Pubertal luteinizing hormone levels in children with chronic kidney disease and association with change in glomerular filtration rate.

BACKGROUND: Children with chronic kidney disease (CKD) are at risk for abnormalities in pubertal development. We aimed to describe the timing of pubertal onset by luteinizing hormone (LH) levels and the association between hormonal onset of puberty with changes in GFR. METHODS: Data from the Chronic Kidney Disease in Children (CKiD) study were collected prospectively. GFR was estimated at annual visits and measured by iohexol clearance every other year. LH was measured from stored repository serum samples in a nested sample of 124 participants. Hormonal onset of puberty was defined as LH level greater than or equal to 0.3 IU/L. A mixed effects model with random intercepts and slopes was used to compare the slope of decline of GFR before and after hormonal onset of puberty. The model was adjusted for age, glomerular disease diagnosis, baseline proteinuria on the log scale, and BMI. RESULTS: Median age at hormonal onset of puberty was 9.9 years (IQR 8.1, 11.9) in girls and 10.2 years (IQR 9.2, 11.0) in boys. The mixed effects model showed faster decline in both estimated GFR and measured GFR in boys after hormonal onset of puberty (p < 0.001), and a similar but attenuated accelerated estimated GFR decline was observed for girls with no difference for measured GFR. CONCLUSIONS: LH levels in the post-pubertal range were observed prior to clinical manifestations of puberty in children with CKD. Hormonal onset of puberty was associated with faster decline in GFR, particularly among boys with CKD.

A Brief Nutrition Questionnaire for Children With Newly Diagnosed Type 1 Diabetes.

Carbohydrate counting is an important component of type 1 diabetes management that is taught at the time of diagnosis. We implemented and validated a nutrition quiz to assess fundamental carbohydrate counting and nutrition knowledge in newly diagnosed patients. An interactive standard assessment for newly diagnosed type 1 diabetes patients was feasible and reliable to implement for patients and caregivers, but participants with public insurance scored lower overall. This assessment may help to identify nutrition knowledge gaps and provide opportunities for timely education, and providers should place additional focus on nutrition education for patients with public insurance.

Improving Continuous Glucose Monitoring Uptake in Underserved Youth with Type 1 Diabetes: The IMPACT Study.

Background: Continuous glucose monitoring (CGM) improves glycemic control. Less than half of youth with type 1 diabetes (T1D) use CGM, with disparities among minority and low-income youth. The aim of this study was to determine if trial CGM use increases uptake of personal CGM. Methods: T1D youth were provided sample CGM placement at the point of care, with CGM education and app setup. Follow-up calls at 5 and 10 days assessed CGM data, and desire to continue using CGM. Follow-up at 3-6 months recorded CGM use, CGM data, and A1c. Participants completed surveys at enrollment, 10 days, and 3 months. Differences were assessed between baseline and follow-up. Results: Of the 26 enrolled participants with T1D, 15 were CGM naive, and 11 were prior CGM users. The mean age was 14.1 ± 2.9 years, 65% male, 42% were Black, 12% were Hispanic, 65% were on public insurance, and 43% had household income of <$50,000. The median duration of diabetes was 4.6 years (interquartile range 2.4-7.7), mean baseline A1c was 10.7% ± 2.4%. After trial CGM use, 85% of participants reported wanting personal CGM, and at 3-6 months follow-up 76% had obtained one and 43% were using a personal CGM. There were no improvements in A1C or time in range, but participants reported an increase in the perceived benefits of CGM usage (4.0 vs. 4.3, p = 0.03). Conclusions: Placing a sample CGM at the point of care can improve uptake of personal CGM and may help mitigate disparities in CGM use in minority and underserved youth. Long-term studies are needed to determine how similar interventions impact glycemic control and patient outcomes. ClinicalTrials.gov: NCT04721145.

Relationship Of Serum Adiponectin Levels With Glycaemic Status In Pregnant Women.

