Waist Circumference and Subclinical Thyroid Dysfunction in a Large Cohort of Chinese Men and Women

Objective: The association between subclinical thyroid dysfunction and waist circumference (WC) is still controversial, especially from the perspective of sex differences. We aimed to explore the impact of sex on this relationship in a large Chinese cohort.Methods: This cross-sectional study recruited 13,505 healthy participants (8,346 males, 5,159 females) who were enrolled in a health check program. Clinical data were collected. The association between subclinical thyroid dysfunction and WC of both sexes was analyzed separately after dividing WC into quartiles. Odds ratios (ORs) were calculated by binary logistic regression models, and linear regression analysis was also performed.Results: The prevalence rates of subclinical hyper-and hypothyroidism were significantly lower in males. Binary logistic regression models showed that WC in females with subclinical hypothyroidism had a detrimental effect with an OR of 1.011, but the effect disappeared when we included other covariates. The other ORs indicated no significant effects. The weak negative relationship between WC and thyrotropin was also indicated by linear regression analyses with very low R² values.Conclusion: The current research did not show WC as a risk factor for subclinical thyroid dysfunction in either sex. Regional and ancestral origin differences may account for the variations with other studies.Abbreviations: ALT = alanine aminotransferase; BMI = body mass index; FT3 = free triiodothyronine; FT4 = free thyroxine; TG = triglycerides; TSH = thyroid-stimulating hormone; UA = uric acid; WC = waist circumference     

Development of an equation to predict net protein requirements for the growth of Zebu beef cattle

The accurate estimation of protein requirements for beef cattle is a key factor in increasing livestock profitability and decreasing the environmental impacts of excessive N excretion due to mismatching between assumed requirements and diet formulation. A meta-analysis was conducted to evaluate and validate a new equation to predict the net protein requirements for growth (NPg) of Zebu beef cattle. For the development of the new approach, a database of 552 observations comprised of bulls, steers, and heifers of different genetic groups (Zebu, beef crossbreed, and dairy crossbreed) was assembled. The new approach was evaluated and compared to current models devised by the international nutrient requirements system committees (Agricultural Research Council, 1980; Beef Cattle Nutrient Requirements Model, 2016; BR-CORTE, 2016) to predict NPg. The model evaluation was performed through the model evaluation system (version 3.1.16) using an independent data set (n = 177 observations). An equation was considered the best estimator of NPg if the following conditions were met: (1) the intercept and slope of the regression between ordinary residues and/or predicted NPg values must have been equal to zero and one, respectively; and (2) the greatest concordance correlation coefficient (CCC) and determination coefficient (R), and lowest mean squared error of prediction (MSEP) were attained. Based on the regression models of the observed v. predicted NPg of Zebu beef cattle, both the new approach and that of the ARC (1980) correctly estimated NPg, since the intercept and slope were not different (P > 0.05) from zero and one, respectively. Additionally, the new approach’s determination coefficient was the greatest and the closest to one. The fact that the new model achieved a higher CCC and lower MSEP than the existing models indicated its superior reproducibility and accuracy. The equations proposed by BR-CORTE (2016) and the BCNRM (2016) did not correctly estimate NPg in that the intercept and slope were different (P < 0.01) from zero and one, respectively. Thus, the equations proposed by the new approach and the ARC (1980) accurately and precisely estimated NPg and are recommended for Zebu cattle. Furthermore, the inclusion of equivalent empty BW (EQEBW) in the new approach improves the estimation of NPg. We suggest the use of the following equation to calculate NPg for Zebu beef cattle: NPg = 176.01 × EBG – 0.381 × EQEBW^0.75 × EBG^1.035 (R = 0.80 and CCC = 0.75); where NPg = net protein requirements for growth, EBG = empty body gain, and EQEBW = equivalent empty BW.     

