also interacts with genome-protective lncRNA NORAD to disrupt its interaction with PUM2, leading to PUM2 stabilisation and its increased turnover of DNA damage response (DDR) transcripts. Confirming clinical relevance, NORAD expression and activity strongly correlate with poor PC clinical outcomes and increased DDR in biopsy RNA-seq studies. In contrast, miR-346 is associated with improved PC survival. INDUCE-seq reveals that miR-346-induced DSBs occur preferentially at binding sites of the most highly-transcriptionally active transcription factors in PC cells, including c-Myc, FOXA1, HOXB13, NKX3.1, and importantly, AR, resulting in target transcript downregulation. Further, RNA-seq reveals widespread miR-346 and shNORAD dysregulation of DNA damage, replication and cell cycle processes. NORAD drives target-directed miR decay (TDMD) of miR-346 as a novel genome protection mechanism: NORAD silencing increases mature miR-346 levels by several thousand-fold, and WT but not TDMD-mutant NORAD rescues miR-346-induced DNA damage. Importantly, miR-346 sensitises PC cells to DNA-damaging drugs including PARP inhibitor and chemotherapy, and induces tumour regression as a monotherapy in vivo, indicating that targeting miR-346:NORAD balance is a valid therapeutic strategy. CONCLUSIONS: A balancing act between miR-346 and NORAD regulates DNA damage and repair in PC. miR-346 may be particularly effective as a therapeutic in the context of decreased NORAD observed in advanced PC, and in transcriptionally-hyperactive cancer cells.

Biomarkers of treatment benefit with atezolizumab plus vemurafenib plus cobimetinib in BRAFV600 mutation-positive melanoma.

BACKGROUND: The phase III IMspire150 study (NCT02908672) demonstrated significantly improved progression-free survival (PFS) with atezolizumab, vemurafenib, and cobimetinib (atezolizumab group) versus placebo, vemurafenib, and cobimetinib (control group) in patients with BRAFV600-mutated advanced melanoma. We report exploratory biomarker analyses to optimize targeting of patients who are more likely to benefit from triplet combination therapy. PATIENTS AND METHODS: Five hundred fourteen patients were randomized to atezolizumab (n = 256) or control (n = 258). Outcomes were evaluated in subgroups defined by key biomarkers, including programmed death-ligand 1 (PD-L1) expression, lactate dehydrogenase (LDH) level, tumor mutational burden (TMB), and interferon-γ (IFN-γ) gene signature. Exploratory recursive partitioning analysis was then used to model associations between PFS and baseline covariates, including key biomarkers. RESULTS: PFS benefit for atezolizumab versus control was greater in patients with high TMB [≥10 mutations/Mb; hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.52-1.02; P = 0.067] versus low TMB (<10 mutations/Mb; HR 0.92; 95% CI 0.65-1.30; P = 0.64) and similar between patients with strong IFN-γ (≥median; HR 0.76; 95% CI 0.54-1.06) versus weak IFN-γ (

Age-related reference data of bone microarchitecture, volumetric bone density, and bone strength parameters in a population of healthy Brazilian men: an HR-pQCT study.

