Zoledronic Acid Treatment in Infants and Toddlers with Osteogenesis Imperfecta is Safe and Effective: A Tertiary Care Centre Experience.

Context: Osteogenesis imperfecta (OI) is a genetic disorder of the extracellular matrix of bone characterized by low bone mass manifesting as frequent fractures, delayed motor development, pain, and impaired quality of life. The intravenous bisphosphonate, pamidronate is an established treatment for OI. Recently, zoledronic acid (ZA) has been used for the management of OI. Aim: To assess the efficacy and safety of ZA in children below five years of age with OI. Settings and Design: A hospital-based prospective observational study. Methods and Material: Patients with OI aged less than five years attending our centre were treated with intravenous ZA at a dose of 0.05 mg/kg every six months. Subjects were closely monitored for clinical and biochemical variables, adverse events, and new-onset fractures. The response to therapy was assessed by monitoring clinical variables including the degree of bony pains, number of fractures, height/length standard deviation score (SDS), and motor developmental milestones. All patients were analysed at baseline and at the end of two years for biochemical parameters and clinical severity score (CSS) as proposed by Aglan et al. with modifications. Results: After two years of treatment, OI patients showed a significant decline in the rate of fractures (p < 0.001), improvement in ambulation (p = 0.005), alleviation of pain (p < 0.001), and improvement in height SDS (p < 0.05). There was a significant improvement in CSS after two years of therapy. Apart from mild flu-like symptoms and mild asymptomatic hypocalcaemia immediately post-infusion, no other adverse effect was noted. Conclusion: ZA therapy in infants and children below five years of age with OI was effective and safe and a more convenient alternative to pamidronate.

4-Methylesculetin ameliorates LPS-induced depression-like behavior through the inhibition of NLRP3 inflammasome.

The pathophysiology of depression is heavily dependent on inflammation. Evidence suggests that the etiology of depression is linked with NLRP3 inflammasome-induced inflammation. Therefore, blocking the activated NLRP3 inflammasome may be beneficial for treating depression. Due to the limitations of currently available antidepressants, it is necessary to develop novel, safe, and affordable drugs for the treatment of depression. A natural coumarin derivative named 4-methylesculetin (4-MESC) possesses anti-inflammatory properties. However, the role of 4-MESC as an antidepressant has not been elucidated. Therefore, in this study, we explored the antidepressant-like effects of 4-MESC and its underlying molecular mechanism through the modulation of the NLRP3 inflammasome. The docking and molecular dynamic simulation studies revealed that 4-MESC has a higher affinity for the NLRP3 PYD. Blood-brain barrier permeability was confirmed using the SwissADME pharmacokinetic tool. High doses (50 mg/kg) of 4-MESC significantly reduced the immobility duration in the tail-suspension test (TST) and forced swim test (FST) without changing the overall locomotor activity in the female Swiss albino mice that were subjected to lipopolysaccharide (LPS). LPS-induced pro-inflammatory cytokines such as IL-6 and TNF-α were reduced in serum and brain tissues using 4-MESC. 4-MESC's neuroprotective effects are mediated by increased brain-derived neurotrophic factor (BDNF) and decreased cortisol levels. 4-MESC markedly reduced LPS-induced elevated levels of ROS and lipid peroxidation (malondialdehyde levels) and enhanced the superoxide dismutase (SOD) activity and glutathione levels, which revealed its anti-oxidant potential against oxidative stress. 4-MESC diminished the expression levels of NF-κBp65, IL-6, NLRP3, caspase-1, gasdermin D, and IL-1ß in the hippocampus. These findings demonstrated that 4-MESC exhibited antidepressant-like effects by inhibiting the NLRP3 inflammasome. However, other antidepressant mechanisms might also be involved which require further studies.

Simultaneous Dispersive Liquid-Liquid Microextraction and Determination of Different Polycyclic Aromatic Hydrocarbons in Surface Water.

Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants of water, and their determination at trace levels in the aquatic ecosystems is essential. In this work, an ultrasound-assisted dispersive liquid-liquid microextraction (DLLME) procedure was suggested utilizing a binary dispersive agent for recovery of different molecular weight polycyclic aromatic hydrocarbons (PAHs) from waters. The detection was carried out by gas chromatography-mass spectrometry (GC-MS) as well as high-performance liquid chromatography with fluorescence and diode-array detection (HPLC-FD/PDA). The method was optimized for the extraction of analytes with respect to the mixture composition, ratios of components, ultrasonication time and centrifugation parameters. The analytical schemes for PAHs extraction from water samples using different ratios of extraction and dispersive solvents are reported. The mixture consisting of chloroform and methanol was applied for the extraction of PAHs containing two or three fused aromatic rings; the mixture of chloroform and acetonitrile is suitable for PAHs containing more than four aromatic rings. The mixture of chloroform:acetone + acetonitrile was applied in the universal scheme and allowed for the simultaneous extraction of 20 PAHs with different structures. The developed sample preparation schemes were combined with GC-MS and HPLC-FD/PDA, which allowed us to determine the analytes at low concentrations (from 0.0002 µg/L) with the recoveries exceeding 80% and relative standard deviations of about 8%. The developed methods for the determination of 20 PAHs were applied to the analysis of water samples from the Karasun Lake (Krasnodar), Azov Sea (Temryuk) and Black Sea (Sochi).

Mechanistic insight into the role of mevalonate kinase by a natural fatty acid-mediated killing of Leishmania donovani.

We evaluated the anti-leishmanial efficacy of different saturated medium-chain fatty acids (FAs, C8-C18) where FA containing C8 chain, caprylic acid (CA), was found to be most potent against Leishmania donovani, the causative agent for visceral leishmaniasis (VL). Different analogs of CA with C8 linear chain, but not higher, along with a carboxyl/ester group showed a similar anti-leishmanial effect. Ergosterol depletion was the major cause of CA-mediated cell death. Molecular docking and molecular dynamic simulation studies indicated the enzyme mevalonate kinase (MevK) of the ergosterol biosynthesis pathway as a possible target of CA. Enzyme assays with purified recombinant MevK and CA/CA analogs confirmed the target with a competitive inhibition pattern. Using biochemical and biophysical studies; strong binding interaction between MevK and CA/CA analogs was established. Further, using parasites with overexpressed MevK and proteomics studies of CA-treated parasites the direct role of MevK as the target was validated. We established the mechanism of the antileishmanial effect of CA, a natural product, against VL where toxicity and drug resistance with current chemotherapeutics demand an alternative. This is the first report on the identification of an enzymatic target with kinetic parameters and mechanistic insights against any organism for a natural medium-chain FA.

Antibiogram guided optimized medical treatment in chronic otitis media: A useful interventional strategy before surgery?

BACKGROUND: Chronic otitis media is a middle ear cleft disease presenting with tympanic membrane perforation and discharge. Wet ear after tympanoplasty and discharging mastoid cavity are problematic in clinical practice. MATERIAL AND METHODS: 1050 patients of age 10 to 50 years presenting with active ear discharge and clinically diagnosed with unilateral chronic suppurative otitis media were included in the study. The patients were equally divided into two equal groups, Group ET, and AT. All patients were prescribed topical ciprofloxacin, oral levocetirizine 5 mg and n-acetyl cysteine 600 mg BD for one week. Swabs of ear discharge were collected in ET groups for antibiogram. Both groups were evaluated on next visit and treatment changed in AT groups and result observed in next visit. Surgical outcome was evaluated at end of 2 yrs. RESULT: A total of 1158 organisms were isolated in culture out of which, 69.94 % were aerobes, 13.47 % anaerobes and 16.58 % were fungi. On the second visit in group AT, treatment of 85.14 % patients was changed in accordance with culture sensitivity report. In patients with mucosal disease, only 46.87 % patients of group ET had a favorable outcome in comparison to 90.28 % patients of group AT while in patients with squamosal disease, 17.56 % patients of group ET and 28.99 % patients in group AT had a dry ear. Surgeries in AT group were found to have statistically significant higher success rate as compared to ET group.

