National nutrition surveillance programmes in 18 countries in South-East Asia and Western Pacific Regions: a systematic scoping review.

Objective: To identify and analyse ongoing nutrition-related surveillance programmes led and/or funded by national authorities in countries in South-East Asian and Western Pacific Regions. Methods: We systematically searched for publications in PubMed® and Scopus, manually searched the grey literature and consulted with national health and nutrition officials, with no restrictions on publication type or language. We included low- and middle-income countries in the World Health Organization South-East Asia Region, and the Association of Southeast Asian Nations and China. We analysed the included programmes by adapting the United States Centers for Disease Control and Prevention's public health surveillance evaluation framework. Findings: We identified 82 surveillance programmes in 18 countries that repeatedly collect, analyse and disseminate data on nutrition and/or related indicators. Seventeen countries implemented a national periodic survey that exclusively collects nutrition-outcome indicators, often alongside internationally linked survey programmes. Coverage of different subpopulations and monitoring frequency vary substantially across countries. We found limited integration of food environment and wider food system indicators in these programmes, and no programmes specifically monitor nutrition-sensitive data across the food system. There is also limited nutrition-related surveillance of people living in urban deprived areas. Most surveillance programmes are digitized, use measures to ensure high data quality and report evidence of flexibility; however, many are inconsistently implemented and rely on external agencies' financial support. Conclusion: Efforts to improve the time efficiency, scope and stability of national nutrition surveillance, and integration with other sectoral data, should be encouraged and supported to allow systemic monitoring and evaluation of malnutrition interventions in these countries.

Design, synthesis, molecular docking study and molecular dynamics simulation of new coumarin-pyrimidine hybrid compounds having anticancer and antidiabetic activity.

Coumarin-pyrimidine hybrid compounds were synthesized by condensation reaction of α,ß-unsaturated ketones of 6-acetyl-5-hydroxy-4-methylcoumarin with guanidine. The reaction yields were of 42-62%. The antidiabetic and anticancer activities of these compounds were examined. These compounds displayed low toxicity to two cancer cell lines (including KB and HepG2 ones), but exhibited remarkably active against α-amylase with IC50 values of 102.32 ± 1.15 µM to 249.52 ± 1.14 µM and against α-glucosidase with IC50 values of 52.16 ± 1.12 µM to 184.52 ± 1.15 µM. Amongst these compounds, 6c was the best inhibitory activity against α-amylase, and 6f had the highest activity against α-glucosidase. The kinetics of inhibitor 6f was competitive α-glucosidase inhibitor property. ADMET predictions showed that almost all synthesized compounds exhibited drug-like activity. IFD and MD simulations were carried out on enzymes 4W93 and 5NN8 to elucidate inhibitory potential of 6c and 6f against tested enzymes. The binding free energy calculation by MM-GBSA approach showed that Coulomb, lipophilic and van der Waals energy terms are major contributors for the inhibitor binding. Molecular dynamics simulations in water solvent system were carried out for the 6f/5NN8 complex to elucidate the variability of active interactions between ligand 6f and active pockets of this enzyme.

Nonsurgical Orthodontic Airway Plate Treatment for Newborns With Robin Sequence.

Despite promising outcomes for >50 years, nonsurgical orthodontic airway plates (OAP) are only infrequently offered for babies with Robin sequence in a few parts of the world. This article demonstrates possibility of providing functional improvement using an OAP to help these babies overcome their functional and structural difficulties on their own. Two consecutively treated cases are presented exemplifying that OAP treatment that had originated from Europe is reproducible and effective in an institution in the United States.

A Systematic Review of Mandibular Distraction Osteogenesis Versus Orthodontic Airway Plate for Airway Obstruction Treatment in Pierre Robin Sequence.

