Factors affecting children's direct learning and productive memory processes in the context of virtual museums.

Informal educational opportunities such as visits to museums, aquariums, and zoos support children's semantic knowledge gain. Most research focuses on outcomes of direct learning, such as factual recall. The extent to which children engage in productive memory processes such as inferential reasoning and self-derivation through memory integration is not yet well understood. We assessed 8- to 9-year-old children's performance on tests of direct (e.g., fact recall) and productive (e.g., inference, integration) learning from virtual museum exhibits. We also examined the influence of children's involvement on learning outcomes, through measuring within-exhibit dyadic conversation and post-exhibit reflection. Children performed successfully on all three tests of learning; fact recall was the most accessible and self-derivation was the least. Both within and post-exhibit involvement predicted overall learning outcomes; within-exhibit conversational phrases predicted self-derivation performance in particular. The current work provides novel insights into mechanisms that support children's informal learning.

Structure prediction of neutral physiological copper(II) compounds with l-cysteine and l-histidine.

Bis(aminoacidato)copper(II) [CuII(aa)2] coordination compounds are the physiological species of copper(II) amino acid compounds in blood plasma. Since there are no experimental data in the literature about the geometries that physiological CuII(aa)2 could form with l-cysteine (Cys), that is, for bis(l-cysteinato)copper(II) [Cu(Cys)2] and the ternary (l-histidinato)(l-cysteinato)copper(II) [Cu(His)(Cys)], this paper computationally examines the possible conformations that the two compounds could form with the Cys ligand having a protonated sulfur, as in the conventional zwitterion, which was determined to be prevailing in aqueous solution. These two amino acids can bind metals in a tridentate fashion and thus form many possible coordination patterns. Density functional calculations were performed for the conformational analyses in the gas phase and in implicitly modeled aqueous solution using a polarizable continuum model. Additionally, we examine which coordination mode, with thiol or thiolate group, is more stable. The Cys coordination via the amino N and carboxylato O atoms (a glycinato mode) is obtained as the most stable one in aqueous Cu(Cys)2, and also in Cu(His)(Cys) when the His glycinato or histaminato mode combines with the intact thiol group. Whereas the conformers with N and thiol S as the copper(II) donor atoms are predicted to be the least stable, those with the Cu-N and Cu-S(thiolate) bonding (and protonated carboxylato group) are the most stable. The differences are explained by different covalent and ionic contributions of Cu-S(thiol) vs. Cu-S(thiolate). The study can contribute to the insight into formation and reactivity of the copper(II) cysteinato complexes in solution.