Fabrication of α-Fe2O3 Nanostructures: Synthesis, Characterization, and Their Promising Application in the Treatment of Carcinoma A549 Lung Cancer Cells.

In the present work, iron nanoparticles were synthesized in the α-Fe2O3 phase with the reduction of potassium hexachloroferrate(III) by using l-ascorbic acid as a reducing agent in the presence of an amphiphilic non-ionic polyethylene glycol surfactant in an aqueous solution. The synthesized α-Fe2O3 NPs were characterized by powder X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, atomic force microscopy, dynamic light scattering, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and ultraviolet-visible spectrophotometry. The powder X-ray diffraction analysis result confirmed the formation of α-Fe2O3 NPs, and the average crystallite size was found to be 45 nm. The other morphological studies suggested that α-Fe2O3 NPs were predominantly spherical in shape with a diameter ranges from 40 to 60 nm. The dynamic light scattering analysis revealed the zeta potential of α-Fe2O3 NPs as -28 ± 18 mV at maximum stability. The ultraviolet-visible spectrophotometry analysis shows an absorption peak at 394 nm, which is attributed to their surface plasmon vibration. The cytotoxicity test of synthesized α-Fe2O3 NPs was investigated against human carcinoma A549 lung cancer cells, and the biological adaptability exhibited by α-Fe2O3 NPs has opened a pathway to biomedical applications in the drug delivery system. Our investigation confirmed that l-ascorbic acid-coated α-Fe2O3 NPs with calculated IC50 ≤ 30 µg/mL are the best suited as an anticancer agent, showing the promising application in the treatment of carcinoma A549 lung cancer cells.

Isolation, antibacterial screening, and identification of bioactive cave dwelling bacteria in Fiji.

Bacteria are well known producers of bioactive secondary metabolites, including some of the most effective antibiotics in use today. While the caves of Oceania are still largely under-explored, they form oligotrophic and extreme environments that are a promising source for identifying novel species of bacteria with biologically active compounds. By using selective media that mimicked a cave environment, and pretreatments that suppressed the growth of fast-growing bacteria, we have cultured genetically diverse bacteria from a limestone cave in Fiji. Partial 16S rRNA gene sequences from isolates were determined and compared with 16S rRNA gene sequences in EzBioCloud and SILVA data bases. Fifty-five isolates purified from culture had Actinomycete-like morphologies and these were investigated for antibacterial activity. Initial screening using a cross streak test with pathogenic bacteria indicated that 34 of the isolates had antibacterial properties. The best matches for the isolates are bacteria with potential uses in the manufacture of antibiotics and pesticides, in bioremediation of toxic waste, in biomining, in producing bioplastics, and in plant growth promotion. Nineteen bacteria were confirmed as Actinomycetes. Thirteen were from the genus Streptomyces and six from genera considered to be rare Actinomycetes from Pseudonocardia, Kocuria, Micromonospora, Nonomuraea. Ten isolates were Firmicutes from the genera Bacillus, Lysinbacillus, Psychrobacillus and Fontibacillus. Two were Proteobacteria from the genera Mesorhizobium and Cupriavidus. Our findings identify a potentially rich source of microbes for applications in biotechnologies.

Current status of nanoscale drug delivery and the future of nano-vaccine development for leishmaniasis - A review.

The study of tropical diseases like leishmaniasis, a parasitic disease, has not received much attention even though it is the second-largest infectious disease after malaria. As per the WHO report, a total of 0.7-1.0 million new leishmaniasis cases, which are spread by 23 Leishmania species in more than 98 countries, are estimated with an alarming 26,000-65,000 death toll every year. Lack of potential vaccines along with the cost and toxicity of amphotericin B (AmB), the most common drug for the treatment of leishmaniasis, has raised the interest significantly for new formulations and drug delivery systems including nanoparticle-based delivery as anti-leishmanial agents. The size, shape, and high surface area to volume ratio of different NPs make them ideal for many biological applications. The delivery of drugs through liposome, polymeric, and solid-lipid NPs provides the advantage of high biocomatibilty of the carrier with reduced toxicity. Importantly, NP-based delivery has shown improved efficacy due to targeted delivery of the payload and synergistic action of NP and payload on the target. This review analyses the advantage of NP-based delivery over standard chemotherapy and natural product-based delivery system. The role of different physicochemical properties of a nanoscale delivery system is discussed. Further, different ways of nanoformulation delivery ranging from liposome, niosomes, polymeric, metallic, solid-lipid NPs were updated along with the possible mechanisms of action against the parasite. The status of current nano-vaccines and the future potential of NP-based vaccine are elaborated here.

