Rats first given 24-h access to 10% sucrose for 4 or 12 days (Stage 1) were then switched to a saccharin solution for a 12-day Stage 2. The initial result of this switch was that these Sucrose groups drank less saccharin than Water groups that had been given only water to drink in Stage 1. This difference was maintained throughout Stage 2 by the females that served in Experiments 1 and 4 and by the males that served in Experiment 3. Experiment 1 also found that access to 10% glucose in Stage 1 produced an essentially identical decrease in subsequent saccharin acceptance as that produced by giving 10% sucrose in Stage 1. The impact on subsequent acceptance of saccharin was also tested in rats given two types of maltodextrin solution. The first type of maltodextrin (Myopure brand) was used with the males in Experiment 2; this failed to find any difference between the Maltodextrin and the Water group. However, when a second type of maltodextrin (SolCarb brand) was given to males in Stage 1 of Experiment 3, the results for this group were similar to those from a group given sucrose in Stage 1. The final experiment confirmed that prior exposure to maltodextrin solutions can reduce saccharin acceptance by female rats. Overall, the results suggest that acceptance of saccharin is sensitive to a contrast effect, in that it is reduced by prior exposure to a solution that is more palatable but not necessarily sweet.

Aptamers are short single-stranded oligonucleotides that are capable of binding various molecules with high affinity and specificity. When the technology of aptamer selection was developed almost a quarter of a century ago, a suggestion was immediately put forward that it might be a revolutionary start into solving many problems associated with diagnostics and the therapy of diseases. However, multiple attempts to use aptamers in practice, although sometimes successful, have been generally much less efficient than had been expected initially. This review is mostly devoted not to the successful use of aptamers but to the problems impeding the widespread application of aptamers in diagnostics and therapy, as well as to approaches that could considerably expand the range of aptamer application.

Although acne is a disease predominant in adolescence, it is being increasingly observed in adult life, including the menopausal period. The etiology of menopausal acne is multifactorial, with hormonal imbalance being the major culprit. There is a relative increase of androgens in the menopausal female that leads to clinical hyperandrogenism manifesting as acne, hirsutism and androgenetic alopecia. Other endocrine disorders including thyroid abnormalities, hyperprolactinemia and insulin resistance also play a role. Genetics, stress, dietary changes, lack of sleep and exercise and other lifestyle changes are implicated as trigger factors. Most menopausal women with isolated few acne lesions have normoandrogenic serum levels and do not require extensive investigations. However, baseline investigations including total testosterone are useful. Patients must also be evaluated for associated comorbidities such as obesity, diabetes, hypertension and dyslipidemia. A detailed history can help to exclude polycystic ovarian syndrome, late-onset congenital adrenal hyperplasia or medications as a cause of acne. The evaluation of menopausal acne and the approach to treatment depend on the severity of acne and associated features. In patients with mild acne without virilization, prolonged topical therapy is the mainstay of treatment. Though combined oral contraceptives are effective, they are relatively contraindicated in the postmenopausal period. Spironolactone is the first choice of therapy in the subset of patients that require oral anti-androgen therapy. Procedural treatment can be useful as it can also help in the treatment of associated acne scars and concomitant skin aging. It is also important to focus on lifestyle changes such as reducing stress, controlling obesity, having a healthy diet, exercise and proper skin care routine to reduce acne. The focus of this article is on the clinical presentation and management challenges of menopausal acne, which represents a special subtype of acne.

No abstract available

This paper presents a discussion of existing methods for the analysis of macromolecular interactions and complexes in crystal packing. Typical situations and conditions where wrong answers may be obtained in the course of ordinary procedures are presented and discussed. The more general question of what the relationship is between natural (in-solvent) and crystallized assemblies is discussed and researched. A computational analysis suggests that weak interactions with K(d) ≥ 100 µM have a considerable chance of being lost during the course of crystallization. In such instances, crystal packing misrepresents macromolecular complexes and interactions. For as many as 20% of protein dimers in the PDB the likelihood of misrepresentation is estimated to be higher than 50%. Given that weak macromolecular interactions play an important role in many biochemical processes, these results suggest that a complementary noncrystallographic study should be always conducted when inferring structural aspects of weakly bound complexes.

Most trackers focus solely on robustness and accuracy. Visual tracking, however, is a long-term problem with a high time limitation. A tracker that is robust, accurate, with long-term sustainability and real-time processing, is of high research value and practical significance. In this paper, we comprehensively consider these requirements in order to propose a new, state-of-the-art tracker with an excellent performance. EfficientNet-B0 is adopted for the first time via neural architecture search technology as the backbone network for the tracking task. This improves the network feature extraction ability and significantly reduces the number of parameters required for the tracker backbone network. In addition, maximal Distance Intersection-over-Union is set as the target estimation method, enhancing network stability and increasing the offline training convergence rate. Channel and spatial dual attention mechanisms are employed in the target classification module to improve the discrimination of the trackers. Furthermore, the conjugate gradient optimization strategy increases the speed of the online learning target classification module. A two-stage search method combined with a screening module is proposed to enable the tracker to cope with sudden target movement and reappearance following a brief disappearance. Our proposed method has an obvious speed advantage compared with pure global searching and achieves an optimal performance on OTB2015, VOT2016, VOT2018-LT, UAV-123 and LaSOT while running at over 50 FPS.