In a cross-sectional cohort of 340 healthy Brazilian men aged 20 to 92 years, data on density, structure, and strength of the distal radius and tibia were obtained using high-resolution peripheral quantitative computed tomography (HR-pQCT) to develop age- and site-specific reference curves. Age-dependent changes differed between the sites and bone compartments (trabecular and cortical). INTRODUCTION: The aim of this study was to establish age-related reference curves for bone densities, microarchitectural properties, and estimated failure load measured by HR-pQCT (distal radius and tibia) in men. Also, to correlate bone stiffness with the other HR-pQCT parameters, areal bone mineral density (BMD) by DXA and trabecular bone score (TBS). METHODS: Healthy Brazilian men (n = 340) between the ages of 20 and 92 years were recruited. Non-dominant radius and left tibia were scanned using HR-pQCT (Xtreme CT I). Standard and automated segmentation methods were performed, and bone strength estimated by FE analysis. Bone mineral density at lumbar spine, total hip, femoral neck, and TBS were measured using DXA (Hologic, QDR4500). RESULTS: Age-related reference curves were constructed at the distal radius and tibia for volumetric bone density, morphometry, and estimated bone strength parameters. There was a linear relationship with age only for thickness measurements of distal radius (trabecular: R2 0.108, p<0.001; cortical: R2 0.062, p=0.002) and tibia (trabecular: R2 0.109, p<0.001; cortical: R2 0.063, p=0.010), and bone strength at distal radius (R2 0.157, p<0.001). The significant correlations (p <0.05) found by Pearson's correlations (r) between bone stiffness and all other variables measured by HR-pQCT and DXA showed to be stronger at the tibia site than the distal radius. CONCLUSION: The current study expands the HR-pQCT worldwide database and presents an adequate methodology for the construction of reference data in other populations. Moreover, the correlation of bone strength estimated by FEA with other bone microstructural parameters provided by HR-pQCT helps to determine the contribution of each of these variables to fracture risk prediction in men.

Insights on sperm assays and cryopreservation in six Neotropical pit vipers.

Breeding snakes in captivity has become more and more relevant due not only to the growing interest on their venoms but also to the increasing number of endangered species worldwide. Unfortunately, studies on the formation of germplasm banks for these reptiles do not follow the same pace, and literature on sperm cryopreservation remains in its infancy when compared to other taxa. Herein, we first validated a sperm-egg binding assay (using chicken egg perivitelline membrane - EPM) and some nonfluorescent staining techniques for semen analysis of two pit viper genera (Bothrops and Crotalus), and then we investigated the protective effects of dimethylacetamide (DMA), dimethylformamide (DMF), and dimethylsulfoxide (DMSO) at different concentrations (3, 6 and 12%) throughout the freezing process in five species of lancehead and one of rattlesnake. Our validation process showed high correlations among sperm functional tests (including sperm-binding to EPM) and motion parameters. A total of 166 fresh ejaculates were acquired from 233 collection attempts, and 63.9% of these samples exhibited minimal motility for freezing (≥20%). During cryopreservation we observed that post-thaw motility and quality was improved by higher levels of cryoprotectants (CPA), regardless the CPA type. Lower concentrations of CPA were less harmful to sperm motility and progressive motility following the equilibrium phase, but were ineffective in protecting these cells from the freeze-thaw cycle. Likewise, higher CPA concentrations increased post-thaw integrity of the acrosome and plasma membrane for most species, except for rattlesnakes in which only 12% DMSO produced better outcomes.

First test-day postcalving risk factors for clinical mastitis in southern Chile dairy farms: A retrospective cohort study.

We conducted a retrospective cohort study to evaluate risk factors associated with clinical mastitis in dairy cows in southern Chile between the first milk test after calving to 200 d in milk (DIM). Data from 8,772 cows were collected from June 2017 to November 2019 on 10 dairy farms selected by convenience in southern Chile. Data were analyzed using a multivariable mixed logistic regression using a manual backward selection process with logit link function and farm as a random effect. The dependent variable was clinical mastitis between the first milking sample collected by monthly milk sampling program up to 200 DIM. Days in milk, fat, urea, parity, season, and somatic cell counts were statistically associated with clinical mastitis in the first 200 d in milk. Cows with higher than average milk yield, parity, urea, and somatic cell count were at greater odds of being diagnosed with clinical mastitis compared with their respective referents. In contrast, higher milk fat was associated with lower odds of clinical mastitis. Significant interactions between days in milk with season and parity were observed, where for every 5-d increase in DIM, the odds of clinical mastitis decreased by different proportions depending on the interaction. Identified risk factors for clinical mastitis using first monthly milk sampling data can help dairy farmers in Chile implement herd-level mastitis prevention and control measures.

The sterile insect technique: an international framework to facilitate transboundary shipments of sterile insects.