OBJECTIVE: Mandibular distraction osteogenesis (MDO) is frequently performed to address airway obstruction in patients with Pierre Robin sequence (PRS), though more recently the technique of orthodontic airway plating (OAP) has gained traction. We aimed to evaluate OAP compared to MDO for airway obstruction in PRS. DESIGN: A systematic literature search across PubMed, Embase, and Google Scholar identified all studies published in English, which involved MDO or any form of OAP as treatments for PRS. All relevant articles were reviewed in detail and reported on, adhering to PRISMA guidelines. MAIN OUTCOME MEASURES: Airway (tracheostomy avoidance, decannulation rate), feeding (full oral feeding tolerance). RESULTS: Literature search identified 970 articles, of which 42 MDO studies and 9 OAP studies met criteria for review. A total of 1159 individuals were treated with MDO, and 322 individuals were treated with OAP. Primary outcomes appear similar for MDO and OAP at face value; however, this must be interpreted with different pretreatment contexts in mind. CONCLUSIONS: Orthodontic airway plating may be considered for airway obstruction in PRS, as some airway-related and feeding-related outcomes appear similar with MDO, per existing evidence in the literature. However, since PRS severity differed between studies, OAP cannot be uniformly considered a replacement for MDO. Further research is required to more comprehensively assess these treatment modalities inclusive of metrics that allow for direct comparison.

Antioxidant, Xanthine Oxidase, α-Amylase and α-Glucosidase Inhibitory Activities of Bioactive Compounds from Rumex crispus L. Root.

The root of Rumex crispus L. has been shown to possess anti-gout and anti-diabetic properties, but the compounds responsible for these pharmaceutical effects have not yet been reported. In this study, we aimed to isolate and purify active components from the root of R. crispus, and to evaluate their anti-radical, anti-gout and anti-diabetic capacities. From the ethyl acetate (EtOAc) extract, two compounds, chrysophanol (1) and physcion (2), were isolated by column chromatography with an elution of hexane and EtOAc at a 9:1 ratio. Their structures were identified by spectrometric techniques including gas chromatography-mass spectrometry (GC-MS), electrospray ionization-mass spectrometry (ESI-MS), X-ray diffraction analyses and nuclear magnetic resonance (NMR). The results of bioassays indicated that (1) showed stronger activities than (2). For antioxidant activity, (1) and (2) exhibited remarkable DPPH radical scavenging capacity (IC50 = 9.8 and 12.1 µg/mL), which was about two times stronger than BHT (IC50 = 19.4 µg/mL). The anti-gout property of (1) and (2) were comparable to the positive control allopurinol, these compounds exerted strong inhibition against the activity of xanthine oxidase (IC50 = 36.4 and 45.0 µg/mL, respectively). In the anti-diabetic assay, (1) and (2) displayed considerable inhibitory ability on α-glucosidase, their IC50 values (IC50 = 20.1 and 18.9 µg/mL, respectively) were higher than that of standard acarbose (IC50 = 143.4 µg/mL). Findings of this study highlight that (1) and (2) may be promising agents to treat gout and diabetes, which may greatly contribute to the medicinal properties of Rumex crispus root.

Phytochemical Analysis and Potential Biological Activities of Essential Oil from Rice Leaf.

Although many investigations on phytochemicals in rice plant parts and root exudates have been conducted, information on the chemical profile of essential oil (EO) and potent biological activities has been limited. In this study, chemical compositions of rice leaf EO and in vitro biological activities were investigated. From 1.5 kg of fresh rice leaves, an amount of 20 mg EO was obtained by distillation and analyzed by gas chromatography-mass spectrometry (GC-MS), electrospray ionization (ESI), and atmospheric pressure chemical ionization (APCI) to reveal the presence of twelve volatile constituents, of which methyl ricinoleate (27.86%) was the principal compound, followed by palmitic acid (17.34%), and linolenic acid (11.16%), while 2-pentadecanone was the least (2.13%). Two phytoalexin momilactones A and B were first time identified in EO using ultra-performance liquid chromatography coupled with electrospray mass spectrometry (UPLC/ESI-MS) (9.80 and 4.93 ng/g fresh weight, respectively), which accounted for 7.35% and 3.70% of the EO, respectively. The assays of DPPH (IC50 = 73.1 µg/mL), ABTS (IC50 = 198.3 µg/mL), FRAP (IC50 = 700.8 µg/mL) and ß-carotene oxidation (LPI = 79%) revealed that EO possessed an excellent antioxidant activity. The xanthine oxidase assay indicated that the anti-hyperuricemia potential was in a moderate level (IC50 = 526 µg/mL) as compared with the standard allopurinol. The EO exerted potent inhibition on growth of Raphanus sativus, Lactuca sativa, and two noxious weeds Echinochloa crus-galli, and Bidens pilosa, but in contrast, the growth of rice seedlings was promoted. Among the examined plants, the growth of the E. crus-galli root was the most inhibited, proposing that constituents found in EO may have potential for the control of the problematic paddy weed E. crus-galli. It was found that the EO of rice leaves contained rich phytochemicals, which were potent in antioxidants and gout treatment, as well as weed management. Findings of this study highlighted the potential value of rice leaves, which may provide extra benefits for rice farmers.

