5 years DKMS Chile: approach, results and impact of the first unrelated stem cell donor center in Chile.

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed worldwide to treat blood cancer and other life-threatening blood disorders. As successful transplantation requires an HLA-compatible donor, unrelated donor centers and registries have been established worldwide to identify donors for patients without a family match. Ethnic minorities are underrepresented in large donor registries. Matching probabilities are higher when donors and patients share the same ethnic background, making it desirable to increase the diversity of the global donor pool by recruiting donors in new regions. Here, we report the establishment and the first 5 years of operation of the first unrelated stem cell donor center in Chile, a high-income country in South America with a population of over 19 million. Methods: We used online and in-person donor recruitment practices through patient appeals and donor drives in companies, universities, the armed forces, and public services. After confirmatory typing donors were subjected to medical work-up and cleared for donation. Results: We recruited almost 170,000 donors in 5 years. There were 1,488 requests received for confirmatory typing and donor availability checks, of which 333 resulted in medical work-up, leading to 194 stem cell collections. Products were shipped to Chile (48.5%) and abroad. Even when the COVID-19 pandemic challenged our activities, the number of donors recruited and shipped stem cell products remained steady. In Chile there was an almost 8-fold increase in unrelated donor transplantation activity from 16 procedures in 2016-2018 to 124 procedures in 2019-2021, mainly for pediatric patients following the center's establishment. We estimate that 49.6% of Chilean patients would find at least one matched unrelated donor in the global DKMS donor pool. Discussion: Establishing a DKMS donor center in Chile has significantly increased donor availability for Chilean patients and contributed to an increase of unrelated donor stem cell transplant activity.

HLA allele and haplotype frequencies of registered stem cell donors in Chile.

Patients in need of hematopoietic stem cell transplantation often rely on unrelated stem cell donors matched in certain human leukocyte antigen (HLA) genes. Donor search is complicated by the extensive allelic variability of the HLA system. Therefore, large registries of potential donors are maintained in many countries worldwide. Population-specific HLA characteristics determine the registry benefits for patients and also the need for further regional donor recruitment. In this work, we analyzed HLA allele and haplotype frequencies of donors of DKMS Chile, the first Chilean donor registry, with self-assessed "non-Indigenous" (n=92,788) and "Mapuche" (n=1,993) ancestry. We identified HLA alleles that were distinctly more abundant in the Chilean subpopulations than in worldwide reference populations, four of them particularly characteristic for the Mapuche subpopulation, namely B*39:09g, B*35:09, DRB1*04:07g, and DRB1*16:02g. Both population subsamples carried haplotypes of both Native American and European origin at high frequencies, reflecting Chile's complex history of admixture and immigration. Matching probability analysis revealed limited benefits for Chilean patients (both non-Indigenous and Mapuche) from donor registries of non-Chilean donors, thus indicating a need for ongoing significant donor recruitment efforts in Chile.

Ultrasound Assessment of Spastic Muscles in Ambulatory Chronic Stroke Survivors Reveals Function-Dependent Changes.

OBJECTIVE: To correlate ultrasound characteristics of spastic muscles with clinical and functional measurements in chronic stroke survivors. METHODS: Ultrasound assessment and clinical and functional assessments were performed in 28 ambulatory stroke survivors (12 females, mean age 57.8 ± 11.8 years, 76 ± 45 months after stroke). RESULTS: Muscle thickness in the affected side was decreased compared with the contralateral side (p < 0.001). The decrease was more evident in the upper limb muscles. On the affected side, the modified Heckmatt scale score was lowest (closer to normal) in the rectus femoris (RF) muscle compared with other muscles (biceps brachii (BB), flexor carpi ulnaris (FCU) and medial gastrocnemius (MG)). Muscle thickness and echogenicity of spastic muscles did not correlate with spasticity, as measured with the modified Ashworth scale (MAS), Fugl-Meyer motor assessment scores, age, or time since stroke. There was a significant negative correlation between grip strength and percentage decrease in muscle thickness for the spastic FCU muscle (r = -0.49, p = 0.008). RF muscle thickness correlated with ambulatory function (Timed Up and Go test (r = 0.44, p = 0.021) and 6-metre walk test (r = 0.41, p = 0.032)). There was no significant correlation between echogenicity and functional assessments Conclusion: Ambulatory chronic stroke survivors had function-dependent changes in muscle thickness on the affected side. Muscle thickness and echogenicity of spastic muscles did not correlate with spasticity, Fugl-Meyer motor assessment scores, age, or time since stroke.