Design, Synthesis of Biaryl Piperidine Derivatives and Their Evaluation as Potential Antileishmanial Agents against Leishmania donovani Strain Ag83.

We have developed a new series of simple biaryl piperidine derivatives (11-19) based on biaryl naphthylisoquinoline alkaloid Ealamine-A. The target compounds were synthesized, analyzed by spectral data, and evaluated for antileishmanial activity against Leishmania donovani strain Ag83 by MTT assay. The compounds have shown the best to moderate antileishmanial activity. The 5'-fluoro-2'-methoxyphenyl derivative 14 and 3',5'-difluorophenyl derivative 16 have inhibited the promastigotes by 86 % and 85 % after 24 h and 92 % and 91 % after 48 h incubation, respectively, at 400 µM concentration. The % inhibition was lower with the lowering of the concentration and increased with the incubation time. Compounds 12, 15, and 18 have solubility issues and proved to be less active than the rest of the compounds. Molecular docking studies were performed on selective active compounds and the results indicate that these compounds may act by binding to the Leishmanolysin and the docking scores are in good correlation with the antileishmanial activity. These results provide an initial insight into the design of new therapeutics for neglected tropical diseases.

Assessment of biodegradable chelating agents in the phytoextraction of heavy metals from multi-metal contaminated soil.

A pot incubation experiment under natural conditions was designed to investigate the effects of three biodegradable chelating agents, namely; the [S,S]-isomer of ethylenediamine disuccinate (EDDS), citric acid (CA), and tetrasodium N,N-Bis(carboxymethyl)-L-glutamate acid (GLDA), on two plant species (Brassica juncea and Brassica rapa) in terms of plant foliar growth, dry matter yield, and heavy metal (HM) accumulation. Both plant species exhibited diminished growth and symptoms of phytotoxicity under HM stress. The application of EDDS and CA affected plant foliar growth, biomass production, and led to the development of chlorotic lesions on leaves. EDDS and CA also decreased the shoot length by 38.5% and 45.2% in B. juncea, and 60.1% and 100% in B. rapa, respectively. In contrast, GLDA relieved HM stress by significantly increasing plant growth (P > 0.05) and was shown to be well tolerated (tolerance index [TI]; B. juncea = 99% and B. rapa = 123%). Among both plants, B. juncea displayed the ability to accumulate a wider range of HMs at higher concentrations. Amongst the three chelators, EDDS induced the highest bioconcentration (BCF) of Pb (2.45), Zn (2.68), and Cd (3.36) while CA achieved better results for Ni (4.01) and Cr (1.45). However, the current results showed that even with the application of chelating agents, HMs were predominantly accumulated in roots and translocation factor was generally <1. The findings of this investigation emphasize that chelate-assisted phytoextraction with Brassica spp. is highly limited in multi-metal settings, making it an unsuitable option for severely contaminated sites.

A micellar mediated novel method for the determination of selenium in environmental samples using a chromogenic reagent.

A novel, simple, sensitive and rapid spectrophotometric method for the determination of selenium(iv) in an acidic medium using rhodamine B hydrazide (RBH) has been developed. The method is based on the micellar mediated oxidation of RBH by Se(iv) in an acidic medium to produce a pinkish violet color of rhodamine B, which was monitored spectrophotometrically at λmax 585 nm. The sensitivity of the method was found to increase when the reaction was performed in a micellar medium. Beer's law was obeyed in the concentration range of 0.002-0.032 µg mL-1. The reaction variables such as time, temperature, reagent concentration, and acidity have been optimized for the reaction. Sandell's sensitivity and molar absorptivity for the reaction system were found to be 0.00004 µg cm-2 and 42.52 × 106 L mol-1 cm-1, respectively. The developed method was successfully applied for the determination of Se(iv) in several real samples with quantitative results.