Isolation and Purification of Bioactive Compounds from the Stem Bark of Jatropha podagrica.

This paper reports the successive isolation and purification of bioactive compounds from the stem bark of Jatropha podagrica, a widely known medicinal plant. The ethyl acetate extract of the stem bark exhibited the strongest antioxidant activity assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, and ferric reducing antioxidant power (FRAP) assays (IC50 = 46.7, 66.0, and 492.6, respectively). By column chromatography (CC) with elution of hexane and ethyl acetate at 8:2, 7:3, and 6:4 ratios, the isolation of this active extract yielded five fractions (C1⁻C5). Chemical structures of the constituents included in C1⁻C5 were elucidated by gas chromatography-mass spectrometry (GC-MS), electrospray ionization-mass spectrometry (ESI-MS), and nuclear magnetic resonance (NMR) and resolved as methyl gallate (C1, C2, C3, C4), gallic acid (C1, C2), fraxetin (C2, C3, C4, C5), and tomentin (C3). Mixture C2 (IC50 DPPH and ABTS = 2.5 µg/mL) and C3 (IC50 FRAP = 381 µg/mL) showed the highest antioxidant properties. Among the isolated fractions, C4 was the most potential agent in growth inhibition of six bacterial strains including Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Listeria monocytogenes, Bacillus subtilis, and Proteus mirabilis (MIC = 5, 20, 30, 20, 25, and 20 mg/mL, respectively). All identified constituents exerted an inhibitory activity on the growth of Lactuca sativa, of which the mixture C3 performed the maximal inhibition on shoot (IC50 = 49.4 µg/mL) and root (IC50 = 47.1 µg/mL) growth. Findings of this study suggest that gallic acid, methyl gallate, fraxetin, and tomentin isolated from J. podagrica possessed antioxidant, antibacterial, and growth inhibitory potentials.

Isolation and Purification of Potent Growth Inhibitors from Piper methysticum Root.

Piper methysticum (kava) root is known to possess promising weed suppressing activity. The present study was conducted to search for potent plant growth inhibitors from the root of this medicinal pepper plant. The ethyl acetate (EtOAc) extract exhibited the strongest reduction on growth of Raphanus sativus (radish) (IC50 shoot and root growth = 172.00 and 51.31 µg/mL respectively) among solvent extracts. From this active extract, nine potent growth inhibitors involved in the inhibitory activities of P. methysticum root were isolated, purified and characterized by column chromatography (CC), gas chromatography-mass spectrometry (GC-MS), electrospray ionization-mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR). The six fractions purified by CC included two flavanones: 5-hydroxy-4',7-dimethoxyflavanone (C1) and 5,7-dihydroxy-4'-methoxy-6,8-dimethylflavanone (matteucinol, C2) and six kavalactones: 5,6-dehydro-kavain (C3), a mixture of kavain and yagonin (C4), yagonin (C5) and dihydro-5,6-dehydrokavain, 7,8-dihydrokavain, dihydromethysticin and methysticin (C6). The amounts of 5-hydroxy-4',7-dimethoxyflavanone, matteucinol, 5,6-dehydrokavain and yangonin were 0.76, 2.50, 2.75 and 2.09 mg/g dry weight (DW), respectively. The two flavanones C1 and C2 exhibited the strongest inhibition on shoot elongation (IC50 = 120.22 and 248.03 µg/mL, respectively), whilst the two kavalactone mixtures C4 and C6 showed the highest suppression on root growth of R. sativus (IC50 = 7.70 and 15.67 µg/mL, respectively). This study was the first to report the purification and inhibitory activities of the two flavanones 5-hydroxy-4',7-dimethoxyflavanone and matteucinol in P. methysticum root. The isolated constituents from P. methysticum root including the flavanones C1 and C2 and the mixtures C4 and C6 may possess distinct modes of action on plant growth. Findings of this study highlighted that the combinations of hexane-ethyl acetate by 9:1 and 8:2 ratios successfully purified flavanones and kavalactones in P. methysticum root.