The sterile insect technique (SIT) has been successfully used since the 1950s as part of an integrated pest management approach in large-scale programmes to prevent, contain, suppress and eradicate key insect pests in many countries throughout the world. During this period, over one trillion live sterile insects have been shipped across borders. The very few adverse incidents from this significant trade were managed and resulted in no significant impacts. The phytosanitary and zoosanitary requirements by importing countries have been simple, facilitating the transboundary shipment of sterile insects, which is carried out mostly under the framework of cooperative agreements between the governments of the countries involved, and under technical cooperation projects of the United Nations. However, the shipment of sterile insects from sources outside this governmental framework, including public-private facilities, has been complicated, despite the availability of harmonised international guidelines in some cases, such as those for fruit flies. The SIT has great potential for the control of endemic pests or against the growing threat of invasive pests that can affect whole regions and even continents. Since SIT is species-specific, with negligible risk of introducing unwanted invasive species to the environment, and with the advantage of reducing insecticide use, a harmonised framework that recognises the low risk of SIT would facilitate shipments of sterile insects across borders and help to expand the use of this effective and environmentally friendly technology. The scope of this paper is limited to insects that have been sterilised using ionising radiation.

La technique de l'insecte stérile (TIS) est utilisée avec succès depuis les années 1950, en tant que composante d'une approche intégrée de gestion des ravageurs mise en place par des programmes de grande envergure appliqués dans de nombreux pays pour prévenir, maîtriser, supprimer et éliminer les principales espèces d'insectes nuisibles. Depuis lors, plus d'un trillion d'insectes stériles vivants ont été transportés au-delà des frontières nationales. Les très rares incidents indésirables survenus en marge de ces volumineux échanges ont été maîtrisés et n'ont eu aucun impact significatif. La simplicité des exigences phytosanitaires et de santé animale requises par les pays importateurs a facilité le transport transfrontalier des insectes stériles, le plus souvent effectué dans le cadre d'accords de coopération conclus entre les gouvernements des pays concernés et de projets de coopération technique des Nations Unies. En revanche, il est plus compliqué de transporter des insectes stériles issus de sources extérieures aux cadres gouvernementaux, en particulier des sites relevant d'une gestion publique-privée, et ce malgré l'existence de directives internationales harmonisées, par exemple celles s'appliquant aux différentes mouches de fruits. La TIS présente un grand potentiel pour lutter contre les ravageurs endémiques ou contre la menace croissante associée aux ravageurs envahissants, qui peuvent affecter des régions entières, voire des continents. Étant donné que la TIS est spécifique pour chaque espèce, qu'elle présente un risque négligeable d'introduire des espèces envahissantes non désirées et qu'elle offre l'avantage de réduire le recours aux insecticides, il conviendrait de disposer d'un cadre harmonisé qui reconnaisse le faible niveau de risque associé à la TIS et facilite ainsi les transports transfrontaliers d'insectes stériles, afin d'aider au déploiement plus large de cette technologie efficace et sans risque pour l'environnement. La portée de cet article se limite aux insectes stérilisés par une exposition aux radiations ionisantes.

Desde el decenio de 1950 se viene empleando con éxito la técnica del insecto estéril (sterile insect technique, SIT), aplicada en el manejo integrado de plagas, como parte de programas que se despliegan a gran escala para prevenir, contener, suprimir y erradicar importantes plagas de insectos en muchos países del mundo. En todos estos años, más de un billón de insectos estériles vivos han sido transportados en cargamentos transfronterizos. Los contados incidentes adversos ocasionados por este voluminoso comercio fueron debidamente manejados y se saldaron sin repercusiones de importancia. Los requisitos fitosanitarios y zoosanitarios impuestos por los países importadores han sido sencillos, cosa que ha facilitado el envío transfronterizo de insectos estériles, que mayoritariamente se inscribe en acuerdos de cooperación suscritos entre los gobiernos de los países en cuestión y en proyectos de cooperación técnica de las Naciones Unidas. Sin embargo, el transporte de insectos estériles procedentes de fuentes no sujetas a estos regímenes oficiales, incluidas instalaciones publico-privadas, ha sido complicado, pese a la existencia de directrices internacionales armonizadas aplicables en ciertos casos, como el de la mosca de la fruta. La técnica del insecto estéril puede ser sumamente útil para luchar contra plagas endémicas o contra la creciente amenaza de plagas invasoras capaces de afectar a regiones enteras o incluso a continentes enteros. Teniendo en cuenta que esta técnica utiliza en cada caso la liberación de insectos estériles para controlar insectos plaga de la misma especie, que entraña por ello un riesgo insignificante de introducir en el medio especies invasoras indeseadas y que además presenta la ventaja de reducir el uso de insecticidas, la existencia de un ordenamiento armonizado que reconozca el escaso nivel de riesgo que presenta la SIT facilitaría el envío transfronterizo de insectos estériles y ayudaría a extender el uso de esta técnica tan eficaz como ambientalmente respetuosa. Las consideraciones que aquí hacen los autores se aplican únicamente al caso de los insectos esterilizados con radiación ionizante.