Predictors of Nonattendance at an Endocrinology Outpatient Clinic

Objective: To identify predictors potentially contributing to patients' nonattendance or to same-day cancellation of scheduled appointments at an adult endocrinology office practice.Methods: A retrospective, records-based, cross-sectional study was conducted using data from 9,305 electronic medical records of patients presenting at a U.S. metropolitan adult endocrinology clinic in 2013. Statistical analyses included multivariate regression, calculated odds ratios, and posttest probabilities.Results: Of 29,178 total patient visits analyzed, 68% were attended by patients. Of total scheduled appointments, 7% resulted in nonattendance and 5% in same-day cancellation. The most significant predictors of nonatten-dance were a previous history of nonattendance (P<.001), uncontrolled diabetes (P<.001), and new patients to the practice (P<.001). Long lead-time to appointment (P = .001), younger age (P<.001), and certain insurance carriers (P<.001) also were significant predictors.Conclusion: Specific predictors of nonattendance at scheduled appointments were identified using statistical analysis of electronic medical record data. Previous history of nonattendance and having uncontrolled diabetes (especially in patients newly referred to the practice) are among these significant predictors. Identifying specific predictors for nonattendance enables targeted strategies to be developed.Abbreviations:APRN = Advanced Practice Registered NurseCI = confidence intervalDM = diabetes mellitusEMR = electronic medical recordHbA1c = glycated hemoglobinNS = no-showOR = odds ratioSDC = same-day cancellation     

Identification of ortho-naphthoquinones as anti-AML agents by highly efficient oxidation of phenols

A straightforward method for synthesizing ortho-naphthoquinones was identified using an easily available cobalt–Schiff base complex. Efficient oxidation of phenols to ortho-naphthoquinones was useful in obtaining compounds with potent biological activity for the treatment of acute myeloid leukemia (AML). Among these compounds, the compound 4h effectively inhibited the proliferation of different AML cell lines in vitro. Further in vivo antitumor studies indicated that 4h at 40 mg/kg/d led to tumor regression in led to tumor regression in an MV4-11 xenograft model without evident toxicity. The cobalt-Schiff base complex was found to be an efficient catalyst in the transformation of phenols to ortho-quinones, and the compound 4h represents a potential scaffold to optimize the production of a treatment for AML.     

Two new glycosides from the whole plant of Anemone rivularis var. flore-minore

Phytochemical investigation on the whole plant of Anemone rivularis var. flore-minore led to the isolation of a new labdane-type diterpene glycoside (1) and a new trihydroxyfuranoid lignanoid glycoside (2), together with three known triterpene and triterpenoid glycosides (3–5). The structures of the two new compounds were elucidated as β-d-glucopyranosyl (13S)-13-hydroxy-7-oxo-labda-8,14-diene-18-oate (1) and (7S,7′R,8R,8′S)-7′-butoxy-7,9′-epoxy-4,4′,9-trihydroxy-3,3′-dimethoxylignane 9-O-β-d-glucopyranoside (2), on the basis of extensive spectral analysis and chemical evidence. Compound 1 is characterized by a glucose (Glc) esterified C-18 carboxyl group, which is a rarely encountered labdane-type diterpene glycoside in nature. The two new compounds (1 and 2) reported here are the first examples of diterpene glycoside and lignanoid glycoside found in the genus Anemone, and the known triterpene and triterpenoid glycosides (3–5) are identified for the first time from the title plant.     

A new subspecies and two new combinations of Nothofagus Blume (Nothofagaceae) from Chile

One new subspecies ofNothofagusBlume,Nothofagus obliquasubsp.andina, is described from Chile, and two new combinations have been madeNothofagus obliquasubsp.valdivianaandNothofagus macrocarpacomb. nov.     

Synthesis of new coumarin tethered isoxazolines as potential anticancer agents

A series of new coumarin tethered isoxazolines (7a-l) were synthesized and evaluated for their cytotoxic potency against human melanoma cancer cell line (UACC 903) as well as fibroblast normal cell line (FF2441). Preliminary results revealed that some of these coumarin tethered isoxazolines 7b, 7c, 7f and 7j exhibited significant antiproliferative effect against human melanoma cancer (UACC 903) with IC₅₀ values of 8.8, 10.5, 9.2 and 4.5?μM respectively. However, compound 7c was non-toxic to normal human cells at the tested concentration. Further, we have chosen compound 7c to check its efficacy in Ehrlich Ascites Carcinoma animal model in-vivo for its antitumor and antiangiogenic properties. Our lead compound significantly reduced the cell viability, body weight, ascites volume and downregulated the formation of neovasculature such as regression of tumor volume. The present study indicates the scope of developing into potent anticancer drug in near future.     