Vinpocetine modulates metabolic activity and function during retinal ischemia.

Vinpocetine protects against a range of degenerative conditions and insults of the central nervous system via multiple modes of action. Little is known, however, of its effects on metabolism. This may be highly relevant, as vinpocetine is highly protective against ischemia, a process that inhibits normal metabolic function. This study uses the ischemic retina as a model to characterize vinpocetine's effects on metabolism. Vinpocetine reduced the metabolic demand of the retina following ex vivo hypoxia and ischemia to normal levels based on lactate dehydrogenase activity. Vinpocetine delivered similar effects in an in vivo model of retinal ischemia-reperfusion, possibly through increasing glucose availability. Vinpocetine's effects on glucose also appeared to improve glutamate homeostasis in ischemic Müller cells. Other actions of vinpocetine following ischemia-reperfusion, such as reduced cell death and improved retinal function, were possibly a combination of the drug's actions on metabolism and other retinal pathways. Vinpocetine's metabolic effects appeared independent of its other known actions in ischemia, as it recovered retinal function in a separate metabolic model where the glutamate-to-glutamine metabolic pathway was inhibited in Müller cells. The results of this study indicate that vinpocetine mediates ischemic damage partly through altered metabolism and has potential beneficial effects as a treatment for ischemia of neuronal tissues.

Neurofibromatosis of the larynx causing stridor and sleep apnea.

BACKGROUND: Neurofibromatosis type 1 can rarely present in the larynx. Patients typically do not present with complete obstructive symptoms, but partial obstruction and stridor. We review our health centers' case series of two patients, the first of whom presented with persistent sleep apnea post tonsillectomy and adenoidectomy, and the second who presented with noisy breathing. Additionally, we will review the literature on the management and treatment options for children with this rare clinical entity. METHODS: Retrospective case review. CASE REPORT & RESULTS: A two-year old male underwent a sleep endoscopy following persistent evidence of obstructive sleep apnea on polysomnography after initial tonsillectomy and adenoidectomy. Family elicited concerns about noisy breathing at night and an accompanying video documented stridor while sleeping during the monitored polysomnography. Flexible fiberoptic laryngoscopy in the operating room revealed what appeared to be a cystic mass along the right aryepiglottic fold causing deviation of the laryngeal introitus towards the contralateral side. Subsequent direct laryngoscopy and excisional biopsy revealed pathology results consistent with a plexiform neurofibroma. A six-month-old patient with stertor and stridor was found to have a laryngeal mass, subglottic stensosis, and progressive airway obstruction due to plexiform neurofirboma in the supraglottis, subglottis, and trachea. We present a series of two patients incidentally diagnosed with neurofibromatosis type 1 by way of a laryngeal neurofibroma and review the literature on management options. Both patients were found to have accompanying café au lait spots. Both patients required tracheostomy for airway management, and one was successfully decannulated. CONCLUSION: Laryngeal neurofibroma is a rare anomaly that can manifest with airway obstruction. Both patients presented here subsequently were noted to have café au lait spots on physical examination. The Otolaryngologist should be reminded of this anomaly when evaluating a child with evidence of a submucosal laryngeal mass. We present our series including that of a patient whose diagnosis was prompted by persistent sleep apnea following adenotonsillectomy tonsillectomy and a patient with airway obstruction and subglottic stenosis due to a neurofibroma. The treatment of choice is complete excision of the neurofibroma while maintaining functionality of the larynx. This can lead to successful decannulation.

Gaze Patterns of Normal and Microtia Ears Pre- and Post-Reconstruction.

