Effects of DDT on Amyloid Precursor Protein Levels and Amyloid Beta Pathology: Mechanistic Links to Alzheimer’s Disease Risk

Background: The interaction of aging-related, genetic, and environmental factors is thought to contribute to the etiology of late-onset, sporadic Alzheimer’s disease (AD). We previously reported that serum levels of p,p′-dichlorodiphenyldichloroethylene (DDE), a long-lasting metabolite of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT), were significantly elevated in patients with AD and associated with the risk of AD diagnosis. However, the mechanism by which DDT may contribute to AD pathogenesis is unknown.Objectives: This study sought to assess effects of DDT exposure on the amyloid pathway in multiple in vitro and in vivo models.Methods: Cultured cells (SH-SY5Y and primary neurons), transgenic flies overexpressing amyloid beta (Aβ), and C57BL/6J and 3xTG-AD mice were treated with DDT to assess impacts on the amyloid pathway. Real time quantitative polymerase chain reaction, multiplex assay, western immunoblotting and immunohistochemical methods were used to assess the effects of DDT on amyloid precursor protein (APP) and other contributors to amyloid processing and deposition.Results: Exposure to DDT revealed significantly higher APP mRNA and protein levels in immortalized and primary neurons, as well as in wild-type and AD-models. This was accompanied by higher levels of secreted Aβ in SH-SY5Y cells, an effect abolished by the sodium channel antagonist tetrodotoxin. Transgenic flies and 3xTG-AD mice had more Aβ pathology following DDT exposure. Furthermore, loss of the synaptic markers synaptophysin and PSD95 were observed in the cortex of the brains of 3xTG-AD mice.Discussion: Sporadic Alzheimer’s disease risk involves contributions from genetic and environmental factors. Here, we used multiple model systems, including primary neurons, transgenic flies, and mice to demonstrate the effects of DDT on APP and its pathological product Aβ. These data, combined with our previous epidemiological findings, provide a mechanistic framework by which DDT exposure may contribute to increased risk of AD by impacting the amyloid pathway. https://doi.org/10.1289/{"type":"entrez-protein","attrs":{"text":"EHP10576","term_id":"372009961","term_text":"EHP10576"}}EHP10576     

Mapping the global literature output on nocturia: A bibliometric and visualized analysis

Purpose:This study aims to facilitate researchers’ and clinicians’ understanding of research frontiers and trends in nocturia. It explores the scientific research outcomes and key bibliometric indices and plots global research on nocturia.Methods:A bibliometric retrospective study was designed, and an online search was conducted in the Web of Science Core Collection database using the potential search keywords related to nocturia in the title field with some specific filtration. HistCite™ and VOSviewer software for windows were used to analyze the data obtained for authors, journals, countries, institutions, keywords, and visualization mapping.Results:The initial search retrieved 1479 hits. A total of 1445 publications were included in the final analysis. Of these, 43.53% were published as articles. The most studied area in nocturia is urology nephrology. The most productive year was 2019 (n = 121, citations = 335), and the most prolific author, both in terms of publications (n = 97) and citations (1658) was Weiss JP. The most cited journal in nocturia research was the Journal of Urology (n = 293, citations = 3050). The most widely used keyword in nocturia publications was nocturia (n = 1249). Visualization mapping shows that the USA was the most influential and highly cited country in nocturia research.Conclusion:This study showed that there has been an increasing research trend in nocturia over the past few years. The current findings provide important empirical evidence for researchers, clinicians, and physicians to understand research frontiers and trends, achievements, collaborative networks, and hotspot research topics in the research field of nocturia.     

An account of the botanical anthelmintics used in traditional veterinary practices in Sahiwal district of Punjab, Pakistan

AIM OF THE STUDY: The present study was aimed at documentation of botanical anthelmintics used in the traditional veterinary practices in Sahiwal district of Punjab, Pakistan. MATERIALS AND METHODS: In rapid rural appraisal, 331 traditional veterinary healers (TVH) were identified as key respondents in the study area followed by participatory rural appraisal for data collection using a well-structured questionnaire. Information was collected through interviews, focused group discussions and field visits over a period of 2 years. RESULTS: A total of 49 traditional recipes, with 41 plant species representing 39 genera and 27 families, were recorded for the treatment of helminthosis in animals. Most frequently used plants (>/=5 times) were Brassica campestris L. and Mallotus philippinensis (Lam.) Muell.-Arg. and most frequently used families (>/=5 times) were Brassicaceae, Euphorbiaceae and Solanaceae. Most frequently used part of the plant was leaves (n=10) followed in order by seeds (n=9), whole fruit (n=5), aerial parts and whole plant (n=4), fruit (n=3), bulb (n=2) and bark, rhizome, stem, stem plus root and twigs (n=1). Five recipes out of 49 (10.2%) contained more than one plant species and rest 44 (89.8%) contained single plant species. CONCLUSIONS: Twenty out of 41 plants (48.78%) are reported for the first time for their traditional use as anthelmintics in Pakistan. Further studies on pharmacokinetics using scientific procedures may prove these plants as promising candidates for their future use as anthelmintics.     

