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This paper introduces the development of an anthropomorphic soft robotic hand integrated with multiple flexible force sensors in the fingers. By leveraging on the integrated force sensing mechanism, grip state estimation networks have been developed. The robotic hand was tasked to hold the given object on the table for 1.5 s and lift it up within 1 s. The object manipulation experiment of grasping and lifting the given objects were conducted with various pneumatic pressure (50, 80, and 120 kPa). Learning networks were developed to estimate occurrence of object instability and slippage due to acceleration of the robot or insufficient grasp strength. Hence the grip state estimation network can potentially feedback object stability status to the pneumatic control system. This would allow the pneumatic system to use suitable pneumatic pressure to efficiently handle different objects, i.e., lower pneumatic pressure (50 kPa) for lightweight objects which do not require high grasping strength. The learning process of the soft hand is made challenging by curating a diverse selection of daily objects, some of which displays dynamic change in shape upon grasping. To address the cost of collecting extensive training datasets, we adopted one-shot learning (OSL) technique with a long short-term memory (LSTM) recurrent neural network. OSL aims to allow the networks to learn based on limited training data. It also promotes the scalability of the network to accommodate more grasping objects in the future. Three types of LSTM-based networks have been developed and their performance has been evaluated in this study. Among the three LSTM networks, triplet network achieved overall stability estimation accuracy at 89.96%, followed by LSTM network with 88.00% and Siamese LSTM network with 85.16%.

Many individuals encounter situations that may elicit body-related concerns and impact how they think and feel about their weight, daily habits, and physical attractiveness. Research shows body image threats can predict poor health behaviors, but approaching those difficult moments with self-compassion-being kind, forgiving, and nonjudgmental-may reduce the impact of that threat and promote engagement in positive health behaviors. However, trait rumination, or tending to perseverate on negative events, may both dampen the benefits of a self-compassionate state and predict poor health behaviors. The present study examined whether a brief self-compassion writing exercise, after recalling a negative body-related event, predicted intent to perform health-promoting behaviors, and whether trait rumination attenuated this relationship. Participants (N = 217) completed a measure of trait rumination, underwent a body image threat, and were randomly assigned to cope with self-compassion or a distraction. Subsequently, participants completed a measure of health behavioral intentions. Analyses revealed participants in the self-compassion condition reported greater health-promoting behavioral intentions compared to control, with no significant main effect of trait rumination. However, a condition-by-rumination interaction emerged, suggesting the self-compassion condition was associated with higher health behavioral intentions, but only for participants with low trait rumination levels. These effects washed out when controlling for participants' self-rated health. The findings suggest that a self-compassion practice can help mitigate the adverse effects of a body image threat and facilitate health-promoting behavioral intentions, although its efficacy may depend on individual levels of trait rumination and perceived health., Competing Interests: Declarations Conflict of interest The authors declare no relevant conflicts of interest. Ethical approval All procedures in the present study in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Institutional Review Board at the authors’ institution (IRB #1069). Consent to participate All participants provided informed consent prior to completing the procedures., (© 2024. The Author(s), under exclusive licence to Marta Olivetti Belardinelli.)

