5-HT3 Receptors on Mitochondria Influence Mitochondrial Function.

The 5-hydroxytryptamine 3 (5-HT3) receptor belongs to the pentameric ligand-gated cation channel superfamily. Humans have five different 5-HT3 receptor subunits: A to E. The 5-HT3 receptors are located on the cell membrane, but a previous study suggested that mitochondria could also contain A subunits. In this article, we explored the distribution of 5-HT3 receptor subunits in intracellular and cell-free mitochondria. Organelle prediction software supported the localization of the A and E subunits on the inner membrane of the mitochondria. We transiently transfected HEK293T cells that do not natively express the 5-HT3 receptor with an epitope and fluorescent protein-tagged 5HT3A and 5HT3E subunits. Fluorescence microscopy and cell fractionation indicated that both subunits, A and E, localized to the mitochondria, while transmission electron microscopy revealed the location of the subunits on the mitochondrial inner membrane, where they could form heteromeric complexes. Cell-free mitochondria isolated from cell culture media colocalized with the fluorescent signal for A subunits. The presence of A and E subunits influenced changes in the membrane potential and mitochondrial oxygen consumption rates upon exposure to serotonin; this was inhibited by pre-treatment with ondansetron. Therefore, it is likely that the 5-HT3 receptors present on mitochondria directly impact mitochondrial function and that this may have therapeutic implications.

Hepatoprotective effect of withanolide-rich fraction in acetaminophen-intoxicated rat: decisive role of TNF-α, IL-1ß, COX-II and iNOS.

CONTEXT: Overdose of acetaminophen (APAP) is common in humans and is often associated with hepatic damage. Withania somnifera (L.) Dunal (Solanaceae) shows multiple pharmacological activities including antioxidant and anti-inflammatory potential. OBJECTIVE: To evaluate the possible mechanism of hepatoprotective activity of withanolide-rich fraction (WRF) isolated from a methanolic extract of Withania somnifera roots. MATERIALS AND METHODS: Hepatotoxicity was induced by oral administration of APAP (750 mg/kg, p.o.) for 14 d. The control group received the vehicle. APAP-treated animals were given either silymarin (25 mg/kg) or graded doses of WRF (50, 100 and 200mg/kg) 2 h prior to APAP administration. Animals were killed on 15th day and blood and liver tissue samples were collected for the further analysis. RESULTS: In WRF-treated group, there was significant and dose-dependent (p < 0.01 and p < 0.001) decrease in serum bilirubin, ALP, AST and ALT levels with significant and dose-dependent (p < 0.01 and p < 0.001) increase in hepatic SOD, GSH and total antioxidant capacity. The level of MDA and NO decreased significantly (p < 0.01) by WRF treatment. Up-regulated mRNA expression of TNF-α, IL-1ß, COX-II and iNOS was significantly down-regulated (p < 0.001) by WRF. Histological alternations induced by APAP in liver were restored to near normality by WRF pretreatment. CONCLUSION: WRF may exert its hepatoprotective action by alleviating inflammatory and oxido-nitrosative stress via inhibition of TNF-α, IL-1ß, COX-II and iNOS.

Effect of macronutrient deficiency on withanolides content in the roots of Withania somnifera and its correlationship with molybdenum content.