Determination and comparison of selected heavy metal concentrations in seawater and sediment samples in the coastal area of Suva, Fiji.

The coastal area of Suva, Fiji is exposed to high degree of metals input from different sources such as land-based industrial activities like metal fabrication and construction, paint manufacturing, petroleum storage and garment manufacturing, food processing and fish cannery as well as activities of bottling plants. It is therefore essential to have continuous monitoring and environmental management for the coastal area. Thus, to assess the degree of contamination of metals, selected metals (Cd, Zn, Pb, Cu and Ni) concentrations were analysed in seawater and sediment samples collected from ten sites in the coastal area of Suva, Fiji. The concentration of these metals in the samples was analysed using flame atomic absorption spectrometer (FAAS). The concentrations of the metal in seawater were in the range: 0.23-0.80 mg/L, 0.08-1.45 mg/L, 0.15-0.25 mg/L, 0.88-1.77 mg/L and 0.88-10.29 mg/L for Ni, Zn, Cd, Pb and Cu, respectively. The corresponding concentrations of metal in the sediment samples in dry weight (dw) basis for Ni, Zn, Cd, Pb and Cu were in the range: 17.24-28.74 mg/kg, 18.55-68.78 mg/kg, 5.49-9.16 mg/kg, 116.96-233.92 mg/kg and 78.43-490.18 mg/kg, respectively. The quality of the seawater was evaluated with respect to WHO established guidelines while the quality of the sediments evaluated using internationally accepted Sediment Quality Guidelines (SQGs). The contamination of the sediments was also assessed in terms of geo-accumulation index (Igeo), contamination factor (Cf) as well as pollution load index (PLI). Zn complied with the guidelines in all ten sites, Cu in eight sites was within the guidelines while Ni complied with the guideline in six sites. However, the levels of contamination recorded for Cd and Pb in all ten sites did not comply with the guidelines.

Correlation of Tympanic Membrane Perforation with Hearing Loss and Its Parameters in Chronic Otitis Media: An Analytical Study.

Chronic otitis media is one of the commonest illnesses in otorhinolaryngological practice which requires medical attention. Intact tympanic membrane acts as a shield for round window niche to create a phase difference in sound wave conduction. 700 patients of age 10-70 years with inactive mucosal chronic otitis media were included in the study. Condition of tympanic membrane and site of tympanic membrane perforation was noted and audiometric analysis was performed. 338 (48.28%) were males and 362 (51.71%) were females. In 1400 membranes examined, 769 (54.85%) presented with perforation. 631 (82.03%) had unilateral perforation and 69 (17.97%) had bilateral perforations. In unilateral cases, 289 (37.50%) had right ear perforation and 342 (44.53%) left ear perforation. Single quadrant perforations were present in 168 (21.74%) membranes and 419 (54.55%) involved two quadrants. Three quadrant perforations were seen in 62 (8.09%) and 120 (15.63%) perforations involved all four quadrants. In 171 (22.26%) ears, perforation was present anterior to handle of malleus and in 243 (31.53%) it was present only posterior to handle. In 355 (46.21%) perforations, handle of malleus was involved. Perforations involving posterior half of tympanic membranes showed greater loss than those involving anterior or inferior half of membrane statistically. Maximum loss (51.56 ± 5.1 dB) was seen in perforation involving all four quadrants. In 631 unilateral cases, conductive loss was seen in 424 (67.10%), 101 (16.10%) showed sensorineural and 74 (11.80%) showed mixed loss. Out of 769 perforated ears having hearing loss, 251 (37.69%) had complaints for 5-10 years with mean loss of 51.15 ± 7.8 dB, 172 (25.68%) had COM for 1-5 years with loss of 39.26 ± 5.1 dB. A mean hearing loss of 52.18 ± 4.2 dB was seen in 110 (16.52%) patients suffering from COM for more than 10 years. 134 (20.12%) patients having disease less than 1 year reported hearing loss of 36.46 ± 8.2 dB. The effects of perforation of tympanic membranes on transmission of sound and its dynamics are not easy to correlate because of additional pathological changes in middle ear.