The nature of intrauterine adhesions following reproductive hysteroscopic surgery as determined by early and late follow-up hysteroscopy: clinical implications

Objective To evaluate the rate and characteristics of postoperative intrauterine adhesions (IUA) that might be formed following hysteroscopic reproductive surgery from both a gross and a histologic perspective as determined by early and late follow-up diagnostic hysteroscopy. Methods Retrospective analysis of 61 women wishing a pregnancy and suffering from a significant intrauterine pathology affecting their reproductive outcome were reviewed. All patients were treated hysteroscopically. Subsequently, they were randomly assigned to perform a follow-up diagnostic hysteroscopy at a variable intervals from their initial surgery. Multiple hysteroscopic-guided biopsies from IUA, when present, were obtained in several cases. Twenty patients were in the early group and had follow-up hysteroscopy performed 2–4 weeks after the initial operation. The late diagnostic group consisted of 41 patients with follow-up hysteroscopy at about 12 months (8–16 months). The two groups were similar to composition. Postoperatively, none of the early diagnostic group underwent hysterosalpingography (HSG) whereas all of the late group performed HSG 4 months following the initial surgery, which showed at least one-third of the cavity free of adhesions. When adhesions were present, no effort was made to lyse them. Results At follow-up hysteroscopy, 25% of both groups had no significant adhesions. Grade I adhesions (thin, filmy) occurred in 60% of the early hysteroscopy patients and in only 12% of the late group (P < 0.05). Grade II adhesions were present in 10% of the early group and in up to 41% in the late group (P < 0.05), whereas Grade III adhesions were present in only 5% of the early hysteroscopy group, but in 22% of the late one (P < 0.05). Correlation between hysteroscopic and histologic findings were good in most of cases in both groups. Follow-up to determine the subsequent reproductive outcome revealed similar conception rates in both groups. Conclusion The IUA that might be formed immediately following hysteroscopic reproductive surgery are histologically different from those appearing a longer time after the original operation. Routine early follow-up hysteroscopy can influence the prognosis resulting from the original surgery.     

Kiwi Omnicup versus Malmstrom metal cup in vacuum assisted delivery: a randomized comparative trial

AIM: To compare the success, clinical outcomes, and maternal and neonatal complications between the Kiwi Omnicup and the Malmstrom metal cup in vacuum assisted delivery. METHODS: This was a prospective randomized comparative trial. Women who required vacuum assisted vaginal delivery were randomized into the Kiwi Omnicup (KO) group and the Malmstrom metal cup (MM) group. The vacuum assisted deliveries were conducted according to hospital protocol. Details of the procedure and delivery outcomes including success and complications were analyzed. RESULTS: One hundred and sixty-four women were recruited - 85 were assigned to vacuum assisted delivery using the KO and 79 the MM. One hundred percent delivery success was achieved with no significant differences between the two instruments in terms of maternal morbidity (P = 0.66). Six women in the MM group sustained post delivery complications in comparison to five in the KO group. Three babies were diagnosed with birth asphyxia in each group. More babies in the MM group were admitted to the Neonatal Intensive Care Unit (NICU) (10 babies versus 5 babies) and suffered complications (14 versus 12 babies), compared to the KO group, although the difference was not statistically significant. There were no intrapartum or neonatal deaths and of those admitted to the NICU, all were discharged within a week without any serious consequences. CONCLUSION: Kiwi Omnicup is an effective alternative to the currently available Malmstrom metal cup for vacuum assisted delivery with no increase in maternal or neonatal morbidity or mortality.     

Effect of Carbon Nanofibers on Physical,Adhesion and Rheological Properties of Liquid Epoxidized Natural Rubber Modified Asphalt

This study aimed to evaluate the effects of carbon nanofibers (CNFs) on the performance of liquid epoxidized natural rubber (LENR)-modified asphalt. The physical, adhesion and rheological properties were determined by several tests such as penetration, elastic recovery, ring and ball softening point, Brookfield rotational viscometer, AFM and dynamic shear rheometer. LENR was used at concentrations of 3, 6, and 9%, while CNFs were used at contents of 0.3, 0.4, and 0.5% by weight of asphalt. Conventional test results showed that the increases in LENR and LENR/CNFs composite contents in binder leads to an increase in the hardness and consistency and a reduction in the temperature susceptibility of base asphalt. Adhesion results revealed that the addition of CNFs significantly increases the adhesion and bonding properties of base and rubberized binders. Rheological properties analysis exhibited that LENR improved the viscoelastic properties and permanent deformation resistance of asphalt at different temperatures and frequencies. On the other hand, it was found that the addition of CNFs significantly improves the stiffness, elasticity, and hardness of LENR-modified binders. The 6% LENR and 0.4% CNFs were found to be the optimum to enhance the physical, adhesion, and rheological properties of asphalt in this study. Thus, it can be stated that the addition of CNFs is promising to improve the performance of rubberized binders for high temperature applications.     

