Who donates? Patterns of blood donation and donor characteristics at a university-affiliated hospital-based donor center.

BACKGROUND: Blood donors are a crucial element of the blood supply chain. Optimal recruitment strategies built upon the robust understanding of local donor behavior and demographics-specifically, the donor characteristics of our university-affiliated hospital-based donor center-improve outreach and retention of donors. STUDY DESIGN AND METHODS: This retrospective study analyzed blood donors' genders, ethnicities, and donation frequencies at a university-affiliated hospital-based donor center from 2014-2019, stratified into seven age cohorts. Donor ethnicity demographics were compared to the reported student, employee, and LA County population. RESULTS: Female donors outnumbered male donors in all age cohorts. The majority of donors self-identified (SI) as White (36.7%), Hispanic/Latino (21.6%), or Asian (19.1%). Older donors (age > 25) donated more frequently (4.1 vs. 2.3 donations per donor) than younger donors (age ≤ 25). Repeat donors who donated in multiple years during the study period were more likely to donate multiple times each year than those donors who only donated during 1 year. DISCUSSION: Our donor demographics more closely reflect the university student and employee demographics than LA County demographics, demonstrating the broad local efforts of recruitment by student groups and donor center recruitment staff. However, non-White populations continue to be underrepresented. The majority of donors only donated once during the study period. Recruitment strategies to increase donor engagement among underrepresented populations and increase the proportion of repeat donors are likely to prove most beneficial.

Relationships between global orientations and attitudes toward integration policies: A sequential explanatory mixed methods approach.

OBJECTIVES: Based upon a mixed methods follow-up explanation model, the present research examined the relationships between global orientations and the attitudes toward integration policies among both locals (majority group) and South Asians (minority group) in Hong Kong. METHODS: In Study 1, quantitative data were collected from a community sample of 1,614 adults comprising 1,007 locals and 607 South Asians in three minority groups (Indians, Nepalese, and Pakistanis). In Study 2, a follow-up explanation phase of qualitative investigation was conducted, with 12 in-depth semistructured focus group discussions among seven locals and 49 South Asians, generating three main themes and six subthemes. RESULTS: Quantitative results showed that the positive link between multicultural acquisition and instrumental integration policies was significantly stronger for South Asians than for locals, and that ethnic protection was negatively associated with a positive attitude toward symbolic integration policies in the majority group but had no effects in the minority group. The three main themes generated from the qualitative results include alleviating minority disadvantage, preserving majority privilege, and embracing diversity for the common good. CONCLUSIONS: The combined quantitative and qualitative results suggest that the differential relationships of multicultural acquisition and ethnic protection with support for specific integration policies can be understood with the underlying structural power asymmetry between the majority and minority groups. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Performance Characteristics of a Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Antigen Detection Assay at a Public Plaza Testing Site in San Francisco.

We evaluated the performance of the Abbott BinaxNOW rapid antigen test for coronavirus disease 2019 (Binax-CoV2) to detect virus among persons, regardless of symptoms, at a public plaza site of ongoing community transmission. Titration with cultured severe acute respiratory syndrome coronavirus 2 yielded a human observable threshold between 1.6 × 104-4.3 × 104 viral RNA copies (cycle threshold [Ct], 30.3-28.8). Among 878 subjects tested, 3% (26 of 878) were positive by reverse-transcription polymerase chain reaction, of whom 15 of 26 had a Ct <30, indicating high viral load; of these, 40% (6 of 15) were asymptomatic. Using this Ct threshold (<30) for Binax-CoV2 evaluation, the sensitivity of Binax-CoV2 was 93.3% (95% confidence interval, 68.1%-99.8%) (14 of 15) and the specificity was 99.9% (99.4%-99.9%) (855 of 856).

Predicting Gambling Propensity and Behavior: The Role of Social Axioms and Distortive Beliefs.

Theory and research have revealed the impact of cognitive factors on propensity for gambling, but the role of generalized beliefs and their underlying mechanisms receive little attention. In the present research, we operationalized generalized beliefs as social axioms (Leung et al. in J Cross Cult Psychol 33:286-302, 2002) and tested how the axiom factors of fate control and social cynicism affected the likelihood to gamble in hypothetical scenarios (Study 1) and the actual behaviour of gambling (Study 2). In Study 1, we found that both fate control and social cynicism positively predicted the propensity to participate in horse betting and casino gambling among university students (n = 184). The effect of fate control was mediated by perceived benefit of gambling, whereas social cynicism affected gambling propensity directly. In Study 2, we showed the same effects of fate control and social cynicism on gambling frequency among at-risk adolescents (n = 547), and identified two types of gambling-related cognition (i.e., distortive gambling cognitions and attitudes towards money) as mediators. Overall, this research provided evidence for the importance of social beliefs in formulating specific gambling cognitions and gambling behaviours, shedding light on intervention strategies for helping frequent gamblers through altering their worldviews in general and risk-taking beliefs in particular.

