Search

The large-scale recording of traits such as feed efficiency (FE) and methane emissions (ME) for use in genetic improvement programs is complex, costly, and time-consuming. Therefore, heritable traits that can be continuously recorded in dairy herds and are correlated with FE and ME traits could provide useful information for genetic evaluation. Rumination time has been suggested to be associated with FE, methane production (MeP; ME in g/d), and production traits at the phenotypic level. Therefore, the objective of this study was to investigate the genetic relationships among rumination time (RT), FE, methane and production traits using 7,358 records from 656 first-lactation Holstein cows. The estimated heritabilities were moderate for RT (0.45 ± 0.14), MeP (0.36 ± 0.12), milk yield (0.40 ± 0.08), fat yield (0.29 ± 0.06), protein yield (0.32 ± 0.07), and energy-corrected milk (0.28 ± 0.07), but were low and nonsignificant for FE (0.15 ± 0.07), which was defined as the residual of the multiple linear regression of DMI on energy-corrected milk and metabolic body weight. A favorable negative genetic correlation was estimated between RT and MeP (-0.53 ± 0.24), whereas a positive favorable correlation was estimated between RT and energy-corrected milk (0.49 ± 0.11). The estimated genetic correlation of RT with FE (-0.01 ± 0.17) was not significantly different from zero but showed a trend of a low correlation with dry matter intake (0.21 ± 0.13). These results indicate that RT is genetically associated with MeP and milk production traits, but high standard errors indicate that further analyses should be conducted to verify these findings when more data for RT, MeP, and FE become available., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background and Purpose: Exercise-based interventions can be a safe alternative to improve and maintain physical and mental health during the aging process. The aim of the present study was to evaluate the effects of a 12-week training program with Dance Exergames on the mood and functional fitness profile of elderly women., Methods: The sample (n = 22) was divided into Exergames (EG, n = 9, 70.6 ± 1.6 years) and Control Groups (CG, n = 13, 73.6 ± 2.2 years). Evaluations were carried out before and after the interventions. Each participant played, in pairs, the electronic game Dance Central 3, with the XBOX 360 Kinect console (Slim, Microsoft, USA). The EG trained for 12 weeks (24 sessions), with two weekly sessions of 50 min and the CG performed manual activities workshops., Results: In functional fitness, both exercise training with exergame (EG) and the intervention model for the CG did not produce significant effects regarding interaction (group*time). Mood state presented significant effect of time intervention regarding tension (p = <0.001), depression (p = 0.001), anger (p = 0.030), fatigue (p = 0.001), and mental confusion (p = 0.004)., Conclusion: Twelve weeks of training with a dance exergame (for, EG) and manual activities (for, CG) is enough to promote improvements in the mood state of healthy elderly women. This is an interesting result, as it shows that social interaction is as important a component as improving functional capacity., Competing Interests: Declaration of competing interest All procedures were carried out according to the strictest ethical principles. All authors are responsible for the contents of the manuscript and have seen and approved its final version. No commercial party supporting this article and with a direct financial interest in the results of the research has or will confer financial benefits to the authors or any organisation with which the authors are associated., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In the dairy industry, mate allocation is dependent on the producer's breeding goals and the parents' breeding values. The probability of pregnancy differs among sire-dam combinations, and the compatibility of a pair may vary due to the combination of gametic haplotypes. Under the hypothesis that incomplete incompatibility would reduce the odds of fertilization, and complete incompatibility would lead to a non-fertilizing or lethal combination, deviation from Mendelian inheritance expectations would be observed for incompatible pairs. By adding an interaction to a transmission ratio distortion (TRD) model, which detects departure from the Mendelian expectations, genomic regions linked to gametic incompatibility can be identified. This study aimed to determine the genetic background of gametic incompatibility in Holstein cattle. A total of 283,817 genotyped Holstein trios were used in a TRD analysis, resulting in 422 significant regions, which contained 2075 positional genes further investigated for network, overrepresentation, and guilt-by-association analyses. The identified biological pathways were associated with immunology and cellular communication and a total of 16 functional candidate genes were identified. Further investigation of gametic incompatibility will provide opportunities to improve mate allocation for the dairy cattle industry., (© 2022. The Author(s).)

