PHACES syndrome with congenital hypothyroidism

The acronym PHACE syndrome stands for Posterior fossa malformations, Hemangiomas, Arterial anomalies, Coarctation of the aorta and other cardiac defects, Eye abnormalities, Sternal clefting and/or a supraumbilical raphe. We report a 20 day old neonate who presented with a large facial hemangioma and Dandy-Walker cyst. This case is unusual because the cyst was detected antenatally and there was associated congenital hypothyroidism, which has been described very rarely with this condition.     

Nager acrofacial dysostosis: An unusual association with both upper and lower eyelid colobomas

Nager acrofacial dysostosis comprises defects of cranio facial region and limbs (mostly upper) with variable associated anomalies. The cranio-facial complex is indistinguishable from the mandibulo facial dysostosis (Treacher Collins syndrome). About 80 cases have been described in the literature. We describe the case of a one-day-old male neonate who presented with the typical features of the disease complex. Although normal life span has been reported, our patient died on the second day due to cardio respiratory failure. We report this case because of its rarity and an unusual associated feature of bilaterally symmetrical upper and lower eyelid colobomas.     

Synthesis and photovoltaic application of NIR-emitting perylene-monoimide dyes with large Stokes-shift

An efficient Sonogashira coupling protocol is developed for tetra-alkynylation at the bay and peri-positions of the perylene-monoimide (PMI) dye in its PMI(Br)₄ form. The absorption band for these PMI dyes covered from the visible to Near-infrared (NIR) region and PMI(NMe₂)₄ is found to exhibit a record-breaking Stokes-shifted NIR emission with good photovoltaic properties.

A series of NIR emitting perylene-monoimide (PMI) dyes were developed via tetra alkynylation of PMI(Br)₄ at bay and peri positions using Sonogashira coupling protocol for organic photovoltaics application.