New cis-ent-clerodanes from Linaria japonica

Five new cis-ent-clerodanes, linarenones A–E (1–5) and two known compounds (6 and 7) were isolated from whole plant of Linaria japonica. The structures of these compounds were determined by various spectroscopic analyses (UV, IR, HR–ESI–MS, 1D and 2D NMR). The absolute configuration of five new diterpenoids was confirmed by circular dichroism (CD) analysis and chemical conversion. Cytotoxicity of the isolated compounds against A549 cell lines and Leishmania major were evaluated. The new cis-ent-clerodane 3 was found to be moderately active against A549 cell lines, and new cis-ent-clerodanes 1, 6 and desacetyl-linarienone (7) were active against L. major.     

New flavonoids from the fruits of Cornus mas,Cornaceae

One new β-hydroxychalcone, 4-acetoxy-5,2′,4′,6′,β-pentahydroxy-3-methoxychalcone (1), one new flavanone, 7,3′-dihydroxy-5,4′-dimethoxyflavanone (2) and seven known compounds, 2R, 3R-trans-aromadendrin (3), naringenin-7-O-methylether (4), myricetin (5), quercetin-3-O-rutinoside (6), ursolic acid (7), gallic acid (8) and d-glucose (9) were isolated from the methanolic fruit extract of Cornus mas L. (=Cornus mascula L.), Cornaceae. The structures of the new compounds were elucidated on the basis of extensive spectroscopic methods, including 2D NMR experiments and of known compounds by comparison of physical and spectral data with literature.     

Acylated flavonol glycosides and δ-truxinate derivative from the aerial parts of Lysimachia clethroides

Phytochemical investigation of the aerial parts of Lysimachia clethroides led to the isolation of a new acylated flavonol glycoside (1) and a new δ-truxinate derivative (2), together with three known acylated flavonol glycosides. The structures of the new compounds were determined by spectroscopic methods and chemical evidence as quercetin-3-O-β-d-(6-O-Z-p-coumaroyl)glucopyranoside (1) and monomethyl 3,3′,4,4′-tetrahydroxy-δ-truxinate (2), respectively. All of the isolates were evaluated for their in vitro inhibitory activity against aldose reductase.     

New sesquiterpene lactones from Inula species

An investigation of Inula helenium, I. royleana, I. salicina and I. bifrons afforded in addition to known sesquiterpene lactones 20 new lactones, the eudesmanolides 3, 6 and 8–12, the germacranolides 14–18 and 20–22, the guaianolides 23 and 25, the pseudoguaianolide 26, the xanthanolides 28 and 32 and the cyclopropane analogue 30. Structures and configurations of these new compounds were established by extensive PMR studies and by some chemical transformations. Some of the investigated species contain besides the widely distributed pentaynene 33 several known thymol derivatives together with a new one (40).     

Biosimilars and New Insulin Versions

Objective: To provide clinicians with an overview of similar biologic products including biosimilars and new insulin versions available in the U.S. and of key issues associated with such products, including differences in manufacturing and regulatory approaches and their impact on clinical use.Methods: We reviewed the relevant clinical and regulatory literature.Results: Patent protections for many biologics including several insulin preparations have or will expire shortly. This opens the door for new insulin versions to enter the U.S. and global marketplace. The development, manufacturing, and approval process for similar biologic products is more complex than for generic versions of small molecules. Most similar biologic products in the U.S. will be submitted for approval under section 351(k), a newly created biosimilar regulatory pathway. However, some biologics, including new insulin versions, will be submitted via the existing 505(b) regulatory pathway. These regulatory pathways have implications for how such products may be labeled, how they may be dispensed, and how patients may perceive them. The immunogenicity of biologics can affect safety and efficacy and can be altered through subtle changes in manufacturing. With the arrival of new insulin versions, health care providers will need to understand the implications of interchangeability, therapeutic equivalence, substitution, switching, and new delivery devices.Conclusion: An understanding of the above topics will be important as physicians, payers, and patients choose between similar versions of a reference listed biologic product.Abbreviations:BLA = biologics license applicationBPCIA = Biologics Price Competition and Innovation ActEU = European UnionFDA = Food and Drug AdministrationINN = international nonproprietary nameNDA = new drug applicationPD = pharmacodynamicPK = pharmacokineticPRCA = pure red cell aplasia     