We established a university-community partnership with the Boys and Girls Clubs of Chicago (BGCC)-named Chicago Antibiotic Discovery La b-to involve middle school students in antibiotic discovery research. In the course of working with a cohort of students from the BGCC, one student isolated a Pseudomonas idahonensis bacterium from a goose feces sample that produced a new cyclic lipodepsipeptide, which was characterized as orfamide N. Orfamide N is composed of ten mixed D/L-amino acids and a ( Z )-3 R -hydroxyhexadec-9-enoic acid residue. The planar structure of orfamide N was elucidated by one-dimensional (1D) and two-dimensional nuclear magnetic resonance (2D NMR), electrospray ionization-mass spectrometry (ESI-MS), and ozone-induced dissociation mass spectrometry (OzID-MS). The absolute configuration was determined by advanced Marfey's analysis, phylogenetic analysis of C-domains within the orfamide N biosynthetic gene cluster, and chiral high-performance liquid chromatography (HPLC) analysis of the hydrolyzed and reduced lipid tail. Orfamide N was cytotoxic against human melanoma and human ovarian cancer cells with IC 50 values of 11.06 and 10.50 μM, respectively. Overall, we demonstrated it is possible to integrate educational outreach with high-end natural product discovery while strengthening the relationship between the university and the community it serves., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Ovarian cancer, the fifth leading cause of cancer-related mortality in women, is the most lethal gynecological malignancy globally. Within various ovarian cancer subtypes, high-grade serous ovarian cancer is the most prevalent and there is frequent emergence of chemoresistance. Aulosirazole, an isothiazolonaphthoquinone alkaloid, isolated from the cyanobacterium Nostoc sp. UIC 10771, demonstrated cytotoxic activity against OVCAR3 cells (IC 50 = 301 ± 80 nM). Using immunocytochemistry, OVCAR3 cells treated with aulosirazole demonstrated increased concentrations of phosphorylated protein kinase B and phosphorylated c-Jun N-terminal kinase with subsequent accumulation of forkhead box O3a (FOXO3a) in the nucleus. The combination of aulosirazole with protein kinase B inhibitors resulted in the most nuclear accumulation of FOXO3a aulosirazole-induced apoptosis based on cleavage of poly(ADP-ribose) polymerase, annexin V staining, and induction of caspase 3/7 activity in OVCAR3, OVCAR5, and OVCAR8. The expression of downstream targets of FOXO3a, including B-cell lymphoma 2 (BCL2) and p53-upregulator modulator of apoptosis, increased following aulosirazole treatment. Aulosirazole upregulated the FOXO3a target, cyclin-dependent kinase inhibitor 1, and increased cell-cycle arrest in the G0/G1 phase. The downregulation of FOXO3a by short hairpin RNA (shRNA) reduced the cytotoxicity after aulosirazole treatment by 3-fold IC 50 (949 ± 16 nM) and eliminated its ability to regulate downstream targets of FOXO3a. These findings underscore FOXO3a as a critical mediator of aulosirazole-induced cytotoxicity. Additionally, aulosirazole was able to decrease migration and invasion while increasing cell death in 3D tumor spheroids. However, in vivo OVCAR8 tumor burden was not reduced by aulosirazole using an intraperitoneal tumor model. Given the mechanism of action of aulosirazole, this class of alkaloids represents promising lead compounds to develop treatments against FOXO3a-downregulated cancers. SIGNIFICANCE STATEMENT: Aulosirazole, an isothiazolonaphthoquinone alkaloid, exhibits potent cytotoxic effects against high-grade serous ovarian cancer by promoting forkhead box O3a (FOXO3a) nuclear accumulation and modulating downstream targets. These findings highlight the potential of aulosirazole as a promising therapeutic intervention for cancers characterized by FOXO3a downregulation., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Introduction: Fungi biosynthesize chemically diverse secondary metabolites with a wide range of biological activities. Natural product scientists have increasingly turned towards bioinformatics approaches, combining metabolomics and genomics to target secondary metabolites and their biosynthetic machinery. We recently applied an integrated metabologenomics workflow to 110 fungi and identified more than 230 high-confidence linkages between metabolites and their biosynthetic pathways., Objectives: To prioritize the discovery of bioactive natural products and their biosynthetic pathways from these hundreds of high-confidence linkages, we developed a bioactivity-driven metabologenomics workflow combining quantitative chemical information, antiproliferative bioactivity data, and genome sequences., Methods: The 110 fungi from our metabologenomics study were tested against multiple cancer cell lines to identify which strains produced antiproliferative natural products. Three strains were selected for further study, fractionated using flash chromatography, and subjected to an additional round of bioactivity testing and mass spectral analysis. Data were overlaid using biochemometrics analysis to predict active constituents early in the fractionation process following which their biosynthetic pathways were identified using metabologenomics., Results: We isolated three new-to-nature stemphone analogs, 19-acetylstemphones G (1), B (2) and E (3), that demonstrated antiproliferative activity ranging from 3 to 5 µM against human melanoma (MDA-MB-435) and ovarian cancer (OVACR3) cells. We proposed a rational biosynthetic pathway for these compounds, highlighting the potential of using bioactivity as a filter for the analysis of integrated-Omics datasets., Conclusions: This work demonstrates how the incorporation of biochemometrics as a third dimension into the metabologenomics workflow can identify bioactive metabolites and link them to their biosynthetic machinery., (© 2024. The Author(s).)

