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The cytokine Interferon-γ (IFN-γ) exerts powerful immunoregulatory effects on the adaptive immune system and also enhances functions of the neutrophil (PMN). The clinical use of IFN-γ has been driven by the finding that its administration to patients with chronic granulomatous disease (CGD) results in decreased incidence and severity of infections. However, IFN-γ has no effect on the characteristic defect of CGD, the inability to convert oxygen to microbicidal metabolites including superoxide anion (O2-) during the phagocytosis associated oxidative burst. We administered varying doses of IFN-γ to adult volunteers and studied the effects on plasma drug levels and response molecules and PMNs isolated from blood drawn at intervals over a 96- hour period. Plasma concentrations of IFN-γ, IP-10 and neopterin, and stimulated release of O2-from PMNs exhibited dose- and time-dependent increases after IFN-γ administration. Gene expression in PMNs was altered for 2775 genes; changes occurred rapidly after administration and returned to baseline in 24–36 hours. Several genes involved with neutrophil host defense were upregulated including those for components of the O2-generating NADPH oxidase; innate-immune and Fc receptors; proteins involved in MHCI and II; a regulator of circulating PMN number; guanylate binding proteins; and a key enzyme in synthesis of an essential NOS cofactor. Coordinate changes were detected in protein levels of representative products from several of these genes. Lysates from isolated neutrophils also demonstrated a spike in NO following IFN-γ administration. IFN-γ appears to increase non-oxygen dependent microbicidal functions of PMNs which could provide strategies to compensate for deficiencies, explain its clinical benefit for CGD patients and expand therapeutic applications of IFN-γ to other disorders.Trial registration:Protocol registered in ClinicalTrials.gov,NCT02609932, Effect of IFN-γ on Innate Immune Cells.

Background The use of motor tricycles in transporting municipal solid waste (MSW) within urban and peri-urban towns in Ghana is on the increase. This activity often leads to the introduction of pathogen-containing bioaerosols into the environment, as well as to the tricycle operators. We sought to investigate the prevalence and associated risk factors of respiratory pathogens among solid waste tricycle operators. Methods A cross-sectional study was conducted among 155 solid waste transporters who use motor tricycles using semi-structured interviews. Nasopharyngeal swabs were obtained from participants and screened for respiratory pathogens using Polymerase Chain Reaction (PCR). Results Pathogens detected in participants were SARS-CoV-2 (n = 10, 6.5%) and Streptococcus pneumoniae (n = 10, 6.5%), constituting an overall prevalence of 12.9% and co-infection rate of 1.3%. The most common self-reported symptoms were cough (n = 67, 43.2%), sore throat (n = 44, 28.4%) and difficulty in breathing (n = 22, 14.2%). Adherence to the use of gloves (n = 117, 75.5%) and nose mask (n = 110, 71.0%) was high. There was a significant association between the detection of respiratory pathogens and the use of gloves, use of more than one PPE and exposure to other pollutants (p < 0.05). Individuals who were exposed to “other pollutants” significantly had lower odds of becoming infected with respiratory pathogens (Adj. OR (95% CI): 0.119(0.015,0.938). Conclusion Although prevalence of respiratory pathogens is generally low, strict adherence to PPE use could further reduce its rates to even lower levels. Governmental health institutions and informal solid waste transporters should address challenges related to exposure to pollutants, use of gloves, and multiple PPE.