Development of a Health Disparities Index: Proof of Concept with Chest Radiography in Asthma.

OBJECTIVES: To develop a tool for quantifying health disparity (Health Disparity Index[HDI]) and explore hospital variation measured by this index using chest radiography (CXR) in asthma as the proof of concept. STUDY DESIGN: This was a retrospective cohort study using the Pediatric Health Information System database including children with asthma between 5 and 18 years old. Inpatient and emergency department (ED) encounters from January 1, 2017, to December 31, 2018, with low or moderate severity were included. Exclusions included hospitals with <10 cases in any racial/ethnic group. The HDI measured variation in CXR use among children with asthma based on race/ethnicity. The HDI was calculated as the absolute difference between maximum and minimum percentages of CXR use (range = 0-100) when there was statistical evidence that the percentages were different. RESULTS: Data from 36 hospitals included 16 744 inpatient and 75 805 ED encounters. Overall, 19.7% of encounters had a CXR (34.3% for inpatient; 16.5% for ED). In inpatient encounters, 47.2% (17/36) of hospitals had a significant difference in imaging across racial/ethnic groups. Of these, the median hospital-level HDI was 19.4% (IQR 13.5-20.1). In ED encounters, 78.8% (28/36) of hospitals had a statistically significant difference in imaging across racial/ethnic groups, with a median hospital-level HDI of 10.2% (IQR 8.3-14.1). There was no significant association between the inpatient HDI and ED HDI (P = .46). CONCLUSIONS: The HDI provides a practical measure of disparity. To improve equity in healthcare, metrics are needed that are intuitive, accurate, usable, and actionable. Next steps include application of this index to other conditions.

Prevalence and Transmission of Severe Acute Respiratory Syndrome Coronavirus Type 2 in Childcare Facilities: A Longitudinal Study.

OBJECTIVE: To evaluate the role of childcare facilities in the transmission of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in a longitudinal study to gain further knowledge of SARS-CoV-2 prevalence, transmission, and spread among preschool children, their parents, and their caregivers. STUDY DESIGN: Children aged 1-6 years, their parents, and their caregivers in 14 childcare facilities in Dresden, Saxony/Germany were invited to participate in the KiTaCoviDD19-study between July 2020 and January 2021. Seroprevalence of SARS-CoV-2 antibodies was assessed up to 4 times during the study period in all participating adults, and demographic characteristics, as well as epidemiologic information on personal SARS-CoV-2 history were obtained. Samples for stool virus shedding of SARS-CoV-2 were analyzed by polymerase chain reaction every 2-4 weeks in all participating children. RESULTS: In total, 318 children, 299 parents and 233 childcare workers were enrolled. By January 2021, 11% of the participating adults were found to be seropositive, whereas the percentage of children shedding SARS-CoV-2 was 6.8%. Overall, we detected 17 children with SARS-CoV-2 virus shedding in 8 different childcare facilities. In 4 facilities, there were a maximum of 3 connected cases in children. Approximately 50% of SARS-CoV-2 infections in the children could not be connected to a secondary case in our study population. CONCLUSIONS: This study does not provide evidence of relevant asymptomatic ("silent") spread of SARS-CoV-2 in childcare facilities in both low- and high-prevalence settings. Our findings add to the evidence that childcare and educational settings do not have a crucial role in driving the SARS-CoV-2 pandemic.

Risk Factors for Pediatric Asthma Readmissions: A Systematic Review.