CONTEXT: The content of withanolides in the roots of Withania somnifera (L.) Dunal (Solanaceae) is important for therapeutic application. Earlier studies have shown that the deficiency of macro- and micronutrients affects the growth of W. somnifera. Therefore, we examined the effect of these deficiencies on the withanolides content of the roots. OBJECTIVE: To examine the effect of molybdenum accretion in nitrogen-, phosphorus-, calcium- and potassium-deficient soils on the accumulation of withanolides in the roots of W. somnifera. Different withanolides have different therapeutic applications hence major bioactive withanolides assume importance. MATERIALS AND METHODS: Methanol extracts of the roots were subjected to HPTLC and individual withanolides were identified by comparing their Rf values with those of the authentic samples. Molybdenum was quantified by atomic absorption spectroscopy. Free radical scavenging activity was monitored by the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay. RESULTS: Molybdenum content in roots of nitrogen-, phosphorus-, calcium-, potassium-deficient, and control plants were 7.02 ± 2.1, 13.1 ± 1.6, 17.1 ± 0.9, 33.5 ± 3.3, and 33.9 ± 1.6 ppm, respectively. Levels of withaferine A increased with the increase in the Mo content in roots from 7.79 ± 2.2 mg/g to 12.57 ± 3.4 mg/g. Antioxidant activity of nitrogen-deficient plants was the lowest (24.7 ± 2.2%) compared to other groups. DISCUSSION AND CONCLUSION: It was observed that nitrogen metabolism-dependent molybdenum uptake influences the withanolides accumulation in the roots.

Effects of phentermine / topiramate extended-release, phentermine, and placebo on ambulatory blood pressure monitoring in adults with overweight or obesity: A randomized, multicenter, double-blind study.

Background: A fixed-dose combination of phentermine and extended-release topiramate (PHEN/TPM - approved for weight management) has demonstrated in-clinic reduction of blood pressure (BP). Ambulatory BP monitoring (ABPM) may be a better predictor of cardiovascular disease risk than in-clinic BP. Methods: This randomized, multicenter, double-blind study enrolled 565 adults with overweight/obesity. Inclusion criteria included participants willing to wear ABPM device for 24 h. Exclusion criteria included screening blood pressure >140/90 mmHg and antihypertensive medications not stable for 3 months prior to randomization. Participants received placebo (n = 184), phentermine 30 mg; (n = 191), or PHEN 15 mg/TPM 92 mg; (n = 190). 24-hour ABPM was performed at baseline and at week 8. The primary endpoint was mean 24-h systolic BP (SBP) as measured by ABPM, in the per protocol population. Results: Participants were mostly female (73.5 â€‹%) and White (81.6 â€‹%), with a mean age of 53.4 years; 32.4 â€‹% had no hypertension diagnosis or treatment, 62.5 â€‹% had hypertension using 0 to 2 antihypertensive medications, and 5.1 â€‹% had hypertension using ≥ 3 antihypertensive medications. Baseline mean SBP/diastolic BP (DBP) was 123.9/77.6 â€‹mmHg. At week 8, mean SBP change was -0.1 â€‹mmHg (placebo), +1.4 â€‹mmHg (phentermine 30 â€‹mg), and -3.3 â€‹mmHg (PHEN/TPM). Between-group difference for PHEN/TPM versus placebo was -3.2 â€‹mmHg (95 â€‹% CI: -5.48, -0.93 â€‹mmHg; p â€‹= â€‹0.0059). The between-group difference for PHEN/TPM versus phentermine 30 â€‹mg was -4.7 â€‹mmHg (95 â€‹% CI: -6.96, -2.45 â€‹mmHg; p â€‹< â€‹0.0001). Common (>2 â€‹% in any treatment group) adverse events (i.e., dry mouth, constipation, nausea, dizziness, paresthesia, dysgeusia, headache, COVID-19, urinary tract infection, insomnia, and anxiety) were mostly mild or moderate. Conclusions: In this randomized, multicenter, double-blind ABPM study, PHEN/ TPM reduced SBP compared to either placebo or phentermine 30 mg (Funding: Vivus LLC; ClinicalTrials.gov: NCT05215418).

Phylogenetic analyses of 5-hydroxytryptamine 3 (5-HT3) receptors in Metazoa.