Isolation and characterization of the chemical constituents from Plumeria rubra

Rubranonoside (=7-O-α-l-rhamnopyranosyl-4′-O-β-d-glucopyranosylnaringenin; (1), a new flavanone glycoside, rubranin (=(2S,3S,4R)-2-{[(2R,16E)-2-hydroxyhexaeico-16-en]amino}octadecane-1,3,4-triol-1-O-β-d-glucopyranoside; (2), a new sphingolipid, rubradoid (plumieridine-1-O-β-d-galactopyranoside; (3), a new iridoid galactoside, rubrajaleelol (4) and rubrajaleelic acid (5), two new nor-terpenoids together with known iridoids: 1-α-plumieride (6), plumieride p-Z-coumarate (7) and plumieride-p-E-coumarate (8) have been isolated from the EtOAc-soluble fraction of the MeOH extract of Plumeria rubra. Their structures were assigned from ¹H, ¹³C NMR spectra and 2D NMR analyses (COSY, NOESY, HMQC and HMBC experiments) in combination with HRMS experiments and comparison with literature data of related compounds. All the isolates (1–8) were tested for their antioxidant, antiurease, cytotoxic and phytotoxic activities and were found almost inactive.     

Quinic acid derivatives and coumarin glycoside from the roots and stems of Erycibe obtusifolia

A new quinic acid derivative (1) and a new coumarin glycoside (8), together with six known compounds (2–7) were isolated from the roots and stems of Erycibe obtusifolia. The structures of the new compounds were elucidated by spectroscopic and chemical analyses. The in vitro antiviral activity against the respiratory syncytial virus (RSV) of seven quinic acid derivatives was evaluated by cytopathic effect (CPE) reduction assay. Among them, the dicaffeoylquinic acids (6 and 7) displayed potent in vitro anti-RSV activity.     

Serratezomines D and E,new Lycopodium alkaloids from Lycopodium serratum var. serratum

Two new Lycopodium alkaloids, serratezomines D (1) and E (2), were isolated from the club moss Lycopodium serratum var. serratum. Serratezomine D (1) is a new lucidine-type alkaloid, while serratezomine E (2) is a new phlegmarane-type alkaloid. The structures and relative stereochemistry of 1 and 2 were elucidated on the basis of spectroscopic data. Serratezomine D (1) exhibited an inhibitory activity against acetylcholinesterase.     

Evaluation of nitrogen excretion equations for ryegrass pasture-fed dairy cows

Accurate and precise estimates of nitrogen (N) excretion in faeces and urine of dairy cattle may provide direct tools to improve N management and thus, to mitigate environmental pollution from dairy production. Empirical equations of N excretion have been evaluated for indoor dairy cattle but there is no evaluation for cows fed high proportions of fresh forage. Therefore, the objective of the current study was to evaluate N excretion equations with a unique data set of zero-grazing experiments. Through literature searches, 89 predictive equations were identified from 13 studies. An independent data set was developed from seven zero-grazing experiments with, in total, 55 dairy Holstein-Friesian cows. Models’ performance was evaluated with statistics derived from a mixed-effect model and a simple regression analysis model. Squared sample correlation coefficients were used as indicators of precision and based on either the best linear unbiased predictions (R²_BLUP) or model-predicted estimates (R²_MDP) derived from the mixed model and simple regression analysis, respectively. The slope (β₀), the intercept (β₁) and the root mean square prediction error (RMSPE_m%) were calculated with the mixed-effect model and used to assess accuracy. The root mean square prediction error (RMSPE_sr%) and the decomposition of the mean square prediction error were calculated with the simple regression analysis and were used to estimate the error due to central tendency (mean bias), regression (systematic bias), and random variation. Concordance correlation coefficient (CCC) were also calculated with the simple regression analysis model and were used to simultaneously assess accuracy and precision. Considering both analysis models, results suggested that urinary N excretion (UN; R²_MDP = 0.76, R²_BLUP = 0.89, RMSPE_m% = 17.2, CCC = 0.82), total manure N excretion (ManN; R²_MDP = 0.83, R²_BLUP = 0.90, RMSPE_m% = 11.0, CCC = 0.84) and N apparently digested (NAD; R²_MDP = 0.97, R²_BLUP = 0.97, RMSPE_m% = 5.3, CCC = 0.95) were closely related to N intake. Milk N secretion was better predicted using milk yield as a single independent variable (MilkN; R²_MDP = 0.77, R²_BLUP = 0.97, RMSPE_m% = 6.0, CCC = 0.74). Additionally, DM intake was a good predictor of UN and ManN and dietary CP concentration of UN and ManN. Consequently, results suggest that several evaluated empirical equations can be used to make accurate and precise predictions concerning N excretion from dairy cows being fed on fresh forage.     