Background: High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of all ovarian cancer-related deaths. Multiple studies have suggested that the fallopian tube epithelium (FTE) serves as the cell of origin of HGSOC. Phosphatase and tensin homolog ( PTEN ) is a tumor suppressor and its loss is sufficient to induce numerous tumorigenic changes in FTE, including increased migration, formation of multicellular tumor spheroids (MTSs), and ovarian colonization. In murine oviductal epithelial (MOE) cells (the equivalent of human FTE) loss of PTEN results in the upregulation of transcripts associated with the extracellular matrix, with a specific focus on the elevation of lysyl oxidase-like 2 ( LOXL2 ). Although LOXL2 is known to drive transformation and invasion in solid tumors and is associated with a poor prognosis in ovarian cancer, its specific role in the tumorigenesis of ovarian cancer originating from FTE remains unclear. Therefore, we aim to investigate whether LOXL2 mediates tumorigenesis from the fallopian tube epithelium., Methods: In this study, we utilized clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (CAS9) technology to delete LOXL2 in PTEN -deficient MOE cells to understand its role in mediating the oncogenic effects of PTEN loss. In addition, CRISPR-CAS9 was used to delete LOXL2 in OVCAR8 ovarian cancer cells. We monitored the changes in tumorigenic properties, such as migration, invasion, and growth of three-dimensional (3D) spheroids, to assess whether the loss of LOXL2 resulted in any changes., Results: We found that a reduction in LOXL2 expression did not significantly change the migration or invasive capabilities of PTEN-depleted MOE or human ovarian cancer cells. However, we found that a reduction in LOXL2 expression resulted in a significant reduction in 3D MTS formation and survival in both lines., Conclusions: These results reveal for the first time that PTEN loss in FTE cells increases LOXL2 expression through downregulation of Pax2 , and LOXL2 deletion blocks 3D spheroid formation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Four new adjacent bis-tetrahydrofuran acetogenins, bullacin C ( 7 ), uvarirufin ( 9 ), and uvariasolins III ( 12 ) and IV ( 13 ), along with 11 known acetogenins, were isolated from the stem of Uvaria rufa . Their structures were elucidated based on spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, and MALDI-MS/MS of the lithium adducts. Absolute configurations were assigned using Mosher ester analysis and ECD measurements. Uvarirufin ( 9 ) possesses a unique C-39 skeleton among acetogenins. Most tested acetogenins exhibited cytotoxicity against human cancer cell lines (HCT 116, 22Rv1, MDA-MB-435, OVCAR3). Squamocin ( 8 ) and uvarirufin ( 9 ) were found to be the most potent, with an IC 50 value of 1.2 μM for both in HCT 116 colon cancer cells. Additionally, a new application of Dragendorff's reagent is proposed herein for the TLC detection of acetogenins.

Diepoxin-η ( 1 ) is a cytotoxic fungal metabolite belonging to the spirobisnaphthalene structural class. In this study, four mono fluorinated analogues ( 2 - 5 ) of diepoxin-η ( 1 ) were semisynthesized in a single-step by selectively fluorinating the naphthalene moiety with Selectfluor. The structures of 2-5 were elucidated using a set of spectroscopic and spectrometric techniques and were further confirmed by means of TDDFT-ECD and isotropic shielding tensors calculations. Compounds 2-5 showed equipotent cytotoxic activity to 1 when tested against OVCAR3 (ovarian) and MDA-MB-435 (melanoma) cancer cell lines with IC 50 values that range from 5.7-8.2 μ M., Competing Interests: The authors declare the following competing financial interest(s): NHO and CJP are members of the Scientific Advisory Board of Clue Genetics, Inc. NHO is also a member of the Scientific Advisory Boards of Mycosynthetix, Inc. and Ionic Pharmaceuticals, LLC.

High-grade serous ovarian cancer (HGSOC) is the most common and lethal ovarian cancer histotype. Lack of early detection methods, limited therapeutic agents, and low 5-year survival rate reflect the urgent need to develop new therapies. Eupenifeldin, a bistropolone, originally isolated from Eupenicillium brefeldianum , is a cytotoxic fungal metabolite. In three HSGOC cell lines (OVCAR3, OVCAR5, OVCAR8), eupenifeldin was found to have an IC 50 value less than 10 nM, while 10 times higher concentrations were required for cytotoxicity in nontumorigenic fallopian tube secretory epithelial cell lines (FTSEC). An in vivo hollow fiber assay showed significant cytotoxicity in OVCAR3. Eupenifeldin significantly increased Annexin V staining in OVCAR3 and -8, but not OVCAR5. Eupenifeldin activated caspases 3/7 in OVCAR3, OVCAR5, and OVCAR8; however, cleaved PARP was only detected in OVCAR3. Quantitative proteomics performed on OVCAR3 implicated ferroptosis as the most enriched cell death pathway. However, validation experiments did not support ferroptosis as part of the cytotoxic mechanism of eupenifeldin. Autophagic flux and LC3B puncta assays found that eupenifeldin displayed weak autophagic induction in OVCAR3. Inhibition of autophagy by cotreatment with bafilomycin reduced the toxicity of eupenifeldin, supporting the idea that induction of autophagy contributes to the cytotoxic mechanism of eupenifeldin.