Background The declaration of COVID-19 as a pandemic on March 11 2020, by the World Health Organisation prompted the need for a sustained and a rapid international response. In a swift response, the Government of Ghana, in partnership with Zipline company, launched the use of Unmanned Automated Vehicles (UAV) to transport suspected samples from selected districts to two foremost testing centres in the country. Here, we present the experiences of employing this technology and its impact on the transport time to the second largest testing centre, the Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR) in Kumasi, Ghana. Methods Swab samples collected from suspected COVID-19 patients were transported to the Zipline office by health workers. Information on the samples were sent to laboratory personnel located at KCCR through a WhatsApp platform to get them ready to receive the suspected COVID-19 samples while Zipline repackaged samples and transported them via drone. Time of take-off was reported as well as time of drop-off. Results A total of 2537 COVID-19 suspected samples were received via drone transport from 10 districts between April 2020 to June 2021 in 440 deliveries. Ejura-Sekyedumase District Health Directorate delivered the highest number of samples (765; 30%). The farthest district to use the drone was Pru East, located 270 km away from KCCR in Kumasi and 173 km to the Zipline office in Mampong. Here, significantly, it took on the average 39 minutes for drones to deliver samples compared to 117 minutes spent in transporting samples by road (p Conclusion The use of drones for sample transport during the COVID-19 pandemic significantly reduced the travel time taken for samples to be transported by road to the testing site. This has enhanced innovative measures to fight the pandemic using technology.

Objective The risk of retinal detachment (RD) following exposure to fluoroquinolone (FQ) has been assessed in multiple studies, however, results have been mixed. This study was designed to estimate the risk of RD following exposure to FQ, other common antibiotics, and febrile illness not treated with antibiotics (FINTA) using a self-controlled case series (SCCS) study design to reduce risk of confounding from unreported patient characteristics. Design Retrospective database analysis–SCCS. Setting Primary and Secondary Care. Study population 40,981 patients across 3 US claims databases (IBM® MarketScan® commercial and Medicare databases, Optum Clinformatics). Outcome RD. Methods Exposures included FQ as a class of drugs, amoxicillin, azithromycin, trimethoprim with and without sulfamethoxazole, and FINTA. For the primary analysis, all drug formulations were included. For the post hoc sensitivity analyses, only oral tablets were included. Risk windows were defined as exposure period (or FINTA duration) plus 30 days. Patients of all ages with RD and exposures in 3 US claims databases between 2012 to 2017 were included. Diagnostics included p value calibration and pre-exposure outcome analyses. Incidence rate ratios (IRR) and 95% confidence interval (CI) comparing risk window time with other time were calculated. Results Our primary analysis showed an increased risk for RD in the 30 days prior to exposure to FQ or trimethoprim without sulfamethoxazole. This risk decreased but remained elevated for 30 days following first exposure. Our post-hoc analysis, which excluded ophthalmic drops, showed no increased risk for RD at any time, with FQ and other antibiotics. Conclusion Our results did not suggest an association between FQ and RD. Oral FQ was not associated with an increased risk for RD during the pre- or post-exposure period. Trial registration ClinicalTrials.gov identifier: NCT03479736-March 21, 2018.

Five-factor model personality traits (neuroticism, extraversion, openness, agreeableness, conscientiousness) are thought to be relatively impervious to environmental demands in adulthood. The coronavirus pandemic is an unprecedented opportunity to examine whether personality changed during a stressful global event. Surprisingly, two previous studies found that neuroticism decreased early in the pandemic, whereas there was less evidence for change in the other four traits during this period. The present research used longitudinal assessments of personality from the Understanding America Study (N = 7,109; 18,623 assessments) to examine personality changes relatively earlier (2020) and later (2021–2022) in the pandemic compared to pre-pandemic levels. Replicating the two previous studies, neuroticism declined very slightly in 2020 compared to pre-pandemic levels; there were no changes in the other four traits. When personality was measured in 2021–2022, however, there was no significant change in neuroticism compared to pre-pandemic levels, but there were significant small declines in extraversion, openness, agreeableness, and conscientiousness. The changes were about one-tenth of a standard deviation, which is equivalent to about one decade of normative personality change. These changes were moderated by age and Hispanic/Latino ethnicity, but not race or education. Strikingly, younger adults showed disrupted maturity in that they increased in neuroticism and declined in agreeableness and conscientiousness. Current evidence suggests the slight decrease in neuroticism early in the pandemic was short-lived and detrimental changes in the other traits emerged over time. If these changes are enduring, this evidence suggests population-wide stressful events can slightly bend the trajectory of personality, especially in younger adults.

