Internal Consistency of the Serbian Translation of the Stanford Social Dimensions Scale and Association to Strengths and Difficulties Questionnaire Scores in Male and Female Individuals on the Autism Spectrum and Non-autistic Individuals.

We aimed to evaluate the internal consistency of Stanford Social Dimensions Scale (SSDS) translated to Serbian and to test it against the Strengths and Difficulties Questionnaire (SDQ). The sample consisted of 200 patients (32% ASD) of the Institute of Mental Health in Belgrade, Serbia (68 females, 132 males, Mage=9.61, SDage=4.06). Internal consistency coefficients were within good/acceptable range for Social Motivation, Affiliation, Recognition and Unusual Approach subscales and below acceptable for Expressive Social Communication subscale. The non-autistic group scored higher on all subscales compared to the ASD group. All SSDS subscales positively correlated with SDQ Prosocial Behaviors scale. The SSDS is a valuable instrument for accessing sociobehavioral phenotype in both individuals on the autism spectrum and non-autistic individuals.

The Electronic Effects of 3-Methoxycarbonylcoumarin Substituents on Spectral, Antioxidant, and Protein Binding Properties.

Coumarin derivatives are a class of compounds with pronounced biological activities that depend primarily on the present substituents. Four 3-methoxycarbonylcoumarin derivatives with substituents of different electron-donating/electron-withdrawing abilities (Br, NO2, OH, and OMe) were investigated structurally by NMR, IR, and UV-VIS spectroscopies and density functional theory methods. The appropriate level of theory (B3LYP-D3BJ/6-311++G(d,p) was selected after comparing similar compounds' experimental and theoretical structural parameters. The natural bond orbital and quantum theory of atoms in molecules were employed to investigate the intramolecular interactions governing stability. The electronic effects of substituents mostly affected the aromatic ring that the substituents are directly attached to. The antioxidant properties were investigated by electron paramagnetic resonance spectroscopy towards HO•, and the percentages of reduction were between 13% (6-Br) and 23% (6-OMe). The protein binding properties towards transport proteins were assessed by spectrofluorimetry, molecular docking, and molecular dynamics (MD). The experimentally determined binding energies were well reproduced by molecular docking, showing that the spontaneity of ibuprofen binding was comparable to the investigated compounds. The flexibility of HSA in MD simulations depended on the substituents. These results proved the importance of electronic effects for the protein binding affinities and antioxidant properties of coumarin derivatives.

Mental Health, Alcohol and Substance Use of Refugee Youth.

This study aims to explore the prevalence of alcohol and substance use among young refugees along with the indicators of experienced psychological difficulties. It is based on a sample of 184 children and adolescents aged 11-18 years old, residing at two refugee centers in the Republic of Serbia. Out of 184 participants, the majority was male (N = 155; 84.29%). More than a half of participants (53.3%) displayed significant symptoms of PTSD. 50% consume energy drinks, 28% use tobacco; 13% use alcohol; 4.6% use marijuana; 1.7% use LSD, amphetamines, glue, tranquilizers and cocaine. Female respondents were more frequently expressing emotional difficulties (p < 0.05) while male participants were more frequent users of alcohol or substances (p < 0.01). Younger children were more frequently expressing symptoms of hyperactivity and prosocial behavior, while they were less frequently using substances. There is also a significant negative correlation between the years of education and individual proneness to substance use. Furthermore, those who resided in a greater number of refugee camps were found to experience greater levels of emotional and behavioral difficulties and face a greater risk of physical abuse. The burden of migration increases proneness to substance use, as a consequence of scarce coping resources and the stress of adjusting. Migrants are vulnerable to substance use, since some of them have commonly witnessed and/or personally experienced pre-and post-migration stress and trauma, including loss of homes and livelihoods, violence, torture and family separation. Preventive programs need to focus on the problem of alcohol and substance use among this vulnerable population.

Evaluation of the MYCOPLASMA IST3 urogenital mycoplasma assay in an international multicentre trial.