OBJECTIVE: To systematically review the literature on pediatric asthma readmission risk factors. STUDY DESIGN: We searched PubMed/MEDLINE, CINAHL, Scopus, PsycINFO, and Cochrane Central Register of Controlled Trials for published articles (through November 2019) on pediatric asthma readmission risk factors. Two authors independently screened titles and abstracts and consensus was reached on disagreements. Full-text articles were reviewed and inclusion criteria applied. For articles meeting inclusion criteria, authors abstracted data on study design, patient characteristics, and outcomes, and 4 authors assessed bias risk. RESULTS: Of 5749 abstracts, 74 met inclusion criteria. Study designs, patient populations, and outcome measures were highly heterogeneous. Risk factors consistently associated with early readmissions (≤30 days) included prolonged length of stay (OR range, 1.1-1.6) and chronic comorbidities (1.7-3.2). Risk factors associated with late readmissions (>30 days) included female sex (1.1-1.6), chronic comorbidities (1.5-2), summer discharge (1.5-1.8), and prolonged length of stay (1.04-1.7). Across both readmission intervals, prior asthma admission was the most consistent readmission predictor (1.3-5.4). CONCLUSIONS: Pediatric asthma readmission risk factors depend on the readmission interval chosen. Prior hospitalization, length of stay, sex, and chronic comorbidities were consistently associated with both early and late readmissions. TRIAL REGISTRATION: CRD42018107601.

Two new species of Tingidae (Hemiptera: Heteroptera) from Panama.

Two new species of Tingidae are described from Panama: Acanthotingis deltoides sp. nov. and Stephanitis joceliae sp. nov. Descriptions and diagnosis for both Acanthotingis Monte and Stephanitis Stål are provided, and a key is given for the separation of the two known species of Acanthotingis. This is the first record of both genera from Panama. A checklist of all Neotropical species of both genera is presented.

Critical properties of the susceptible-exposed-infected model with correlated temporal disorder.

In this paper we study the critical properties of the nonequilibrium phase transition of the susceptible-exposed-infected (SEI) model under the effects of long-range correlated time-varying environmental noise on the Bethe lattice. We show that temporal noise is perturbatively relevant changing the universality class from the (mean-field) dynamical percolation to the exotic infinite-noise universality class of the contact process model. Our analytical results are based on a mapping to the one-dimensional fractional Brownian motion with an absorbing wall and is confirmed by Monte Carlo simulations. Unlike the contact process, our theory also predicts that it is quite difficult to observe the associated active temporal Griffiths phase in the long-time limit. Finally, we also show an equivalence between the infinite-noise and the compact directed percolation universality classes by relating the SEI model in the presence of temporal disorder to the Domany-Kinzel cellular automaton in the limit of compact clusters.

Acculturation and Campus Carry: Examining the Effect of Mexico Versus United States Cultural Orientations on College Students' Support for Campus Carry.

Several U.S. states have authorized carrying concealed firearms on campuses. These measures are controversial, with support falling along ideological lines. This study examines whether cultural proximity to the U.S., relative to Mexico, influences support for campus carry. Using a random sample of 1,447 college students from two Texas public universities, structural equation modeling results revealed that individuals more oriented toward U.S. culture were more likely to support campus carry than individuals oriented more toward Mexican culture. Besides this direct effect, acculturation also indirectly influenced support for campus carry through public attitudes toward the police. Specifically, individuals more oriented toward the U.S. held more favorable views of the police, which in turn predicted greater support for campus carry. Collectively, these findings suggest that cultural values influence support for public policies such as campus carry.

Immunogenetics in stem cell donor registry work: The DKMS example (Part 1).

Currently, stem cell donor registries include more than 35 million potential donors worldwide to provide HLA-matched stem cell products for patients in need of an unrelated donor transplant. DKMS is a leading stem cell donor registry with more than 9 million donors from Germany, Poland, the United States, the United Kingdom, India and Chile. DKMS donors have donated hematopoietic stem cells more than 80,000 times. Many aspects of donor registry work are closely related to topics from immunogenetics or population genetics. In this two-part review article, we describe, analyse and discuss these areas of donor registry work by using the example of DKMS. Part 1 of the review gives a general overview on DKMS and includes typical donor registry activities with special focus on the HLA system: high-throughput HLA typing of potential stem cell donors, HLA haplotype frequencies and resulting matching probabilities, and donor file optimization with regard to HLA diversity.