The 5-hydroxytrptamine 3 (5-HT3) receptor is a member of the 'Cys-loop' family and the only pentameric ligand gated ion channel among the serotonin receptors. 5-HT3 receptors play an important role in controlling growth, development, and behaviour in animals. Several 5-HT3 receptor antagonists are used to treat diseases (e.g., irritable bowel syndrome, nausea and emesis). Humans express five different subunits (A-E) enabling a variety of heteromeric receptors to form but all contain 5HT3A subunits. However, the information available about the 5-HT3 receptor subunit occurrence among the metazoan lineages is minimal. In the present article we searched for 5-HT3 receptor subunit homologs from different phyla in Metazoa. We identified more than 1000 5-HT3 receptor subunits in Metazoa in different phyla and undertook simultaneous phylogenetic analysis of 526 5HT3A, 358 5HT3B, 239 5HT3C, 70 5HT3D, and 173 5HT3E sequences. 5-HT3 receptor subunits were present in species belonging to 11 phyla: Annelida, Arthropoda, Chordata, Cnidaria, Echinodermata, Mollusca, Nematoda, Orthonectida, Platyhelminthes, Rotifera and Tardigrada. All subunits were most often identified in Chordata phylum which was strongly represented in searches. Using multiple sequence alignment, we investigated variations in the ligand binding region of the 5HT3A subunit protein sequences in the metazoan lineage. Several critical amino acid residues important for ligand binding (common structural features) are commonly present in species from Nematoda and Platyhelminth gut parasites through to Chordata. Collectively, this better understanding of the 5-HT3 receptor evolutionary patterns raises possibilities of future pharmacological challenges facing Metazoa including effects on parasitic and other species in ecosystems that contain 5-HT3 receptor ligands.

AlCl3@ZnO nanostructured material: an efficient green catalyst for the one-pot solvent-free synthesis of 1,4-dihydropyridines.

AlCl3-loaded ZnO nanoparticles have been explored as an efficient catalyst for 1,4-dihydropyridine synthesis under ambient temperature and solvent-free conditions. For this purpose, ZnO nanoparticles were synthesized by a simple solution-based precipitation technique using a stoichiometric amount of zinc sulfate and oxalic acid. The AlCl3@ZnO nanocrystalline catalyst was prepared by loading 20% AlCl3 on ZnO nanoparticles by a simple wet-impregnation technique. This catalyst efficiently performed Hantzsch pyridine reactions with various aromatic aldehydes, ethyl acetoacetate and ammonium acetate. The nanostructured AlCl3-loaded ZnO catalyst was characterized by UV-DRS, XRD, FESEM, EDS, FETEM-STEM-EDS and XPS techniques. The comprehensive characterization reveals the formation of AlCl3-loaded ZnO catalysts with an average particle size of 70-80 nm. The loading of AlCl3 on the ZnO surface was confirmed by minor shifts in the XPS and XRD peaks. FETEM-STEM-EDS also indicates reasonable AlCl3 loading on ZnO nanoparticles. The 20% AlCl3-loaded ZnO nanocatalyst (AlCl3@ZnO) confers 92% yield for the synthesis of 1,4-dihydropyridine under solvent-free and ambient temperature conditions. The synthesized 1,4-dihydropyridines were characterized by 1H-NMR, 13C-NMR, HRMS and FT-IR spectroscopic techniques. The reported catalyst is highly efficient, environmentally friendly and could become an alternative to homogenous and heterogenous catalytic reactions.

Correction: AlCl3@ZnO nanostructured material: an efficient green catalyst for the one-pot solvent-free synthesis of 1,4-dihydropyridines.

[This corrects the article DOI: 10.1039/D3RA04277D.].

Diagnostic reliability of fine needle aspiration cytology against histopathology for the diagnosis of oral squamous cell carcinoma and oral leukoplakia.