Hypothemycin, an epoxide derivative of (5 Z )-7-oxozeaenol, was used in the semisynthesis of a series of C8-C9 diol derivatives, with many inhibiting TAK1 at submicromolar concentrations. A step-economical approach was chosen, whereby nonselective reactions functionalized the diol to generate multiple analogues in a single reaction. Using this approach, 35 analogues were synthesized using 12 reactions, providing a wealth of information about the role that the C8-C9 diol plays in TAK1 inhibition and cytotoxicity in ovarian and breast cancer cell lines. Monofunctionalized analogues exhibited strong inhibition of TAK1, showing potential for modification of this section of the molecule to assist with solubility, formulation, and other desirable properties. Most analogues were cytotoxic, and three compounds had similar or slightly increased potency with >100-fold improvement in solubility profiles.

Many consumers are turning to kratom ( Mitragyna speciosa ) to self-manage pain and opioid addiction. In the United States, an array of capsules, powders, and loose-leaf kratom products are readily available. Additionally, several online sites supply live kratom plants. A prerequisite to establishing quality control and quality assurance standards for the kratom industry, or understanding how alkaloid levels effect clinical outcomes, is the identification and quantitation of major and minor alkaloid constituents within available products and preparations. To this end, an ultra-high performance liquid chromatography-high resolution mass spectrometry method was developed for the analysis of 8 indole alkaloids (7-hydroxymitragynine, ajmalicine, paynantheine, mitragynine, speciogynine, isopaynantheine, speciociliatine, and mitraciliatine) and 6 oxindole alkaloids (isomitraphylline, isospeciofoleine, speciofoline, corynoxine A, corynoxeine, and rhynchophylline) in US-grown kratom plants and commercial products. These commercial products shared a qualitatively similar alkaloid profile, with 12 - 13 detected alkaloids and high levels of the indole alkaloid mitragynine (13.9 ± 1.1 - 270 ± 24 mg/g). The levels of the other major alkaloids (paynantheine, speciociliatine, speciogynine, mitraciliatine, and isopaynantheine) and the minor alkaloids varied in concentration from product to product. The alkaloid profile of US-grown M. speciosa "Rifat" showed high levels of the indole alkaloid speciogynine (7.94 ± 0.83 - 11.55 ± 0.18 mg/g) and quantifiable levels of isomitraphylline (0.943 ± 0.033 - 1.47 ± 0.18 mg/g). Notably, the alkaloid profile of a US-grown M. speciosa seedling was comparable to the commercial products with a high level of mitragynine (15.01 ± 0.20 mg/g). This work suggests that there are several M. speciosa chemotypes., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The known solid-tumor-selective cytotoxin aulosirazole ( 1 ) was identified from bioactive extracts from the culture medium of the cyanobacterium Nostoc sp. UIC 10771. Here, we demonstrate that 1 induces the nuclear accumulation of FOXO3a in OVCAR3 using both Western blot analysis and immunofluorescence confocal microscopy. We also report the discovery of two additional analogues, aulosirazoles B ( 2 ) and C ( 3 ). Structures for compounds 2 and 3 were determined using HR-ESI-LC-MS/MS and 1D and 2D NMR experiments. Aulosirazoles B ( 2 ) and C ( 3 ) represent the first natural analogues of the FOXO-activating compound aulosirazole ( 1 ) and are the second and third isothiazole-containing metabolites reported from this phylum.