Near-infrared (NIR) absorbing dyes are gaining a great deal of attention both in research and technology because of their widespread applications in diverse areas of bio-imaging, photothermal therapy, NIR triggered drug release and advanced optoelectronics.^3,4 NIR dyes are crucial for solar cell applications since the NIR region of the solar spectrum comprises almost 45% of the total energy transferred to the Earth through sunlight.⁵ The theoretical calculation also showed significant augmentation in output power of solar cells fabricated using NIR absorbing materials.^6,7 Considering this, NIR dyes have attracted appreciable attention for their solar cell applications.⁸ Most efficient NIR dyes follow the widespread D–π–A (D = Donor, π = conjugated bridge, A = Acceptor) framework for tuning ground and exited-state potentials.³ This class of dyes is popularly known as intramolecular charge transfer (ICT) dyes, and they rely on strong donors to destabilize the ground-state potentials and acceptors to stabilize the exited-state potentials. This can be achieved either by extending the conjugation length or by covalently linking suitable donor–acceptor moiety with a π-bridge.³Rylene based dyes are highly π-conjugated polyaromatic hydrocarbon (PAH) with outstanding chemical, thermal and photochemical stability.^9,10 Among the rylene dyes, perylene-monoimides (PMIs) are found to be suitable with more number of available positions (i.e., ortho, bay and peri-) for chemical functionalization. Additionally, their strong optical absorptions can be tuned from visible to NIR regions by judicious modification.^11–13 This class of dyes has shown a wide range of applications in organic photovoltaics,¹⁴ solar cells, dye lasers, optical sensors, photosensitizers,¹⁵ optical memory device,¹² and bio-labels.¹⁶ In this regard, tetra-brominated PMI is considered a versatile starting material for the synthetic modification at both bay and peri positions.^17,18 The extension of π-conjugation along peri-positions has a strong impact on the photophysical properties due to energetic optical transition (S₀–S₁).^17,19–21 The extension of π-conjugation along bay-positions can be used for fine-tuning of their optical properties.²²Effect of π-conjugation along one of the peri-position of PMI through ethynylene linker (Fig. 1) has been extensively studied to impact on optical properties.^23,24 Imahor group has expanded the perylene core through π-conjugation along two bay (1,6-) and one peri (9-)position via ethynylene linker between perylene core and triarylamine.¹⁵ However expanding the PMI core through π-conjugation along both peri and bay-positions is still unexplored due to the limited access to the key building block, i.e., PMI(Br)₄. Fortunately, our recent report on an elegant method for the synthesis of PMI(Br)₄ allowed the desirable tetra-alkynylation of PMI in both bay and peri-position.¹⁸Open in a separate windowFig. 1Structure and functionalization possibility of PMI derivatives and NIR-emitting tetra-coupled PMI.In this work, the synthetic protocol for expanding the π-conjugation along both bay and peri-positions is demonstrated using fourfold Sonogashira cross-coupling reaction. Later, the effect of tetra-alkynylation on electronic, photophysical and redox properties is extensively investigated. Furthermore, the photovoltaic applicability has been studied to establish the prominent significance of the NIR-emitting PMI-derivatives.To exploit this work, we have synthesized compounds 2a–c by Sonogashira coupling reaction using different donor substituents at bay and peri-positions of the perylene core (Scheme 1). The synthesis commenced with the treatment of compound 1 with 4-ethynylanisole as the donor group in toluene : TEA (1 : 1) at 80 °C for 18 h using Pd₂(dba)₃ and P(o-tolyl)₃ as the catalyst and ligand respectively. This afforded the compound 2b in 10% yield, and the same protocol was utilized to synthesize 2a, but the reaction was unsuccessful. This prompted us to optimize the reaction conditions and thus compound 2a was synthesized in 45% yield by coupling 4-ethynyl-N,N-dimethyl aniline with compound 1 in THF : DIPEA (1 : 1) at 80 °C for 18 h using tetrakis(triphenylphosphine) palladium (0) and CuI as the catalyst and co-catalyst respectively. The same approach failed to yield the compound 2b by using 4-ethynylanisole as the alkyne linker while keeping other reaction conditions same. Unfortunately, a mixture of isomers was obtained, which were difficult to isolate through column chromatography. For the synthesis of compounds 2b and 2c, further modification was carried out by employing a different palladium-based catalyst i.e., PdCl₂(PPh₃)₂. The reaction was performed via the treatment of compound 1 with 4-ethynylanisole in THF : TEA (1 : 1) at 80 °C for 18 h with PdCl₂(PPh₃)₂ and CuI as the catalyst and co-catalyst respectively. The residue was purified using column chromatography using DCM : Hexane (1 : 1) as the eluent and silica gel as the stationary phase. By following the optimized protocol compound 2b–c were isolated in 60% and 71% yields respectively. This protocol involving the catalyst PdCl₂(PPh₃)₂ was also tested to synthesize the compound 2a but the yield of the reaction was only 15%. Further, all the compounds 2a–c were characterized by NMR and HRMS.Open in a separate windowScheme 1Synthetic protocol for the preparation of tetra-coupled PMI derivatives 2a–c.Single crystals of 2c are grown by slow diffusion of methanol into a solution of the compound 2c in hexane. The molecules are packed in the triclinic space group P$\bar{1}$ (for details see ESI^†). In the crystal structure (see Fig. 2a), the bond angle between C C of the two TIPS groups attached at both peri-positions of PMI is distorted to an angle of 10–11° from 180° due to the steric congestion between bulky TIPS groups. Additionally, there is a twist of 16° in the perylene core due to TIPS groups at bay positions (Fig. 2b).Open in a separate windowFig. 