AIM: The purpose of this study was to determine the possibility of using fine needle aspiration cytology (FNAC) as a primary diagnostic test in oral leukoplakia and squamous cell carcinoma. MATERIALS AND METHODS: This study consisted of clinically diagnosed 15 cases of leukoplakia and 15 cases of oral squamous cell carcinomas. FNAC and biopsy were done on all the cases. A cytological and histopathological correlation was undertaken to determine the proportion of cancers. A 23-gauge sterile disposable needle was attached to a disposable syringe and introduced into the lesion at the proposed biopsy site in one movement. In leukoplakias, the center of the lesion or erythroplakic areas and, in squamous cell carcinomas, proliferative areas and edges of the ulcers were chosen. RESULTS: In leukoplakia group, out of 15 biopsy samples, one (6.67%) sample was negative and 14 (93.33%) were positive. Whereas out of 15 FNAC samples, 14 (93.33%) were negative and one (6.67%) sample was positive. In squamous cell carcinoma, out of 15 biopsy samples, no sample was negative and all (100.00%) were positive. Whereas out of 15 FNAC samples, two (13.33%) were negative and 13 (86.67%) sample were positive. CONCLUSION: It is noted that FNAC can be employed as a sound diagnostic tool for rapid diagnosis of oral squamous cell carcinoma. It may be particularly useful in cases, where formal biopsy procedure is difficult or contraindicated due to medical reasons or in cases of advanced malignancy. CLINICAL SIGNIFICANCE: FNAC has been shown to be reliable and safe technique in the diagnosis of malignant in the head and neck. When the aspirations are performed by cytopathologists, it is easy to perform a rapid staining of the first smear and within 10 to 15 minutes to ensure that the material is sufficient and diagnosable and to suggest a preliminary diagnosis.

Phentermine/Topiramate for the Treatment of Adolescent Obesity.

BACKGROUND: Antiobesity medication may be useful for the treatment of pediatric obesity, yet few safe and effective options exist. We evaluated phentermine/topiramate (PHEN/TPM) for weight management in adolescents with obesity. METHODS: This 56-week, randomized, double-blind trial enrolled adolescents 12 to less than 17 years of age with obesity. Participants were randomly assigned 1:1:2 to receive either placebo (n=56), mid-dose PHEN/TPM (7.5 mg/46 mg; n=54), or top-dose PHEN/TPM (15 mg/92 mg; n=113), respectively. All participants received lifestyle therapy. The primary end point was mean percent change in body-mass index (BMI) from randomization to week 56. RESULTS: Participants had a mean (±SD) age of 14.0±1.4 years and a mean (±SD) BMI of 37.8±7.1 kg/m2; 54.3% were female. The primary end point of percent change in BMI at week 56 showed differences from placebo of -10.44 percentage points (95% CI, -13.89 to -6.99; P<0.001) and -8.11 percentage points (95% CI, -11.92 to -4.31; P<0.001) for the top and mid doses of PHEN/TPM, respectively. Differences from placebo in percent change in triglycerides nominally favored PHEN/TPM (mid dose, -21%; 95% CI, -40 to -2; and top dose, -21%; 95% CI, -38 to -4), as did differences in percent change in high-density lipoprotein cholesterol (HDL-C) (mid dose, 10%; 95% CI, 3 to 18; and top dose, 9%; 95% CI, 2 to 15). The incidence of participants reporting at least one adverse event was 51.8%, 37.0%, and 52.2% in the placebo, mid-dose, and top-dose groups, respectively. Serious adverse events were reported for two participants in the top-dose group. CONCLUSIONS: PHEN/TPM at both the mid and top doses offered a statistically significant reduction in BMI and favorably impacted triglyceride and HDL-C levels in adolescents with obesity. (Funded by VIVUS LLC, with project support provided by Covance LLC; ClinicalTrials.gov number, NCT03922945.).

Nucleobindin 1 is a calcium-regulated guanine nucleotide dissociation inhibitor of G{alpha}i1.