Natural products have been a primary source of medicines throughout the history of human existence. It is estimated that close to 70 % of small molecule pharmaceuticals on the market are derived from natural products. With increasing antibiotic resistance, natural products remain an important source for the discovery of novel antimicrobial compounds. The plant rosemary (Rosmarinus officinalis), has been widely and commonly used as a food preservative due to its antimicrobial potential. To evaluate the antimicrobial profile of this plant, we used bioassay-guided fractionation and bioinformatics approaches. Through bioassay-guided fractionation, we tested in vitro activities of a R. officinalis extract and fractions thereof, as well as pure compounds micromeric acid (1), oleanolic acid (2), and ursolic acid (3) against methicillin-resistant Staphylococcus aureus (MRSA). Compounds 1 and 3 showed complete inhibition of MRSA (with MIC values of 32 μg/mL and 8 μg/mL, respectively) while compound 2 displayed only partial inhibition (MIC > 64 μg/mL). In addition, we utilized orthogonal partial least square-discriminant analysis (OPLS-DA) and selectivity ratio (SR) analysis to correlate the isolated compounds 1-3 with the observed antimicrobial activity, as well as to identify antimicrobials present in trace quantities. For mass spectrometry (MS) data collected in the negative ionization mode, compound 1 was the most positively correlated with activity, while for MS data collected in the positive ion mode, compounds 2-3 had the highest positive correlation. Using the bioinformatics approaches, we highlighted additional antimicrobials associated with the antimicrobial activity of R. officinalis, including genkwanin (4), rosmadial (5a) and/or 16-hydroxyrosmadial (5b), rosmanol (6), and hesperetin (7). Compounds 1-3 resulting from the bioassay-guided fractionation were identified by MS-MS fragmentation patterns and 1 H NMR spectra. Among the compounds highlighted by the biochemical analysis, compound 6 was identified by comparison with its commercial standard by employed ultra-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS), while 4, 5a-b and 7 were putatively identified based on MS data and in comparison with the literature. This is the first reported antimicrobial activity of micromeric acid (1) against MRSA., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The safety and efficacy of kratom (Mitragyna speciosa) for treatment of pain is highly controversial. Kratom produces more than 40 structurally related alkaloids, but most studies have focused on just two of these, mitragynine and 7-hydroxymitragynine. Here, we profiled 53 commercial kratom products using untargeted LC-MS metabolomics, revealing two distinct chemotypes that contain different levels of the alkaloid speciofoline. Both chemotypes were confirmed with DNA barcoding to be M. speciosa. To evaluate the biological relevance of variable speciofoline levels in kratom, we compared the opioid receptor binding activity of speciofoline, mitragynine, and 7-hydroxymitragynine. Mitragynine and 7-hydroxymitragynine function as partial agonists of the human µ-opioid receptor, while speciofoline does not exhibit measurable binding affinity at the µ-, δ- or ƙ-opioid receptors. Importantly, mitragynine and 7-hydroxymitragynine demonstrate functional selectivity for G-protein signaling, with no measurable recruitment of β-arrestin. Overall, the study demonstrates the unique binding and functional profiles of the kratom alkaloids, suggesting potential utility for managing pain, but further studies are needed to follow up on these in vitro findings. All three kratom alkaloids tested inhibited select cytochrome P450 enzymes, suggesting a potential risk for adverse interactions when kratom is co-consumed with drugs metabolized by these enzymes.

Hydrastis canadensis, commonly known as goldenseal, is a botanical native to the southeastern United States that has been used for the treatment of infection. The activity of goldenseal is often attributed to the presence of alkaloids (cyclic, nitrogen-containing compounds) present within its roots. Chemical components of botanical supplements like goldenseal may face degradation if not stored properly. The purpose of the research was to analyze the stability of known and unknown metabolites of H. canadensis during exposure to different storage conditions using mass spectrometry. Three abundant metabolites of H. canadensis , berberine, canadine, and hydrastine, were chosen for targeted analysis, and the stability of unknown metabolites was evaluated using untargeted metabolomics. The analysis and evaluation of H. canadensis samples were performed utilizing LC-MS and Principal Component Analysis (PCA). The research project focused on identifying the chemical changes in the metabolite content of H. canadensis under different temperature conditions (40°C ± 5°C, 20°C ± 5°C , and 4°C ± 5°C), different light:dark (hr:hr) cycles (16:8, 12:12, and 0:24), and different sample conditions (powdered roots versus whole roots) over a six month period. The results of this 6-month study revealed that the storage conditions evaluated had no significant effects on the chemical composition of H. canadensis roots. Hence, as long as H. canadensis roots are stored within the storage conditions tested in the study, no significant changes in chemical compositions of metabolites are expected., (Copyright ©2020, Yale Journal of Biology and Medicine.)