Heavy metals contamination and risk assessment in sediments of Laucala Bay, Suva, Fiji.

Spatial distribution of metals (Cd, Cr, Cu, Fe, Ni, Pb and Zn) were studied in the surficial sediments from 20 sampling sites of Laucala Bay Suva, Fiji to assess the significance of wastewater effluent discharged from Kinoya Wastewater Treatment Plant (KWWTP) into Laucala Bay as a major source. The bioavailability of these metals was also assessed using the fractionation technique. The total concentrations of individual metals varied from 1.7-6.0 mg/kg Cd, 24.2-49.1 mg/kg Cr, 54-170 mg/kg Cu, 13,733-68,492 mg/kg Fe, 23.5-34.8 mg/kg Ni, 50-80 mg/kgPb and 15.5-157.0 mg/kg Zn. All the metals studied except Ni showed significant increase around the KWWTP effluent discharge sites indicating that prolong discharge of wastewater could be a major source of their accumulation in Laucala Bay. The multivariate statistical analysis confirmed that Cd, Cu and Pb could be attributed to similar sources like wastewater effluent. The study confirmed that the spatial distribution of the metals in Laucala Bay was affected by the hydrodynamic of Laucala Bay as pollutants were dispersed from the point sources. The Risk Assessment Code (RAC) assessed from the bioavailable fraction data confirmed that apart from Cd and Pb, the rest of the metals analysed had medium risk of toxicity. Owing to the persistent nature of metals and the results obtained from this study, there is a high probability of these metals to accumulate and increase in concentration in the future which could also lead to increase in their risk of toxicity to living beings.

Carbon dot cross-linked polyvinylpyrrolidone hybrid hydrogel for simultaneous dye adsorption, photodegradation and bacterial elimination from waste water.

The creation of a polymeric hydrogel from polyvinylpyrrolidone (PVP) cross-linked by Carbon Quantum Dots (CD) for the adsorption and photocatalytic degradation of both cationic and anionic dyes. PVP, an important biocompatible constituent and often surplus in cosmetic industry, was carboxylated through NaOH refluxing and covalently conjugated to surface amine functionality of CD derived from lemon juice and Cysteamine. The hybrid hydrogel was obtained from PVP-CD covalent conjugate by careful manipulation of pH and found to possess better rheological properties than only carboxylate-PVP. The monolayer physisorption of the dyes on the hydrogel was affected by hydrogen bonding, dispersion or inductive effect, and π-π interaction with the polymer backbone as well as the CD that followed pseudo-second-order kinetics. Degradation of the adsorbed dyes was instated by the unique Reactive Oxygen Species (ROS) generating ability of the CD embedded in the hydrogel matrix upon exposure to sunlight, the mechanism of which is also unveiled. The same CD-induced ROS was found to effectively annihilate both gram-positive and gram-negative bacteria in real polluted water in less than 10 min of photoexcitation of the hydrogel. The hydrogel was restored by mild acid wash that is able to perform dye adsorption and photo-degradation upto four cycles.

A novel catalytic kinetic method for the determination of mercury(ii) in water samples.

Mercury(ii) ions act as catalyst in the substitution of cyanide ion in hexacyanoruthenate(ii) by pyrazine (Pz) in an acidic medium. This property of Hg(ii) has been utilized for its determination in aqueous solutions. The progress of reaction was followed spectrophotometrically by measuring the increase in absorbance of the yellow colour product, [Ru(CN)5Pz]3- at 370 nm (λ max, ε = 4.2 × 103 M-1 s-1) under the optimized reaction conditions; 5.0 × 10-5 M [Ru(CN)6 4-], 7.5 × 10-4 M [Pz], pH 4.00 ± 0.02, ionic strength (I) = 0.05 M (KCl) and temp. 45.0 ± 0.1 °C. The proposed method is based on the fixed time procedure under optimum reaction conditions. The linear regression (calibration) equations between the absorbance at fixed times (t = 15, 20 and 25 min) and [Hg(ii)] were established in the range of 1.0 to 30.0 × 10-6 M. The detection limit was found to be 1.5 × 10-7 M of Hg(ii). The effect of various foreign ions on the proposed method was also studied and discussed. The method was applied for the determination of Hg(ii) in different wastewater samples. The present method is simple, rapid and sensitive for the determination of Hg(ii) in trace amount in the environmental samples.