OBJECTIVES: To evaluate the accuracy, susceptibility and specificity of MYCOPLASMA IST3, the next generation of the most popular culture-based in vitro diagnostic device designed to detect, identify and test the susceptibility of urogenital mycoplasma infections. METHODS: MYCOPLASMA IST3 was evaluated against culture- and molecular-based gold standard methodologies to detect, identify, enumerate and determine antimicrobial resistance for Mycoplasma hominis and Ureaplasma species in 516 clinical samples collected across France, Serbia and the UK. Sample types included vulvovaginal/endocervical or urethral swabs (dry swab or eSwab®), semen and urine samples, which included blinded analysis following addition of a panel of 80 characterized control strains. RESULTS: Overall species identification was excellent for both Ureaplasma spp. (98.4% sensitivity, 99.7% specificity) and M. hominis (95.7% sensitivity, 100% specificity) relative to combined colony morphology on agar and quantitative PCR standards. Non-dilution-based bacterial load estimation by the assay was accurate between 83.7% (M. hominis) and 86.3% (Ureaplasma spp.) of the time (increased to 94.2% and 100%, respectively, if ±10-fold variance was allowed) relative to colonies counted on agar. Resistance accuracy for Ureaplasma spp. varied from gold standards for only 11/605 of individual tests (major error rate = 1.8%) and for 14/917 individual tests for M. hominis (major error rate = 1.5%). CONCLUSIONS: The redesigned MYCOPLASMA IST3 assay eliminated previous shortcomings by providing independent accurate resistance screening of M. hominis and Ureaplasma species, even in mixed infections, with CLSI-compliant thresholds. Specificity, sensitivity and enumeration estimates correlated closely with the confirmatory methods.

Analysis of lesional color to differentiate infantile hemangiomas from port-wine birthmarks in infants less than 3 months old: A pilot study.

BACKGROUND: In their early phase, infantile hemangiomas (IH) can sometimes be difficult to differentiate from port-wine birthmarks (PWB). Until recently, inexpensive diagnostic tools have not been readily available. OBJECTIVE: To determine the diagnostic utility of widely available colorimetric technology when differentiating PWB from IH in photographs of infants less than 3 months old. METHODS: Multi-center, retrospective analysis of RGB (red, green, and blue) and HSL (hue, saturation, lightness) values collected using electronic colorimeters from images of clinically confirmed untreated IH or PWB. Subgroup analysis of flat vascular birthmarks was subsequently performed. RESULTS: Images of 119 IH (specifically, 45 flat IH) and 59 PWB were identified. PWB had significantly (P < .001) higher RGB values of all primary colors, most notably for blue and green (mean difference: >50), irrespective of thickness. RGB or RGB with HSL values had an excellent accuracy (90%), sensitivity (92%), specificity (98%), and positive predictive value (98%) when discriminating PWB from flat IH. IH could be distinctly clustered from PWB when combining their RGB with HSL values. CONCLUSION: Electronic colorimeters with emphasis on blue and green values, are able to differentiate PWB from IH, irrespective of thickness, with a high degree of accuracy. A larger scale evaluation is now required.

COVID-19 Vaccine and Biologics: An Impending Dilemma.

The COVID-19 pandemic has forced healthcare providers across all specialties to adjust their methods of clinical practice. In Dermatology, focus on the continued safe usage of immunomodulating biologic therapies has attracted particular interest as the COVID-19 virus represents a novel infection risk. While guidance on biologic initiation and continuation has been established,1 the return to normalcy will likely involve a safe and effective vaccine. This vaccine(s) will represent a new clinical hurdle for prescribers who have continued patients on biologic therapy throughout the pandemic.

Current Practices in Pediatric Dermatology Laser Therapy: An International Survey.

BACKGROUND AND OBJECTIVES: To date, there are no well-established guidelines regarding laser therapy for the treatment of cutaneous lesions in pediatric patients. We aim to ascertain the types of lasers commonly used, types of lesions treated, and factors that affect the selection of specific laser modalities in pediatric patients. STUDY DESIGN/MATERIALS AND METHODS: An anonymous online survey was distributed to healthcare providers who treat children with lasers through listservs of four major national and international dermatology and laser organizations. RESULTS: Outpatient office-based procedure rooms are the most common clinical setting for laser procedures (74.4%), and pulsed dye laser is the most commonly used laser (95.4%). Conditions routinely treated with lasers included port wine stains (95.4%), infantile hemangiomas (81.5%), other vascular lesions (81.5%), scars (77.7%), and hair (60.8%). 84.4% of respondents expressed concern about general anesthesia in patients <2 years old. Nevi of Ota is treated with laser more frequently (52.3%) than other pigmented lesions. LIMITATIONS: Limited generalizability of case examples to general conditions. CONCLUSIONS: Vascular lesions are the most common lesions treated with lasers in pediatric dermatology patients, and most providers are using these devices in the outpatient setting. Many providers are concerned about the effects of repeated general anesthesia in infants, and there appears to be a trend toward providing laser therapy in the outpatient setting without general anesthesia. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Core Outcome Set for Actinic Keratosis Clinical Trials.