OBJECTIVES: To understand attentional preferences for normal and microtia ears. METHODS: Eye-tracking technology was used to characterize gaze preferences. A total of 71 participants viewed images of 5 patients with unilateral microtia. Profile images of patient faces and isolated ears including normal, microtia, and post-reconstruction microtia ears were shown. Total time of fixation in predefined areas of interest (AOI) was measured. Inferential statistics were used to assess significance of fixation differences between AOIs within and between facial or auricular features. RESULTS: The ear received most visual attention in lateral view of the face (1.91 s, 1.66-2.16 s) [mean, 95% CI], followed by features of the "central triangle"-the eyes (1.26 s, 1.06-1.46), nose (0.48 s, 0.38-0.58), and mouth (0.15 s, 0.15-0.20). In frontal view, microtia ears received less attention following surgical reconstruction (0.74 s vs. 0.4 s, p < 0.001). The concha was the most attended feature for both normal (2.97 s, 2.7-3.23) and reconstructed microtia ears (1.87 s, 1.61-2.13). Scars on reconstructed ears altered the typical visual scanpath. CONCLUSION: The ear is an attentional gaze landmark of the face. Attention to microtia ears, both pre- and post-reconstruction, differs from gaze patterns of normal ears. The concha was the most attended to subunit of the ear. Attentional gaze may provide an unbiased method to determine what is important in reconstructive surgery. LEVEL OF EVIDENCE: NA Laryngoscope, 134:3136-3142, 2024.

Anxiety and its risk factors among non-Japanese residents living in Japan undergoing COVID-19 situation: A cross-sectional survey.

INTRODUCTION: In the context of collective efforts taken in Japan to control the spread of COVID-19, the state of emergency and social distancing have caused a negative impact on the mental health of all residents, including foreign communities in Japan. This study aimed to evaluate the level of anxiety and its associated factors among non-Japanese residents residing in Japan during the COVID-19 pandemic. METHODS: A web-based survey in 13 languages was conducted among non-Japanese residents living in Japan during the COVID-19 situation. The State-Trait Anxiety Inventory assessed the level of anxiety-State (STAI-S) scores prorated from its six-item version. The multivariable logistic regression using the Akaike Information Criterion (AIC) method was performed to identify the associated factors of anxiety among participants. RESULTS: From January to March 2021, we collected 392 responses. A total of 357 valid responses were analyzed. 54.6% of participants suffered from clinically significant anxiety (CSA). In multivariable logistic model analysis, the CSA status or the high level of anxiety was associated with three factors, including having troubles/difficulties in learning or working, decreased sleep duration, and decreased overall physical health (p<0.05). CONCLUSION: Our study suggests several possible risk factors of anxiety among non-Japanese residents living in Japan undergoing the COVID-19 pandemic, including the troubles or difficulties in learning or working, the decrease in sleep duration, and the decrease in overall physical health.

Climate as a contributing factor in the demise of Angkor, Cambodia.

The "hydraulic city" of Angkor, the capitol of the Khmer Empire in Cambodia, experienced decades-long drought interspersed with intense monsoons in the fourteenth and fifteenth centuries that, in combination with other factors, contributed to its eventual demise. The climatic evidence comes from a seven-and-a-half century robust hydroclimate reconstruction from tropical southern Vietnamese tree rings. The Angkor droughts were of a duration and severity that would have impacted the sprawling city's water supply and agricultural productivity, while high-magnitude monsoon years damaged its water control infrastructure. Hydroclimate variability for this region is strongly and inversely correlated with tropical Pacific sea surface temperature, indicating that a warm Pacific and El Niño events induce drought at interannual and interdecadal time scales, and that low-frequency variations of tropical Pacific climate can exert significant influence over Southeast Asian climate and society.

Tuning the fluorescence of Dy3+ via the structure of borophosphate glasses.

The optical characteristics of Dy3+-doped phosphate and borophosphate glasses with different divalent network modifiers prepared by melt-quenching are studied. The glass sets (A) with a molar composition of 40MO-60P2O5 and (B) with a molar composition of 40MO-20B2O3-40 P2O5 are investigated, both with M = (Zn2+, Mg2+, Ca2+, Sr2+, or Ba2+) and all doped with 0.1 mol% Dy2O3. Raman and fluorescence spectroscopy are used to analyse the structure and optical characteristics of these glasses. Four typical Dy3+ emission bands in the yellow (572 nm), blue (483 nm) and red (633 and 752 nm) regions of the spectrum are observed in both sets. The fluorescence lifetimes in each glass set are correlated to the network modifier's ionic field strength. The Mg2+ and Zn2+ containing glasses have the longest fluorescence lifetimes. The yellow to blue emission intensity ratio of the respective bands can be used to indicate a symmetric environment around Dy3+ ions and varies with the ionic field strength of the modifier cations: a higher ionic field strength leads to a higher yellow to blue ratio, which in turn indicates a higher asymmetrical local coordination environment of Dy3+ ions in the glassy host network.

