Real-time management of intra-hospital patient transport requests.

This paper addresses the management of patients' transportation requests within a hospital, a very challenging problem where requests must be scheduled among the available porters so that patients arrive at their destination timely and the resources invested in patient transport are kept as low as possible. Transportation requests arrive during the day in an unpredictable manner, so they need to be scheduled in real-time. To ensure that the requests are scheduled in the best possible manner, one should also reconsider the decisions made on pending requests that have not yet been completed, a process that will be referred to as rescheduling. This paper proposes several policies to trigger and execute the rescheduling of pending requests and three approaches (a mathematical formulation, a constructive heuristic, and a local search heuristic) to solve each rescheduling problem. A simulation tool is proposed to assess the performance of the rescheduling strategies and the proposed scheduling methods to tackle instances inspired by a real mid-size hospital. Compared to a heuristic that mimics the way requests are currently handled in our partner hospital, the best combination of scheduling method and rescheduling strategy produces an average 5.7 minutes reduction in response time and a 13% reduction in the percentage of late requests. Furthermore, since the total distance walked by porters is substantially reduced, our experiments demonstrate that it is possible to reduce the number of porters - and therefore the operating costs - without reducing the current level of service.

Essential oils: An eco-friendly alternative for controlling toxigenic fungi in cereal grains.

Fungi are widely disseminated in the environment and are major food contaminants, colonizing plant tissues throughout the production chain, from preharvest to postharvest, causing diseases. As a result, grain development and seed germination are affected, reducing grain quality and nutritional value. Some fungal species can also produce mycotoxins, toxic secondary metabolites for vertebrate animals. Natural compounds, such as essential oils, have been used to control fungal diseases in cereal grains due to their antimicrobial activity that may inhibit fungal growth. These compounds have been associated with reduced mycotoxin contamination, primarily related to reducing toxin production by toxigenic fungi. However, little is known about the mechanisms of action of these compounds against mycotoxigenic fungi. In this review, we address important information on the mechanisms of action of essential oils and their antifungal and antimycotoxigenic properties, recent technological strategies for food industry applications, and the potential toxicity of essential oils.

The mGluR5 positive allosteric modulator VU0409551 improves synaptic plasticity and memory of a mouse model of Huntington's disease.

Huntington's Disease (HD) is an autosomal-dominant neurodegenerative disorder, characterized by involuntary body movements, cognitive impairment, and psychiatric disorder. The metabotropic glutamate receptor 5 (mGluR5) plays an important role in HD and we have recently demonstrated that mGluR5-positive allosteric modulators (PAMs) can ameliorate pathology and the phenotypic signs of a mouse model of HD. In this study, we investigated the molecular mechanisms involved in mGluR5 PAMs effect on memory. Our results demonstrate that subchronic treatment with the mGluR5 PAM VU0409551 was effective in reversing the memory deficits exhibited by BACHD mice, a mouse model for HD. Moreover, VU0409551 treatment stabilized mGluR5 at the cellular plasma membrane of BACHD mice, increasing the expression of several genes important for synaptic plasticity, including c-Fos, brain-derived neurotrophic factor, Arc/Arg3.1, syntaxin 1A, and post-synaptic density-95. In addition, VU0409551 treatment also increased dendritic spine density and maturation and augmented the number of pre-synaptic sites. In conclusion, our results demonstrate that VU0409551 triggered the activation of cell signaling pathways important for synaptic plasticity, enhancing the level of dendritic spine maturation and rescuing BACHD memory impairment. OPEN PRACTICES: Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/.

Characterization of methicillin-resistant coagulase-negative staphylococci in milk from cows with mastitis in Brazil.

