Resolution of Praziquantel

The drug praziquantel (PZQ) is used very widely in both animal and human medicine, where it is the mainstay of the treatment of the neglected tropical disease schistosomiasis. The drug is currently manufactured and administered as a racemate (1∶1 mixture of enantiomers) but for various reasons the large-scale production of PZQ as the single active enantiomer is very desirable. We describe here the preparation of praziquantel as a single enantiomer using classical resolution. The protocols are experimentally simple and inexpensive. One method was found and validated by an unusual research mechanism—open science—where the details of the collaboration (involving academic and industrial partners) and all research data were available on the web as they were acquired, and anyone could participate. The other route was found in parallel by a contract research organisation. Besides being possible routes by which praziquantel may be produced in large quantities for the affected communities, it is also hoped that these methods can be used for the production of smaller quantities of enantiopure PZQ for pharmacological studies

Diving into the digital landscape: assessing the quality of online information on neonatal jaundice for parents

Background: Hyperbilirubinemia is a common condition in newborns. While mild cases of jaundice are common and typically resolve spontaneously, severe hyperbilirubinemia can lead to serious neurologic complications if left untreated. With the constant adaptation of guidelines, clinical management has significantly improved, and treatment has become routine for pediatricians. However, for parents of affected children, managing the condition is not routine. In today’s digital age, parents often seek additional information by accessing a wide range of medical resources on the internet. While this can be empowering, it also presents challenges, as the quality and accuracy of online medical information can vary widely. Therefore, we analyzed the current quality of information on jaundice found on the internet by parents. Methods: A simulated internet search (using the Google search engine) was conducted from a layperson’s perspective using German (“Neugeborenes Gelbsucht”, “Baby Gelbsucht”) and English (“jaundice newborn”, “jaundice baby”) search terms. Subsequently, the quality of the search results was assessed by two independent neonatologists based on the DISCERN Plus Score, HONcode certification, and the JAMA criteria. Results: Websites targeting non-medical laypersons exhibited significant variability in quality. Notably, the content of English websites was superior to that of websites in the German language. The majority of English sites were predominantly institutional, whereas most German sites were commercially oriented. Conclusions: Although information on jaundice is readily accessible online for non-medical individuals, there were notable differences in quality based on language and significant variability in the quality of information warranting attention from healthcare professionals. Furthermore, German websites providing information on jaundice were often hosted by commercial organizations. We propose that pediatric societies engage in developing and maintaining organization-based medical information to improve online resources for parents

Open source drug discovery - A limited tutorial

Open science is a new concept for the practice of experimental laboratory-based research, such as drug discovery. The authors have recently gained experience in how to run such projects and here describe some straightforward steps others may wish to take towards more openness in their own research programmes. Existing and inexpensive online tools can solve many challenges, while some psychological barriers to the free sharing of all data and ideas are more substantia

Surveillance of acute SARS-CoV-2 infections in elementary schools and daycare facilities in Bavaria, Germany (09/2020–03/2021)

Introduction: Here we report our results of a multi-center, open cohort study ("COVID-Kids-Bavaria") investigating the distribution of acute SARS-CoV-2 infections among children and staff in 99 daycare facilities and 48 elementary schools in Bavaria, Germany. Materials and Methods: Overall, 2,568 children (1,337 school children, 1,231 preschool children) and 1,288 adults (466 teachers, 822 daycare staff) consented to participate in the study and were randomly tested in three consecutive phases (September/October 2020, November/December 2020, March 2021). In total, 7,062 throat swabs were analyzed for SARS-CoV-2 by commercial RT-PCR kits. Results: In phase I, only one daycare worker tested positive. In phase II, SARS-CoV-2 was detected in three daycare workers, two preschool children, and seven school children. In phase III, no sample tested positive. This corresponds to a positive test rate of 0.05% in phase I, 0.4% in phase II and 0% in phase III. Correlation of a positive PCR test result with the local-7-day incidence values showed a strong association of a 7-day-incidence of more than 100/100,000 as compared to <100/100,000 (OR = 10.3 [1.5-438], p < 0.005). After phase III, antibody testing was offered to 713 study participants in elementary schools. A seroprevalence rate of 7.7% (students) and 4.5% (teachers) was determined. Discussion: During the initial waves of the SARS-CoV-2 pandemic, the risk of a positive SARS-CoV-2 result correlated positively with the local 7-day incidence. Hence, the occurrence of SARS-CoV-2 infections were reflected in schools and daycare facilities. An increased risk of SARS-CoV-2 transmission in the setting of daycare and elementary schooling was unlikely

Dual-source computed tomography of the lung with spectral shaping and advanced iterative reconstruction: potential for maximum radiation dose reduction