BACKGROUND: Adiponectin plays an important role in glucose metabolism and released in response to insulin. It helps to decrease glucose levels and insulin resistance; however, this relation is not been studied in pregnant ladies. Objective was to determine serum adiponectin level and glycaemic status in pregnant women belonging to Peshawar, Khyber Pakhtunkhwa (KPK) and to find any possible relationship between them. METHODS: Hundred pregnant women with gestational diabetes mellitus (GDM) and 100 healthy pregnant women without GDM were randomly selected in a cross-sectional study. After an overnight fast, their blood samples were taken for determination of serum adiponectin, glycosylated haemoglobin (HbA1c) and fasting blood glucose (FBG). The relationship of adiponectin with glycaemic status was determined with Pearson Correlations coefficient (r). RESULTS: Pregnant women with GDM when compared to healthy pregnant women showed significantly low levels of serum adiponectin (µg/mL) (2.2±0.2 vs. 11.25±4.8, p<0.05) and significantly high level of FBG (mg/dl) (182.7±64.2 vs. 93.6±5.9, p<0.05) and HbA1c (%) (7.4±0.1 vs. 5.4±0.1, p<0.05). Serum adiponectin level showed a statistically significant negative correlation with FBG (r = -0.203, p=0.042) and HbA1c (r = -0.744, p=0.000) in pregnant women with GDM. CONCLUSIONS: Serum adiponectin concentration is markedly decreased in pregnant women with GDM which concludes that Hypoadiponectinemia is related with deranged (elevated) glycaemic status in pregnancy. Moreover, adiponectin is associated negatively with FBG and HbA1c in the studied population.

Multiple endocrine neoplasia type 1 presenting with concurrent insulinoma and prolactinoma in early-adolescence.

BACKGROUND: Multiple Endocrine Neoplasia Type 1 (MEN1) is a rare autosomal dominant disease that generally presents with primary hyperparathyroidism. However, initial presentation may vary and continued reevaluation of etiology of symptoms is required for appropriate diagnosis. CASE PRESENTATION: Twelve year old female presented with altered mental status that self-resolved and hypoglycemia. Laboratory evaluation revealed pituitary dysfunction with central hypothyroidism and adrenal insufficiency in the setting of hyperprolactinemia. Macroadenoma was confirmed on imaging. Despite medical treatment of pituitary hormone disorders, she continued to have significant hypoglycemia and further workup revealed hyperinsulinism. Insulinoma was identified and confirmed by endoscopic ultrasound. Hypoglycemia resolved after laproscopic enucleation of the insulinoma. CONCLUSION: Children presenting with one endocrine tumor should be investigated for other potential endocrine tumors. Multiple imaging modalities may be required to confidently identify neuroendocrine tumors for appropriate surgical intervention.

Turmeric powder and its derivatives from Curcuma longa rhizomes: Insecticidal effects on cabbage looper and the role of synergists.

Curcuma longa has well-known insecticidal and repellent effects on insect pests, but its impact on Trichoplusia ni is unknown. In this study, the compound ar-turmerone, extracted and purified from C. longa rhizomes, was identified, and its insecticidal effects, along with turmeric powder, curcuminoid pigments and crude essential oil were evaluated against this important agricultural pest. The role of natural (sesamol and piperonal) and synthetic [piperonyl butoxide (PBO)] synergists under laboratory and greenhouse conditions were also evaluated. The concentration of ar-turmerone in C. longa rhizomes harvested was 0.32% (dwt). Turmeric powder and its derivatives caused 10-20% mortality in third instar T. ni at a very low dose (10 µg/larva). Addition of PBO increased toxicity of turmeric powder and its derivatives (90-97% mortality) in most binary combinations (5 µg of turmeric powder or its derivatives +5 µg of PBO), but neither piperonal nor sesamol were active as synergists. The compound ar-turmerone alone and the combination with PBO reduced larval weight on treated Brassica oleracea in the laboratory and in greenhouse experiments, compared with the negative control. The compound ar-turmerone could be used as a low cost botanical insecticide for integrated management of cabbage looper in vegetable production.

Dhilirolides E-N, meroterpenoids produced in culture by the fungus Penicillium purpurogenum collected in Sri Lanka: structure elucidation, stable isotope feeding studies, and insecticidal activity.