Staphylococci are one of the most prevalent microorganisms in bovine mastitis. Staphylococcus spp. are widespread in the environment, and can infect animals and humans as opportunistic pathogens. The objective of this study was to determine the frequency of methicillin-resistance (MR) among coagulase-negative staphylococci (CoNS) previously obtained from milk of mastitic cows in Brazil and to characterize the antimicrobial resistance phenotype/genotype and the SCCmec type of MRCoNS isolates. Identification of MRCoNS was based on both biochemical and molecular methods. Susceptibility testing for eleven antimicrobials was performed by disk-diffusion agar. Antimicrobial resistance genes and SCCmec were investigated by specific PCRs. Twenty-six MRCoNS were detected (20 % of total CoNS), obtained from 24 animals, and were identified as follows: S. epidermidis (7 isolates), S. chromogenes (7), S. warneri (6), S. hyicus (5) and S. simulans (1). All MRCoNS isolates carried mecA while the mecC gene was not detected in any CoNS. The SCCmec IVa was demonstrated in nine MRCoNS, while the remaining 17 isolates harbored non-typeable SCCmec cassettes. In addition to oxacillin and cefoxitin resistance, MRCoNS showed resistance to tetracycline (n = 7), streptomycin (n = 6), tobramycin (n = 6), and gentamicin (n = 4), and harbored the genes tet(K) (n = 7), str (n = 3), ant(4') (n = 6) and aac(6')-aph(2″) (n = 4), respectively. In addition, seven strains showed intermediate resistance to clindamycin and two to streptomycin, of which two harboured the lnu(B) and lsa(E) genes and two the aad(E) gene, respectively. One isolate presented intermediate erythromycin and clindamycin resistance and harbored an erm(C) gene with an uncommon 89-bp deletion rendering a premature stop codon. MRCoNS can be implicated in mastitis of cows and they constitute a reservoir of resistance genes that can be transferred to other pathogenic bacteria.

Deoxynivalenol and zearalenone in Brazilian barley destined for brewing.

Barley is an important cereal worldwide. However, fungal contamination during pre and postharvest is a recurrent problem for barley production, causing a direct impact on the quality of the grains and their by-products due to spoilage and mycotoxin accumulation. The Fusarium graminearum species complex is the main contaminant during preharvest and some species can produce deoxynivalenol and zearalenone, important mycotoxins that represent a risk to human and animal health. This study evaluated the fungal diversity and the levels of DON and ZEN in barley grains produced in Brazil. The results showed high frequency (60%) of Fusariumcontamination in barley grains. Additionally, mycotoxin levels ranged from 46 to 2074 µg/kg for DON and from 74 to 556 µg/kg for ZEN. Co-occurrence of DON and ZEN was observed in 40% of the samples and 30% of barley samples had DON and ZEN levels higher than the maximum levels established by Brazilian and European legislations. .

The Impact of Low-Level Benzalkonium Chloride Exposure on Staphylococcus spp. Strains and Control by Photoinactivation.

Exposure of bacteria to low concentrations of biocides can facilitate horizontal gene transfer, which may lead to bacterial adaptive responses and resistance to antimicrobial agents. The emergence of antibacterial resistance not only poses a significant concern to the dairy industry but also adds to the complexity and cost of mastitis treatment. This study was aimed to evaluate how selective stress induced by benzalkonium chloride (BC) promotes antibiotic non-susceptibility in Staphylococcus spp. In addition, we investigated the efficacy of photodynamic inactivation (PDI) in both resistant and susceptible strains. The study determined the minimum inhibitory concentration (MIC) of BC using the broth microdilution method for different Staphylococcus strains. The experiments involved pairing strains carrying the qacA/qacC resistance genes with susceptible strains and exposing them to subinhibitory concentrations of BC for 72 h. The recovered isolates were tested for MIC BC and subjected to disc diffusion tests to assess changes in susceptibility patterns. The results demonstrated that subinhibitory concentrations of BC could select strains with reduced susceptibility and antibiotic resistance, particularly in the presence of S. pasteuri. The results of PDI mediated by toluidine blue (100 µM) followed by 60 min irradiation (total light dose of 2.5 J/cm2) were highly effective, showing complete inactivation for some bacterial strains and a reduction of up to 5 logs in others.