Nucleobindin 1 (NUCB1) is a widely expressed multidomain calcium-binding protein whose precise physiological and biochemical functions are not well understood. We engineered and heterologously expressed a soluble form of NUCB1 (sNUCB1) and characterized its biophysical and biochemical properties. We show that sNUCB1 exists as a dimer in solution and that each monomer binds two divalent calcium cations. Calcium binding causes conformational changes in sNUCB1 as judged by circular dichroism and fluorescence spectroscopy experiments. Earlier reports suggested that NUCB1 might interact with heterotrimeric G protein α subunits. We show that dimeric calcium-free sNUCB1 binds to expressed Gα(i1) and that calcium binding inhibits the interaction. The binding of sNUCB1 to Gα(i1) inhibits its basal rate of GDP release and slows its rate and extent of GTPγS uptake. Additionally, our tissue culture experiments show that sNUCB1 prevents receptor-mediated Gα(i)-dependent inhibition of adenylyl cyclase. Thus, we conclude that sNUCB1 is a calcium-dependent guanine nucleotide dissociation inhibitor (GDI) for Gα(i1). To our knowledge, sNUCB1 is the first example of a calcium-dependent GDI for heterotrimeric G proteins. We also show that the mechanism of GDI activity of sNUCB1 is unique and does not arise from the consensus GoLoco motif found in RGS proteins. We propose that cytoplasmic NUCB1 might function to regulate heterotrimeric G protein trafficking and G protein-coupled receptor-mediated signal transduction pathways.

Combined treatment with formoterol and tiotropium is more efficacious than treatment with tiotropium alone in patients with chronic obstructive pulmonary disease, regardless of smoking status, inhaled corticosteroid use, baseline severity, or gender.

A recent randomized, double-blind, parallel-group, active-controlled, multicenter study of 255 patients ≥ 40 years of age with chronic obstructive pulmonary disease (COPD) showed that combined formoterol (FOR) and tiotropium (TIO) treatment in patients with COPD significantly improved lung function as well as symptoms and other patient-reported outcomes compared with TIO alone. FOR and TIO are long-acting bronchodilators that represent the ß2-adrenergic agonist and anticholinergic classes, respectively. However, the possible influence of smoking status, inhaled corticosteroid (ICS) use, baseline disease severity, and gender differences on bronchodilator efficacy requires further investigation. Using data from the previously published study mentioned above, a post hoc analysis was performed to examine the efficacy of combined FOR + TIO treatment compared with TIO monotherapy in subgroup analyses of men and women, current and ex-smokers, ICS users and non-ICS users, and patients with moderate and severe/very severe COPD. Efficacy comparisons were based on the changes in forced expiratory volume in 1 s measured 0-4 h after the morning dose (FEV1 AUC0₋4h). After a run-in period, patients were treated for 12 weeks with either FOR 12 µg twice daily (BID) plus TIO 18 µg once daily (QD) in the morning (AM, n = 124) or with FOR placebo BID plus TIO 18 µg QD AM (n = 131). The least squares mean change from baseline in the normalized FEV1 AUC0₋4h was assessed using analysis of covariance. With the exception of treatment differences at week 4 in smokers and subjects with "very severe" COPD, and at weeks 4, 8, and 12 for ICS users and non-ICS users (p values not determined), FOR + TIO was significantly superior (P < 0.05) to TIO alone at all time points (weeks 4, 8, 12, and endpoint), regardless of gender, smoking status, ICS use, or COPD severity. We conclude that coadministered FOR + TIO significantly improves lung function compared with TIO treatment alone in COPD patients regardless of differences in patient subgroups.

Indian Academy of Pediatrics Guidelines for Pediatric Skin Care.

OBJECTIVE: To develop standard recommendations for skin care in neonates, infants and children to aid the pediatrician to provide quality skin care to infants and children. JUSTIFICATION: Though skin is the largest organ in the body with vital functions, skin care in children especially in newborns and infants, is not given the due attention that is required. There is a need for evidence-based recommendations for the care of skin of newborn babies and infants in India. PROCESS: A committee was formed under the auspices of Indian Academy of Pediatrics in August, 2018 for preparing guidelines on pediatric skin care. Three meetings were held during which we reviewed the existing guidelines/ recommendations/review articles and held detailed discussions, to arrive at recommendations that will help to fill up the knowledge gaps in current practice in India. The initial draft of the manuscript based on the available evidence and experience, was sent to all members for their inputs, after which it was finalized. RECOMMENDATIONS: Vernix caseosa should not be removed. First bath should be delayed until 24 hours after birth, but not before 6 hours, if it is not practically possible to delay owing to cultural reasons. Duration of bath should not exceed 5-10 minutes. Liquid cleanser with acidic or neutral pH is preferred, as it will not affect the skin barrier function or the acid mantle. Cord stump must be kept clean without any application. Diaper area should be kept clean and dry with frequent change of diapers. Application of emollient in newborns born in families with high risk of atopy tends to reduce the risk of developing atopic dermatitis. Oil massage has multiple benefits and is recommended. Massage with sunflower oil, coconut oil or mineral oil are preferred over vegetable oils such as olive oil and mustard oil, which have been found to be detrimental to barrier function.