Leptospirosis is a zoonosis caused by the pathogenic bacterium Leptospira. The Microscopic Agglutination Test (MAT) is widely used as the gold standard for diagnosis of leptospirosis. In this method, diluted patient serum is mixed with serotype-determined Leptospiras, and the presence or absence of aggregation is determined under a dark-field microscope to calculate the antibody titer. Problems of the current MAT method are 1) a requirement of examining many specimens per sample, and 2) a need of distinguishing contaminants from true aggregates to accurately identify positivity. Therefore, increasing efficiency and accuracy are the key to refine MAT. It is possible to achieve efficiency and standardize accuracy at the same time by automating the decision making process. In this study, we built an automatic identification algorithm of MAT using a machine learning method to determine aggregation within microscopic images. The machine learned the features from 316 positive and 230 negative MAT images created with sera of Leptospira- infected (positive) and non-infected (negative) hamsters, respectively. In addition to the acquired original images, wavelet-transformed images were also considered as features. We utilized a support vector machine (SVM) as a proposed decision method. We validated the trained SVMs with 210 positive and 154 negative images. When the features were obtained from original or wavelet-transformed images, all negative images were misjudged as positive, and the classification performance was very low with sensitivity of 1 and specificity of 0. In contrast, when the histograms of wavelet coefficients were used as features, the performance was greatly improved with sensitivity of 0.99 and specificity of 0.99. We confirmed that the current algorithm judges the positive or negative of agglutinations in MAT images and gives the further possibility of automatizing MAT procedure.

The present work addresses the thermal remodelling of flexible plant viruses with a helical structure and virus-like particles (VLPs). Here, for the first time, the possibility of filamentous Alternanthera mosaic virus (AltMV) virions’ thermal transition into structurally modified spherical particles (SP) has been demonstrated. The work has established differences in formation conditions of SP from virions (SPV) and VLPs (SPVLP) that are in accordance with structural data (on AltMV virions and VLPs). SP originate from AltMV virions through an intermediate stage. However, the same intermediate stage was not detected during AltMV VLPs’ structural remodelling. According to the biochemical analysis, AltMV SPV consist of protein and do not include RNA. The structural characterisation of AltMV SPV/VLP by circular dichroism, intrinsic fluorescence spectroscopy and thioflavin T fluorescence assay has been performed. AltMV SPV/VLP adsorption properties and the availability of chemically reactive surface amino acids have been analysed. The revealed characteristics of AltMV SPV/VLP indicate that they could be applied as protein platforms for target molecules presentation and for the design of functionally active complexes.

Objective To describe the laboratory parameters and biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases. Methods A search with standardized descriptors and synonyms was performed on November 28th, 2020 of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, LILACS, and IBECS to identify studies of interest. Grey literature searches and snowballing techniques were additionally utilized to identify yet-unpublished works and related citations. Two review authors independently screened the retrieved titles and abstracts, selected eligible studies for inclusion, extracted data from the included studies, and then assessed the risk of bias using the Newcastle-Ottawa Scale. Eligible studies were those including laboratory parameters—including serum interleukin-6 levels—from mild, moderate, or severe COVID-19 cases. Laboratory parameters, such as interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer, were extracted from the studies. Meta-analyses were conducted using the laboratory data to estimate mean differences with associated 95% confidence intervals. Data synthesis The database search yielded 9,620 records; 40 studies (containing a total of 9,542 patients) were included in the final analysis. Twenty-one studies (n = 4,313) assessed laboratory data related to severe COVID-19 cases, eighteen studies (n = 4,681) assessed predictors for fatal COVID-19 cases and one study (n = 548) assessed laboratory biomarkers related to severe and fatal COVID-19 cases. Lymphopenia, thrombocytopenia, and elevated levels of interleukin-6, ferritin, D-dimer, aspartate aminotransferase, C-Reactive-Protein, procalcitonin, creatinine, neutrophils and leucocytes were associated with severe and fatal COVID-19 cases. Conclusions This review points to interleukin-6, ferritin, leukocytes, neutrophils, lymphocytes, platelets, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer as important biomarkers of cytokine storm syndrome. Elevated levels of interleukin-6 and hyperferritinemia should be considered as red flags of systemic inflammation and poor prognosis in COVID-19.