Review of the Evaluation and Treatment of Vasovagal Reactions in Outpatient Procedures.

BACKGROUND: A vasovagal reaction is a commonly encountered event in outpatient procedures. There is a paucity of discussion on vasovagal reactions (VVRs) in the dermatologic surgery literature. However, recent investigations in the physiology, evaluation, and treatment of VVRs have been reported in other specialties. OBJECTIVE: A comprehensive review of the physiology, evaluation, treatment, and prevention of VVRs. MATERIALS AND METHODS: A search as performed using the PubMed/MEDLINE databases. Search terms included "vasovagal," "vasovagal reaction," "syncope," "reflex syncope," "neurocardiogenic syncope," and "fainting." RESULTS: Studies demonstrate greater understanding in the physiology of a vasovagal reaction. Although permanent sequelae are uncommon, it is important to respond in a prompt manner. A variety of treatment and prevention options are presented. CONCLUSION: Vasovagal reactions should be carefully evaluated. Additional studies may provide greater data in understanding and managing vasovagal reactions.

Finer Needles Reduce Pain Associated With Injection of Local Anesthetic Using a Minimal Insertion Injection Technique.

BACKGROUND: The injection of local anesthetic into the skin is often the only memorable event described by the patient after dermatologic procedures. OBJECTIVE: The authors compared the pain felt during injection of local anesthetic using a minimal needle insertion technique with a 30- or 33-gauge needle. MATERIALS AND METHODS: Three hundred eighteen patients with tumors on the head and neck were injected with lidocaine using a previously described technique with either a 30- or 33-gauge needle. After injection, patients were surveyed using the visual assessment scale for pain. RESULTS: Seventy-seven percent of patients felt no pain with injection on the face using a 33-gauge needle compared with 64% with a 30 gauge, whereas 94% of patients felt no pain on the scalp with a 33-gauge needle compared with 54% with a 30 gauge. Visual analog scale scores were also significantly decreased on the face and scalp using the smaller needle. There was no difference in pain between the 2 needles with injection on the neck. CONCLUSION: This study further validates the use of this technique for the injection of lidocaine and the preference of a 33 gauge over a 30-gauge needle for the initial injection on the face and scalp.

MinorityReport, software for generalized analysis of causal genetic variants.

BACKGROUND: The widespread availability of next generation genome sequencing technologies has enabled a wide range of variant detection applications, especially in cancer and inborn genetic disorders. For model systems and microorganisms, the same technology may be used to discover the causative mutations for any phenotype, including those generated in response to chemical perturbation. In the case of pathogenic organisms, these approaches have allowed the determination of drug targets by means of resistance selection followed by genome sequencing. RESULTS: MinorityReport is open source software written in python that facilitates the comparison of any two sets of genome alignments for the purpose of rapidly identifying the spectrum of nonsynonymous changes, insertions or deletions, and copy number variations in a presumed mutant relative to its parent. Specifically, MinorityReport relates mapped sequence reads in SAM format output from any alignment tool for both the mutant and parent genome, relative to a reference genome, and produces the set of variants that distinguishes the mutant from the parent, all presented in an intuitive, straightforward report format. MinorityReport features tunable parameters for evaluating evidence and a scoring system that prioritizes reported variants based on relative proportions of read counts supporting the variant in the mutant versus parent data sets. The utility of MinorityReport is demonstrated using previously published publicly available data sets to find the determinants of resistance for novel anti-malarial drugs. CONCLUSIONS: MinorityReport is readily available (github: JeremyHorst/MinorityReport) to identify the genetic mechanisms of drug resistance in Plasmodium, genotype-phenotype relationships in human diads, or genomic variations between any two related organisms.

Synovial inflammation plays a greater role in post-traumatic osteoarthritis compared to idiopathic osteoarthritis in the Hartley guinea pig knee.