Extracts of laboratory cultures of the fungus Penicilium purpurogenum obtained from rotting fruit of the tree Averrhoa bilimbi growing in Sri Lanka have yielded 10 new meroterpenoids, dhilirolides E-N (5-14). The structures of the new dhilirolides have been elucidated by analysis of spectroscopic data and a single-crystal X-ray diffraction analysis of dhilirolide L (12). Dhilirolides A-N (1-14) represent the four unprecedented and rearranged dhilirane, isodhilirane, 14,15-dinordhilirane, and 23,24-dinorisodhilirane meroterpenoid carbon skeletons. Stable isotope feeding studies have confirmed the meroterpenoid biogenetic origin of the dhilirolides and provided support for a proposed genesis of the new carbon skeletons. Dhilirolide L (12) showed significant feeding inhibition and sublethal developmental disruption in the cabbage looper Trichoplusia ni, an important agricultural pest, at low concentrations.

Horizontal transfer of diatomaceous earth and botanical insecticides in the common bed bug, Cimex lectularius L.; hemiptera: cimicidae.

BACKGROUND: Horizontal transfer of insecticide occurs when insects contact or ingest an insecticide, return to an aggregation or a nest, and transfer the insecticide to other conspecific insects through contact. This phenomenon has been reported in a number of insects including social insects, however it has not been reported in bed bugs. Since horizontal transfer can facilitate the spread of insecticide into hard to reach spaces, it could contribute greatly to the management of these public health pests. METHODOLOGY/RESULTS: To demonstrate horizontal transfer of diatomaceous earth and botanical insecticides in C. lectularius, an exposed (donor) bed bug, following a 10-minute acquisition period, was placed with unexposed (recipient) bed bugs. Mortality data clearly demonstrates that diatomaceous earth (DE 51) was actively transferred from a single exposed bug to unexposed bugs in a concentration dependent manner. LC50 values varied from 24.4 mg at 48 h to 5.1 mg at 216 h when a single exposed bed bug was placed with 5 unexposed bed bugs. LT50 values also exhibited a concentration response. LT50 values varied from 1.8 days to 8.4 days when a 'donor' bug exposed to 20 and 5 mg of dust respectively was placed with 5 'recipient' bugs. Dust was also actively transferred from adult bed bugs to the nymphs. In addition we observed horizontal transfer of botanical insecticides including neem, ryania, and rotenone to varying degrees. CONCLUSION/SIGNIFICANCE: Our data clearly demonstrate horizontal transfer of diatomaceous earth and botanical insecticides in the common bed bug, C. lectularius. Use of a fluorescent dust provided visual confirmation that contaminated bed bugs transfer dust to untreated bed bugs in harborage. This result is important because bedbugs live in hard-to-reach places and interaction between conspecifics can be exploited for delivery and dissemination of management products directed at this public health pest.

Chemical constituents and cytotoxic effect of the main compounds of Lythrum salicaria L.

Lythrum salicaria L. (Lythraceae), a herbaceous plant growing widely in Iran, has been well known for many centuries for its astringent and styptic properties. A phytochemical investigation of this plant, based on spectroscopic analysis, identified fourteen compounds: 5-hydroxypyrrolidin-2-one (1), umbelliferone-6-carboxylic acid (2), 3,3',4'-tri-O-methylellagic acid-4-O-beta-D-(2"-acetyl)-glucopyranoside (3), 3,3',4'-tri-O-methylellagic acid-4-O-beta-D-glucopyranoside (4), daucosterol (5), phytol (6), dodecanoic acid (7), oleanolic acid (8), 3,3',4'-tri-O-methylellagic acid (9), corosolic acid (10), beta-sitosterol (11), peucedanin (12), buntansin (13), and erythrodiol (14). All compounds, except for 8 and 11, have been isolated from L. salicaria for the first time. Cytotoxic activities of the compounds were examined against three cancerous cell lines, colon carcinoma (HT-29), leukemia (K-562), and breast ductal carcinoma (T47D), and Swiss mouse embryo fibroblast (NIH-3T3) cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and methotrexate as positive control. Compounds 5, 10, 11, and 14 were the most active against the HT-29 cell line with IC50 values of 192.7, 36.8, 38.2, and 12.8 microg/mL, respectively. Compounds 14, 11, 5, and 10 were 6.4, 2.8, 2.6, and 1.4 times, respectively, more selective than methotrexate. Compound 5 was the most active against the K-562 cell line (IC50 = 50.2 microg/mL), with a selectivity exceeding that of methotrexate 13.3 times. The results of the cytotoxic assay confirmed that growth and proliferation of the cancer cell lines are predominantly influenced by triterpene derivatives and sterols of this plant.