Two Cases of Hidradenitis Suppurativa Treated with Adalimumab at the Department of Dermatology and Venereology, Clinical Hospital Mostar.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease primarily affecting apocrine gland-rich areas of the body and presenting with painful nodules, abscesses, sinus tracts, and scarring (1). HS is a defect of the follicular epithelium; some have therefore called for the naming the disease acne inversa instead of hidradenitis suppurativa. The term acne inversa links the pathogenesis to acne and reflects the fact that it is an expression of follicular occlusion in localizations inverse to acne vulgaris (2). HS typically occurs after puberty. Studies have shown that the average onset is in the second or third decades of life (3). One of the most frequently cited risk factors for HS is cigarette smoking. Another significant risk factor for HS is obesity. About one-third of patients with HS have reported a family history of the disease (4). A clinically relevant staging and disease severity assessment is essential for the development of evidence-based treatments. There are several scoring systems for the assessment of disease severity of HS, including Hurley staging, HS Physician's Global Assessment (PGA), the modified Sartorius score (MSS), and the HS Severity Index (HSSI). Each of these assessments has both advantages and limitations in daily practice; there is currently no gold standard (5-8). The Hurley staging system is the simplest and most widely used instrument for HS classification in routine clinical practice. It classifies HS into three stages. HS-PGA is relatively easy to apply and is frequently used to measure clinical improvement in clinical trials of medical treatments (5). The system describes six disease stages, increasing in severity on a scale from 1 to 6 (9). MSS is a more detailed and dynamic classification system based on the counting of individual nodules and fistulas within seven anatomical regions. The system, which was developed by Sartorius et al. and later modified, is the first disease-specific instrument for dynamically measuring clinical severity of HS (10). The treatment of HS includes topical clindamycin, triamcinolone acetonide, clobetasol, topical resorcinol, oral antibiotics, hormonal therapy, oral retinoids, and biologic therapies (11). Biologic therapies are increasingly used in patients who fail to sufficiently respond to antibiotic and hormonal treatments. Adalimumab, infliximab, and etanercept have all been tested in the treatment of HS but vary in effectiveness and in how well they have been studied. Subcutaneous weekly adalimumab (160 mg at week 0, 80 mg at week 2, and 40 mg each week thereafter) is the only biologic agent approved by the US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) for the treatment of HS, and it is recommended as first-line therapy for patients with moderate-to-severe disease who are intolerant or unresponsive to oral antibiotics (12). The first male patient aged 59 years was referred to our Department with very long history of HS. The first symptoms had been unrecognized and presented as a pilonidal cyst 25 years ago as well as cysts on the intergluteal region treated with multiple surgical interventions and systemic antibiotics. The first hospitalization at our Department was in 2016. In addition to HS, the patient had diabetes mellitus (DM) type II and hypertension. A physical examination showed multiple abscesses, fistulas, and nodules in the axillary, inguinal, perianal, gluteal, and intergluteal regions; Hurley staging: stage II, PGA staging: IV, DLQI: 24 (Figure 1, Figure 2). Microbiological repeated swabs showed numerous bacteria such as Esch.coli, S.aureus, Serratia.spp, Enterococcus spp, St.epidermidis, and Proteus mirabilis. Laboratory tests which included complete blood cell count, biochemistry, serology for syphilis, HIV, and hepatitis B and C infection together with chest X-rays were all within normal limits. Abdominal ultrasound examination found no abnormalities. Quantiferon test was positive. After the monotherapy with isoniazid, a repeated Quantiferon test two months later was negative. The patient was treated with betadine solution and pus drainage until 2018, when at the Department of Dermatology and Venerology prescribed adalimumab in doses of 80 mg initially, 40 mg ×2 on the first day and the day after that, then 80 mg after fifteen days followed by 40 mg every ten days. After 16 weeks of treatment with adalimumab, Hurley staging was II, PGA IV, DLQI 3. The second male patient aged 28 years was referred to our Department with a shorter history: the first symptoms were presented as pilonidal sinus in 2012, after that in 2015 as inflamed nodules and fistulas in the axillary and inguinal regions. In 2018, physical examination showed the same nodules with a more intense character as well as furuncles on the scalp and skin of the back, with Hurley staging stage II, PGA staging III, DLQI 14 (Figure 3, Figure 4). Until the disease was diagnosed, the patient was treated several times with peroral antibiotics, while laboratory tests which included complete blood cell count, biochemistry, serology for syphilis, HIV, and hepatitis B and C infection together with chest X-rays were all within normal limits with the exception of elevated cholesterol (6.1). Abdominal ultrasound examination found no abnormalities. Quantiferon test was negative. The following therapy was administered during hospitalization: Humira (adalimumab) initial dose 160 mg, a dose of 80 mg after 14 days, and after 7 days 40 mg, in addition to local therapy with 10% resorcinol solution at the location of the skin changes. After 16 weeks of treatment with adalimumab, Hurley staging was II, PGA staging was III, and DLQI index was 3. Hidradenitis suppurativa is a chronic, recurrent inflammatory and debilitating skin disease of the terminal hair follicle that usually presents after puberty with painful, deep seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly the axillary, inguinal, and anogenital region (3). Biological therapies have been increasingly used for patients who failed to sufficiently respond to antibiotics and hormonal treatments. Adalimumab, infliximab, and etanercept have all been tested in the treatment of hidradenitis suppurativa but vary in effectiveness and in how well they have been studied. Subcutaneous weekly adalimumab (160 mg at week, 80 mg at week 2, and 40 mg each week thereafter) is the only biologic agent approved by the US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) for the treatment of HS and is recommended as first-line therapy for patients who moderate-to-severe disease and who are intolerant or unresponsive to oral antibiotics (5,12). Treatment of hidradenitis suppurativa remains a considerable challenge and should be individualized according to the state and extent of the disease. Therapeutic options for hidradenitis suppurativa were long restricted to the use of local disinfectants and systemic antibiotics as well as repeated incisions and drainage, which produce only short-term benefits. Our patients showed regression of lesions after sixteen weeks of biological therapy.