BACKGROUND: The objective of this study was to evaluate the extent of stromal cell-derived factor-1's (SDF-1) involvement in the pathogenesis of idiopathic versus post-traumatic OA by comparing differences in synovial membrane morphology, SDF-1 synovial fluid (SF) concentrations, and matrix metalloproteinase-13 (MMP-13) SF concentrations. METHODS: Thirty-six 3-month-old Hartley guinea pigs were obtained and divided into 6 groups. Upon sacrifice, India Ink staining was used to evaluate gross morphology, Safranin O/Fast green staining was used to assess cartilage damage, H/E staining was employed to visualize the synovium, and SF samples were obtained for biochemical analyses. Sandwich ELISA was used to quantify the SF concentrations of SDF-1 and MMP-13. RESULTS: 12 month-old, idiopathic OA guinea pigs and 5.5 month-old ACLT animals had comparable cartilage damage when evaluated by the Modified Mankin Score. SDF-1 and MMP-13 concentrations were not statistically different between the two groups. The synovial membrane of the 5.5 month ACLT group had severe synovitis compared to the idiopathic OA group. CONCLUSION: In this study, it was found that synovial inflammation, independent of cartilage morphology, SDF-1 concentration, and MMP-13 concentration, was markedly different between idiopathic and post-traumatic OA. These results highlight the differing morphological and biochemical profiles of post-traumatic versus idiopathic osteoarthritis and calls for a more thorough examination of the sole of the synovial membrane in the pathogenesis of post-traumatic osteoarthritis.

A chemical rescue screen identifies a Plasmodium falciparum apicoplast inhibitor targeting MEP isoprenoid precursor biosynthesis.

The apicoplast is an essential plastid organelle found in Plasmodium parasites which contains several clinically validated antimalarial-drug targets. A chemical rescue screen identified MMV-08138 from the "Malaria Box" library of growth-inhibitory antimalarial compounds as having specific activity against the apicoplast. MMV-08138 inhibition of blood-stage Plasmodium falciparum growth is stereospecific and potent, with the most active diastereomer demonstrating a 50% effective concentration (EC50) of 110 nM. Whole-genome sequencing of 3 drug-resistant parasite populations from two independent selections revealed E688Q and L244I mutations in P. falciparum IspD, an enzyme in the MEP (methyl-d-erythritol-4-phosphate) isoprenoid precursor biosynthesis pathway in the apicoplast. The active diastereomer of MMV-08138 directly inhibited PfIspD activity in vitro with a 50% inhibitory concentration (IC50) of 7.0 nM. MMV-08138 is the first PfIspD inhibitor to be identified and, together with heterologously expressed PfIspD, provides the foundation for further development of this promising antimalarial drug candidate lead. Furthermore, this report validates the use of the apicoplast chemical rescue screen coupled with target elucidation as a discovery tool to identify specific apicoplast-targeting compounds with new mechanisms of action.

Azelaic Acid: Evidence-based Update on Mechanism of Action and Clinical Application.

Azelaic acid is a complex molecule with many diverse activities. The latter include anti-infective and anti-inflammatory action. The agent also inhibits follicular keratinization and epidermal melanogenesis. Due to the wide variety of biological activities, azelaic acid has been utilized as a management tool in a broad spectrum of disease states and cutaneous disorders. This paper reviews the clinical utility of azelaic acid, noting the quality of the evidence supporting each potential use.

Zosteriform metastasis of rectal adenocarcinoma: a case report.

Cutaneous metastases manifesting as zosteriform eruptions are uncommon. To our knowledge, we report the second case of zosteriform cutaneous metastasis arising from a rectal carcinoma in a 58-year-old man who presented with a painless popular eruption in the T12 dermatomal distribution nine months after his primary diagnosis of rectal carcinoma was made. Furthermore, we discuss a review of the literature regarding zosteriform cutaneous metastases and the possible pathogenesis of these lesions.

Trends of keratinocyte carcinoma mortality rates in the United States as reported on death certificates, 1999 through 2010.

BACKGROUND: From 1969 to 1998, keratinocyte carcinoma (KC) mortality rates declined as reported on death certificates, despite increasing incidence of KC. OBJECTIVE: To estimate KC mortality trends from 1999 to 2010 in the United States. METHODS: Descriptive and linear regression analysis using population-based death certificate data from the US National Center for Health Statistics. RESULTS: On average, 1,491 deaths from nongenital KC and 1,058 deaths from genital KC were reported annually. Keratinocyte carcinoma mortality rates were stable or increasing over the study period. Highest nongenital mortality rates were seen in those older than 85 years (p < .001), men (p < .001), whites (p < .001), the South for white males (p = .001) and white females (p = .018), and nonmetropolitan areas for white males (p <.001), white females (p < .001), and black females (p = .005). Correlation between state UV Index and KC mortality existed for men (p = .004) but not for women (p = .379). Genital KC deaths increased with age (p < .001), in women (p < .001), and in less urbanized areas for white males (p < .001). CONCLUSION: Keratinocyte carcinoma poses a serious health burden, which may be underestimated by death certificate reporting. Mortality rates are no longer declining. Increasing awareness of genital and nongenital KC, especially the elderly, and population-based studies with controlled reporting of KC mortality are needed.

High-yield production of recombinant human myelin oligodendrocyte glycoprotein in SHuffle bacteria without a refolding step.

