The impact of bullying in childhood and adolescence.

PURPOSE OF REVIEW: Bullying is a common adversity affecting many children and adolescents. It has been shown to negatively impact the psychological well being not only of targets of bullying, but also that of bullying perpetrators and those witnessing bullying. Bullying is linked to depression and poorer mental health and functioning among children and adolescents. Given the high prevalence of bullying among children and adolescents and the negative mental health sequelae of bullying, this is an area of urgent public health concern. This narrative review brings forth recent research findings in this arena, which could help shape public health policies for addressing and preventing bullying. RECENT FINDINGS: Recent findings demonstrate an association of bullying among children and adolescents with depression, nonsuicidal self-injury, sleep loss, reduced health-related quality of life, poorer rates of graduation from high school and later mental health problems. A recent systematic review also showed an association of peer-victimization among children and adolescents with activation of amygdala, left parahippocampal gyrus and fusiform gyrus, and alterations in other brain areas. SUMMARY: Evidence indicates that bullying in childhood and adolescence is associated with higher odds of developing mental health problems; therefore, early identification and timely intervention is crucial.

The Impact of Paid Maternity Leave on the Mental and Physical Health of Mothers and Children: A Review of the Literature and Policy Implications.

For decades, national paid maternity leave policies of 12 weeks or more have been established in every industrialized country except the United States. Despite women representing 47% of the current U.S. labor force, only 16% of all employed American workers have access to paid parental leave through their workplace. As many as 23% of employed mothers return to work within ten days of giving birth, because of their inability to pay living expenses without income. We reviewed recent studies on the possible effects of paid maternity leave on the mental and physical health of mothers and children. We found that paid maternity leave is associated with beneficial effects on (1) the mental health of mothers and children, including a decrease in postpartum maternal depression and intimate partner violence, and improved infant attachment and child development, (2) the physical health of mothers and children, including a decrease in infant mortality and in mother and infant rehospitalizations, and an increase in pediatric visit attendance and timely administration of infant immunizations, and (3) breastfeeding, with an increase in its initiation and duration. Given the substantial mental and physical health benefits associated with paid leave, as well as favorable results from studies on its economic impact, the United States is facing a clear, evidence-based mandate to create a national paid maternity leave policy. We recommend a national paid maternity leave policy of at least 12 weeks.

Novel p-Functionalized Chromen-4-on-3-yl Chalcones Bearing Astonishing Boronic Acid Moiety as MDM2 Inhibitor: Synthesis, Cytotoxic Evaluation and Simulation Studies.

BACKGROUND: Novel 4-[3-(6/7/8-Substituted 4-Oxo-4H-chromen-3-yl)acryloyl]phenylboronic acid derivatives (5a-h) as well as other 6/7/8-substituted-3-(3-oxo-3-(4-substitutedphenyl) prop-1-enyl)-4H-chromen-4-one derivatives (3a-u) have been designed as p53-MDM2 pathway inhibitors and reported to possess significant cytotoxic properties against several cancer cell lines. OBJECTIVES: The current project aims to frame the structure-anticancer activity relationship of chromen-4-on-3-yl chalcones (3a-u/5a-h). In addition, docking studies were performed on these chromeno-chalcones in order to have an insight into their interaction possibilities with MDM2 protein. METHODS: Twenty-nine chromen-4-on-3-yl chalcone derivatives (3a-u/5a-h) were prepared by utilizing silica supported-HClO4 (green route with magnificent yield) and tested against four cancer cell lines (HCT116, MCF-7, THP-1, NCIH322). RESULTS: Among the series 3a-u, compound 3b exhibited the highest anticancer activity (with IC50 values ranging from 8.6 to 28.4 µM) overall against tested cancer cell lines. Interestingly, para- Boronic acid derivative (5b) showed selective inhibition against colon cancer cell line, HCT-116 with an IC50 value of 2.35 µM. Besides the emblematic hydrophobic interactions of MDM2 inhibitors, derivative 5b was found to exhibit extra hydrogen bonding with GLN59 and GLN72 residues of MDM2 in molecular dynamics (MD) simulation. All the compounds were virtually nontoxic against normal fibroblast cells. CONCLUSION: Novel compounds were obtained with good anticancer activity especially 6- Chlorochromen-4-one substituted boronic acid derivative 5b. The molecular docking study proposed good activity as a MDM-2 inhibitor suggesting hydrophobic as well as hydrogen bonding interactions with MDM2.