The antibiotic resistant threat is continuing to grow, due in part to the overuse of antibiotics in livestock feed. Many nations in Europe have banned the use of antibiotics in feed, leading to higher rates of infection in livestock animals and reduced productivity for the food market. Increasingly, researchers are looking into the efficacy of phytopreparations to replace antibiotics in feed, allowing for increased animal health without the development of resistance. Macleaya cordata , or Chinese plume poppy, shows promise as a food additive. To evaluate the antimicrobial efficacy of this plant, we tested in vitro activity of M. cordata extract, as well as pure compounds sanguinarine and chelerythrine against wild-type, methicillin-resistant, and multiply-resistant strains of Staphylococcus aureus (SA1199, AH1263, and IA116, respectively). Combination tests to evaluate synergy, additivity, and antagonism within the extract were also completed for the first time. Sanguinarine and chelerythrine showed complete growth inhibition of all strains of S. aureus at concentrations ranging from 3-10 µg/mL, and were equal in activity or were more potent than the reference compound chloramphenicol. Combination studies of pure sanguinarine and chelerythrine with M. cordata extract revealed additivity or indifference of mixture components with these compounds. Because sanguinarine and chelerythrine represent the major active constituents of M. cordata , the pooled amounts of these two compounds may be useful for establishing potency for quality control purposes. This is the first report of activity of chelerythrine and sanguinarine against methicillin-resistant S. aureus AH1263 and multiply-resistant S. aureus IA116, and illustrates the promise of M. cordata extract as an alternative to antibiotics in feed additives., Competing Interests: Conflicts of Interest The authors declare that there are no conflicts of interest.

Unlabelled: In order to assess the prevalence of point-of-sale promotions of infant and young child feeding products in Phnom Penh, Cambodia; Kathmandu Valley, Nepal; Dakar Department, Senegal; and Dar es Salaam, Tanzania, approximately 30 retail stores per site, 121 in total, were visited. Promotional activity for breastmilk substitutes (BMS) and commercially produced complementary foods in each site were recorded. Point-of-sale promotion of BMS occurred in approximately one-third of sampled stores in Phnom Penh and Dakar Department but in 3.2% and 6.7% of stores in Kathmandu Valley and Dar es Salaam, respectively. Promotion of commercially produced complementary foods was highly prevalent in Dakar Department with half of stores having at least one promotion, while promotions for these products occurred in 10% or less of stores in the other three sites. While promotion of BMS in stores is legal in Senegal, it is prohibited in Cambodia without prior permission of the Ministry of Health/Ministry of Information and prohibited in both Nepal and Tanzania. Strengthening legislation in Senegal and enforcing regulations in Cambodia could help to prevent such promotion that can negatively affect breastfeeding practices., Key Messages: Even in countries such as Cambodia, Nepal and Tanzania where point-of-sale promotion is restricted, promotions of BMS were observed (in nearly one-third of stores in Phnom Penh and less than 10% in Dar es Salaam and Kathmandu). Limited promotion of commercially produced complementary foods was evident (less than 10% of stores had a promotion for such foods), except in Dakar Department, where promotions were found in half of stores. Efforts are needed to strengthen monitoring, regulation and enforcement of restrictions on the promotion of BMS. Manufacturers and distributors should take responsibility for compliance with national regulations and global policies pertaining to the promotion of breastmilk substitutes., (© 2016 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Background: Thiamine deficiency is common in parts of Asia and causes beriberi. Pharmacokinetics of thiamine in deficient populations are unknown., Objective: We characterized thiamine pharmacokinetics in Cambodian mothers and their breastfed infants., Design: Total plasma thiamine, whole-blood thiamine diphosphate (TDP), and breast milk total thiamine were measured in 16 healthy Cambodian mothers and their infants before and after mothers received oral thiamine hydrochloride (100 mg for 5 d). Assays were also performed in 16 healthy American mothers., Results: On day 1, Cambodian mothers were thiamine deficient, with median (range) total plasma thiamine and TDP concentrations of 2.4 nmol/L (0-4.4 nmol/L) and 58.0 nmol/L (27-98 nmol/L), respectively. After a single oral dose, the mean ± SD maximal concentration of thiamine and net area under the thiamine concentration-time curve were 73.4 ± 45.6 nmol/L and 465 ± 241 h · nmol ∙ L⁻¹. Day 6 median maternal total plasma thiamine and TDP concentrations were normal [18.6 nmol/L (13.4-25.3 nmol/L) and 76.5 nmol/L (48-107 nmol/L), respectively; P ≤ 0.001 compared with day 1]. Median Cambodian total breast milk thiamine concentration increased from 180 nmol/L (85-359 nmol/L) on day 1 to 403 nmol/L (314-415 nmol/L) on day 2 and 503 nmol/L (360-808 nmol/L) on day 6; the corresponding American breast milk value was 500 nmol/L (114-622 nmol/L). Median Cambodian infant total plasma thiamine and TDP concentrations increased from 3.0 nmol/L (0-7.3 nmol/L) and 38.5 nmol/L (23-57 nmol/L), respectively, on day 1 to 5.6 nmol/L (0-9.7 nmol/L) and 45.5 nmol/L (32-70 nmol/L), respectively, on day 6., Conclusions: Thiamine-deficient Cambodian mothers effectively absorb oral thiamine, with sharp increases in breast milk thiamine concentrations, but their breastfed infants remain thiamine deficient after 5 d of maternal supplementation. Longer-term maternal supplementation may be necessary to correct thiamine deficiency in breastfed infants. This trial was registered at clinicaltrials.gov as NCT01864057.