Experimental autoimmune encephalomyelitis (EAE) is a model for central nervous system (CNS) autoimmune demyelinating diseases such as multiple sclerosis (MS) and MOG antibody-associated disease (MOGAD). Immunization with the extracellular domain of recombinant human MOG (rhMOG), which contains pathogenic antibody and T cell epitopes, induces B cell-dependent EAE for studies in mice. However, these studies have been hampered by rhMOG availability due to its insolubility when overexpressed in bacterial cells, and the requirement for inefficient denaturation and refolding. Here, we describe a new protocol for the high-yield production of soluble rhMOG in SHuffle cells, a commercially available E. coli strain engineered to facilitate disulfide bond formation in the cytoplasm. SHuffle cells can produce a soluble fraction of rhMOG yielding >100 mg/L. Analytical size exclusion chromatography multi-angle light scattering (SEC-MALS) and differential scanning fluorimetry of purified rhMOG reveals a homogeneous monomer with a high melting temperature, indicative of a well-folded protein. An in vitro proliferation assay establishes that purified rhMOG can be processed and recognized by T cells expressing a T cell receptor (TCR) specific for the immunodominant MOG35-55 peptide epitope. Lastly, immunization of wild-type, but not B cell deficient, mice with rhMOG resulted in robust induction of EAE, indicating a B cell-dependent induction. Our SHuffle cell method greatly simplifies rhMOG production by combining the high yield and speed of bacterial cell expression with enhanced disulfide bond formation and folding, which will enable further investigation of B cell-dependent EAE and expand human research of MOG in CNS demyelinating diseases.

Efficient evolution of human antibodies from general protein language models.

Natural evolution must explore a vast landscape of possible sequences for desirable yet rare mutations, suggesting that learning from natural evolutionary strategies could guide artificial evolution. Here we report that general protein language models can efficiently evolve human antibodies by suggesting mutations that are evolutionarily plausible, despite providing the model with no information about the target antigen, binding specificity or protein structure. We performed language-model-guided affinity maturation of seven antibodies, screening 20 or fewer variants of each antibody across only two rounds of laboratory evolution, and improved the binding affinities of four clinically relevant, highly mature antibodies up to sevenfold and three unmatured antibodies up to 160-fold, with many designs also demonstrating favorable thermostability and viral neutralization activity against Ebola and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudoviruses. The same models that improve antibody binding also guide efficient evolution across diverse protein families and selection pressures, including antibiotic resistance and enzyme activity, suggesting that these results generalize to many settings.

Social axioms and psychological toll: A study of emotional, behavioral, and cognitive responses across 35 cultures during the COVID-19 pandemic.

The COVID-19 pandemic has significantly affected the psychological well-being of individuals worldwide. Previous research has indicated that values and beliefs, particularly social axioms, are associated with psychological responses during crises. However, most of the studies have focused on specific regions; the impact of social axioms on a global scale remains unclear. We conducted a multinational study comprising stratified samples of 18,171 participants from 35 cultures. Using multilevel modeling, we examined the associations between social axioms, personal worry, normative concerns, trust, and individuals' psychological responses to the pandemic. The results showed that greater personal worry and normative concerns predicted more negative psychological responses. Furthermore, the study also identified significant buffering effects at the societal level, as cultures with higher overall levels of fate control, religiosity, or reward for application exhibited weaker associations between personal worry and negative responses. Our findings reveal the influence of social axioms on psychological responses during the pandemic, with varying effects across cultures. The buffering effects of fate control, religiosity, and reward for application underscore the importance of considering cultural differences and individual variability when examining the impact of social axioms on psychological outcomes.

Optimization of diastereomeric dihydropyridines as antimalarials.

The increase in research funding for the development of antimalarials since 2000 has led to a surge of new chemotypes with potent antimalarial activity. High-throughput screens have delivered several thousand new active compounds in several hundred series, including the 4,7-diphenyl-1,4,5,6,7,8-hexahydroquinolines, hereafter termed dihydropyridines (DHPs). We optimized the DHPs for antimalarial activity. Structure-activity relationship studies focusing on the 2-, 3-, 4-, 6-, and 7-positions of the DHP core led to the identification of compounds potent (EC50 < 10 nM) against all strains of P. falciparum tested, including the drug-resistant parasite strains K1, W2, and TM90-C2B. Evaluation of efficacy of several compounds in vivo identified two compounds that reduced parasitemia by >75 % in mice 6 days post-exposure following a single 50 mg/kg oral dose. Resistance acquisition experiments with a selected dihydropyridine led to the identification of a single mutation conveying resistance in the gene encoding for Plasmodium falciparum multi-drug resistance protein 1 (PfMDR1). The same dihydropyridine possessed transmission blocking activity. The DHPs have the potential for the development of novel antimalarial drug candidates.