Use of Convolutional Neural Networks to Evaluate Auricular Reconstruction Outcomes for Microtia.

OBJECTIVES: The objective of this study is to determine whether machine learning may be used for objective assessment of aesthetic outcomes of auricular reconstructive surgery. METHODS: Images of normal and reconstructed auricles were obtained from internet image search engines. Convolutional neural networks were constructed to identify auricles in 2D images in an auto-segmentation task and to evaluate whether an ear was normal versus reconstructed in a binary classification task. Images were then assigned a percent score for "normal" ear appearance based on confidence of the classification. RESULTS: Images of 1115 ears (600 normal and 515 reconstructed) were obtained. The auto-segmentation task identified auricles with 95.30% accuracy compared to manually segmented auricles. The binary classification task achieved 89.22% accuracy in identifying reconstructed ears. When the confidence of the classification was used to assign percent scores to "normal" appearance, the reconstructed ears were classified to a range of 2% (least like normal ears) to 98% (most like normal ears). CONCLUSION: Image-based analysis using machine learning can offer objective assessment without the bias of the patient or the surgeon. This methodology could be adapted to be used by surgeons to assess quality of operative outcome in clinical and research settings. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2413-2416, 2023.

Effect of Pharmacist-Led Interventions on Medication Adherence among Vietnamese Patients with Asthma: A Randomized Controlled Trial.

BACKGROUND: Medication adherence in asthmatic patients enhances the effectiveness of treatments, but some studies in low and middle-income countries still show some limitations. Our study aimed to determine if pharmacist-led interventions could increase medication adherence, improve treatment effectiveness, and relieve symptom severity in outpatients with asthma. METHODS: We conducted a randomized, controlled trial on 247 asthmatic outpatients (aged ≥ 16) with a 1:1 ratio randomization at the hospitalization time and repeated after 1-month discharge. The primary outcome was to detect the difference in medication adherence between groups. Adherence was assessed by the general medication adherence scale (GMAS). Data collected by questionnaire was coded and entered into SPSS_20 for statistical analysis; Results: 247 patients (123 intervention, 124 control) were enrolled (61.1% male). After intervention, the adherence rate was higher among the intervention group than the control group (94.3% vs. 82.8%, p = 0.001). Patient behavior and knowledge were enhanced in the intervention group (p < 0.05). Asthma symptoms were relieved in the intervention group (p = 0.014). Pharmacist-led interventions on adherence rate were higher with OR: 3.550, 95% CI: 1.378-9.143, p = 0.009. CONCLUSIONS: pharmaceutical intervention could improve medication adherence, treatment efficacy, and the outcome should not be taken for granted; further research should be carried out in this regard.

ß-Adrenergic receptor expression in vascular tumors.

Propranolol has recently emerged as an effective therapy for infantile hemangiomas causing regression. The ß-adrenergic receptor (AR) antagonist is thought to cause vasoconstriction by its effect on nitric oxide, block angiogenesis by its effect on vascular endothelial growth factor (VEGF), and induce apoptosis. In a prior report, we identified expression of ß2-AR (B2-AR) and its phosphorylated form (B2-ARP) in a case of infantile hemangioma that responded to propranolol treatment. We now explore the expression of ßARs on a variety of vascular lesions utilizing a tissue microarray containing 141 lesions, including infantile hemangiomas, angiosarcomas, hemangiomas, hemangioendotheliomas, and various vascular malformations. The array was immunostained for B2-AR, B2-ARP, and ß3-AR (B3-AR), and the results scored for the intensity of endothelial cell expression as negative, weak positive, or strong positive. All phases of infantile hemangiomas had strong expression of all three receptors, with the exception of only weak expression of B2-ARP in the proliferative phase infantile hemangioma. Strong expression of all three receptors was present in many hemangiomas, hemangioendotheliomas, and vascular malformations. Absent to weak expression of all three receptors was seen in glomus tumor, hobnail hemangioendothelioma, pyogenic granuloma, and reactive vascular proliferations. This is the first study to report ß-AR expression in a variety of vascular lesions. Although immunohistochemical expression of the receptors does not necessarily indicate that similar pathways of responsiveness to ß-blockade are present, it does raises the possibility that ß-blockade could potentially affect apoptosis and decrease responsiveness to VEGF. Additional study is warranted, as therapeutic options are limited for some patients with these lesions.