Objective: To evaluate the effectiveness of Sprinkles alongside infant and young child feeding (IYCF) education compared with IYCF education alone on anemia, deficiencies in iron, vitamin A, and zinc, and growth in Cambodian infants., Design: Cluster-randomized effectiveness study., Setting: Cambodian rural health district., Participants: Among 3112 infants aged 6 months, a random subsample (n = 1350) was surveyed at baseline and 6-month intervals to age 24 months., Intervention: Daily micronutrient Sprinkles alongside IYCF education vs IYCF education alone for 6 months from ages 6 to 11 months., Main Outcome Measures: Prevalence of anemia; iron, vitamin A, and zinc deficiencies; and growth via biomarkers and anthropometry., Results: Anemia prevalence (hemoglobin level <11.0 g/dL [to convert to grams per liter, multiply by 10.0]) was reduced in the intervention arm compared with the control arm by 20.6% at 12 months (95% CI, 9.4-30.2; P = .001), and the prevalence of moderate anemia (hemoglobin level <10.0 g/dL) was reduced by 27.1% (95% CI, 21.0-31.8; P < .001). At 12 and 18 months, iron deficiency prevalence was reduced by 23.5% (95% CI, 15.6-29.1; P < .001) and 11.6% (95% CI, 2.6-17.9; P = .02), respectively. The mean serum zinc concentration was increased at 12 months (2.88 μg/dL [to convert to micromoles per liter, multiply by 0.153]; 95% CI, 0.26-5.42; P = .03). There was no statistically significant difference in the prevalence of zinc and vitamin A deficiencies or in growth at any time., Conclusions: Sprinkles reduced anemia and iron deficiency and increased the mean serum zinc concentration in Cambodian infants. Anemia and zinc effects did not persist beyond the intervention period. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12608000069358.

Cancer can be a major cause of poverty. This may be due either to the costs of treating and managing the illness as well as its impact upon people's ability to work. This is a concern that particularly affects countries that lack comprehensive social health insurance systems and other types of social safety nets. The ACTION study is a longitudinal cohort study of 10,000 hospital patients with a first time diagnosis of cancer. It aims to assess the impact of cancer on the economic circumstances of patients and their households, patients' quality of life, costs of treatment and survival. Patients will be followed throughout the first year after their cancer diagnosis, with interviews conducted at baseline (after diagnosis), three and 12 months. A cross-section of public and private hospitals as well as cancer centers across eight member countries of the Association of Southeast Asian Nations (ASEAN) will invite patients to participate. The primary outcome is incidence of financial catastrophe following treatment for cancer, defined as out-of-pocket health care expenditure at 12 months exceeding 30% of household income. Secondary outcomes include illness induced poverty, quality of life, psychological distress, economic hardship, survival and disease status. The findings can raise awareness of the extent of the cancer problem in South East Asia and its breadth in terms of its implications for households and the communities in which cancer patients live, identify priorities for further research and catalyze political action to put in place effective cancer control policies.