Pregnancy-related emergencies: Profile and outcome.

BACKGROUND: National efforts to reduce maternal mortality with respect to community services have primarily focused on upgrading transportation infrastructure and formalizing training for care providers. There is, however, a paucity of baseline data on the profile and outcomes of pregnant women presenting to the Emergency Department (ED) in India. METHODS: This retrospective study enrolled all pregnant women presenting to a large tertiary medical care center in India, between November 2016 and November 2017. RESULTS: There were 696 ED visits by pregnant women during the study period. The mean age was 26.85 (SD: 4.88) years. Pregnant women in the first trimester contributed to 50.8% of all visits, and 54% being multigravida. The most common presenting complaints were bleeding/spotting per vaginum (PV) (38.2%) and abdominal pain (37.6%) followed by fever (21.6%) and vomiting (21.5%). Obstetric causes contributed to 53.2% of the ED visits, while nonobstetric causes amounted to 43.2%. Over a third (39.7%) required hospital admission. Of these patients, 73% delivered in CMC with live births amounting to 62.3% while 3.5% ended in fetal deaths. The miscarriages rate was as high as 28%. More than half (51.1%) of the deliveries were by normal vaginal delivery. There were no maternal deaths during the time of admission. CONCLUSIONS: Our study sheds new light on the profile of emergency visits among pregnant patients and their relationship to the outcome of pregnancy. First trimester visits were most common with complaints of bleeding PV and abdominal pain. This could explain the high rate of miscarriages among this population.

Nanostructured N doped TiO2 efficient stable catalyst for Kabachnik-Fields reaction under microwave irradiation.

Herein, we report nitrogen-doped TiO2 (N-TiO2) solid-acid nanocatalysts with heterogeneous structure employed for the solvent-free synthesis of α-aminophosphonates through Kabachnik-Fields reaction. N-TiO2 were synthesized by direct amination using triethylamine as a source of nitrogen at low temperature and optimized by varying the volume ratios of TiCl4, methanol, water, and triethylamine, under identical conditions. An X-ray diffraction (XRD) study showed the formation of a rutile phase and the crystalline size is 10 nm. The nanostructural features of N-TiO2 were examined by HR-TEM analysis, which showed they had rod-like morphology with a diameter of ∼7 to 10 nm. Diffuse reflectance spectra show the extended absorbance in the visible region with a narrowing in the band gap of 2.85 eV, and the high resolution XPS spectrum of the N 1s region confirmed successful doping of N in the TiO2 lattice. More significantly, we found that as-synthesized N-TiO2 showed significantly higher catalytic activity than commercially available TiO2 for the synthesis of a novel series of α-amino phosphonates via Kabachnik-Fields reaction under microwave irradiation conditions. The improved catalytic activity is due to the presence of strong and Bronsted acid sites on a porous nanorod surface. This work signifies N-TiO2 is an efficient stable catalyst for the synthesis of α-aminophosphonate derivatives.

Indian Academy of Pediatrics Position Paper on Kawasaki Disease.