Validation of a Portuguese version of the Groningen radiotherapy-induced xerostomia questionnaire.

BACKGROUND: The aim of this study was to validate and determine at pretest level the reliability of the Portuguese version of the Groningen radiotherapy-induced xerostomia questionnaire. MATERIAL AND METHODS: This study employed 37 head and neck cancer patients. Each patient signed an informed consent and responded to the Portuguese version of the questionnaire in the form of an interview. This was repeated again after 2 weeks. A standard single question provided a validity check. Data were analyzed using Cronbach's α to test its reliability and total and interitem correlation, and intraclass correlation to determine its internal consistency and test-retest reliability. Construct validity supported by objective measurements as salivary secretion was also investigated. Significance was set at .05. RESULTS: Cronbach's α was 0.91 and 0.89 for the first and second test administrations, respectively, which indicates that the internal consistency was excellent. The intraclass correlation coefficient value for the test-retest reliability was 0.70. The correlation between the total score of the questionnaire and standard single dry mouth question was 0.72 for the first round, indicating a good correlation. CONCLUSIONS: Demonstrating very good psychometric properties, the Portuguese version of the Groningen radiotherapy-induced xerostomia questionnaire is a valid tool and can be considered a reliable instrument to measure xerostomia in head and neck cancer patients.

Incidence and risk factors for osteoporotic non-vertebral fracture in low-income community-dwelling elderly: a population-based prospective cohort study in Brazil. The São Paulo Ageing and Health (SPAH) study.

We ascertained the incidence of non-vertebral fracture in a low-income Brazilian elderly cohort. To the best of our knowledge, this is the first population-based study to demonstrate the frequency of non-vertebral fracture in elderly Latin Americans. Age, prior fracture, and bone mineral density (BMD) at hip were predictors of fracture. INTRODUCTION: No data on incidence of osteoporotic non-vertebral fracture have been reported in low-income countries where the population's aging has been faster. Even in developed countries, currently available prospective data on major fracture rates beyond hip are scarce. The aim of this study is to describe the incidence and risk factors for non-vertebral fracture in a longitudinal prospective Brazilian population-based elderly cohort. METHODS: Seven hundred seven older adults (449 women, 258 men) were evaluated at baseline and after a mean follow-up of 4.3 ± 0.8 years. Clinical questionnaire, bone mineral density (BMD), and laboratory tests were performed at baseline. New non-vertebral fracture (hip, proximal humerus, rib, forearm) was determined during the follow-up. Multivariate Poisson regression models were used to identify independent predictors of fracture. RESULTS: The age-standardized incidence of non-vertebral fracture was 1562.3/100,000 (1085.7-2248.1/100,000) person-years (pyr) in women and 632.8/100,000 (301.7-1327.3/100,000) in men. Concerning to hip fractures, the incidence was 421.2/100,000 (210.7-842.3/100,000) pyr in women and 89.9/100,000 (12.7-638.5/100,000) in men. In a multivariate analysis, age (RR 2.07, 95% CI 1.13-3.82, p = 0.019, each 10-year increase), prior non-vertebral fracture (RR 3.08, 95% CI 1.36-6.95, p = 0.007), and total hip BMD (RR 1.68, 95% CI 1.11-2.56, p = 0.015, each 1 SD decrease) were predictors of new non-vertebral fracture. In men, fitting a model of risk factors for fracture was prevented by the limited number of events in male sample. CONCLUSION: This is the first population-based study to ascertain the incidence of major non-vertebral fractures in elderly Latin Americans, confirming the high frequency of the disorder. Age, prior fracture, and hip BMD were predictors of the short-term incidence of fracture.