Isoindole Derivatives: Propitious Anticancer Structural Motifs.

Isoindole derivatives constitute an important class of biologically active heterocyclic compounds and continue to attract considerable attention due to their diverse pharmacological profile such as, antimicrobial, anthelmintic, insecticidal, cyclooxygenase isoenzyme (COX-2) and thrombin inhibition with special emphasis on anticancer activity. This review highlights anticancer properties of isoindole derivatives and its related structures and hoping that it would further help in generation of new concepts towards rational design and development of more potent and less toxic anticancer agents.

Imidazo[1,2-a]pyridine Scaffold as Prospective Therapeutic Agents.

Imidazo[1,2-a]pyridine is one of the most potential bicyclic 5-6 heterocyclic rings that is recognized as a "drug prejudice" scaffold due to its broad range of applications in medicinal chemistry such as anticancer, antimycobacterial, antileishmanial, anticonvulsant, antimicrobial, antiviral, antidiabetic, proton pump inhibitor, insecticidal activities. This scaffold has also been represented in various marketed preparations such as zolimidine, zolpidem, alpidem. Therefore, several attempts were made to carry out the structural modifications of this scaffold to discover and develop novel therapeutic agents. This review provides a valuable insight into the research findings of wide range of derivatives of imidazo[1,2-a]pyridine scaffold leading to promising heterocyclic compounds which could be explored further for the synthesis of new derivatives as well as construction of potential drug-like chemical libraries for biological screening in search of new therapeutic agents.

Soluble curcumin amalgamated chitosan microspheres augmented drug delivery and cytotoxicity in colon cancer cells: In vitro and in vivo study.

In present investigation, initially curcumin was complexed with 2-HP-ß-CD (curcumin-2-HP-ß-CD-complex) in 1:1 ratio and later amalgamated with chitosan microspheres (curcumin-2-HP-ß-CD-CMs) for selective delivery in colon only through oral route of administration. Various analytical, spectral and in-silico docking techniques revealed that the curcumin was deeply inserted in the 2-HP-ß-CD cavity with apparent stability constant of 3.35×10-3M. Furthermore, the mean particle size of 6.8±2.6µm and +39.2±4.1mV surface charge of curcumin-2-HP-ß-CD-complex-CMs in addition to encapsulation efficiency of about 79.8±6.3% exhibited that the tailored microspheres were optimum for colon delivery of curcumin. This was also demonstrated in dissolution testing and standard cell proliferation assay in which curcumin-2-HP-ß-CD-complex-CMs exhibited maximum release in simulated colonic fluid (SCF, pH ∼7.0-8.0, almond emulsion-ß-glucosidase) with improved therapeutic index in HT-29 cells. Consistently, curcumin-2-HP-ß-CD-complex-CMs successively enhanced the colonic bio-distribution of curcumin by ∼8.36 folds as compared to curcumin suspension in preclinical pharmacokinetic studies. In conclusion, curcumin-2-HP-ß-CD-complex-CMs warrant further in vivo tumor regression study to establish its therapeutic efficacy in experimental colon cancer.

Sigma-2 receptor ligand anchored telmisartan loaded nanostructured lipid particles augmented drug delivery, cytotoxicity, apoptosis and cellular uptake in prostate cancer cells.

Recently, the anticancer activity of telmisartan (TEL) has been discovered against prostate cancer. Nevertheless, despite favorable therapeutic profile, poor aqueous solubility and suboptimal oral bioavailability hamper the anticancer efficacy of TEL. Therefore, in this investigation, sigma-2 receptor ligand, 3-(4-cyclohexylpiperazine-1-yl) propyl amine (CPPA) anchored nanostructured lipid particles of telmisartan (CPPA-TEL-NLPs) were engineered using stearic acid for targeting prostate cancer, PC-3 cells. The mean particle size of TEL-NLPs was measured to be 25.4 ± 3.2 nm, significantly (p < 0.05) lower than 32.6 ± 5.3 nm of CPPA-TEL-NLPs. Correspondingly, the zeta-potential of TEL-NLPs was measured to be -15.4 ± 2.3 mV significantly (p < 0.05) higher than -9.6 ± 2.7 mV of CPPA-TEL-NLPs. The encapsulation efficiency of CPPA-TEL-NLPs was estimated to be 72.7 ± 4.3%, significantly (p < 0.05) lower than 77.5 ± 5.4%, displayed by TEL-NLPs. In addition, FT-IR and PXRD confirmed the molecular encapsulation of the drug in amorphous state. In vitro drug release study was conducted to determine the drug delivery potential of tailored nanoparticles. TEL-NLPs released 93.36% of drug significantly (p < 0.05) higher than 85.81%, released by CPPA-TEL-NLPs in 24 h. The IC50 of CPPA-TEL-NLPs was measured to be 20.3 µM significantly (p < 0.05) lower than 36.3 µM presented by TEL-NLPs in PC-3 cells. In contrast, CPPA-TEL-NLPs displayed the IC50 of 41.3 µM, significantly (p > 0.05) not different from 43.4 µM, exhibited by TEL-NLPs in PNT-2 cells. We elucidated that CPPA-TEL-NLPs entered the PC-3 cells via receptor mediated endocytosis pathway and thus exhibited superior cytotoxicity, apoptosis and greater extent of cellular uptake in PC-3 cells. In conclusion, CPPA-TEL-NLPs may be a promising nanomedicine and warrant further in vivo investigations for gaining clinical success.