OBJECTIVE: To formulate practice guidelines on diagnosis and management of Kawasaki disease (KD) for Indian children. JUSTIFICATION: KD is a systemic vasculitis that predominantly affects infants and children less than 5 years of age. Coronary artery abnormalities (CAA) develop in around 15-25% of untreated children with KD. Coronary artery involvement can lead to long-term cardiovascular implications such as development of premature coronary artery disease. Diagnosis of KD is essentially clinical based on recognition of a constellation of characteristic symptoms and signs. Timely diagnosis and initiation of intravenous immunoglobulin (IVIG) therapy is known to produce five-fold reduction in the incidence of CAA. As there is no confirmatory laboratory test for KD, the diagnosis may be missed if one is not familiar with the nuances of clinical diagnosis. PROCESS: A committee was formed under the auspices of Indian Academy of Pediatrics in early 2018 for preparing guidelines on KD in Indian children. A meeting of the consultative committee was held in Mumbai, and a draft protocol was devised. All members scrutinized the recent publications on the subject and an attempt was made to arrive at a broad consensus. Published guidelines on the subject were also reviewed. RECOMMENDATIONS: The diagnosis is clinical and is aided by laboratory and 2D echocardiography. First line of therapy is IVIG, and should be started expeditiously once the diagnosis is made.

Formoterol and tiotropium compared with tiotropium alone for treatment of COPD.

Combined use of beta(2)-agonists and anticholinergic bronchodilators may have complementary benefits in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to compare combination treatment with formoterol (FORM) plus tiotropium (TIO) versus treatment with TIO alone in patients with COPD. In this active-controlled, double-blind, multicenter trial, a total of 255 subjects with diagnosed COPD were randomized to 12 weeks of either a combination of FORM 12 microg twice-daily plus TIO 18 microg once-daily in the morning (QD AM) or monotherapy with TIO 18 microg QD AM. The primary efficacy variable was the area under the curve for forced expiratory volume in 1 second measured 0 to 4 hours after AM dosing (FEV(1) AUC(0-4h)). Significantly greater improvements in the FEV(1) AUC(0-4h) were seen with FORM + TIO (n = 116) versus TIO (n = 124) at all time points. The increase in FEV(1) 5 minutes after the first dose was 180 mL with FORM + TIO versus 40 mL with TIO (p < 0.001). At endpoint, FEV(1) AUC(0-4h) increased 340 mL with FORM + TIO versus 170 mL with TIO (p < 0.001). Improvements in trough FEV(1) with FORM + TIO versus TIO were 180 mL and 100 mL, respectively (p < 0.01). Significantly greater reductions from baseline in symptom scores (p < 0.05) and daytime albuterol use (p < 0.04) were seen at endpoint with combination FORM + TIO versus TIO monotherapy. Both treatments were well tolerated. This study demonstrated that concurrent treatment with FORM + TIO results in greater therapeutic benefits than TIO alone.

Cytological diagnosis of cysticercosis: Role of FNAC with On-Site evaluation.

Cysticercosis is a zoonotic disease, caused by the larval form of pork tapeworm Taenia solium. This disease is a public health problem in a country such as India, but its incidence is likely underestimated. With the advent of fine needle aspiration cytology (FNAC) with rapid on-site evaluation (ROSE), early detection of this disease is possible, especially when the lesion is in anatomically approachable superficial locations. We report a case of cysticercosis confirmed by FNAC in the Department of Pathology where ROSE using toluidine blue was done as a part of routine cytology procedure. FNAC diagnosis of cysticercosis can be easily made provided the reporting cytologist is aware of the morphological criteria.

ZnCl2 loaded TiO2 nanomaterial: an efficient green catalyst to one-pot solvent-free synthesis of propargylamines.