Dishabituating long-term memory for gustatory habituation in the cabbage looper, Trichoplusia ni.

The gustatory rejection response of the cabbage looper, Trichoplusia ni (Lepidoptera: Noctuidae), habituates to antifeedant compounds, allowing for the consumption of deterrent yet nontoxic plant materials. In the present study, we demonstrate that habituation to an antifeedant compound (quinine) persists through the moult between larval instars. As an indirect test of whether the memory was protein synthesis-dependent, we tested whether disrupting protein synthesis would block memory reconsolidation after a reminder. The results indicated that disrupting protein synthesis in habituated larvae following a reminder treatment (reexposure to quinine) eliminated the memory for habituation and restored the antifeedant properties of the quinine. We then examined whether the learned memory could be dishabituated and whether this would disrupt or eliminate long-term memory. We show that 6 hr after exposure to a novel/noxious stimulus (a second antifeedant, xanthotoxin) habituated larvae showed a transient dishabituation-like effect in which the quinine deterred feeding again. However, this effect did not permanently eliminate the habituation produced by the extended exposure as larvae tested 72 hr after xanthotoxin exposure again showed a willingness to consume the quinine treated leaves, indicating that the earlier habituation was still present.

Dialkoxybenzene and dialkoxyallylbenzene feeding and oviposition deterrents against the cabbage looper, Trichoplusia ni: potential insect behavior control agents.

The antifeedant, oviposition deterrent, and toxic effects of individual dialkoxybenzene compounds/sets and of hydroxy- or alkoxy-substituted allylbenzenes, obtained through Claisen rearrangement of substituted allyloxybenzenes, were assessed against the cabbage looper, Trichoplusia ni , in laboratory bioassays. Most of the compounds/sets strongly deterred larval feeding, with some exhibiting mild toxic and oviposition deterrent effects as well. Some of the compounds/sets were more active than the commercial insect repellent, DEET (N,N-diethyl-m-toluamide), as both feeding and oviposition deterrents against the cabbage looper. On the basis of the obtained oviposition data a general hypothesis was proposed regarding the oviposition sites: one binding mode with the alkyl and allyl groups on the same side of the benzene ring resulted in deterrence, the other with alkyl and allyl groups on opposite sides of the benzene ring resulted in stimulation. The results suggest some structure-activity relationships useful in improving the efficacy of the compounds and designing new, nontoxic insect control agents for agriculture.

Comparative toxicity of essential oils of Litsea pungens and Litsea cubeba and blends of their major constituents against the cabbage looper, Trichoplusia ni.

Contact toxicity of essential oils of Litsea pungens Hemsl. and L. cubeba (Lour.) Pers. (Lauraceae) and of blends of their major constituents was assessed against third-instar Trichoplusia ni larvae via topical application. Both oils showed moderate activity against T. ni larvae with LD(50) values of 87.1 and 112.5 microg/larva, respectively. 1,8-Cineole from the essential oil of L. pungens and gamma-terpinene from the oil of L. cubeba accounted for much of the toxicity of the oils to T. ni larvae. The toxicity of blends of selected constituents indicated a synergistic effect among putatively active and inactive constituents, with the presence of all constituents necessary for full toxicity of the natural oils. The results show that essential oils of L. pungens and L. cubeba and some of their constituents have potential for development as botanical insecticides.

Screening of dialkoxybenzenes and disubstituted cyclopentene derivatives against the cabbage looper, Trichoplusia ni, for the discovery of new feeding and oviposition deterrents.