Class and Kinetics of Weakly Reactive Pretransplant Donor-specific HLA Antibodies Predict Rejection in Kidney Transplant Recipients.

BACKGROUND: The clinical impact of weakly reactive pretransplant donor-specific antibody (DSA) in kidney transplantation is controversial. While some evidence suggests that weakly reactive DSA can lead to rejection, it is unclear which patients are at risk for rejection and whether posttransplant changes in weakly reactive DSA are clinically meaningful. METHODS: We retrospectively studied 80 kidney transplant recipients with weakly reactive pretransplant DSA between 2007 and 2014. We performed a multivariate Cox regression analysis to identify immunologic factors most associated with risk of biopsy-proven rejection. RESULTS: Biopsy-proven rejection occurred in 13 of 80 (16%) patients. The presence of both class I and II DSA before transplant (hazards ratio 17.4, P < 0.01) and any posttransplant increase in DSA reactivity above a mean fluorescence intensity of 3000 (hazards ratio 7.8, P < 0.01) were each significantly associated with an increased risk of rejection, which primarily occurred within the first 18 months. CONCLUSIONS: Pretransplant DSA class and DSA kinetics after transplantation are useful prognostic indicators in patients with weak DSA reactivity. These results identify a small, high-risk patient group that warrants aggressive posttransplant DSA monitoring and may benefit from alternative donor selection.

High-resolution characterization of 12 classical and non-classical HLA loci in Southern Brazilians.

The human leukocyte antigen (HLA) are the most polymorphic genes in the human genome. Because of their importance for antigen recognition, HLA molecules play a central role in host defense and graft rejection upon transplantation. The aim of this study was to characterize allelic diversity of the classical HLA genes HLA-A, -B, -C, -DRA, -DRB1, -DQA1, -DQB1, -DPA1, -DPB1, and the non-classical class I genes HLA-E, -F and -G at high-resolution for a population of predominantly European ancestry from Curitiba, Brazil. Genotyping of 108 individuals was performed by next-generation sequencing on the MiSeq platform and also by Sanger sequencing. The genotype distributions of all loci were in accordance with Hardy-Weinberg equilibrium (P > 0.05) and a total of 202 HLA variants at second field resolution were observed for the 12 loci. The strongest linkage disequilibrium (r2 = 1.0, P < 10-5 ) was observed for the following pairs of alleles: HLA-B*42:01:01 ~ HLA-DRB1*03:02:01; HLA-B*14:02:01 ~ HLA-C*08:02:01; B*42:01:01 ~ HLA-C*17:01:01; HLA-DRB1*03:01:01 ~ HLA-DQB1*02:01:01 ~ DRB1*03:01:01 ~ HLA-DQB1*02:01:01; DRB1*13:01:01~ HLA-DQB1*06:03:01 and HLA-DRB1*09:01:02 ~ HLA-DQA1*03:02. This is the first study to characterize all 12 HLA genes at high resolution in a single population. On the basis of the allelic frequencies of worldwide populations and principal component analysis, we confirmed the similarity of the study population to European and other Euro-descendant populations.

Acculturation and Capital Punishment: The Effect of Mexico Versus United States Cultural Orientations on Public Support for the Death Penalty.

Few studies have explored how the intersection of vastly different cultures, like those of the United States and Mexico, influences death penalty support. The present study uses the Acculturation Rating Scale for Mexican Americans-II to examine whether individuals who are more closely aligned with U.S. culture are more likely to support the death penalty than individuals more closely aligned with Mexican culture. Findings support this conclusion. Findings also reveal that the significance of predictors for death penalty support varies between Mexican- and U.S.-oriented subsamples. Thus, this study reaffirms the importance for researchers to consider cultural context when examining public attitudes toward the death penalty, especially when using samples from a single, multicultural country such as the United States.