Synthesis, Cytotoxicity, ADMET and Molecular Docking Studies of Some Quinoline-Pyrimidine Hybrid Compounds: 3-(2-Amino-6-arylpyrimidin-4- yl)-4-hydroxy-1-methylquinolin-2(1H)-ones.

AIMS: This study aims are the synthesis of 3-(2-amino-6-arylpyrimidin-4-yl)-4-hydroxy-1- methylquinolin-2(1H)-ones and estimation their anticancer activities on HepG2 and KB cancer lines. BACKGROUND: Many derivatives of quinoline-2-on have been interested to synthesize and evaluate their biological properties by organic chemists due to their various biological effects, including antibacterial, antioxidant, anti-inflammatory, anticancer activities. Quinoline-pyrimidine hybrid compounds exhibited various biological activities, such as antituberculosis, antibacterial, anticancer, antifungal, etc. The connection of 4-hydroxyquinoline-2-one with 2-amino-pyrimidine could initiate the new activities. OBJECTIVE: α,ß-Unsaturated ketones of 3-acetyl-4-hydroxy-N-methylquinolin-2-one were prepared. Novel 2-amino-6-aryl-4-(4'-hydroxy-N-methylquinolin-2'-on-3'-yl)pyrimidines have been synthesized by reaction of these corresponding α,ß-unsaturated ketones with guanidine hydrochloride. Human hepatocellular carcinoma HepG2 and squamous cell carcinoma KB cancer lines were used for screening their cytotoxicity. METHODS: 3-Acetyl-4-hydroxy-N-methylquinolin-2-one was prepared from N-methylaniline and diethyl malonate. Reaction of (un)substituted benzaldehydes with this 4-hydroxyquinoline-2-one produced corresponding substituted α,ß-unsaturated ketones in the presence of piperidine as catalyst. 2- Amino-6-aryl-4-(4'-hydroxy-N-methylquinolin-2'-on-3'-yl)pyrimidines have been synthesized from these α,ß-unsaturated ketones of 3-acetyl-4-hydroxy-N-methylquinolin-2-one by reaction of corresponding α,ß-unsaturated ketones with guanidine hydrochloride. All obtained pyrimidines were screened for anticancer activity using MTT bio-assay method. RESULTS: Seven substituted (E)-4-hydroxy-3-(3-(aryl)acryloyl)-1-methylquinolin-2(1H)-ones were prepared and converted to corresponding substituted 2-amino-6-aryl-4-(4'-hydroxy-N-methylquinolin- 2'-on-3'-yl)pyrimidines with yields of 58-74%. All the synthesized pyrimidines were screened for their in vitro anticancer activity against human hepatocellular carcinoma HepG2 and squamous cell carcinoma KB cancer lines. Compounds 6b and 6e had the best activity in the series, with IC50 values equal to 1.32 and 1.33 µM, respectively. ADMET properties showed that compounds 6b, 6e, and 6f possessed the drug-likeness behavior. Cross-docking results indicated that residues GLN778(A), DT8(C), DT9(D), DA12(F), and DG13(F) in the binding pocket as potential ligand binding hot-spot residues for compounds 6b, 6e, and 6f. CONCLUSION: New substituted 2-amino-6-aryl-4-(4'-hydroxy-N-methylquinolin-2'-on-3'-yl)pyrimidines were obtained and displayed significant inhibition against human hepatocellular carcinoma HepG2 and squamous cell carcinoma KB cancer lines.

Post-Tonsillectomy Ibuprofen: Is There a Dose-Dependent Bleeding Risk?