Three new glycosides from the whole plant of Clematis lasiandra Maxim and their cytotoxicity

Phytochemical investigation on the whole plant of Clematis lasiandra Maxim led to the isolation of two new phenolic glycosides (1 and 2), one new lignanoid glycoside (3), together with three known lignanoid glycosides (4–6). The structures of the new compounds were elucidated as 4-O-β-d-galactopyranosyl-ethyl-E-caffeate (1), 4-O-β-d-galactopyranosyl-3-hydroxyl-phenylethene (2) and (8R)-3,3′-dimethoxy-4,4′,9,9′-tetrahydroxy-5′,8-lignan 3′-O-β-d-glucopyranoside (3), on the basis of extensive spectral analysis and chemical evidence. The characteristic of the polymerized C-5′–C-8 type lignanoid aglycone in glycoside 3 was found from genus Clematis for the first time. Compounds 1–6 were evaluated for their cytotoxicity against human tumor cell lines HL-60, Hep-G2 and SGC-7901, the new glycosides 1 and 2 showed significant cytotoxicity against those three tumor cell lines with IC₅₀ in the range from 9.73 to 22.31 μM, while lignanoid glycosides 3–6 showed weak cytotoxicity to those test cell lines with IC₅₀ value more than 52.71 μM.     

Flavonoid glycosides from the aerial parts of Curcuma comosa

Four new flavonoid glycosides, curcucomosides A–D (1–4), three known flavonoid glycosides, 5–7, and four known diarylheptanoids, 8–11, were isolated from the ethanol extract of the aerial parts of Curcuma comosa. The structures of the new compounds were established as rhamnazin 3-O-α-l-arabinopyranoside (1), rhamnocitrin 3-O-α-l-arabinopyranoside (2), rhamnazin 3-O-α-l-rhamnopyranosyl-(1→2)-O-α-l-arabinopyranoside (3), and rhamnocitrin 3-O-α-l-rhamnopyranosyl-(1→2)-O-α-l-arabinopyranoside (4) by spectroscopic analysis and chemical reactions whereas those of the known compounds were identified by spectral comparison with those of the reported values.     

Four new iridoid glucoside p-coumaroyl esters from Ajuga decumbens

From the methanolic extract of the dried whole plant ofAjuga decumbens, four new iridoid glucosidecis- andtrans-p-coumaroyl esters, decumbeside A (1), B (2), C (7) and D (8) were isolated together with the known reptoside (6) and 8-acetylharpagide (9). The structures of the new compounds have been elucidated on the basis of spectroscopic and chemical evidence.     

Bioactive new withanolides from the cultured soft coral Sinularia brassica

Continuing study of the ethyl acetate (EtOAc) extract of the cultured soft coral Sinularia brassica afforded five new withanolides, sinubrasolides H–L (1–5). The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The cytotoxicities of new compounds 1–5 and a known compound sinubrasolide A (6) against the proliferation of a limited panel of cancer cell lines were assayed. The anti-inflammatory activities of compounds 1–6 were evaluated by measuring their ability to suppress N-formyl-methionyl-leucyl-phenyl-alanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release in human neutrophils.