Giardia is the commonest parasitic diarrheal pathogen affecting humans and a frequent cause of waterborne/foodborne parasitic diseases worldwide. Prevalence of giardiasis is higher in children, living in poor, low hygiene settings in developing countries, and in travelers returning from highly endemic areas. The clinical picture of giardiasis is heterogeneous, with high variability in severity of clinical disease. It can become chronic or be followed by post-infectious sequelae. An alarming increase in cases refractory to the conventional treatment with nitroimidazoles (ie, metronidazole) has been reported in low prevalence settings, such as European Union countries, especially in patients returning from Asia. In view of its relevance, we aim in this review to recapitulate present clinical knowledge about Giardia, with a special focus on the challenge of treatment-refractory giardiasis. We propose a working definition of clinically drug-resistant giardiasis, summarize knowledge regarding resistance mechanisms, and discuss its clinical management according to research-based evidence and medical practice. Advances in development and identification of novel drugs and potential non-pharmacological alternatives are also reviewed with the overall aim to define knowledge gaps and suggest future directions for research.

No abstract available

Genetic databases contain a variety of annotation errors that often go unnoticed due to the large size of modern genetic data sets. Interpretation of these data sets requires bioinformatics tools that may contribute to this problem. While providing gene symbol annotations for identifiers (IDs) such as microarray probe set, RefSeq, GenBank, and Entrez Gene is seemingly trivial, the accuracy is fundamental to any subsequent conclusions. We examine gene symbol annotations and results from three commercial pathway analysis software (PAS) packages: Ingenuity Pathways Analysis, GeneGO, and Pathway Studio. We compare gene symbol annotations and canonical pathway results over time and among different input ID types. We find that PAS results can be affected by variation in gene symbol annotations across software releases and the input ID type analyzed. As a result, we offer suggestions for using commercial PAS and reporting microarray results to improve research quality. We propose a wiki type website to facilitate communication of bioinformatics software problems within the scientific community.

There are a large number of remedies in traditional medicine focused on relieving pain and inflammation. Flavanones have been a potential source in the search for leading compounds and biologically active components, and they have been the focus of much research and development in recent years. Eysenhardtia platycarpa is used in traditional medicine for the treatment of kidney diseases, bladder infections, and diabetes mellitus. Many compounds have been isolated from this plant, such as flavones, flavanones, phenolic compounds, triterpenoid acids, chalcones, sugars, and fatty acids, among others. In this paper, natural flavanone 1 (extracted from Eysenhardtia platycarpa) as lead compound and flavanones 1a-1d as its structural analogues were screened for anti-inflammatory activity using Molinspiration® and PASS Online in a computational study. The hydro alcoholic solutions (FS) of flavanones 1, 1a-1d (FS1, FS1a-FS1d) were also assayed to investigate their in vivo anti-inflammatory cutaneous effect using two experimental models, a rat ear edema induced by arachidonic acid (AA) and a mouse ear edema induced by 12-O-tetradecanoylphorbol acetate (TPA). Histological studies and analysis of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were also assessed in AA-inflamed rat ear tissue. The results showed that the flavanone hydro alcoholic solutions (FS) caused edema inhibition in both evaluated models. This study suggests that the evaluated flavanones will be effective when used in the future in skin pathologies with inflammation, with the results showing 1b and 1d to be the best.

Cold physical plasma is a partially ionized gas generating various reactive oxygen and nitrogen species (ROS/RNS) simultaneously. ROS/RNS have therapeutic effects when applied to cells and tissues either directly from the plasma or via exposure to solutions that have been treated beforehand using plasma processes. This review addresses the challenges and opportunities of plasma-treated solutions (PTSs) for cancer treatment. These PTSs include plasma-treated cell culture media in experimental research as well as clinically approved solutions such as saline and Ringer's lactate, which, in principle, already qualify for testing in therapeutic settings. Several types of cancers were found to succumb to the toxic action of PTSs, suggesting a broad mechanism of action based on the tumor-toxic activity of ROS/RNS stored in these solutions. Moreover, it is indicated that the PTS has immuno-stimulatory properties. Two different routes of application are currently envisaged in the clinical setting. One is direct injection into the bulk tumor, and the other is lavage in patients suffering from peritoneal carcinomatosis adjuvant to standard chemotherapy. While many promising results have been achieved so far, several obstacles, such as the standardized generation of large volumes of sterile PTS, remain to be addressed.