Physical and ecological isolation contribute to maintain genetic differentiation between fire salamander subspecies.

Landscape features shape patterns of gene flow among populations, ultimately determining where taxa lay along the continuum between panmixia to complete reproductive isolation. Gene flow can be restricted, leading to population differentiation in two non-exclusive ways: "physical isolation", in which geographic distance in combination with the landscape features restricts movement of individuals promoting genetic drift, and "ecological isolation", in which adaptive mechanisms constrain gene flow between different environments via divergent natural selection. In central Iberia, two fire salamander subspecies occur in parapatry across elevation gradients along the Iberian Central System mountains, while in the adjacent Montes de Toledo Region only one of them occurs. By integrating population and landscape genetic analyses, we show a ubiquitous role of physical isolation between and within mountain ranges, with unsuitable landscapes increasing differentiation between populations. However, across the Iberian Central System, we found strong support for a significant contribution of ecological isolation, with low genetic differentiation in environmentally homogeneous areas, but high differentiation across sharp transitions in precipitation seasonality. These patterns are consistent with a significant contribution of ecological isolation in restricting gene flow among subspecies. Overall, our results suggest that ecological divergence contributes to reduce genetic admixture, creating an opportunity for lineages to follow distinct evolutionary trajectories.

Food consumption on campus is associated with meal eating patterns among college students.

This is a cross-sectional analysis of data obtained in the baseline of the Longitudinal Study on the Lifestyle and Health of University Students (n 685) carried out in a public Brazilian university. Food intake was assessed using a 24-h dietary recall. Dietary patterns (DP) for breakfast, lunch and dinner were identified using principal component analysis. Generalised linear models were used to analyse the variables associated with each DP. Three DP were extracted for each meal: breakfast: 'White bread and butter/margarine', 'Coffee and tea' and 'Sausages, whole wheat bread and cheese'; lunch: 'Traditional', 'Western' and 'Vegetarian' and dinner: 'Beans, rice and processed juice', 'White bread and butter/margarine' and 'White meat, eggs and natural juice'. Students who had meals at the campus showed greater adherence to the 'White bread and butter/margarine' (exp (ßadj) = 1·15, 95 % CI 1·11, 1·19) and 'Coffee and tea' (exp (ßadj) = 1·06, 95 % CI 1·02, 1·10) breakfast patterns; 'Western' lunch pattern (exp (ßadj) = 1·04, 95 % CI 1·01, 1·08) and to the 'Beans, rice and processed juice' dinner pattern (exp (ßadj) = 1·10, 95 % CI 1·06, 1·14). Having meals at the campus was associated with lower adherence to the 'Sausages, whole wheat bread and cheese' breakfast pattern (exp (ßadj) = 0·93, 95 % CI 0·89, 0·97), 'Traditional' lunch pattern (exp (ßadj) = 0·96, 95 % CI 0·93, 0·99) and to the 'White bread and butter/margarine' (exp (ßadj) = 0·96, 95 % CI 0·93, 0·99) and 'White meat, eggs and natural juice' (exp (ßadj) = 0·96, 95 % CI 0·93, 0·99) dinner pattern. The food environment at campus may influence students' DP. Recognising meal eating patterns is important to support healthy eating promotion strategies on campus. Adjustments in the University Canteen menu could contribute to healthier eating choices among students.

Biofilm of Candida albicans: formation, regulation and resistance.