Staphylococcus aureus is increasingly recognized as a facultative intracellular pathogen, although the significance and pervasiveness of its intracellular lifestyle remain controversial. Here, we applied fluorescence microscopy-based infection assays and automated image analysis to profile the interaction of 191 S. aureus isolates from patients with bone/joint infections, bacteremia, and infective endocarditis, with four host cell types, at five times post-infection. This multiparametric analysis revealed that almost all isolates are internalized and that a large fraction replicate and persist within host cells, presenting distinct infection profiles in non-professional vs. professional phagocytes. Phenotypic clustering highlighted interesting sub-groups, including one comprising isolates exhibiting high intracellular replication and inducing delayed host death in vitro and in vivo. These isolates are deficient for the cysteine protease staphopain A. This study establishes S. aureus intracellular lifestyle as a prevalent feature of infection, with potential implications for the effective treatment of staphylococcal infections., (© 2022. The Author(s).)

Dairy farmers are motivated to ensure cows become pregnant in an optimal and timely manner. Although timed artificial insemination (TAI) is a successful management tool in dairy cattle, it masks an animal's innate fertility performance, likely reducing the accuracy of genetic evaluations for fertility traits. Therefore, separating fertility traits based on the recorded management technique involved in the breeding process or adding the breeding protocol as an effect to the model can be viable approaches to address the potential bias caused by such management decisions. Nevertheless, there is a lack of specificity and uniformity in the recording of breeding protocol descriptions by dairy farmers. Therefore, this study investigated the use of 8 supervised machine learning algorithms to classify 1,835 unique breeding protocol descriptions from 981 herds into the following 2 classes: TAI or other than TAI. Our results showed that models that used a stacking classifier algorithm had the highest Matthews correlation coefficient (0.94 ± 0.04, mean ± SD) and maximized precision and recall (F1-score = 0.96 ± 0.03) on test data. Nonetheless, their F1-scores on test data were not different from 5 out of the other 7 algorithms considered. Altogether, results presented herein suggest machine learning algorithms can be used to produce robust models that correctly identify TAI protocols from dairy cattle breeding records, thus opening the opportunity for unbiased genetic evaluation of animals based on their natural fertility., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The development of an extensive toolkit for potential point-of-care diagnostics that is expeditiously adaptable to new emerging pathogens is of critical public health importance. Recently, a number of novel CRISPR-based diagnostics have been developed to detect SARS-CoV-2. Herein, we outline the development of an alternative CRISPR nucleic acid diagnostic utilizing a Cas13d ribonuclease derived from Ruminococcus flavefaciens XPD3002 (CasRx) to detect SARS-CoV-2, an approach we term SENSR (sensitive enzymatic nucleic acid sequence reporter) that can detect attomolar concentrations of SARS-CoV-2. We demonstrate 100% sensitivity in patient-derived samples by lateral flow and fluorescence readout with a detection limit of 45 copy/μL. This technology expands the available nucleic acid diagnostic toolkit, which can be adapted to combat future pandemics.