Background: Progressive left ventricular (LV) diastolic dysfunction due to hypertension (HTN) alters left atrial (LA) contractile function in a predictable manner. While increased LA size is a marker of LV diastolic dysfunction and has been shown to be predictive of adverse cardiovascular outcomes, the prognostic significance of altered LA contractile function is unknown., Methods: A consecutive group of patients with chronic hypertension but without significant valvular disease or prior MI underwent clinically-indicated CMR for assessment of left ventricular (LV) function, myocardial ischemia, or viability. Calculation of LA volumes used in determining LA emptying functions was performed using the biplane area-length method., Results: Two-hundred and ten patients were included in this study. During a median follow-up of 19 months, 48 patients experienced major adverse cardiac events (MACE), including 24 deaths. Decreased LA contractile function (LAEF(Contractile)) demonstrated strong unadjusted associations with patient mortality, non-fatal events, and all MACE. For every 10% reduction of LAEF(Contractile), unadjusted hazards to MACE, all-cause mortality, and non-fatal events increased by 1.8, 1.5, and 1.4-folds, respectively. In addition, preservation of the proportional contribution from LA contraction to total diastolic filling (Contractile/Total ratio) was strongly associated with lower MACE and patient mortality. By multivariable analyses, LAEF(Contractile) was the strongest predictor in each of the best overall models of MACE, all-cause mortality, and non-fatal events. Even after adjustment for age, gender, left atrial volume, and LVEF, LAEF(Contractile) maintained strong independent associations with MACE (p < 0.0004), all-cause mortality (p < 0.0004), and non-fatal events (p < 0.0004)., Conclusions: In hypertensive patients at risk for left ventricular diastolic dysfunction, a decreased contribution of LA contractile function to ventricular filling during diastole is strongly predictive of adverse cardiac events and death.

Twenty-nine domestic piglets from pig farms located in three provinces of Thailand between 2003 and 2004 were used as sentinel animals for Japanese encephalitis virus (JEV) circulation. Piglets were used as sentinel to underline, on one hand, the role of domestic pigs as JEV amplifying host and, on another hand, to point out the interest of using sentinel animals for Japanese encephalitis surveillance. JEV activity was demonstrated through i/ antibody detection using a specific ELISA test for the identification of Immunoglobulins of class M and G, ii/ virus isolation on cell culture, after experimental mosquito inoculation for virus amplification. Almost 100% and 83% of the piglets, respectively, had specific IgG and IgM JEV antibodies and 35% yielded a virus isolate. Piglets of the growing farm industry act as virus amplifier increasing the risk of transmission for the human community. Conclusively, since piglets JEV infection appears early in life and is generally clinically unnoticed, it represents an exceptional sentinel model for human health threats, which has to be considered by health authorities.

Background: Opioid-based anesthetic techniques are commonly used during neurosurgical procedures. In the present randomized prospective study, we studied emergence after 4 anesthetic regimens combining intermediate duration opioids with isoflurane and nitrous oxide (N(2)O), in patients undergoing craniotomy for large (> 30 mm diameter with intracranial mass effect) intracranial tumors., Methods: One hundred seven patients were randomized into 4 groups: Group A: fentanyl (≤ 5 µg/kg) + isoflurane (≤ 1 minimum alveolar concentration [MAC]), Group B: sufentanil (1-2 µg/kg plus infusion) + isoflurane (≤ 0.5 MAC), Group C: sufentanil (2 µg/kg bolus only) + isoflurane (≤ 1 MAC), and Group D: alfentanil (100 µg/kg plus infusion) + isoflurane (≤ 0.5 MAC). Boluses were administered as divided doses during induction, laryngoscopy, head pinning, and incision. Blood pressure was controlled at ±25% of baseline levels. All infusions were discontinued at the start of dural closure. Emergence was assessed using a mini-neurologic examination consisting of 7 questions. Groups were compared on time to emergence using survival analysis methods., Results: The groups did not differ regarding extubation time, which occurred at a median of 4 to 6 minutes across groups after discontinuing N(2)O. The median emergence time ranged from 15 to 22.5 minutes and did not differ among groups. However, across all groups more women had emerged by 30 minutes compared with men (83% vs 57%, P  =  .002). The median emergence time in women was found to be significantly shorter (0-15 minutes) than in men (15-30 minutes) (P  =  .012)., Conclusions: No between-group differences in emergence time were observed; the study was stopped early because of evidence that no differences were likely to be found if the study were continued. However, in a post hoc analysis, female gender was associated with faster emergence.