Candida albicans is the most common human fungal pathogen, causing infections that range from mucous membranes to systemic infections. The present article provides an overview of C. albicans, with the production of biofilms produced by this fungus, as well as reporting the classes of antifungals used to fight such infections, together with the resistance mechanisms to these drugs. Candida albicans is highly adaptable, enabling the transition from commensal to pathogen due to a repertoire of virulence factors. Specifically, the ability to change morphology and form biofilms is central to the pathogenesis of C. albicans. Indeed, most infections by this pathogen are associated with the formation of biofilms on surfaces of hosts or medical devices, causing high morbidity and mortality. Significantly, biofilms formed by C. albicans are inherently tolerant to antimicrobial therapy, so the susceptibility of C. albicans biofilms to current therapeutic agents remains low. Therefore, it is difficult to predict which molecules will emerge as new clinical antifungals. The biofilm formation of C. albicans has been causing impacts on susceptibility to antifungals, leading to resistance, which demonstrates the importance of research aimed at the prevention and control of these clinical microbial communities.

Methionine precursor effects on lactation performance of dairy cows fed raw or heated soybeans.

Two experiments were conducted to evaluate the effect of isopropyl ester of 2-hydroxy-4-(methylthio) butanoic acid (HMBi) on lactation performance of dairy cows. Experiment 1 evaluated the effect of HMBi in diets with 15.3% crude protein (CP) and with different proportions of rumen-degradable and undegradable protein. Variation in rumen-degradable and undegradable protein was achieved by replacing raw with heated soybeans. Experiment 2 was an on-farm trial to evaluate HMBi with a large number of observations and using a farm-formulated diet (17.2% CP). In experiment 1, 20 Holsteins at 100 ± 41 d in milk were allocated to 5 replicated 4 × 4 Latin squares with 21-d periods. Treatments were formed by a 2 × 2 factorial arrangement of raw or heated soybeans with or without HMBi. Paper capsules with HMBi were orally administered twice daily to each cow. Dosage of HMBi was 7.6 g of digestible Met/cow per day. There was no interaction between soybean type and HMBi. Heat-treated soybeans increased the yields of milk, protein, fat, and lactose, and reduced urea N in milk and plasma (PUN) compared with raw soybeans. Rumen microbial yield, dry matter intake (DMI), and the total-tract apparent digestibility of nutrients did not differ between soybean types. There was no evidence for HMBi-driven effects on DMI, milk and components yield, or diet digestibility. Urinary purine derivative excretion and PUN concentration were reduced in HMBi-fed cows compared with cows fed diets without HMBi. In experiment 2, 294 Holstein cows were blocked by parity and milk yield, and randomly assigned to HMBi (8.9 g of digestible Met/cow per day) or control. The final data set had 234 cows (215 ± 105 days in milk; 96 primiparous and 138 multiparous; 114 on control and 120 on HMBi) housed in 4 freestall groups (1 group/treatment per parity). The freestall group was the experimental unit for DMI, diet and orts composition, and feed availability. The HMBi supplement was top dressed for 28 d on the first daily meal of each cow, immediately after feed delivery of the same batch of feed to all 4 freestall groups (3 times per day). Sample collection and feed analysis occurred during the last 5 d. Spot urine samples and blood samples from each cow were obtained for analysis of the urinary allantoin to creatinine ratio and PUN. Feed availability, the contents of CP and neutral detergent fiber in diets and orts, and DMI did not differ. Cows fed with HMBi had greater milk protein yield and concentration compared with control and had no change in milk fat and lactose. Rumen microbial yield was greater and PUN was lower in HMBi-fed cows compared with control. In experiment 1, HMBi decreased rumen microbial yield and did not affect lactation performance, but it increased ruminal microbial yield and the secretion of milk protein in experiment 2. These results suggest that lactation response to HMBi may be partially mediated by ruminal events. Heated soybeans increased the efficiency of N utilization and the yields of milk, protein, fat, and lactose, but did not interact with HMBi supplementation.

Treatment practices after calving-related events on 45 dairy farms in California.