Heart Failure after Laboratory Confirmed Influenza Infection (FLU-HF)

Background:Influenza has been shown to exacerbate heart failure (HF). Importantly, no study to date has examined the relationship between HF hospitalizations (HFH) with laboratory confirmed influenza infections. This study evaluated the association between laboratory confirmed influenza infection and HFH in the two largest hospitals in Saskatchewan, Canada.Methods:We used a retrospective self-controlled case series design to evaluate the association between laboratory-confirmed influenza infection and HFH. We compared the incidence ratio for HFH during the influenza risk interval with the control interval. We defined the influenza risk interval as the seven days after a laboratory confirmed influenza result and the control interval as one year before and after the risk interval.Results:We identified 114 HFH that occurred within one year before and after a positive test result for influenza between April 1, 2010, and April 30, 2018. Of these, 28 (28 admissions per week) occurred during the risk interval and 86 (0.853 admissions per week) occurred during the control interval. The incidence ratio of a HFH during the risk interval as compared with the control interval was 33.53 (95% confidence interval [CI], 21.89 to 51.36). A decline in incidence was observed after day seven; between days 8 to 14 and 14 to 28 incidence ratios was 0.91 (95% CI, 0.13 to 6.52) and 0.91 (95% CI, 0.22 to 3.68) respectively.Conclusion:We have observed a significant association between acute influenza infection and HFH. However, further research with a larger sample size and involving a multicenter setting is warranted.Highlights

• Influenza may contribute and exacerbate heart failure events especially during annual influenza season.
• Early identification of influenza among patients with heart failure, could lead to earlier treatment with antiviral medication, reduce unnecessary antibiotic use, and tail off the morbidity and mortality.
• In this study, despite our efficient study design, our sample size was limited to only the two largest hospitals in the province, possibly excluding a significant population in remote areas.

     

Aggregation induced emission based fluorenes as dual-channel fluorescent probes for rapid detection of cyanide: applications of smartphones and logic gates

Rational modification of molecular structure by incorporating electron donating groups can play a potential role for designing aggregation induced emission (AIE) active fluorescent probes. Based on this principle, fluorescent probes (1a–c) were synthesized, and they displayed excellent aggregation induced emission (AIE) behavior in a H₂O/DMF (4 : 1, v/v) mixture due to restrictions in intramolecular charge transfer (ICT). As a comparison, probe 1d was synthesized by installing an electron withdrawing (–NO₂) group that surprisingly quenched the aggregation behaviour. Additionally, AIE active probes 1a–c displayed a highly sensitive dual channel (fluorometric and colorimetric) response towards rapid detection of CN⁻, which is an active toxic material. Probes 1a–c showed selectively enhanced fluorescence emission behavior towards CN⁻ with detection limits of 1.34 ppb, 1.38 ppb, and 1.54 ppb, respectively. The sensing mechanism involves Michael type adduct formation due to the nucleophilic addition reaction of cyanide with probes and was confirmed through ¹H NMR titration experiments. In contrast, probe 1d containing an electron withdrawing moiety showed insensitivity towards CN⁻. Therefore, this study provides the efficient strategy to induce AIE character in fluorescent probes and expands the mechanistic approach toward the sensing of toxic CN⁻.

Rational modification of molecular structure by incorporating electron donating groups can play a potential role for designing aggregation induced emission (AIE) active fluorescent probes.     

Impact of Stunting on Development of Children between 1–3 Years of Age

BackgroundStunting occurs due to chronic malnutrition and is a major problem for children in developing countries. It is important to evaluate the impact of stunting on the development of children. This study aimed to investigate the impact of stunting on the development of children between 1–3 years of age.MethodsThis cross-sectional study was conducted from July 2020 to March 2021 in Surabaya, Indonesia. A questionnaire and growth assessment were done, following the development measurement to stunted and non-stunted children who met the inclusion and exclusion criteria. Development was measured by the Denver Developmental Screening Test II (DDST-II), and Cognitive Adaptive Test/Clinical Linguistic & Auditory Milestone (CAT/CLAMS) scales.ResultsThree hundred children are included in this study, consisting of 150 stunted and 150 non-stunted children. Stunted children had a higher risk to be suspected of delayed development compared to non-stunted children. The Crude Odd Ratio was 2.98, 4.24, 4.75 with the p-value 0.006, 0.001. and 0.001 respectively. The Adjusted Odd Ratio was 0.34, 0.24, 0.21 with p-value of 0.008, 0.001, and 0.001 respectively.ConclusionStunting is associated with suspected development delay among children 1–3 years of age. Initiatives related to prevention need to be established and nutrition advice needs to be provided.