Prevalence and Associated Factors of Thyroid Incidentaloma among Adult People Attending Gondar University Hospital, Northwest Ethiopia Temesgen Tadesse1

BACKGROUND: Incidentally discovered thyroid lesions have become highly common in the development and more frequent utilization of highly sensitive imaging modalities, like ultrasound. However, little is known about its prevalence and associated factors in Ethiopia. The aim of this study was to determine the prevalence of thyroid incidentalomas and associated factors through ultrasound (US) among adults attending Gondar University Hospital.METHODS: A hospital-based cross-sectional study was carried out on 290 adults aged 15 years and above. Out of the adults who visited the hospital during the study, those who neither had history of thyroid disease, thyroid surgery, nor clinically palpable thyroid nodules were involved in the investigation. The participants were examined using a high frequency linear-array transducer (7MHz). For comparing men and women, the unpaired t-test wasused. Binary logistic analysis was used to identify the associated factors, and a P-value < 0.05 was considered statistically significant.RESULT: The frequency of thyroid incidentaloma was found to be 33.4% (95% CI: 27.9, 38.9). Thyroid incidentaloma was detected in 42.4% of the females and 22.7% of the males (P<0.001). About 63% had single and 37% multiple thyroid nodules. About 25.8% had thyroid nodules greater than 1cm. In the multivariable logistic regression analysis, increasing age (AOR=5.96; 2.34, 15.15) and female sex (AOR=3.01; 1.73, 5.26) were significantly associated with thyroid incidentalomas.CONCLUSION: The frequency of thyroid incidentaloma (TI) was found to be high in this study and much higher among older women. Solitary and small sized thyroid nodules were commonly seen in the study.

WNT activates the AAK1 kinase to promote clathrin-mediated endocytosis of LRP6 and establish a negative feedback loop

beta-Catenin-dependent WNT signal transduction governs development, tissue homeostasis, and a vast array of human diseases. Signal propagation through a WNT-Frizzled/LRP receptor complex requires proteins necessary for clathrin-mediated endocytosis (CME). Paradoxically, CME also negatively regulates WNT signaling through internalization and degradation of the receptor complex. Here, using a gain-of-function screen of the human kinome, we report that the AP2 associated kinase 1 (AAK1), a known CME enhancer, inhibits WNT signaling. Reciprocally, AAK1 genetic silencing or its pharmacological inhibition using a potent and selective inhibitor activates WNT signaling. Mechanistically, we show that AAK1 promotes clearance of LRP6 from the plasma membrane to suppress the WNT pathway. Time-course experiments support a transcription-uncoupled, WNT-driven negative feedback loop; prolonged WNT treatment drives AAK1-dependent phosphorylation of AP2M1, clathrin-coated pit maturation, and endocytosis of LRP6. We propose that, following WNT receptor activation, increased AAK1 function and CME limits WNT signaling longevity2617993FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2013/50724-5; 2016/17469-0M.B.M. acknowledges support from the NIH (RO1-CA187799 and U24-DK116204-01). M.J.A. received financial support from NIH T32 Predoctoral Training Grants in Pharmacology (T32-GM007040-43 and T32-GM007040-42), an Initiative for Maximizing Student Diversity Grant (R25-GM055336-16), and the NIH National Cancer Institute (NCI) NRSA Predoctoral Fellowship to Promote Diversity in Health-Related Research (F31CA228289). M.P.W. received support from the Lymphoma Research Foundation (337444) and the NIH (T32-CA009156-35). Y.N. was supported by grants-in-aid from the Japan Society for the Promotion of Science (JSPS) (15KK0356 and 16K11493). T.T. was supported by the Howard Hughes Medical Institute Gilliam Fellowship for Advanced Study. M.V.G. was supported by Cancer Research UK (grants C7379/A15291 and C7379/A24639 to Mariann Bienz). The UNC Flow Cytometry Core Facility is supported in part by Cancer Center Core Support Grant P30 CA016086 to the UNC Lineberger Comprehensive Cancer Center, and research reported in this publication was supported by the Center for AIDS Research (award number 5P30AI050410), and the content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The Structural Genomics Consortium (SGC) is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, the Canada Foundation for Innovation, the Eshelman Institute for Innovation, Genome Canada, the Innovative Medicines Initiative (European Union [EU]/European Federation of Pharmaceutical Industries and Associations [EFPIA]) (ULTRA-DD grant no. 115766), Janssen, Merck & Company, Merck KGaA, Novartis Pharma AG, the Ontario Ministry of Economic Development and Innovation, Pfizer, the São Paulo Research Foundation (FAPESP) (2013/50724-5), Takeda, and the Wellcome Trust (106169/ZZ14/Z). R.R.R. received financial support from FAPESP (2016/17469-0). We would also like to thank Claire Strain-Damerell and Pavel Savitsky for cloning various mutants of AAK1 and BMP2K proteins that were used in the crystallization trials. Additionally, we thank Dr. Sean Conner for providing the AAK1 plasmids, Dr. Stephane Angers for kindly providing the HEK293T DVL TKO cells, and Dr. Mariann Bienz for providing comments and feedback. We would like to thank members of the Major laboratory for their feedback and expertise regarding experimental design and project directio