2Single crystal X-ray structure of compound 2c (a) front view (b) side view to show the twisting in the perylene core.The synthesized PMI derivatives, 2a, 2b, and 2c appear green, violet and pink respectively, in the solution phase with large absorption coefficients in the range of 10⁶ M⁻¹ cm⁻¹ (see Fig. 3a). As is clear from the UV-Vis spectra, these compounds exhibit a broad absorption band covering most of the visible region and some part of NIR region which is a unique characteristic of a push–pull type PMI-based chromophore. The UV-Vis spectra of the tetra-coupled PMI (2a–c) in CHCl₃ showed their longest maxima at 665, 614 and 575 nm respectively and were bathochromically shifted by 65–150 nm with respect to the unsubstituted PMI with an absorption maximum at around 510 nm. It should be noted that for push–pull PMIs, orbital partitioning plays a very important role.¹⁸ The orbital partitioning occurs when the HOMO coefficients on the donor part and the LUMO coefficient on the acceptor part in the same molecule are high. Here, in these molecules, this broad absorption in the visible region can be attributed to the orbital partitioning arising from the introduction of strong electron-donating substituents like –NMe₂, –MeO and TIPS at the bay and peri positions of the perylene core. Notably, the significant red-shifted absorption in PMI-(NMe₂)₄ can also be justified by the presence of lone pairs on nitrogen atoms which effectively enhances the conjugation length of the π-system in the molecule. Therefore, a drastic bathochromic shift can be achieved by suitable functionalization of the PMI core with strong electron donating groups.Open in a separate windowFig. 3(a) UV-Vis absorption spectra (5 μM) of the PMI derivatives in CHCl₃ (b) normalized emission spectra (5 μM) in CHCl₃ (C) fluorescence lifetime decay plot for the PMI derivatives in toluene and (d) cyclic voltammograms of the compounds in DCM (electrolyte: 0.1 M n-Bu₄NPF₆, ferrocene as the internal), arrows show the direction of CV scan.The normalized fluorescence spectra of compounds 2a–c in CHCl₃ are shown in Fig. 3b. From the emission characteristics of the derivatives, it can be ascertained that a significant red-shifted emission maximum by 30–210 nm are observed for all the derivatives. Notably, compound PMI-(NMe₂)₄2a is found to have the broadest emission overlapping with the whole visible region and a significant part of NIR with a shoulder end at 1200 nm. This compound shows the emission maxima at 869 nm thus displaying a large Stokes shift of 204 nm as compared to methoxy and TIPS substituted analogs 2b and 2c (30–45 nm) with emission maxima at 660 nm and 606 nm respectively.These low energy bands in these spectra are a characteristic of a strong emission from a charge transfer absorption arising from the electron donating groups present at bay and peri-positions to the electron accepting imide group through the π-conjugated system. PMI based ICT dyes are sensitive to the chemical environment, and consequently, their optical properties are highly-dependent on concentration, solvent polarity, and temperature. To check the effect of solvent polarity on the optical properties of these derivatives, the solvent-dependent absorption and emission spectra for all the compounds in various solvents are measured at 298 K (See Fig. S2–4, S6–8, and S10–12^†). The fluorescence maxima are largely red-shifted in case of 2b and 2c while no significant change was observed in the absorption maxima under the same conditions indicating an increase in the dipole moment of the excited state compared to the ground state (see ESI^†).^25,26 For example, for compounds 2b and 2c, a red shift in the emission maxima by ca. 40 nm and 20 nm respectively was observed while going from least polar to the most polar solvent. We obtained a linear correlation between Stokes-shift and solvent polarity parameter (E_T(N), Fig. S13^†). The large Stokes-shift in case of 2a may also be due to the intramolecular twisting.^15,27 Such intramolecular twisting should be significant enough to cause a shift in the emission and not too large to destroy the conjugation and planarity. Further, the fluorescence lifetime of the compounds 2a–c was found to be 2.1, 4.3 and 5.5 ns in toluene (Fig. 3c). The electrochemical properties of these dyes were investigated by cyclic voltammetry in CH₂Cl₂ solution containing 0.1 M n-Bu₄NPF₆ as the supporting electrolyte and ferrocene as the internal standard. The obtained redox potentials and the calculated values for the HOMO–LUMO energy levels are summarized in Fig. 3d). The CV curve for compound 2a shows two reversible oxidation waves at E_ox values of 0.35–0.76 V and two reversible reduction waves at E_red values of −0.99 to −1.36 V, which indicates the formation of radical cations by oxidation and radical anions upon reduction. Contrary to this, curve for compound 2b undergoes one quasi-reversible oxidation at E_ox value of 0.87 V and two reversible reductions at E_red values of −0.94 to −1.30 V. This can be attributed to the replacement of –NMe₂ group with –OMe leading to the shift in the value to the positive direction for reduction as well as oxidation. Compound 2c on the other hand shows one oxidation wave at E_ox value of 1.28 V and two reversible waves at E_red values of −0.93 to −1.36 V. One interesting feature observed in these calculations was that depending on the substitution at peri and bay-positions the onset potentials can be easily tuned with significant values. This observation was further validated using DFT calculations which were performed using B3LYP as functional and DNP as the basis set. The optimized FMO of 2a and 2b are depicted in Fig. S14 and 15.^† Furthermore, as expected the HOMO potential on varying the substituents at peri position were in good agreement with the data obtained from the electrochemical and optical measurements. Also, from the theoretical and experimental data, it was observed that there was a marked reduction in the band gap values for these compounds concerning the unsubstituted PMI.Summary of the optical and electrochemical properties of tetra-coupled PMI derivatives