Development of genome editing methods created new opportunities for the development of etiology-based therapies of hereditary diseases. Here, we demonstrate that CRISPR/Cas9 can correct p.F508del mutation in theCFTRgene in the CFTE29o- cells and induced pluripotent stem cells (iPSCs) derived from patients with cystic fibrosis (CF). We used several combinations of Cas9, sgRNA and ssODN and measured editing efficiency in the endogenousCFTRgene and in the co-transfected plasmid containing theCFTRlocus with the p.F508del mutation. The non-homologous end joining (NHEJ) frequency in theCFTRgene in the CFTE29o- cells varied from 1.25% to 2.54% of alleles. The best homology-directed repair (HDR) frequency in the endogenousCFTRlocus was 1.42% of alleles. In iPSCs, the NHEJ frequency in theCFTRgene varied from 5.5% to 12.13% of alleles. The best HDR efficacy was 2.38% of alleles. Our results show that p.F508del mutation editing using CRISPR/Cas9 in CF patient-derived iPSCs is a relatively rare event and subsequent cell selection and cultivation should be carried out.

BackgroundStudies from high-income countries reported reduced life expectancy in children with cerebral palsy (CP), while no population-based study has evaluated mortality of children with CP in sub-Saharan Africa. This study aimed to estimate the mortality rate (MR) of children with CP in a rural region of Uganda and identify risk factors and causes of death (CODs).Methods and findingsThis population-based, longitudinal cohort study was based on data from Iganga-Mayuge Health and Demographic Surveillance System in eastern Uganda. We identified 97 children (aged 2-17 years) with CP in 2015, whom we followed to 2019. They were compared with an age-matched cohort from the general population (n = 41 319). MRs, MR ratios (MRRs), hazard ratios (HRs), and immediate CODs were determined. MR was 3952 per 100 000 person years (95% CI 2212-6519) in children with CP and 137 per 100 000 person years (95% CI 117-159) in the general population. Standardized MRR was 25·3 in the CP cohort, compared with the general population. In children with CP, risk of death was higher in those with severe gross motor impairments than in those with milder impairments (HR 6·8; p = 0·007) and in those with severe malnutrition than in those less malnourished (HR = 3·7; p = 0·052). MR was higher in females in the CP cohort, with a higher MRR in females (53·0; 95% CI 26·4-106·3) than in males (16·3; 95% CI 7·2-37·2). Age had no significant effect on MR in the CP cohort, but MRR was higher at 10-18 years (39·6; 95% CI 14·2-110·0) than at 2-6 years (21·0; 95% CI 10·2-43·2). Anaemia, malaria, and other infections were the most common CODs in the CP cohort.ConclusionsRisk of premature death was excessively high in children with CP in rural sub-Saharan Africa, especially in those with severe motor impairments or malnutrition. While global childhood mortality has significantly decreased during recent decades, this observed excessive mortality is a hidden humanitarian crisis that needs to be addressed.