Molecular characterization of persistent subclinical mastitis-causing Staphylococcus aureus from dairy farms.

The study aimed to evaluate the genetic diversity of Staphylococcus aureus causing subclinical mastitis (SM) isolated from dairy cows and to assess the effect of the infection status (transient vs. persistent) on the milk and component yield. A total of six dairy farms in São Paulo state were used for the selection of cows with SM caused by S. aureus. S. aureus strains (n = 56) obtained from three biweekly aseptic mammary quarter milk samplings (n = 1140 from 95 cows) were subjected to MALDI-TOF MS analysis for species confirmation and further PFGE analysis. Intramammary infections (IMI) caused by S. aureus were categorized as transient (T: when only one out of 3 milk samplings had positive isolation of any pulsotype) or persistent (P: when two (P2) or three (P3) milk samplings had positive isolation of identical pulsotype over the consecutive episodes of SM. The SmaI macrorestriction fragment profiles of 56 S. aureus isolates showed a dominant S. aureus clonal pattern (PFGE type A; n = 50; 89.3%) within and among the herds. The SM-causing S. aureus represented a reduction of quarter milk yield of 26.2% in transient and 54.8% in persistent cases as well as a reduction of total solid yield of 38.1% and 49.4%, respectively, when compared with the healthy control quarters. Overall, the greater chance of S. aureus to be persistent is when a dominant clonal pattern is present in the herd which consequently may be associated with the cause of accentuated milk loss.

Synthesis, characterization and application of antibacterial lactoferrin nanoparticles.

Lactoferrin (L) and gellan gum (G) nanoparticles were produced in different biopolymer proportions through electrostatic complexation to enhance the antimicrobial properties of lactoferrin. The nanoparticles were characterized according to size, charge density, morphology and antimicrobial activity against S. aureus and E. coli, in two different broths to show the effect of the broth composition on the nanoparticle activity. The 9L:1G particles showed the highest positive zeta potential (+21.20 mV) and reduced diameter (92.03 nm) which resulted in a minimum inhibitory concentration six times smaller (0.3 mg/ml) than pure lactoferrin (2 mg/ml). However, the bacteriostatic action of nanoparticles was inhibited in the presence of divalent cations. When applied to strawberries as a coating, lactoferrin nanoparticles extended fruit shelf-life up to 6 days in the presence of carboxymethylcellulose (CMC). Therefore, lactoferrin-gellan gum complexation was proved to be a promising tool to enhance lactoferrin antimicrobial action and broaden its application as a food preserver.

The Impact of Selective Dry Cow Therapy Adopted in a Brazilian Farm on Bacterial Diversity and the Abundance of Quarter Milk.

We aimed to evaluate the impact of selective dry cow therapy (SDCT) (protocol 1: antimicrobial combined with internal teat sealant (ITS); vs. protocol 2: ITS alone) on bacterial diversity and the abundance of quarter milk. Eighty high production cows (parity ≤ 3 and an average milk yield of 36.5 kg/cow/day) from the largest Brazilian dairy herd available were randomly selected; milk quarter samples were collected for microbiological culture (MC) on the day of drying-off (n = 313) and on day 7 post-calving (n = 313). Based on the results of the MC before and after calving, 240 quarters out of 313 were considered healthy, 38 were cured, 29 showed new infections and 6 had persistent infections. Mammary quarters were randomly selected based on intramammary information status and SDCT protocols for bacterial diversity analyses. The bacterial diversity was similar when comparing both healthy and cured quarters submitted to both drying-off protocols. Despite healthy cows that were treated at dry-off using only teat sealant showing no alteration in the alpha and beta bacterial diversity, they did show a higher abundance of bacterial groups that may be beneficial to or commensals of the mammary gland, which implies that antibiotic therapy should be reserved for mammary quarters with a history of mastitis.

mGluR5 ablation leads to age-related synaptic plasticity impairments and does not improve Huntington's disease phenotype.

