Hepatitis A Vaccination in Adults

https://scholarworks.uvm.edu/fmclerk/1698/thumbnail.jp

Interaction effect: Are you doing the right thing?

How to correctly interpret interaction effects has been largely discussed in scientific literature. Nevertheless, misinterpretations are still frequently observed, and neuroscience is not exempt from this trend. We reviewed 645 papers published from 2019 to 2020 and found that, in the 93.2% of studies reporting a statistically significant interaction effect (N = 221), post-hoc pairwise comparisons were the designated method adopted to interpret its results. Given the widespread use of this approach, we aim to: (1) highlight its limitations and how it can lead to misinterpretations of the interaction effect; (2) discuss more effective and powerful ways to correctly interpret interaction effects, including both explorative and model selection procedures. The paper provides practical examples and freely accessible online materials to reproduce all analyses

Quality and safety of traditional foods: the role of microbiology

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Pavlovian threat learning shapes the kinematics of action

Prompt response to environmental threats is critical to survival. Previous research has revealed mechanisms underlying threat-conditioned physiological responses, but little is known about how threats shape action. Here we tested if threat learning shapes the kinematics of reaching in human adults. In two different experiments conducted on independent samples of participants, after Pavlovian threat learning, in which a stimulus anticipated the delivery of an aversive shock, whereas another did not, the peak velocity and acceleration of reaching increased for the shocked-paired stimulus, relative to the unpaired one. These kinematic changes appeared as a direct consequence of learning, emerging even in absence of an actual threat to body integrity, as no shock occurred during reaching. Additionally, they correlated with the strength of sympathetic response during threat learning, establishing a direct relationship between previous learning and subsequent changes in action. The increase in velocity and acceleration of action following threat learning may be adaptive to facilitate the implementation of defensive responses. Enhanced action invigoration may be maladaptive, however, when defensive responses are inappropriately enacted in safe contexts, as exemplified in a number of anxiety-related disorders

Physical PEGylation to Prevent Insulin Fibrillation

Insulin is one of the most marketed therapeutic proteins worldwide. However, its formulation suffers from fibrillation, which affects the long-term storage limiting the development of novel devices for sustained delivery including portable infusion devices. We have investigated the effect of physical PEGylation on structural and colloidal stability of insulin by using 2 PEGylating agents terminating with polycyclic hydrophobic moieties, cholane and cholesterol: mPEG5kDa-cholane and mPEG5kDa-cholesterol, respectively. Microcalorimetric analyses showed that mPEG5kDa-cholane and mPEG5kDa-cholesterol efficiently bind insulin with binding constants (Ka) of 3.98 104 and 1.14 105 M-1, respectively. At room temperature, the 2 PEGylating agents yielded comparable structural stabilization of \u3b1-helix conformation and decreased dimerization of insulin. However, melting studies showed that mPEG5kDa-cholesterol has superior stabilizing effect of the protein conformation than mPEG5kDa-cholane. Furthermore, the fibrillation study showed that at a 1:1 and 1:5 insulin/polymer molar ratios, mPEG5kDa-cholesterol delays insulin fibrillation 40% and 26% more efficiently, respectively, as compared to mPEG5kDa-cholane which was confirmed by transmission electron microscopy imaging. Insulin was released from the mPEG5kDa-cholane and mPEG5kDa-cholesterol assemblies with comparable kinetic profiles. The physical PEGylation has a beneficial effect on the stabilization and shielding of the insulin structure into the monomeric form, which is not prone to fibrillation and aggregation

Ca2+-activated K+ channels modulate microglia affecting motor neuron survivalin hSOD1G93A mice

Recent studies described a critical role for microglia in amyotrophic lateral sclerosis (ALS), where these CNS-resident immune cells participate in the establishment of an inflammatory microenvironment that contributes to motor neuron degeneration. Understanding the mechanisms leading to microglia activation in ALS could help to identify specific molecular pathways which could be targeted to reduce or delay motor neuron degeneration and muscle paralysis in patients. The intermediate-conductance calcium-activated potassium channel KCa3.1 has been reported to modulate the "pro-inflammatory" phenotype of microglia in different pathological conditions. We here investigated the effects of blocking KCa3.1 activity in the hSOD1G93AALS mouse model, which recapitulates many features of the human disease. We report that treatment of hSOD1G93A mice with a selective KCa3.1 inhibitor, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), attenuates the "pro-inflammatory" phenotype of microglia in the spinal cord, reduces motor neuron death, delays onset of muscle weakness, and increases survival. Specifically, inhibition of KCa3.1 channels slowed muscle denervation, decreased the expression of the fetal acetylcholine receptor γ subunit and reduced neuromuscular junction damage. Taken together, these results demonstrate a key role for KCa3.1 in driving a pro-inflammatory microglia phenotype in ALS