A Prospective Study of Causes of Illness and Death in Preterm Infants in Ethiopia: The SIP Study Protocol

Background With nearly 15 million annual preterm births globally, preterm birth is the most common cause of neonatal death. Forty to 60 % of neonatal deaths are directly or indirectly associated with preterm mortality. As countries aim to meet the Sustainable Development Goals to reduce neonatal mortality, significant reductions in preterm mortality are needed. This study aims to identify the common causes of preterm illness and their contribution to preterm mortality in low-resource settings. This article will describe the methods used to undertake the study. Methods This is a prospective, multi-centre, descriptive clinical study. Socio-demographic, obstetric, and maternal factors, and clinical and laboratory findings will be documented. The major causes of preterm mortality will be identified using clinical, laboratory, imaging, and autopsy methods and use the national Ethiopian guidelines on management of preterm infants including required investigations to reach final diagnoses. The study will document the clinical and management protocols followed in these settings. The approach consists of clinical examinations and monitoring, laboratory investigations, and determination of primary and contributory causes of mortality through both clinical means and by post-mortem examinations. An independent panel of experts will validate the primary and contributory causes of mortality. To obtain the estimated sample size of 5000 preterm births, the study will be undertaken in five hospitals in three regions of Ethiopia, which are geographically distributed across the country. All preterm infants who are either born or transferred to these hospitals will be eligible for the study. Three methods (last menstrual period, physical examination using the New Ballard Score, and ultrasound) will be used to determine gestational age. All clinical procedures will be conducted per hospital protocol and informed consent will be taken from parents or caretakers prior to their participation in the study as well as for autopsy if the infant dies. Discussion This study will determine the major causes of death and illness among hospitalized preterm infants in a low-resource setting. The result will inform policy makers and implementers of areas that can be prioritized in order to contribute to a significant reduction in neonatal mortality

Molasses grass induces direct and indirect defense responses in neighbouring maize plants

Plants have evolved intricate defence strategies against herbivore attack which can include activation of defence in response to stress-related volatile organic compounds (VOCs) emitted by neighbouring plants. VOCs released by intact molasses grass (Melinis minutiflora), have been shown to repel stemborer, Chilo partellus (Swinhoe), from maize and enhance parasitism by Cotesia sesamiae (Cameron). In this study, we tested whether the molasses grass VOCs have a role in plant-plant communication by exposing different maize cultivars to molasses grass for a 3-week induction period and then observing insect responses to the exposed plants. In bioassays, C. partellus preferred non-exposed maize landrace plants for egg deposition to those exposed to molasses grass. Conversely, C. sesamiae parasitoid wasps preferred volatiles from molasses grass exposed maize landraces compared to volatiles from unexposed control plants. Interestingly, the molasses grass induced defence responses were not observed on hybrid maize varieties tested, suggesting that the effect was not simply due to absorption and re-emission of VOCs. Chemical and electrophysiological analyses revealed strong induction of bioactive compounds such as (R)-linalool, (E)-4,8-dimethyl-1,3,7-nonatriene and (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene from maize landraces exposed to molasses grass volatiles. Our results suggest that constitutively emitted molasses grass VOCs can induce direct and indirect defence responses in neighbouring maize landraces. Plants activating defences by VOC exposure alone could realize enhanced levels of resistance and fitness compared to those that launch defence responses upon herbivore attack. Opportunities for exploiting plant-plant signalling to develop ecologically sustainable crop protection strategies against devastating insect pests such as stemborer C. partellus are discussed