Since its first emergence from China in late 2019, the SARS-CoV-2 virus has spread globally despite unprecedented containment efforts, resulting in a catastrophic worldwide pandemic. Successful identification and isolation of infected individuals can drastically curtail virus spread and limit outbreaks. However, during the early stages of global transmission, point-of-care diagnostics were largely unavailable and continue to remain difficult to procure, greatly inhibiting public health efforts to mitigate spread. Furthermore, the most prevalent testing kits rely on reagent- and time-intensive protocols to detect viral RNA, preventing rapid and cost-effective diagnosis. Therefore the development of an extensive toolkit for point-of-care diagnostics that is expeditiously adaptable to new emerging pathogens is of critical public health importance. Recently, a number of novel CRISPR-based diagnostics have been developed to detect COVID-19. Herein, we outline the development of a CRISPR-based nucleic acid molecular diagnostic utilizing a Cas13d ribonuclease derived from Ruminococcus flavefaciens (CasRx) to detect SARS-CoV-2, an approach we term SENSR (Sensitive Enzymatic Nucleic-acid Sequence Reporter). We demonstrate SENSR robustly detects SARS-CoV-2 sequences in both synthetic and patient-derived samples by lateral flow and fluorescence, thus expanding the available point-of-care diagnostics to combat current and future pandemics.

Basing on a library of thiadiazole derivatives showing anti-trypanosomatidic activity, we have considered the thiadiazoles opened forms and reaction intermediates, thiosemicarbazones, as compounds of interest for phenotypic screening against Trypanosoma brucei (Tb), intracellular amastigote form of Leishmania infantum (Li) and Trypanosoma cruzi (Tc). Similar compounds have already shown interesting activity against the same organisms. The compounds were particularly effective against T. brucei and T. cruzi. Among the 28 synthesized compounds, the best one was (E)-2-(4-((3.4-dichlorobenzyl)oxy)benzylidene) hydrazinecarbothioamide (A14) yielding a comparable anti-parasitic activity against the three parasitic species (TbEC 50  = 2.31 μM, LiEC 50  = 6.14 μM, TcEC 50  = 1.31 μM) and a Selectivity Index higher than 10 with respect to human macrophages, therefore showing a pan-anti-trypanosomatidic activity. (E)-2-((3'.4'-dimethoxy-[1.1'-biphenyl]-3-yl)methyle ne) hydrazinecarbothioamide (A12) and (E)-2-(4-((3.4-dichlorobenzyl)oxy)benzylidene)hydrazine carbothioamide (A14) were able to potentiate the anti-parasitic activity of methotrexate (MTX) when evaluated in combination against T. brucei, yielding a 6-fold and 4-fold respectively Dose Reduction Index for MTX. The toxicity profile against four human cell lines and a panel of in vitro early-toxicity assays (comprising hERG, Aurora B, five cytochrome P450 isoforms and mitochondrial toxicity) demonstrated the low toxicity for the thosemicarbazones class in comparison with known drugs. The results confirmed thiosemicarbazones as a suitable chemical scaffold with potential for the development of properly decorated new anti-parasitic drugs., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Flavonoids have previously been identified as antiparasitic agents and pteridine reductase 1 (PTR1) inhibitors. Herein, we focus our attention on the chroman-4-one scaffold. Three chroman-4-one analogues ( 1 - 3 ) of previously published chromen-4-one derivatives were synthesized and biologically evaluated against parasitic enzymes ( Trypanosoma brucei PTR1- Tb PTR1 and Leishmania major-Lm PTR1) and parasites ( Trypanosoma brucei and Leishmania infantum ). A crystal structure of Tb PTR1 in complex with compound 1 and the first crystal structures of Lm PTR1-flavanone complexes (compounds 1 and 3 ) were solved. The inhibitory activity of the chroman-4-one and chromen-4-one derivatives was explained by comparison of observed and predicted binding modes of the compounds. Compound 1 showed activity both against the targeted enzymes and the parasites with a selectivity index greater than 7 and a low toxicity. Our results provide a basis for further scaffold optimization and structure-based drug design aimed at the identification of potent anti-trypanosomatidic compounds targeting multiple PTR1 variants.