Beneficial Treatment Outcomes of Severe COVID-19 Patients Treated Entirely in Primary Care Settings With Dexamethasone Including Regimen-Case Series Report.

Even in 2021, coronavirus disease 2019 (COVID-19) remains a major global health concern, especially in developing countries. The burden of this disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which affects not only primary respiratory but also other organ systems, keeps rising as the pandemic continues. Primary health care centers are the first line where COVID-19 patients are managed and should be able to manage the vast majority of them successfully. In this paper, we present a case series and concept of beneficial management of even deteriorating and severe patients treated entirely in our primary health center. The management is based on well-timed and rational dexamethasone use, as well as on various other pharmacological and nonpharmacological treatments and interventions, and is supported by provided statistical data. According to the presented experience and positive outcomes achieved, it seems that even deteriorating and severe COVID-19 patients can be treated successfully to some extent or even completely in primary care settings. This kind of approach could be particularly beneficial in conditions of overload of higher-level health care institutions.

Facile Synthesis of L-Cysteine Functionalized Graphene Quantum Dots as a Bioimaging and Photosensitive Agent.

Nowadays, a larger number of aggressive and corrosive chemical reagents as well as toxic solvents are used to achieve structural modification and cleaning of the final products. These lead to the production of residual, waste chemicals, which are often reactive, cancerogenic, and toxic to the environment. This study shows a new approach to the modification of graphene quantum dots (GQDs) using gamma irradiation where the usage of reagents was avoided. We achieved the incorporation of S and N atoms in the GQD structure by selecting an aqueous solution of L-cysteine as an irradiation medium. GQDs were exposed to gamma-irradiation at doses of 25, 50 and 200 kGy. After irradiation, the optical, structural, and morphological properties, as well as the possibility of their use as an agent in bioimaging and photodynamic therapy, were studied. We measured an enhanced quantum yield of photoluminescence with the highest dose of 25 kGy (21.60%). Both S- and N-functional groups were detected in all gamma-irradiated GQDs: amino, amide, thiol, and thione. Spin trap electron paramagnetic resonance showed that GQDs irradiated with 25 kGy can generate singlet oxygen upon illumination. Bioimaging on HeLa cells showed the best visibility for cells treated with GQDs irradiated with 25 kGy, while cytotoxicity was not detected after treatment of HeLa cells with gamma-irradiated GQDs.

Conformational Analyses of Physiological Binary and Ternary Copper(II) Complexes with l-Asparagine and l-Histidine; Study of Tridentate Binding of Copper(II) in Aqueous Solution.

This study explores the structural properties and energy landscapes of the physiologically important bis(l-asparaginato)copper(II) [Cu(l-Asn)2] and (l-histidinato)(l-asparaginato)copper(II) [Cu(l-His)(l-Asn)]. The conformational analyses in the gas phase and implicitly modeled water medium, and magnetic parameters of electron paramagnetic resonance spectra were attained using density functional theory calculations. The apical CuII coordination and hydrogen bonding were analyzed. Predicted lower-energy structures enabled the confirmation and, for apical bonding, also the refinement of structural proposals from literature. Available experimental results were indecisive regarding the amido-group binding in the CuII equatorial plane in solutions, but the examination of the relative stability of Cu(l-Asn)2 conformers in 30 binding modes confirms the glycine-like mode as the most stable one. Previously reported experimental results for Cu(l-His)(l-Asn) were interpreted for l-His to have a tridentate histamine-like mode. However, the aqueous conformers with l-His in the glycinato mode are also predicted to have low energies, which does not contradict the tridentate l-His binding. The predicted magnetic parameters of conformers with an apical oxygen atom (intramolecular or from a water molecule) can reproduce the experimental data. An extent of conformational flexibility and abundance of l-His-containing ternary copper(II) amino acid complexes under physiological conditions may be related.