Glutamate receptors, including mGluR5, are involved in learning and memory impairments triggered by aging and neurological diseases. However, each condition involves distinct molecular mechanisms. It is still unclear whether the mGluR5 cell signaling pathways involved in normal brain aging differ from those altered due to neurodegenerative disorders. Here, we employed wild type (WT), mGluR5-/-, BACHD, which is a mouse model of Huntington's Disease (HD), and mGluR5-/-/BACHD mice, at the ages of 2, 6 and 12 months, to distinguish the mGluR5-dependent cell signaling pathways involved in aging and neurodegenerative diseases. We demonstrated that the memory impairment exhibited by mGluR5-/- mice is accompanied by massive neuronal loss and decreased dendritic spine density in the hippocampus, similarly to BACHD and BACHD/mGluR5-/- mice. Moreover, mGluR5 ablation worsens some of the HD-related alterations. We also show that mGluR5-/- and BACHD/mGluR5-/- mice have decreased levels of PSD95, BDNF, and Arc/Arg3.1, whereas BACHD mice are mostly spared. PSD95 expression was affected exclusively by mGluR5 ablation in the aging context, making it a potential target to treat age-related alterations. Taken together, we reaffirm the relevance of mGluR5 for memory and distinguish the mGluR5 cell signaling pathways involved in normal brain aging from those implicated in HD.

[(2R,3S,6S)-3-Acet-yloxy-6-(1-phenyl-1H-1,2,3-triazol-4-yl)-3,6-dihydro-2H-pyran-2-yl]methyl acetate.

In the title compound, C(18)H(19)N(3)O(5), the 3,6-dihydro-2H-pyran ring adopts a half-chair, distorted towards a half-boat, conformation with Q(T) = 0.5276(14) Å. The benzene ring is twisted out of the place of the triazole ring [dihedral angle = 23.54 (8)°]. In the crystal, supra-molecular layers in the ac plane are formed through C-H⋯O and C-H⋯π(triazole) inter-actions. These stack along the b axis being connected by C-H⋯N contacts.

Synaptic Elimination in Neurological Disorders.

Synapses are well known as the main structures responsible for transmitting information through the release and recognition of neurotransmitters by pre- and post-synaptic neurons. These structures are widely formed and eliminated throughout the whole lifespan via processes termed synaptogenesis and synaptic pruning, respectively. Whilst the first process is needed for ensuring proper connectivity between brain regions and also with the periphery, the second phenomenon is important for their refinement by eliminating weaker and unnecessary synapses and, at the same time, maintaining and favoring the stronger ones, thus ensuring proper synaptic transmission. It is well-known that synaptic elimination is modulated by neuronal activity. However, only recently the role of the classical complement cascade in promoting this phenomenon has been demonstrated. Specifically, microglial cells recognize activated complement component 3 (C3) bound to synapses targeted for elimination, triggering their engulfment. As this is a highly relevant process for adequate neuronal functioning, disruptions or exacerbations in synaptic pruning could lead to severe circuitry alterations that could underlie neuropathological alterations typical of neurological and neuropsychiatric disorders. In this review, we focus on discussing the possible involvement of excessive synaptic elimination in Alzheimer's disease, as it has already been reported dendritic spine loss in post-synaptic neurons, increased association of complement proteins with its synapses and, hence, augmented microglia-mediated pruning in animal models of this disorder. In addition, we briefly discuss how this phenomenon could be related to other neurological disorders, including multiple sclerosis and schizophrenia.

Presence of Immune Evasion Cluster and Molecular Typing of Methicillin-Susceptible Staphylococcus aureus Isolated from Food Handlers.