Retained fetal membranes (RFM), dystocia, and twinning are common postpartum events that increase the risk of metritis, impair reproductive performance, and contribute to antimicrobial use on dairies. The overall objective of this study was to describe treatment decisions after RFM, severe dystocia (cesarean section and fetotomy), nonsevere dystocia (nonmechanical and mechanical assistance to extract the calf), and twinning. A total of 44 dairies from California's San Joaquin Valley (39 Holstein and 6 Jersey or crossbreed herds) with 450 to 9,500 lactating cows were enrolled in this study. Researchers visited each dairy once to observe cow-side fresh cow health evaluations and to interview health evaluators and maternity workers, using a standardized survey tool. The survey included questions about antimicrobial (class, dose, and duration) and nonantimicrobial therapies for calving-related events. Antimicrobial therapy was used in all 44 dairies to treat RFM at 24 (n = 23), 48 (n = 10), or 72 h (n = 5) after calving, or when puerperal metritis signs were observed (n = 6). Antimicrobial therapy was used after all severe dystocia cases, and after nonsevere dystocia (n = 27) and twinning (n = 15). Ceftiofur products were the most common antimicrobial class; they were used to treat RFM cases (n = 29), nonsevere dystocia (n = 13), and twinning (n = 10). Supportive therapy for calving-related events included nonantimicrobial intrauterine treatments, nonsteroidal antiinflammatory drugs, oxytocin, i.v. calcium, or oral drenches. Our study highlights opportunities to reduce extra-label use of antimicrobials in postpartum cows affected with RFM, and the need for education and outreach efforts on judicious use of antimicrobials. Furthermore, antimicrobial treatment choices differed largely across dairies, indicating a need to reach consensus and promote standardized practices within the industry.

Integration of statistical inferences and machine learning algorithms for prediction of metritis cure in dairy cows.

The study's objectives were to identify cow-level and environmental factors associated with metritis cure to predict metritis cure using traditional statistics and machine learning algorithms. The data set used was from a previous study comparing the efficacy of different therapies and self-cure for metritis. Metritis was defined as fetid, watery, reddish-brownish discharge, with or without fever. Cure was defined as an absence of metritis signs 12 d after diagnosis. Cows were randomly allocated to receive a subcutaneous injection of 6.6 mg/kg of ceftiofur crystalline-free acid (Excede, Zoetis) at the day of diagnosis and 3 d later (n = 275); and no treatment at the time of metritis diagnosis (n = 275). The variables days in milk (DIM) at metritis diagnosis, treatment, season of the metritis diagnosis, month of metritis diagnostic, number of lactation, parity, calving score, dystocia, retained fetal membranes, body condition score at d 5 postpartum, vulvovaginal laceration score, the rectal temperature at the metritis diagnosis, fever at diagnosis, milk production from the day before to metritis diagnosis, and milk production slope up to 5, 7, and 9 DIM were offered to univariate logistic regression. Variables included in the multivariable logistic regression model were selected from the univariate analysis according to P-value. Variables were offered to the model to assess the association between these factors and metritis cure. Additionally, the univariate logistic regression variables were offered to a recursive feature elimination to find the optimal subset of features for a machine learning algorithms analysis. Cows without vulvovaginal laceration had 1.91 higher odds of curing of metritis than cows with vulvovaginal laceration. Cows that developed metritis at >7 DIM had 2.09 higher odds of being cured than cows that developed metritis at ≤7 DIM. For rectal temperature, each degree Celsius above 39.4°C led to lower odds to be cured than cows with rectal temperature ≤39.4°C. Furthermore, milk production slope and milk production difference from the day before to the metritis diagnosis were essential variables to predict metritis cure. Cows that had reduced milk production from the day before to the metritis diagnosis had lower odds to be cured than cows with moderate milk production increase. The results from the multivariable logistic regression and receiver operating characteristic analysis indicated that cows developing metritis at >7 DIM, with increase in milk production, and with a rectal temperature ≤39.40°C had increased likelihood of cure of metritis with an accuracy of 75%. The machine learning analysis showed that in addition to these variables, calving-related disorders, season, and month of metritis event were needed to predict whether the cow will cure or not from metritis with an accuracy ≥70% and F1 score (harmonic mean between precision and recall) ≥0.78. Although machine learning algorithms are acknowledged as powerful tools for predictive classification, the current study was unable to replicate its potential benefits. More research is needed to optimize predictive models of metritis cure.