The antifeedant, oviposition deterrent, and toxic effects of dialkoxybenzene minilibraries and of disubstituted cyclopentene minilibraries (i.e., consisting of four to five compounds) along with their pure constituent compounds were assessed against third instar larvae and adults of the cabbage looper, Trichoplusia ni, in laboratory bioassays in a search for new insect control agents. These compounds mimic naturally occurring bioactive odorants and tastants and are relatively easily prepared from commodity chemicals. Most of these libraries strongly deterred larval feeding, with some exhibiting strong toxic and oviposition deterrent effects as well. Our results suggest some structure-function relationships within these libraries. Replacement of a methyl group with larger alkyl substituents increased the feeding deterrent effects in most cases. The presence of a free hydroxyl group, irrespective of the carbon framework or alkyl substituent, served to reduce feeding deterrent effects in all series of compounds. Further, exceeding a certain group size also generally had a detrimental effect. This information will be useful in designing new insect control agents for agriculture. Some of these libraries and compounds may have potential for development as commercial insecticides.

Insecticidal activity of the essential oil of Ligusticum mutellina roots.

The essential oil obtained from roots of different collections of Ligusticum mutellina was tested against 3rd instar armyworms, Pseudaletia unipuncta (Lepidoptera: Noctuidae), for insecticidal activity. The main compounds were isolated and their structures were elucidated using 2D-NMR techniques. Our collections contained dillapiole, ligustilide and myristicin as major compounds. The previously reported sarisan was not present, moreover its occurrence in L. mutellina should be revised based on our findings.

Generalization of a habituated feeding deterrent response to unrelated antifeedants following prolonged exposure in a generalist herbivore, Trichoplusia ni.

The possibility of generalization of habituated response to unrelated feeding deterrents following prolonged exposure was examined in third instar Trichoplusia ni (Lepidoptera: Noctuidae) larvae by rearing them on antifeedants and then testing with other unrelated antifeedants. We introduced neonate larvae (< 24-hr old) onto cabbage leaves treated with crude seed extracts of Melia volkensii (Meliaceae) or oil of Origanum vulgare ("oregano") (Lamiaceae) and allowed them to feed until early in the third instar. Naive larvae were reared on cabbage leaves treated with carrier solvent alone. Both experienced and naïve larvae were tested for feeding deterrent response with the same and the different extracts in a leaf disc choice bioassay. Habituation was generalized to both M. volkensii and oregano following prolonged exposure to either plant extract and also to a pure allelochemical, thymol, following prolonged exposure to either digitoxin or xanthotoxin. However, there was no generalization of the habituated response to oregano following prolonged exposure to digitoxin or thymol, or to thymol or xanthotoxin following prolonged exposure to oregano or M. volkensii. Our results demonstrate that habituated response to feeding deterrents in a polyphagous insect herbivore can be generalized among and between plant extracts and pure allelochemicals, but not in all situations. The implications of such behavioral plasticity in herbivorous insects for the use of antifeedants as crop protectants or for host plant shifts is discussed.

Larval exposure to oviposition deterrents alters subsequent oviposition behavior in generalist, Trichoplusia ni and specialist, Plutella xylostella moths.

The present study was undertaken to determine the effects of larval feeding experience on subsequent oviposition behavior of the resulting moths. Larvae of the cabbage looper (Trichoplusia ni, Noctuidae) and the diamondback moth (Plutella xylostella, Plutellidae) were exposed to the phenylpropanoid allelochemical trans-anethole (at 100 ppm fw in artificial diet) or the limonoid allelochemical toosendanin (10 ppm sprayed on cabbage leaves). Both compounds had been shown to deter oviposition in naive moths in previous choice tests. Moths developing from "experienced" larvae (both sexes) showed a decrease in oviposition deterrence response when given a choice between control and treated leaves, unlike naïve moths. This phenomenon, analogous to habituation to feeding deterrents in lepidopteran larva, occurred irrespective of duration of feeding on the deterrent compound. We also observed that F1 larvae resulting from experienced moths (previously exposed to toosendanin as larvae) grew as well on toosendanin-treated foliage as on control foliage. In contrast, growth of F1 larvae from naïve moths was significantly impaired by toosendanin. These results demonstrate that host-selection behavior in cabbage looper (a generalist) and diamondback moth (a specialist) may be shaped by feeding experience according to Hopkins' Host Selection Principle in addition to chemical legacy.