Abstract Background Radiation dose at CT should be as low as possible without compromising diagnostic quality. Objective To assess the potential for maximum dose reduction of pediatric lung dual-source CT with spectral shaping and advanced iterative reconstruction (ADMIRE). Materials and methods We retrospectively analyzed dual-source CT acquisitions in a full-dose group (FD: 100 kV, 64 reference mAs) and in three groups with spectral shaping and differing reference mAs values (Sn: 100 kV, 96/64/32 reference mAs), each group consisting of 16 patients (age mean 11.5 years, standard deviation 4.8 years, median 12.8 years, range 1.3–18 years). Advanced iterative reconstruction of images was performed with different strengths (FD: ADMIRE Level 2; Sn: ADMIRE Levels 2, 3 and 4). We analyzed dose parameters and measured noise. Diagnostic confidence and detectability of lung lesions as well as anatomical structures were assessed using a Likert scale (from 1 [unacceptable] to 4 [fully acceptable]). Results Compared to full dose, effective dose was reduced to 16.7% in the Sn 96 group, 11.1% in Sn64, and 5.5% in Sn32 (P3 was reached in Sn64ADM4 regarding diagnostic confidence (3.2) and detectability of lung lesions (3.3). For detectability of most anatomical structures, no significant differences were found between FDAM2 and Sn64ADM4 (P≥0.05). Conclusion In pediatric lung dual-source CT, spectral shaping together with ADMIRE 4 enable radiation dose reduction to about 10% of a full-dose protocol while maintaining an acceptable diagnostic quality

The Implications of Multiple Circadian Clock Origins

Michael Rosbash considers whether the mechanisms that govern circadian rhythms in different organisms have arisen multiple times in evolution, and discusses the implications for our understanding of circadian clocks

Maternal SARS-CoV-2 infection during pregnancy: possible impact on the infant

The risk and potential consequences of mother-to-child transmission of severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) during pregnancy are still a matter of debate. We studied the impact of SARS-CoV-2 infection on 56 complete households, including 27 newborns whose mothers were pregnant when exposed to the virus. Two PCR-confirmed perinatal SARS-CoV-2 transmissions with mild symptoms in affected neonates were recorded. In addition, we observed a severe eye malformation (unilateral microphthalmia, optic nerve hypoplasia, and congenital retinopathy) associated with maternal SARS-CoV-2 infection in weeks 5 and 6 of embryonic development. This embryopathy could not be explained by other infectious agents, genetic factors, drug use, or maternal disease during pregnancy. Eight other women with a history of SARS-CoV-2 infection prior to gestational week 12, however, delivered healthy infants. Conclusion: The repeated occurrence of mother-to-child transmission in our cohort with risks that remain incompletely understood, such as long-term effects and the possibility of an embryopathy, should sensitize researchers and stimulate further studies as well as support COVID-19 vaccination recommendations for pregnant women. Trial registration number: NCT04741412. Date of registration: November 18, 202

First Universities Allied for Essential Medicines (UAEM) Neglected Diseases and Innovation Symposium

Universities Allied for Essential Medicines organized its first Neglected Diseases and Innovation Symposium to address expanding roles of public sector research institutions in innovation in research and development of biomedical technologies for treatment of diseases, particularly neglected tropical diseases. Universities and other public research institutions are increasingly integrated into the pharmaceutical innovation system. Academic entities now routinely undertake robust high-throughput screening and medicinal chemistry research programs to identify lead compounds for small molecule drugs and novel drug targets. Furthermore, product development partnerships are emerging between academic institutions, non-profit entities, and biotechnology and pharmaceutical companies to create diagnostics, therapies, and vaccines for diseases of the poor. With not for profit mission statements, open access publishing standards, open source platforms for data sharing and collaboration, and a shift in focus to more translational research, universities and other public research institutions are well-placed to accelerate development of medical technologies, particularly for neglected tropical diseases

Changes in behavior and quality of life in German young children during the COVID-19 pandemic—results from the COVID kids bavaria study

Introduction The COVID-19 pandemic with its containment measures such as closures of schools and daycare facilities led to numerous restrictions in daily life, putting developmental opportunities and health-related quality of life in children at risk. However, studies show that not every family was impacted equally by the pandemic and that this exceptional health and societal situation reinforced pre-existing health inequalities among the vulnerable. Our study aimed at analyzing changes in behavior and health-related quality of life of children attending elementary schools and daycare facilities in Bavaria, Germany in spring 2021. We also sought to identify associated factors contributing to inequalities in quality of life. Methods Data from a multi-center, open cohort study (“COVID Kids Bavaria”) conducted in 101 childcare facilities and 69 elementary schools across all electoral districts of Bavaria were analyzed. Children attending these educational settings (aged 3-10 years) were eligible for participation in a survey on changes in behavior and health-related quality of life. The KINDLR questionnaire (based on children’s self-report and parental report) was administered about one year after the onset of the pandemic (spring 2021). Descriptive and logistic regression analyses and comparisons to pre-pandemic KiGGS (German Health Interview and Examination Survey for Children and Adolescents) data were undertaken. Results Among respondents, a high percentage of parents reported changes in their children's eating and sleeping behavior, sports and outdoor activities as well as altered screen time. Health-related quality of life in KINDLR analyses compared to pre-pandemic population averages were lower in all age groups (for 3–6-year-old KINDLR-total score: COVID Kids Bavaria MD 74.78 ± 10.57 vs KiGGS data 80.0 ± 8.1; 7-10 years-old KINDLR-total score: COVID Kids Bavaria MD 73.88 ± 12.03 vs KiGGS data 79.30 ± 9.0). No significant differences were detected with regard to associated factors, namely type of institution, sex of the child, migration background, household size and parental education. Conclusion These findings suggest a relevant impact of the COVID-19 pandemic on children’s behavior and health-related quality of life one year after the onset of the pandemic. Further analyses in large-scale longitudinal studies are needed to determine the effects of specific pandemic or crisis associated factors contributing to health inequalities