One-pot green synthesis of propargylamines using ZnCl2 loaded TiO2 nanomaterial under solvent-free conditions has been effectively accomplished. The aromatic aldehydes, amines, and phenylacetylene were reacted at 100 °C in the presence of the resultant catalyst to form propargylamines. The nanocrystalline TiO2 was initially synthesized by a sol-gel method from titanium(iv) isopropoxide (TTIP) and further subjected to ZnCl2 loading by a wet impregnation method. X-ray diffraction (XRD) patterns revealed the formation of crystalline anatase phase TiO2. Field emission scanning electron microscopy (FESEM) showed the formation of agglomerated spheroid shaped particles having a size in the range of 25-45 nm. Transmission electron microscopy (TEM) validates cubical faceted and nanospheroid-like morphological features with clear faceted edges for the pure TiO2 sample. Surface loading of ZnCl2 on spheroid TiO2 nanoparticles is evident in the case of the ZnCl2 loaded TiO2 sample. X-ray photoelectron spectroscopy (XPS) confirmed the presence of Ti4+ and Zn2+ species in the ZnCl2 loaded TiO2 catalyst. Energy-dispersive X-ray (EDS) spectroscopy also confirmed the existence of Ti, O, Zn and Cl elements in the nanostructured catalyst. 15% ZnCl2 loaded TiO2 afforded the highest 97% yield for 3-(1-morpholino-3-phenylprop-2-ynyl)phenol, 2-(1-morpholino-3-phenylprop-2-ynyl)phenol and 4-(1,3-diphenylprop-2-ynyl)morpholine under solvent-free and aerobic conditions. The proposed nanostructure-based heterogeneous catalytic reaction protocol is sustainable, environment-friendly and offers economic viability in terms of recyclability of the catalyst.

Indian Academy of Pediatrics Guidelines on the Fast and Junk Foods, Sugar Sweetened Beverages, Fruit Juices, and Energy Drinks.

JUSTIFICATION: In view of easy availability and increasing trend of consumption of fast foods and sugar sweetened beverages (fruit juices and drinks, carbonated drinks, energy drinks) in Indian children, and their association with increasing obesity and related non-communicable diseases, there is a need to develop guidelines related to consumption of foods and drinks that have the potential to increase this problem in children and adolescents. OBJECTIVES: To review the evidence and formulate consensus statements related to terminology, magnitude of problem and possible ill effects of junk foods, fast foods, sugar-sweetened beverages and carbonated drinks; and to formulate recommendations for limiting consumption of these foods and beverages in Indian children and adolescents. PROCESS: A National Consultative group constituted by the Nutrition Chapter of the Indian Academy of Pediatrics (IAP), consisting of various stakeholders in private and public sector, reviewed the literature and existing guidelines and policy regulations. Detailed review of literature was circulated to the members, and the Group met on 11th March 2019 at New Delhi for a day-long deliberation on framing the guidelines. The consensus statements and recommendations formulated by the Group were circulated to the participants and a consensus document was finalized. CONCLUSIONS: The Group suggests a new acronym 'JUNCS' foods, to cover a wide variety of concepts related to unhealthy foods (Junk foods, Ultra-processed foods, Nutritionally inappropriate foods, Caffeinated/colored/carbonated foods/beverages, and Sugar-sweetened beverages). The Group concludes that consumption of these foods and beverages is associated with higher free sugar and energy intake; and is associated with higher body mass index (and possibly with adverse cardiometabolic consequences) in children and adolescents. Intake of caffeinated drinks may be associated with cardiac and sleep disturbances. The Group recommends avoiding consumption of the JUNCS by all children and adolescents as far as possible and limit their consumption to not more than one serving per week. The Group recommends intake of regional and seasonal whole fruits over fruit juices in children and adolescents, and advises no fruit juices/drinks to infants and young children (age <2y), whereas for children aged 2-5 y and >5-18 y, their intake should be limited to 125 mL/day and 250mL/day, respectively. The Group recommends that caffeinated energy drinks should not be consumed by children and adolescents. The Group supports recommendations of ban on sale of JUNCS foods in school canteens and in near vicinity, and suggests efforts to ensure availability and affordability of healthy snacks and foods. The Group supports traffic light coding of food available in school canteens and recommends legal ban of screen/print/digital advertisements of all the JUNCS foods for channels/magazines/websites/social media catering to children and adolescents. The Group further suggests communication, marketing and policy/taxation strategies to promote consumption of healthy foods, and limit availability and consumption of the JUNCS foods.