Bio-molecule functionalized rapid one-pot green synthesis of silver nanoparticles and their efficacy toward the multidrug resistant (MDR) gut bacteria of silkworms (Bombyx mori)

The present study aimed to synthesise bio-molecule functionalized silver nanoparticles (AgNPs) using leaf extract from mulberry variety S-1635 (Morus alba L.) and to explore its antibacterial efficacy against multidrug resistant (MDR) gut bacteria isolated from natural infection observed from silkworm larvae in rearing conditions. AgNPs formation was established by surface plasmon resonance at 480 nm. The crystallinity of the synthesised AgNPs was checked by HR-TEM and XRD analysis. SEM and TEM characterisation further exhibited the spherical, monodispersed, well scattered nature of the AgNPs with an average particle size of 11.8 nm ± 2.8. The presence of (111), (200), (220) and (311) planes in Bragg''s reflections confirmed the face-cantered-cubic crystalline silver. EDX analysis confirmed the presence of elemental silver. FT-IR spectra revealed functional groups were responsible for the reduction of silver ions. The zeta potential value of −17.3 mV and −25.6 mV was recorded in MH and DMEM/F-12 media, respectively. The LC-QTOF/MS and HRMS spectra disclosed the presence of bioactive compounds like flavonoid, gallic acid, and stigmasterol, which are probably involved in the reduction and functionalization of AgNPs. The antibacterial efficacy of bio-molecule functionalized AgNPs and the naked AgNPs was tested on Gram-positive and Gram-negative bacteria isolated from silkworms and characterized by using 16S rDNA and gyrB genes. The cytotoxicity of AgNPs was tested on WRL-68, HEK-293, ACHN, and HUH-7 cell lines using MTT assay. This study provides an insight into the application of bio-molecule functionalized AgNPs for combating various silkworm pathogens which severely affect the agro-rural economy of developing countries.

We aimed to synthesise bio-molecule functionalized silver nanoparticles using leaf extract from mulberry variety S-1635 (Morus alba L.) and to explore its antibacterial effect on multidrug resistant gut bacteria isolated from natural infection observed from silkworm larvae.     