The hands and noses of food handlers colonized by Staphylococcus aureus are an important source of food contamination in restaurants and food processing. Several virulence factors can be carried by mobile elements in strains of S. aureus, including the immune evasion cluster (IEC). This gene cluster improves the capacity of S. aureus to evade the human immune response. Many studies have reported the transmission of strains between animals and humans, such as farm workers that have close contact with livestock. However, there are few studies on the transmission between food and food handlers. The aim of this study was to detect the IEC and the mecA gene in strains isolated from food handlers and to type these strains using the spa typing method. Thirty-five strains of S. aureus isolated from the noses and hands of food handlers in three different kitchens were analyzed for the presence of the mecA gene and IEC and by spa typing. All strains were negative for the mecA gene, and the presence of IEC was observed in 10 (28.6%) strains. Fifteen different spa types were observed, with the most frequent being t127 (42.85%) and t002 (11.42%). Strains from the two most prevalent spa types and a novel spa type were typed by multilocus sequence typing. spa types t127, t002, and t13335 were determined to be multilocus sequence types (ST) ST-30, ST-5, and ST-45, respectively. The food handlers may have been contaminated by these strains of S. aureus through food, which is suggested by the low frequency of IEC and by ST that are observed more commonly in animals.

Resource use by two electric fishes (Gymnotiformes) of the National Forest Saracá-Taquera, Oriximiná, Pará

Fishes of the order Gymnotiformes have high diversity of oral and head morphology, which suggests trophic specializations within each clade. The aim of this study was to describe resource use patterns by two fish species (Gymnorhamphichthys rondoni and Gymnotus coropinae) in the National Forest Saracá-Taquera, Oriximiná - Pará, analyzing microhabitat use, diet composition, feeding strategies, niche breadth and niche overlap. Stomach contents of 101 individuals (41 G. rondoni and 60 G. coropinae), sampled in 23 headwater streams were analyzed and volume of food items was quantified to characterize their feeding ecology. Gymnorhamphichthys rondoni was captured mainly on sandy bottoms, whereas G. coropinae in crevices. Both species had a zoobenthivorous diet and consumed predominantly Sediment/Detritus and Diptera larvae, but also included allochthonous prey in their diet. These species had high niche overlap, with small variations related to the higher consumption of Ceratopogonidae larvae by G. rondoni and of Chironomidae larvae by G. coropinae. Both species had a generalist feeding strategy, but G. coropinae had a broader niche breadth. Our results demonstrate that G. rondoni and G. coropinae occupy different microhabitats but rely on similar food resources.(AU)

Peixes da ordem Gymnotiformes apresentam alta diversidade morfológica, o que sugere a existência de especializações tróficas dentro dos clados. O objetivo deste estudo foi analisar o uso de recursos por duas espécies de peixes elétricos (Gymnorhamphichthys rondoni e Gymnotus coropinae) na Floresta Nacional Saracá-Taquera, Oriximiná - Pará, analisando o uso de microhabitats, composição da dieta, estratégias alimentares, amplitude de nicho e sobreposição de nicho. Conteúdos estomacais de 101 indivíduos (41 G. rondoni e 60 G. coropinae), capturados em 23 igarapés de cabeceira, foram analisados e quantificados volumetricamente para a caracterização da ecologia trófica. Gymnorhamphichthys rondoni foi registrada principalmente em bancos de areia, enquanto G. coropinae em fendas. Ambas as espécies apresentaram dieta zoobentívora e consumiram predominantemente sedimento/detritos e larvas de Diptera, mas também consumiram presas alóctones. Foi observada alta sobreposição de nicho trófico e a baixa variação encontrada foi relacionada à maior utilização de larvas de Chironomidae por G. rondoni e de larvas de Ceratopogonidae por G. coropinae. Ambas as espécies apresentaram estratégia alimentar generalista, porém G. coropinae apresentou maior amplitude de nicho. Nossos resultados demonstram que G. rondoni e G. coropinae ocupam microhabitats diferentes, mas dependem de recursos alimentares similares.(AU)