Sarcoidosis is a chronic multisystem disease of unknown etiology characterized by noncaseating granulomas that most often involves the lungs, but frequently has extrapulmonary manifestations, which might be difficult to treat in individual patients.

We investigate the glass polymorphism of dilute LiCl-H2O in the composition range of 0-5.8 mol % LiCl. The solutions are vitrified at ambient pressure (requires hyperquenching with ∼106 K s-1) and transformed to their high-density state using a special high-pressure annealing protocol. Ex situ characterization was performed via isobaric heating experiments using X-ray diffraction and differential scanning calorimetry. We observe signatures from a distinct high-density and a distinct low-density glass for all solutions with a mole fraction xLiCl of ≤ 4.3 mol %, where the most notable are (i) the jumplike polyamorphic transition from high-density to low-density glass and (ii) two well-separated glass-to-liquid transitions Tg,1 and Tg,2, each pertaining to one glass polymorph. These features are absent for solutions with xLiCl ≥ 5.8 mol %, which show only continuous densification and relaxation behavior. That is, a switch from water-dominated to solute-dominated region occurs between 4.3 mol % LiCl and 5.8 mol % LiCl. For the water-dominated region, we find that LiCl has a huge impact only on the low-density form. This is manifested as a shift in halo peak position to denser local structures, a lowering of Tg,1, and a significant change in relaxation dynamics. These effects of LiCl are observed both for hyperquenched samples and low-density samples obtained via heating of the high-density glasses, suggesting path independence. Such behavior further necessitates that LiCl is distributed homogeneously in the low-density glass. This contrasts earlier studies in which structural heterogeneity is claimed: ions were believed to be surrounded by only high-density states, thereby enforcing a phase separation into ion-rich high-density and ion-poor low-density glasses. We speculate the difference arises from the difference in cooling rates, which are higher by at least 1 order of magnitude in our case.

Mastectomy skin flap necrosis (MSFN) has a reported incidence of 5%-30% in the literature. It is often a significant and underappreciated problem. The aim of this article was to review the associated challenges and possible solutions.

Results of a study to determine the stability of tacrolimus solutions stored in polyolefin containers under various temperature conditions are reported.

The skin is colonized by a large number of microorganisms, most of which are beneficial or harmless. However, disease states of skin have specific microbiome compositions that are different from those of healthy skin. Gut microbiome modulation through fecal transplant has been proven as a valid therapeutic strategy in diseases such as Clostridium difficile infections. Therefore, techniques to modulate the skin microbiome composition may become an interesting therapeutic option in diseases affecting the skin such as psoriasis or acne vulgaris.

Rare diseases are often underdiagnosed, and their management is frequently complicated by a lack of access to treatment and information about the diseases. To allow for better policy planning, we sought to examine the current status of managing rare diseases in Malaysia.

Cellular organisms regulate electrolyte composition in the cytosol to optimize intracellular molecular interactions at the same time as balancing external osmotic pressure. While osmotic pressure can be tuned using multiple ionic, zwitterionic, and nonionic solutes, interactions between proteins and other macromolecules are sensitive to the precise composition of the medium. Nonetheless, the roles of individual ions and nonionic solutes in mediating cellular interactions remain relatively unexplored, and standard buffer solutions used in laboratory studies often contain only a few simple salts. Here, we report on model experiments investigating the combined effect of ionic and zwitterionic solutes on interaction forces across electrolytes, revealing a clear role for zwitterions in modifying interactions compared to simple salt solutions. First, we find that zwitterions act to disrupt water layering at interfaces, leading to smoothed interaction potentials. Second, we find that zwitterions strengthen electrostatic repulsions by enhancing effective surface charge. Third, zwitterions enhance the effective dielectric permittivity of the solution, and this "dielectricizer" effect extends the range of electrostatic repulsions compared to solutions without zwitterion present. The latter two effects are likely important in stabilizing proteins and other macromolecules when external osmotic and mechanical pressure are very high and simple ionic solutes alone would lead to collapse.

No abstract available

Most feature selection methods identify only a single solution. This is acceptable for predictive purposes, but is not sufficient for knowledge discovery if multiple solutions exist. We propose a strategy to extend a class of greedy methods to efficiently identify multiple solutions, and show under which conditions it identifies all solutions. We also introduce a taxonomy of features that takes the existence of multiple solutions into account. Furthermore, we explore different definitions of statistical equivalence of solutions, as well as methods for testing equivalence. A novel algorithm for compactly representing and visualizing multiple solutions is also introduced. In experiments we show that (a) the proposed algorithm is significantly more computationally efficient than the TIE* algorithm, the only alternative approach with similar theoretical guarantees, while identifying similar solutions to it, and (b) that the identified solutions have similar predictive performance.