Arsenic-induced mitochondrial instability leading to programmed cell death in the exposed individuals

In West Bengal, India, more than 6 million people in nine districts are exposed to arsenic through drinking water. It is regarded as the greatest arsenic calamity in the world. Arsenic is a well-documented human carcinogen, which does not induce cancer in any other animal model. Interestingly, at lower concentrations, arsenic is known to induce apoptosis in various cancer cell lines in vitro. We have studied apoptosis in human peripheral blood mononuclear cells (PBMC) of 30 arsenic exposed skin lesion individuals by annexin V-FITC staining and compared with 28 unexposed individuals. The percentage of apoptotic cells in individuals with skin lesions was significantly higher (p<0.001) in comparison to unexposed individuals. In the exposed individuals with skin lesions, there were elevated levels of intracellular reactive oxygen species (ROS), mitochondrial membrane permeability and increased cytochrome c release, leading to increased downstream caspase activity. Arsenic-induced DNA damage was confirmed by DNA ladder formation and confocal microscopy. We also observed that chronic arsenic exposure reduced Bcl-2/Bax ratio and also resulted in cell cycle arrest of PBMC in G0/G1 phase. All these observations indicate that mitochondria-mediated pathway may be responsible for arsenic-induced apoptosis.     

Acute Toxicity and Oxidative Stress Responses in Tadpole of Skittering Frog, <Emphasis Type="Italic">Euphlyctis cyanophlyctis</Emphasis> (Schneider, 1799) to Sodium Fluoride Exposure

This study evaluated the acute toxicity and oxidative stress responses to sodium fluoride (NaF) exposure in tadpoles of the skittering frog, Euphlyctis cyanophlyctis (Schneider 1799). The 96 h LC₅₀ value was found to be 647 mg/L. Biochemical tests were conducted at 10%, 20%, 30%, 40%, 50%, 60%, 70% and 80% of the 96 h LC₅₀ dose. Cholinesterase (ChE) activity was unaffected. Lipid peroxidation levels significantly increased (p?<?0.05) at lower concentrations, but decreased significantly with increasing NaF concentrations. Glutathione S-transferase (GST) activity also increased significantly with increasing NaF concentrations. Alkaline phosphatase levels steadily decreased with increasing concentrations of NaF. The responses for the biochemical tests were summarized using an integrated biomarker response (IBR) index approach, which indicated that lower NaF exposures caused higher levels of oxidative stress responses overall. These findings suggest that the IBR index approach may be useful for the quantitative monitoring of NaF toxicity in amphibians.     

A geospatial analysis of noncommunicable disease (NCD) burden in Indian agro-climatic and political regions

Aim

To examine the burden of noncommunicable diseases (NCDs) in the Indian agro-climatic and political regions.

Subjects and methods

Data from two rounds of National Sample Survey (NSS) 68th (2011–12) and 71st (2014) was used to estimate the subnational spatial heterogeneity of NCD burden across 87 agro-climatic and political regions in India. Quantile maps, local Moran’s I, LISA cluster and significance maps were generated.

Results

Results show a high spatial heterogeneity in disease burden across the agro-climatic regions. Moran’s I scatterplot depict a significantly high level of regional dependence (Moran’s I?=?0.558) of NCDs with larger concentration of disease in southern states like Kerala (northern and southern), Tamil Nadu (inland, coastal, and northern-coastal), Karnataka (inland, coastal and Ghats) and Pondicherry. The proportion of the elderly population, those belonging to urban areas, widowed/divorced/separated population, high  per capita alcohol and tobacco consumption were more likely to affect the prevalence of NCDs.

Conclusion

Findings call for an immediate programmatic attention at the subnational level due to significantly high regional dependence of NCDs. Policies and programme should focus on strengthening the implementation of existing  policies with a special focus on geriatric population to combat the disease burden.

     

Low-Cost National Media-Based Surveillance System for Public Health Events,Bangladesh

We assessed a media-based public health surveillance system in Bangladesh during 2010–2011. The system is a highly effective, low-cost, locally appropriate, and sustainable outbreak detection tool that could be used in other low-income, resource-poor settings to meet the capacity for surveillance outlined in the International Health Regulations 2005.