A progressive, treadmill-based VO2max is the gold standard of cardiorespiratory fitness determination but is rarely used in pediatric clinics due to time requirements and cost. Simpler and shorter fitness tests such as the Squat Test or Step Test may be feasible and clinically useful alternatives. However, performance comparisons of these tests to treadmill VO2max tests are lacking. The primary aim of this cross-sectional study was to assess the correlation between Squat and Step Test scores and VO2max in a pediatric population. As secondary outcomes, we calculated correlations between Rated Perceived Exertion Scale (RPE) scores, NIH PROMIS Physical Activity scores, and BMI z-score with VO2max, and we also evaluated the ability of each fitness test to discriminate low and high-risk patients based on the FITNESSGram. Forty children aged 10-17 completed these simple cardiorespiratory fitness tests. Statistically significant correlations were observed between VO2max and the Step Test (r = -0.549) and Squat Test (r = -0.429) scores, as well as participant BMI z-score (r = -0.458). RPE and PROMIS scores were not observed to be correlated with VO2max. Area Under the Receiver Operator Curve was relatively high for BMI z-scores and the Step Test (AUC = 0.813, 0.713 respectively), and lower for the Squat Test (AUC = 0.610) in discriminating risk according to FITNESSGram Scores. In this sample, the Step Test performed best overall. These tests were safe, feasible, and may add great value in assessing cardiorespiratory fitness in a clinical setting.

Background Mental health is considered an integral part of human health. Reliable and valid measurement instruments are needed to assess various facets of mental health in the native language of the people involved. This paper reports on five studies examining evidence for the factorial validity of the Twi versions of five mental health and well-being measurement instruments: Affectometer-2 (AFM-2); Automatic Thought Questionnaire-Positive (ATQ-P); Generalized Self-Efficacy Scale (GSEs); Patient Health Questionnaire-9 (PHQ-9); and Satisfaction with Life Scale (SWLS) in a rural Ghanaian adult sample. Method Measures were translated and evaluated using a research-committee approach, pilot-tested, and administered to adults (N = 444) randomly selected from four rural poor communities in Ghana. We applied confirmatory factor analysis (CFA), bifactor CFA, exploratory structural equation modeling (ESEM), and bifactor ESEM to the AFM-2, ATQ-P, and the PHQ-9, and CFA to the GSEs and the SWLS. The omega coefficient of composite reliability was computed for each measure. Results A two-factor bifactor ESEM model displayed superior model fit for the AFM-2. The total scale and the Negative Affect subscale, but not the Positive Affect subscale, attained sufficient reliability. Two models (a four-factor 22-item bifactor ESEM model and a 5-factor 22-item ESEM model) fitted the data best for the ATQ-P. The bifactor ESEM model displayed a high reliability value for the total scale and satisfactory reliability values for three of its four subscales. For the GSEs, a one-factor CFA model (residuals of items 4 and 5 correlated) demonstrated superior model fit with a high reliability score for the total scale. A two-factor ESEM model outperformed all other models fitted for the PHQ-9, with moderate and satisfactory reliability scores for the subscales. A one-factor CFA model (residuals of item 4 and 5 correlated) demonstrated superior model fit for the SWLS, with a satisfactory reliability value for the total scale. Conclusions Findings established evidence for the factorial validity of the Twi versions of all five measures, with the global scores, but not all subscale scores, demonstrating satisfactory reliability. These validated measurement instruments can be used to assess mental health and well-being in the research and practice contexts of the current sample.

We are at the dawn of the efforts to describe and understand the origins of genetic diversity in Argentina from high-throughput data. This knowledge is a primary step in the intent of deciphering the specific genetic bases of diseases and drug response in the country. Similarly to other populations across the Americas, genetic ancestry in Argentinean populations traces back into African, European and Native American ancestors, reflecting a complex demographic history with multiple migration and admixture events in pre- and post-colonial times. However, little is known about the sub-continental origins of these three main ancestries. We present new high-throughput genotyping data for 87 admixed individuals across Argentina. This data was combined to previously published data for admixed individuals in the region and then compared to different reference panels specifically built to run population structure analyses at a sub-continental level. Concerning the European and African ancestries, we confirmed previous results about their main origins, and we provide new insights into the presence of other origins that reflect historical records. As for the Native American ancestry, leveraging genotype data for archeological samples in the region in order to gain temporal depth in our analyses, we could identify four Native American components segregating in modern Argentinean populations . Three of them are also found in modern South American populations and are specifically represented in Central Chile/Patagonia, Lowlands and Central Andes geographic areas. The fourth one may be specific to the Central Western region of Argentina. Identifying such component has not been straightforward since it is not well represented in any genomic data from the literature. Altogether, we provide useful insights into the multiple population groups from different continents that have contributed to present-days genetic diversity in Argentina. We encourage the generation of massive genotype data locally to further describe the genetic structure in Argentina., Facultad de Ciencias Naturales y Museo, Instituto Multidisciplinario de Biología Celular