Importance: Although various treatments have been found in clinical trials to be effective in treating actinic keratosis (AK), researchers often report different outcomes. Heterogeneous outcome reporting precludes the comparison of results across studies and impedes the synthesis of treatment effectiveness in systematic reviews. Objective: To establish an international core outcome set for all clinical studies on AK treatment using systematic literature review and a Delphi consensus process. Evidence Review: Survey study with a formal consensus process. The keywords actinic keratosis and treatment were searched in PubMed, Embase, CINAHL, and the Cochrane Library to identify English-language studies investigating AK treatments published between January 1, 1980, and July 13, 2015. Physician and patient stakeholders were nominated to participate in Delphi surveys by the Measurement of Priority Outcome Variables in Dermatologic Surgery Steering Committee members. All participants from the first round were invited to participate in the second round. Outcomes reported in randomized controlled clinical trials on AK treatment were rated via web-based e-Delphi consensus surveys. Stakeholders were asked to assess the relative importance of each outcome in 2 Delphi survey rounds. Outcomes were provisionally included, pending the final consensus conference, if at least 70% of patient or physician stakeholders rated the outcome as critically important in 1 or both Delphi rounds and the outcome received a mean score of 7.5 from either stakeholder group. Data analysis was performed from November 5, 2018, to February 27, 2019. Findings: A total of 516 outcomes were identified by reviewing the literature and surveying key stakeholder groups. After deduplication and combination of similar outcomes, 137 of the 516 outcomes were included in the Delphi surveys. Twenty-one physicians and 12 patients participated in round 1 of the eDelphi survey, with 17 physicians (81%) retained and 12 patients (100%) retained in round 2. Of the 137 candidate outcomes, 9 met a priori Delphi consensus criteria, and 6 were included in the final outcomes set after a consensus meeting: complete clearance of AKs, percentage of AKs cleared, severity of adverse events, patient perspective on effectiveness, patient-reported future treatment preference, and recurrence rate. It was recommended that treatment response be assessed at 2 to 4 months and recurrence at 6 to 12 months, with the AK rate of progression to cutaneous squamous cell carcinoma reported whenever long-term follow-up was possible. Conclusions and Relevance: Consensus was reached regarding a core outcome set for AK trials. Further research may help determine the specific outcome measures used to assess each of these outcomes.

Quantitative evaluation of skin shrinkage associated with non-invasive skin tightening: a simple method for reproducible linear measurement using microtattoos.

Non-invasive skin-tightening devices can induce thermal denaturation and skin shrinkage via externally applied radiofrequency emissions or high-frequency ultrasound. Therefore, the purpose of this study is to develop and test a method for measurement of skin reduction associated with application of such energy devices. Twenty-five healthy participants with mild to moderate skin laxity of the arms were enrolled. Pinpoint microtattoos were placed at each of the treatment sites to delineate two 6 × 12 cm rectangles per subject. A non-stretchable filament, tape and marking pen apparatus was used to measure the size of each rectangle before treatment and at follow-up visit by two blinded investigators. After randomization, one side received a single pass with a radiofrequency device (6.78 MHz), while the contralateral side received multiple passes. Participants underwent two treatment sessions to each side 2 weeks apart, and returned for follow-up 4 weeks after the second treatment. Length and area measurement were analyzed to assess precision and accuracy of measurements and to compare efficacy of treatment between pre- and post-treatment. Concordance correlation coefficients (CCC) demonstrated substantial inter-investigator reliability and precision in length measurements (CCC, 0.94 to 0.98 in pre-treatment; 0.95 to 0.98 in post-treatment). Measurements at the 6-week post-treatment follow-up demonstrated a statistically significant skin reduction in all six of the measured parameters. A simple skin measurement method requiring minimal instrumentation can quantitatively evaluate skin shrinkage associated with non-invasive skin-tightening devices.

Functional evidence for TCR-intrinsic specificity for MHCII.