Etiology of hospital mortality in children living in low- and middle-income countries:a systematic review and meta-analysis

In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, and total admissions. We excluded studies with data before 2,000 or without a full text. Two authors independently screened and extracted data. We performed methodological assessment using domains adapted from the Quality in Prognosis Studies tool. Data were pooled using random-effects models where possible. We reported prevalence as a proportion of cause of death or admission per 1,000 admissions with 95% confidence intervals (95% CI). Our search identified 29,637 texts. After duplicate removal and screening, we analyzed 253 studies representing 21.8 million pediatric hospitalizations in 59 LMICs. All-cause pediatric hospital mortality was 4.1% [95% CI 3.4%–4.7%]. The most common causes of mortality (deaths/1,000 admissions) were infectious [12 (95% CI 9–14)]; respiratory [9 (95% CI 5–13)]; and gastrointestinal [9 (95% CI 6–11)]. Common causes of admission (cases/1,000 admissions) were respiratory [255 (95% CI 231–280)]; infectious [214 (95% CI 193–234)]; and gastrointestinal [166 (95% CI 143–190)]. We observed regional variation in estimates. Pediatric hospital mortality remains high in LMICs. Global child health efforts must include measures to reduce hospital mortality including basic emergency and critical care services tailored to the local disease burden. Resources are urgently needed to promote equity in child health research, support researchers, and collect high-quality data in LMICs to further guide priority setting and resource allocation

The Burden of Type 1 and Type 2 Diabetes Among Adolescents and Young Adults in 24 Western European Countries, 1990–2019:Results From the Global Burden of Disease Study 2019

Objectives: As little is known about the burden of type 1 (T1DM) and type 2 diabetes (T2DM) in adolescents in Western Europe (WE), we aimed to explore their epidemiology among 10–24 year-olds. Methods: Estimates were retrieved from the Global Burden of Diseases Study (GBD) 2019. We reported counts, rates per 100,000 population, and percentage changes from 1990 to 2019 for prevalence, incidence and years lived with disability (YLDs) of T1DM and T2DM, and the burden of T2DM in YLDs attributable to high body mass index (HBMI), for 24 WE countries. Results: In 2019, prevalence and disability estimates were higher for T1DM than T2DM among 10–24 years old adolescents in WE. However, T2DM showed a greater increase in prevalence and disability than T1DM in the 30 years observation period in all WE countries. Prevalence increased with age, while only minor differences were observed between sexes. Conclusion: Our findings highlight the substantial burden posed by DM in WE among adolescents. Health system responses are needed for transition services, data collection systems, education, and obesity prevention.</p

The Burden of Type 1 and Type 2 Diabetes Among Adolescents and Young Adults in 24 Western European Countries, 1990–2019:Results From the Global Burden of Disease Study 2019

Objectives: As little is known about the burden of type 1 (T1DM) and type 2 diabetes (T2DM) in adolescents in Western Europe (WE), we aimed to explore their epidemiology among 10–24 year-olds. Methods: Estimates were retrieved from the Global Burden of Diseases Study (GBD) 2019. We reported counts, rates per 100,000 population, and percentage changes from 1990 to 2019 for prevalence, incidence and years lived with disability (YLDs) of T1DM and T2DM, and the burden of T2DM in YLDs attributable to high body mass index (HBMI), for 24 WE countries. Results: In 2019, prevalence and disability estimates were higher for T1DM than T2DM among 10–24 years old adolescents in WE. However, T2DM showed a greater increase in prevalence and disability than T1DM in the 30 years observation period in all WE countries. Prevalence increased with age, while only minor differences were observed between sexes. Conclusion: Our findings highlight the substantial burden posed by DM in WE among adolescents. Health system responses are needed for transition services, data collection systems, education, and obesity prevention.</p