Toll-Like Receptor-4 Disruption Suppresses Adipose Tissue Remodeling and Increases Survival in Cancer Cachexia Syndrome.

Cancer-induced cachexia, characterized by systemic inflammation, body weight loss, adipose tissue (AT) remodeling and muscle wasting, is a malignant metabolic syndrome with undefined etiology. Here, we show that both genetic ablation and pharmacological inhibition of TLR4 were able to attenuate the main clinical markers of cachexia in mice bearing Lewis lung carcinoma (LLC). AT remodelling was not found in LLC tumor-bearing (TB) TLR4-/- mice due to reduced macrophage infiltration and adipocyte atrophy. TLR4-/- mice were also resistant to cold-induced browning of subcutaneous AT (scAT). Importantly, pharmacological inhibition of TLR4 (Atorvastatin) reproduced the main protective effect against AT remodeling found in TLR4-/- TB mice. Moreover, the treatment was effective in prolonging survival and attenuating tumor mass growth when compared to non-treated-TB animals. Furthermore, tumor-induced elevation of circulating pro-inflammatory cytokines was similarly abolished in both genetic ablation and pharmacological inhibition of TLR4. These data suggest that TLR4 is a critical mediator and a promising target for novel anti-cachexia therapies.

A new species of Paraceratotingis Henry, Montemayor & Knudson from Guyana (Hemiptera, Heteroptera, Tingidae).

Paraceratotingishenryi sp. n., is described from Guyana. Color photographs and a diagnostic key are provided to aid in distinguishing the species of Paraceratotingis Henry, Montemayor, and Knudson. Diagnoses are also provided.

Facial-Aging Mobile Apps for Smoking Prevention in Secondary Schools in Brazil: Appearance-Focused Interventional Study.

BACKGROUND: Most smokers start smoking during their early adolescence, often with the idea that smoking is glamorous. Interventions that harness the broad availability of mobile phones as well as adolescents' interest in their appearance may be a novel way to improve school-based prevention. A recent study conducted in Germany showed promising results. However, the transfer to other cultural contexts, effects on different genders, and implementability remains unknown. OBJECTIVE: In this observational study, we aimed to test the perception and implementability of facial-aging apps to prevent smoking in secondary schools in Brazil in accordance with the theory of planned behavior and with respect to different genders. METHODS: We used a free facial-aging mobile phone app ("Smokerface") in three Brazilian secondary schools via a novel method called mirroring. The students' altered three-dimensional selfies on mobile phones or tablets and images were "mirrored" via a projector in front of their whole grade. Using an anonymous questionnaire, we then measured on a 5-point Likert scale the perceptions of the intervention among 306 Brazilian secondary school students of both genders in the seventh grade (average age 12.97 years). A second questionnaire captured perceptions of medical students who conducted the intervention and its conduction per protocol. RESULTS: The majority of students perceived the intervention as fun (304/306, 99.3%), claimed the intervention motivated them not to smoke (289/306, 94.4%), and stated that they learned new benefits of not smoking (300/306, 98.0%). Only a minority of students disagreed or fully disagreed that they learned new benefits of nonsmoking (4/306, 1.3%) or that they themselves were motivated not to smoke (5/306, 1.6%). All of the protocol was delivered by volunteer medical students. CONCLUSIONS: Our data indicate the potential for facial-aging interventions to reduce smoking prevalence in Brazilian secondary schools in accordance with the theory of planned behavior. Volunteer medical students enjoyed the intervention and are capable of complete implementation per protocol.

A Skin Cancer Prevention Facial-Aging Mobile App for Secondary Schools in Brazil: Appearance-Focused Interventional Study.