Discovery of a novel quinoxalinhydrazide with a broad-spectrum anticancer activity

Previously, we discovered a novel class of salicylhydrazide compounds with remarkable activity in hormone-dependent and -independent human cancer cells. We then designed and synthesized numerous analogues. Among these analogues, a quinoxalinhydrazide compound, SC144, exhibited desirable physicochemical and drug-like properties and therefore was selected for further preclinical investigation. In the present study, we evaluated the in vitro activity of SC144 in a range of drug-sensitive and -resistant cancer cell lines as well as its in vivo efficacy in MDA-MB-435 and HT29 mice xenograft models. The broad-spectrum cytotoxicity of SC144 is especially highlighted by its potency in ovarian cancer cells resistant to cisplatin, breast-cancer cells resistant to doxorubicin, and colon cancer cells resistant to oxaliplatin. Furthermore, its activity was independent of p53, HER-2, estrogen and androgen receptor expressions. We also examined the effect of SC144 on cell cycle progression and apoptosis in select cell lines. Considering its cytotoxicity profile in a variety of in vitro and in vivo cancer models as well as its effects on cell cycle regulation and apoptosis, SC144 appears to represent a promising agent for further clinical development

Moving Buffalo Farming beyond Traditional Areas: Performances of Animals, and Quality of Mozzarella and Forages

An observational case study was designed to highlight issues associated with a possible expansion of dairy buffalo (Bubalus bubalis) farming outside the traditional coastal plains of southern Italy. Twenty pregnant buffaloes were transferred to a hilly inland farm. After calving, production and reproduction data were collected monthly throughout lactation. From 4 to 6 months of lactation, buffaloes were enrolled in a feeding trial to evaluate the effects of locally grown forages (maize silage vs. hay) on milk production and in vivo digestibility. Sensory properties of mozzarella cheese produced at a local dairy were also evaluated. No obvious effects of diet were found. Compared to the data recorded in the previous lactation completed in the farm of origin, milk yield was reduced by 37.2%, and milk protein by 6.1%, whereas milk fat improved (+4.5%). A lower pregnancy rate (−13.3%), increased days open (+122%), and a prolonged intercalving period (+26.9%) were also observed. Lactation length was shorter than the standard value of 270 d. The results showed that peculiar reproductive characteristics, lower environmental temperatures, and the specificity of the mozzarella production process are the main problems to be addressed in an expansion of buffalo farming outside traditional area

The wooden shelf surface and cheese rind mutually exchange microbiota during the traditional ripening process

The rind acts as a protective barrier for internally-bacterial ripened cheeses. Unlike surface-inoculated smear cheeses, centripetal maturation is not assumed to occur in these cheeses. This research was aimed to evaluate the microbial diversity of the wooden shelves used for the ripening of Protected Denomination of Origin (PDO) Pecorino di Filiano and Protected Geographical Indication (PGI) Canestrato di Moliterno cheeses. The microorganisms associated with the rind of these cheeses were also investigated. Both wooden shelf surfaces and cheese rinds were sampled by brushing method to collect their biofilms. Wooden shelves showed levels of total mesophilic microorganisms (TMM) between 5.6 and 7.2 log CFU/cm2, while cheese rinds between 6.1 and 7.8 log CFU/cm2. The major dairy pathogens (Salmonella spp., Listeria monocytogenes, Escherichia coli, and Staphylococcus aureus) were never detected, while mesophilic and thermophilic bacteria dominated the surfaces of all wooden shelves and cheese rinds. LAB community was represented by Enterococcus spp., Leuconostoc spp., and Marinilactibacillus spp. Among yeasts, Debaryomyces spp., Candida spp., were identified, while Aspergillus spp., and Penicillium spp., dominated the community of filamentous fungi. MiSeq Illumina analysis identified 15 phyla, 13 classes, 28 orders, 54 families, and 56 genera among bacteria. Staphylococcus spp. was identified from all wooden surfaces, with a maximum abundance of 71 %. Brevibacterium, Corynebacterium and halophilic bacteria were detected in almost all samples. Regarding fungi, wooden shelves mainly hosted Aspergillus, Penicillium and Debaryomyces hansenii, while cheese rinds especially Penicillium and D. hansenii. Alpha diversity confirmed a strict correlation between the microbiota of wooden shelves and that of cheese rinds for the majority of factories. This study confirmed that the wooden shelves used for cheese ripening are microbiologically active and represent safe systems. Furthermore, the results of this work clarified the transfer flow between wooden shelves and PDO Pecorino di Filiano and PGI Canestrato di Moliterno cheese surfaces: smear-active microorganisms are mainly transferred from wooden shelves to cheese rind, which potentially contribute to the development of the final organoleptic characteristics; meanwhile, cheeses transfer LAB that are potentially involved in defining the safety aspects of the shelve