How T cells become restricted to binding antigenic peptides within class I or class II major histocompatibility complex molecules (pMHCI or pMHCII, respectively) via clonotypic T-cell receptors (TCRs) remains debated. During development, if TCR-pMHC interactions exceed an affinity threshold, a signal is generated that positively selects the thymocyte to become a mature CD4(+) or CD8(+) T cell that can recognize foreign peptides within MHCII or MHCI, respectively. But whether TCRs possess an intrinsic, subthreshold specificity for MHC that facilitates sampling of the peptides within MHC during positive selection or T-cell activation is undefined. Here we asked if increasing the frequency of lymphocyte-specific protein tyrosine kinase (Lck)-associated CD4 molecules in T-cell hybridomas would allow for the detection of subthreshold TCR-MHC interactions. The reactivity of 10 distinct TCRs was assessed in response to selecting and nonselecting MHCII bearing cognate, null, or "shaved" peptides with alanine substitutions at known TCR contact residues: Three of the TCRs were selected on MHCII and have defined peptide specificity, two were selected on MHCI and have a known pMHC specificity, and five were generated in vitro without defined selecting or cognate pMHC. Our central finding is that IL-2 was made when each TCR interacted with selecting or nonselecting MHCII presenting shaved peptides. These responses were abrogated by anti-CD4 antibodies and mutagenesis of CD4. They were also inhibited by anti-MHC antibodies that block TCR-MHCII interactions. We interpret these data as functional evidence for TCR-intrinsic specificity for MHCII.

Engineering of novel Staphylococcal Protein A ligands to enable milder elution pH and high dynamic binding capacity.

We describe novel Staphylococcal Protein A ligands that enable milder elution pH for use in affinity chromatography. The change in elution pH is the result of point mutations to the protein sequence. Two novel ligands are investigated in this study. The first, designated Z(H18S)4, represents a histidine to serine substitution single mutation. The second, designated Z(H18S, N28A)4, is a double mutant comprising histidine to serine and asparagine to alanine mutations. Both are compared against the unmutated sequence, designated Z4, which is currently utilized in a commercially available Protein A stationary phase for the purification of molecules containing Fc domains. The ligands are coupled to a chromatography support matrix and tested against a panel of antibodies and an Fc fusion protein for elution pH, dynamic binding capacity, step-wise elution, and capture from clarified culture media. Results demonstrate that the novel ligands result in milder elution pH, on average >0.5 pH units, when tested in a pH gradient. For step-wise elution at pH 4.0, the Z(H18S, N28A)4 ligand showed on average a greater than 30% increase in yield compared to Z4. Importantly, for the antibodies tested the mutations did not result in a decrease in dynamic binding capacity or other desirable attributes such as selectivity. A potential application of the novel ligands is shown with a pH sensitive molecule prone to aggregation under acidic conditions.

Evaluating spine micro-architectural texture (via TBS) discriminates major osteoporotic fractures from controls both as well as and independent of site matched BMD: the Eastern European TBS study.

The aim of the study was to assess the clinical performance of the model combining areal bone mineral density (aBMD) at spine and microarchitecural texture (TBS) for the detection of the osteoporotic fracture. The Eastern European Study is a multicenter study (Serbia, Bulgaria, Romania and Ukraine) evaluating the role of TBS in routine clinical practice as a complement to aBMD. All scans were acquired on Hologic Discovery and GE Prodigy densitometers in a routine clinical manner. The additional clinical values of aBMD and TBS were analyzed using a two steps classification tree approach (aBMD followed by TBS tertiles) for all type of osteoporotic fracture (All-OP Fx). Sensitivity, specificity and accuracy of fracture detection as well as the Net Reclassification Index (NRI) were calculated. This study involves 1031 women subjects aged 45 and older recruited in east European countries. Clinical centers were cross-calibrated in terms of BMD and TBS. As expected, areal BMD (aBMD) at spine and TBS were only moderately correlated (r (2) = 0.19). Prevalence rate for All-OP Fx was 26 %. Subjects with fracture have significant lower TBS and aBMD than subjects without fracture (p < 0.01). TBS remains associated with the fracture even after adjustment for age and aBMD with an OR of 1.27 [1.07-1.51]. When using aBMD T-score of -2.5 and the lowest TBS tertile thresholds, both BMD and TBS were similar in terms of sensitivity (35 vs. 39 %), specificity (78 vs. 80 %) and accuracy (64 vs. 66 %). aBMD and TBS combination, induced a significant improvement in sensitivity (+28 %) and accuracy (+17 %) compared to aBMD alone whereas a moderate improvement was observed in terms of specificity (+9 %). The overall combination gain was 36 % as expressed using the NRI. aBMD and TBS combination decrease significantly the number of subjects needed to diagnose from 7 for aBMD alone to 2. In a multi-centre Eastern European cohort, we have shown that the use of TBS in addition to the aBMD permit to reclassified correctly more than one-third of the overall subjects. Furthermore, the number of subjects needed to diagnose fell to 2 subjects. Economical studies have to be performed to evaluate the gain induced by the use of TBS for the healthcare system.