BACKGROUND: The incidence of melanoma is increasing faster than any other major cancer both in Brazil and worldwide. Southeast Brazil has especially high incidences of melanoma, and early detection is low. Exposure to ultraviolet (UV) radiation is a primary risk factor for developing melanoma. Increasing attractiveness is a major motivation among adolescents for tanning. A medical student-delivered intervention that takes advantage of the broad availability of mobile phones and adolescents' interest in their appearance indicated effectiveness in a recent study from Germany. However, the effect in a high-UV index country with a high melanoma prevalence and the capability of medical students to implement such an intervention remain unknown. OBJECTIVE: In this pilot study, our objective was to investigate the preliminary success and implementability of a photoaging intervention to prevent skin cancer in Brazilian adolescents. METHODS: We implemented a free photoaging mobile phone app (Sunface) in 15 secondary school classes in southeast Brazil. Medical students "mirrored" the pupils' altered 3-dimensional (3D) selfies reacting to touch on tablets via a projector in front of their whole grade accompanied by a brief discussion of means of UV protection. An anonymous questionnaire capturing sociodemographic data and risk factors for melanoma measured the perceptions of the intervention on 5-point Likert scales among 356 pupils of both sexes (13-19 years old; median age 16 years) in grades 8 to 12 of 2 secondary schools in Brazil. RESULTS: We measured more than 90% agreement in both items that measured motivation to reduce UV exposure and only 5.6% disagreement: 322 (90.5%) agreed or strongly agreed that their 3D selfie motivated them to avoid using a tanning bed, and 321 (90.2%) that it motivated them to improve their sun protection; 20 pupils (5.6%) disagreed with both items. The perceived effect on motivation was higher in female pupils in both tanning bed avoidance (n=198, 92.6% agreement in females vs n=123, 87.2% agreement in males) and increased use of sun protection (n=197, 92.1% agreement in females vs n=123, 87.2% agreement in males) and independent of age or skin type. All medical students involved filled in a process evaluation revealing that they all perceived the intervention as effective and unproblematic, and that all pupils tried the app in their presence. CONCLUSIONS: The photoaging intervention was effective in changing behavioral predictors for UV protection in Brazilian adolescents. The predictors measured indicated an even higher prospective effectiveness in southeast Brazil than in Germany (>90% agreement in Brazil vs >60% agreement in Germany to both items that measured motivation to reduce UV exposure) in accordance with the theory of planned behavior. Medical students are capable of complete implementation. A randomized controlled trial measuring prospective effects in Brazil is planned as a result of this study.

Frequencies of gene variant CCR5-Δ32 in 87 countries based on next-generation sequencing of 1.3 million individuals sampled from 3 national DKMS donor centers.

Homozygous carriers of CCR5-Δ32, a gene variant of CC-type chemokine receptor 5 (CCR5), are highly resistant to infections with human immunodeficiency virus type 1 (HIV-1) and therefore preferred stem cell donors for HIV-infected patients. We analyzed CCR5 typing data of 1,333,035 potential hematopoietic stem cell donors enlisted with three national DKMS donor centers. Allele and genotype frequencies were determined for 87 countries of origin as self-assessed by the donors. CCR5-Δ32 allele frequencies ranged from 16.4% in the Norwegian sample to 0 in donors from Ethiopia. The highest CCR5-Δ32/Δ32 genotype frequency was found in the sample from the Faroe Islands (2.3%), whereas in 27 samples, predominantly of donors from Africa, Asia and South America, none of the individuals carried this genotype. The characteristic CCR5-Δ32 allele frequency decline from Northern to Southeastern Eurasia supports findings of earlier studies. With available HLA haplotype frequency information for the patient's ethnicity, our data allows upfront estimation of the probability that an HLA-matched donor with CCR5-Δ32/Δ32 genotype can be found for a patient in need of hematopoietic stem cell transplantation.

Review of the Genus Ambotingis Drake and Ruhoff (Hemiptera: Heteroptera: Tingidae).

Dictyla ainsliei (Drake and Poor) is transferred to the genus Ambotingis Drake and Ruhoff, redescribed, and reported from Costa Rica for the first time. Ambotingis senta (Drake and Hambleton) is also diagnosed, and a key for the separation of the two species is provided.