OBJECTIVES/HYPOTHESIS: Post-tonsillectomy hemorrhage (PTH) is a potentially life-threatening complication. A recent meta-analysis suggests that ibuprofen may increase the risk of PTH. The aims of this study were to 1) re-evaluate the effect of ibuprofen on PTH given additional recent evidence and 2) to evaluate a potential dose effect of ibuprofen. STUDY DESIGN: Meta-analysis and meta-regression; single-institution retrospective review. METHODS: We conducted a systematic review of the literature and a meta-analysis of 12 studies comparing postoperative ibuprofen analgesia to non-nonsteroidal anti-inflammatory drug (NSAID) controls. Next, we performed a meta-regression analysis to assess for an effect of dose, if any, on rates of PTH. Five studies specifying a dose of 5 mg/kg (828 patients, 1,411 controls) and 7 studies using 10 mg/kg (5,633 patients, 7,656 controls) were included. We then conducted a novel single-institution, retrospective review of data for 1,046 patients prescribed intermediate-dose 7.5 mg/kg ibuprofen. RESULTS: Ibuprofen was not associated with an increased rate of PTH (log odds ratio [OR], 0.21; 95% confidence interval [CI] -0.15, 0.57). Meta-regression showed that ibuprofen dose (5 and 10 mg/kg) did not have a statistically significant effect on PTH (OR, 1.32; 95% CI 0.30, 5.84). Uncontrolled, aggregate rates of PTH across all studies were 2.29% (N = 828) for 5 mg/kg and 4.65% (N = 5,633) for 10 mg/kg dosing. The rate of secondary hemorrhage in patients prescribed 7.5 mg/kg ibuprofen was 3.10% (N = 1,046). CONCLUSION: We found no statistically significant increased risk of PTH when ibuprofen is prescribed at the low or high range of commonly used clinical dosages, compared to a non-ibuprofen regimen. Further studies with less heterogeneity are needed to determine if there is a clinically relevant dose-dependent difference in PTH with ibuprofen. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1473-1481, 2022.

Isolation and Identification of Constituents Exhibiting Antioxidant, Antibacterial, and Antihyperuricemia Activities in Piper methysticum Root.

The aqueous extract of kava (Piper methysticum) root is known as a traditional beverage for daily intake in the Western Pacific Islands, such as Fiji, Tonga, and Vanuatu, to induce relaxation and health-beneficial effects. In this study, the antioxidant, anti-hyperuricemia, and antibacterial properties of kava root were investigated through the isolation and purification of bioactive compounds in ten fractions separated by column chromatography (CC). They included six flavonoids, 5-hydroxy-4',7-dimethoxyflavanone (C1), matteucinol (C2), isosakuranetin (C3), 5,7- dimethoxyflavanone (C4), 2',4'-dihydroxy-6'-methoxydihydrochalcone (in MC5) and alpinetin (C10), and seven kavalactones, 5,6-dehydrokawain (DK) (in MC5 and C6), kavain (in MC7), yangonin (in MC7 and C8), dihydro-5,6-dehydrokavain (DDK) (in MC9), 7,8-dihydromethysticin (in MC9), dihydromethysticin (in MC9), methysticin (in MC9). The chemical structures of the compounds were illustrated by the analyses of gas chromatography-mass spectrometry (GC-MS), electrospray ionization-mass spectrometry (ESI-MS), nuclear magnetic resonance (1H and 13C-NMR), and X-ray diffraction. The evaluation of the free radical scavenging activity of the isolated substances via the DPPH and ABTS assays revealed that C3 (IC50: ABTS = 76.5; DPPH = 74.8 µg/mL) possessed the strongest antioxidant property. In terms of anti-hyperuricemia activity evaluated via the xanthine oxidase inhibitory in vitro assay, the compound C10 was the most promising inhibitor, revealing an IC50 of 134.52 µg/mL. The two kavalactone mixtures in MC5 and a pure compound C6 inhibited the growth of bacteria Listeria monocytogenes, while MC7 can constrain the development of Klebsiella pneumoniae. This is the first study to isolate, purify, and identify the flavonoids isosakuranetin, 2',4'-dihydroxy-6'-methoxydihydrochalcone and alpinetin in kava root and report their pharmaceutical potential. The identified bioactive compounds showed potent antioxidant, anti-hyperuricemia, and antibacterial activity and thus can enhance the value of beverages and foods derived from kava root.