Telmisartan complex augments solubility, dissolution and drug delivery in prostate cancer cells.

Telmisartan (TEL) requires superior bioavailability in cancer cell compartments. To meet these challenges, we have synthesized a 2-HP-ß-CD-TEL complex with stability constant (Kc) of 2.39 × 10(-3)mM. The absence in the FTIR spectrum of 2-HP-ß-CD-TEL complex of the characteristic peaks of TEL at 1,699 cm(-1) (carboxylic acid) and 741 and 756 cm(-1) (1,2-disubstituted benzene ring vibrations), is indicative of the encapsulation of TEL in the 2-HP-ß-CD cavity. DSC and PXRD also confirmed the synthesis and amorphous structure of complex. The interaction of TEL with 2-HP-ß-CD was examined by NMR and 2D-ROESY which affirms the encapsulation of TEL in the 2-HP-ß-CD cavity in at least two orientations with equal binding energies. The complex also exhibited its superiority in both in vitro release and cytotoxicity experiments on prostate cancer, PC-3 cells as compared to free drug. These data warrant an in depth in vivo to scale-up the technology for the management of prostate cancer.

Cytotoxic activity of 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones and 4-oxo-4H-chromene-3-carbothioic acid N-phenylamides.

6/6,7-Substituted-3-formylchromones (8a-g) were reacted with 2 equivalents thiobenzamide (9) in refluxing toluene to furnish substituted-3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones (10a-g) in high yields. Similarly, when substituted-2-anilino-3-formylchromones (8a-d) were reacted with thiobenzamide (9, 2 equivalents) in refluxing xylene, 4-oxo-4H-chromene-3-carbothioic acid N-phenylamides (11a-d) were obtained in high yields. All the compounds (10a-g) and (11a-d) display significant cytotoxic activity against a number of human cancer cell lines. Among these compounds 10e (IC(50) = 10 microM), 10b (IC(50) = 14.6 microM) and 10a (IC(50) = 10.5 microM) showed maximum cytotoxic activity on neuroblastoma. Also, the compound 10c (IC(50) = 10.5 microM) showed maximum cytotoxic activity on ovarian cancer cell line.

Mechanism of unusual formation of 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones and 4-oxo-4H-chromene-3-carbothioic acid N-phenylamides and their antimicrobial evaluation.

6/6,7-Substituted 3-formylchromones (9a-e) react with 2 equivalents of 2-phenyl-4-dimethylamino-1-thia-3-azabuta-1,3-diene (10) or thiobenzamide (11) in refluxing toluene to furnish novel substituted 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones (12a-e). However, reactions of substituted 2-anilino-3-formylchromones (15a-d) with thiobenzamide (11, 2 equivalents) in refluxing xylene furnish 4-oxo-4H-chromene-3-carbothioic acid N-phenylamide (17a-d) in high yields. A mechanistic rationalization of the conversion of 2-anilino-3-formylchromones (15a-d) to N-phenylamides (17a-d), and 3-formylchromones (9a-e) to the corresponding thioaldehydes, is proffered. All the compounds (12a-e, 17a-d) display very high antifungal and antibacterial activities against a number of strains. Dithiazole 12d exhibits a very high antifungal activity (MIC 5 microg/ml) against Geotrichum candidum, better than fluconazole (MIC 09 microg/ml) and also possesses good antibacterial activity (MIC 52 microg/ml) against Shigella flexneri.