This study explored topic interest, perceived learning and actual recall of exhibit content in 979 children and adolescents and 1,184 adults who visited informal science learning sites and interacted with an adult or youth educator or just the exhibit itself as part of family visits to the sites. Children in early childhood reported greater topic interest and perceived learning, but actually recalled less content, than participants in middle childhood or adolescence. Youth visitors reported greater interest after interacting with a youth educator than just the exhibit, and perceived that they learn more if they interact with an educator (youth or adult). Participants in middle childhood recall more when they encounter a youth educator. Adult visitors reported greater interest after interaction with a youth educator than with the exhibit alone or an adult educator. They also perceived that they learn more if they interact with an educator (youth or adult) than just the exhibit and perceived that they learned more if they interacted with a youth educator than an adult educator. Results highlight the benefits of educators in informal science learning sites and document the importance of attention to developmental needs.

Background 18F-fluorodeoxyglucose (FDG) PET/CT is recommended for evaluation of intermediate-risk indeterminate pulmonary nodules (IPNs). While highly sensitive, the specificity of FDG remains suboptimal for differentiating malignant from benign nodules, particularly in areas where fungal lung diseases are prevalent. Thus, a cancer-specific imaging probe is greatly needed. In this study, we tested the hypothesis that a PET radiotracer (S)-4-(3-[18F]-fluoropropyl)-L-glutamic acid (FSPG) improves the diagnostic accuracy of IPNs compared to 18F-FDG PET/CT. Methods This study was conducted at a major academic medical center and an affiliated VA medical center. Twenty-six patients with newly discovered IPNs 7-30mm diameter or newly diagnosed lung cancer completed serial PET/CT scans utilizing 18F-FDG and 18F-FSPG, without intervening treatment of the lesion. The scans were independently reviewed by two dual-trained diagnostic radiology and nuclear medicine physicians. Characteristics evaluated included quantitative SUVmax values of the pulmonary nodules and metastases. Results A total of 17 out of 26 patients had cancer and 9 had benign lesions. 18F-FSPG was negative in 6 of 9 benign lesions compared to 7 of 9 with 18F-FDG. 18F-FSPG and 18F-FDG were positive in 14 of 17 and 12 of 17 malignant lesions, respectively. 18F-FSPG detected brain and intracardiac metastases missed by 18F-FDG PET in one case, while 18F-FDG detected a metastasis to the kidney missed by 18F-FSPG. Conclusion In this pilot study, there was no significant difference in overall diagnostic accuracy between 18F-FSPG and 18F-FDG for the evaluation of IPNs and staging of lung cancer. Additional studies will be needed to determine the clinical utility of this tracer in the management of IPNs and lung cancer.

This study explored relations between COVID-19 news source, trust in COVID-19 information source, and COVID-19 health literacy in 194 STEM-oriented adolescents and young adults from the US and the UK. Analyses suggest that adolescents use both traditional news (e.g., TV or newspapers) and social media news to acquire information about COVID-19 and have average levels of COVID-19 health literacy. Hierarchical linear regression analyses suggest that the association between traditional news media and COVID-19 health literacy depends on participants’ level of trust in their government leader. For youth in both the US and the UK who used traditional media for information about COVID-19 and who have higher trust in their respective government leader (i.e., former US President Donald Trump and UK Prime Minister Boris Johnson) had lower COVID-19 health literacy. Results highlight how youth are learning about the pandemic and the importance of not only considering their information source, but also their levels of trust in their government leaders.