Members of the ATP-binding cassette (ABC)-type transporter superfamily have been implicated in multidrug resistance in malaria, and various mechanistic models have been postulated to explain their interaction with diverse antimalarial drugs. To gain insight into the pharmacological benefits of inhibiting ABC-type transporters in malaria chemotherapy, we investigated the in vitro chemosensitization potential of various P-glycoprotein inhibitors. A fluorescent chloroquine derivative was synthesized and used to assess the efflux dynamics of chloroquine in MDR and wild type Plasmodium falciparum parasites. This novel BODIPY-based probe accumulated in the digestive vacuole (DV) of CQ-sensitive parasites but less so in MDR cells. Pre-exposure of the MDR parasites to non-cytocidal concentrations of unlabeled chloroquine resulted in a diffused cytoplasmic retention of the probe whereas a similar treatment with the CQR-reversing agent, chlorpheniramine, resulted in DV accumulation. A diffused cytoplasmic distribution of the probe was also obtained following treatment with the P-gp specific inhibitors zosuquidar and tariquidar, whereas treatments with the tyrosine kinase inhibitors gefitinib or imatinib produced a partial accumulation within the DV. Isobologram analyses of the interactions between these inhibitors and the antimalarial drugs chloroquine, mefloquine, and artemisinin revealed distinct patterns of drug synergism, additivity and antagonism. Taken together, the data indicate that competitive tyrosine kinase and noncompetitive P-glycoprotein ATPase-specific inhibitors represent two new classes of chemosensitizing agents in malaria parasites, but caution against the indiscriminate use of these agents in antimalarial drug combinations., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Although it is well known in the literature that high triglyceride serum (TG) levels can jeopardize the metabolic control, little is known about the influence of low TG on type 1 diabetes patients (T1D). The aim of this study is to investigate the distribution of TG serum levels in individuals with T1D and its relationship with metabolic control., Findings: We reviewed the medical charts of 180 patients with T1D, who were classified in groups according to TG levels: 1) low (below 50 mg/dL); 2) normal (50-150 mg/dL); 3) high (above 150 mg/dL). TG were low in 21.1% (n = 38; group 1), normal in 68.6% (n = 123; group 2) and high in 10.6% (n = 19; group 3). High TG was associated with a poor metabolic control (p < 0.001). Patients with TG lower than 50 mg/dL had a lower HbA1c than those with TG between 50 and 150 mg/dL (7.41+/-1.50% vs 8.56%+/-1.94%; p = 0.002)., Conclusion: TG lower than 50 mg/dL was common and might be associated with a better metabolic control in patients with T1D, although it is not clear whether the former is the cause or consequence for the latter.

This study aimed to show the needs to standardize nursing care related to hyperbaric oxygenation and regulate working conditions for nursing staff that works on this area. They approach the legislation at the Brazilian Society of Hyperbaric Medicine, on Brazilian Chapter of the Undersea and Hyperbaric Medical Society, on Regulating Rules of the Ministry of Labor and on the Code of Ethics of Nursing Professionals, as instruments still insufficient to legalize the Hyperbaric Nurse, its procedures in hyperbaric conditions and pressurized environments. It allowed pondering on the disclosure of the state of art of hyperbaric nursing, as well as the incorporation of this activity in relation to the specialties on the COFEN Resolution 290/2004 and postgraduate courses in Nursing.

The authors discuss nursing activities in hyperbaric oxygen therapy through an experience report developed at the Medical Clinical of the Naval Hospital Marcílio Dias. This article presents a brief history of the procedure, its therapeutic effects, indications, collateral effects and complications. The authors believe that efforts are needed to create awareness about nursing activities in this new role as a labor market alternative in this growing specialty area.

Operative Nursing (EO) allows for a new perspective in military nursing education. This case study from a qualitative approach aimed to describe the construction process of EO at the School of Health (ES) of a Brazilian Navy (MB) Hospital and to characterize "military nurses'" care performance in "crash" situations. Data collection started in 2002 through a literature review, combined with meetings between military to discuss the rules and bases of this modality, which gave rise to the reorganization of the curriculum, infrastructure and normative instruments and the review of ethical-legal aspects. This study discloses a valuing sense of human life and allows for the search to legitimize the activities of a differentiated nursing before competent organs.