Hybrid DNA-Carbon Dot-Poly(vinylpyrrolidone) Hydrogel with Self-Healing and Shape Memory Properties for Simultaneous Trackable Drug Delivery and Visible-Light-Induced Antimicrobial Photodynamic Inactivation.

A two-step methodology for simultaneous conjugation of DNA and poly(vinylpyrrolidone) (PVP) polymer to a single carbon quantum dot (CD) is demonstrated for the first time to fabricate a pH-responsive DNA-CD-PVP hybrid hydrogel. Cross-linking in the hydrogel was achieved using CD as the common nucleus through the formation of DNA I-motif conformation at neutral to acidic pH and noncovalent interaction of PVP that infuse self-healing and shape memory properties in the hydrogel. The hydrogel is capable of loading and sustained delivery of drugs for more than 2 weeks as demonstrated using a model drug, Hemin. The quenching of fluorescence of CD by Hemin was trackable even through simple visual monitoring, which showed that Hemin can diffuse from the loaded part to the unloaded part of the hydrogel during the self-healing process. Most significantly, the chosen CD generates reactive oxygen species (ROS) upon visible light irradiation, armoring the hydrogel with worthy antimicrobial activity. Biocompatibility of the DNA-CD-PVP hydrogel was established on human fibroblast cells, indicating their potential use in biomedical area pertaining to wound healing.

Synthesis, characterization, and mechanistic studies of a gold nanoparticle-amphotericin B covalent conjugate with enhanced antileishmanial efficacy and reduced cytotoxicity.

BACKGROUND: Amphotericin B (AmB) as a liposomal formulation of AmBisome is the first line of treatment for the disease, visceral leishmaniasis, caused by the parasite Leishmania donovani. However, nephrotoxicity is very common due to poor water solubility and aggregation of AmB. This study aimed to develop a water-soluble covalent conjugate of gold nanoparticle (GNP) with AmB for improved antileishmanial efficacy and reduced cytotoxicity. METHODS: Citrate-reduced GNPs (~39 nm) were functionalized with lipoic acid (LA), and the product GNP-LA (GL ~46 nm) was covalently conjugated with AmB using carboxyl-to-amine coupling chemistry to produce GNP-LA-AmB (GL-AmB ~48 nm). The nanoparticles were characterized by dynamic light scattering, transmission electron microscopy (TEM), and spectroscopic (ultraviolet-visible and infrared) methods. Experiments on AmB uptake of macrophages, ergosterol depletion of drug-treated parasites, cytokine ELISA, fluorescence anisotropy, flow cytometry, and gene expression studies established efficacy of GL-AmB over standard AmB. RESULTS: Infrared spectroscopy confirmed the presence of a covalent amide bond in the conjugate. TEM images showed uniform size with smooth surfaces of GL-AmB nanoparticles. Efficiency of AmB conjugation was ~78%. Incubation in serum for 72 h showed <7% AmB release, indicating high stability of conjugate GL-AmB. GL-AmB with AmB equivalents showed ~5-fold enhanced antileishmanial activity compared with AmB against parasite-infected macrophages ex vivo. Macrophages treated with GL-AmB showed increased immunostimulatory Th1 (IL-12 and interferon-γ) response compared with standard AmB. In parallel, AmB uptake was ~5.5 and ~3.7-fold higher for GL-AmB-treated (P<0.001) macrophages within 1 and 2 h of treatment, respectively. The ergosterol content in GL-AmB-treated parasites was ~2-fold reduced compared with AmB-treated parasites. Moreover, GL-AmB was significantly less cytotoxic and hemolytic than AmB (P<0.01). CONCLUSION: GNP-based delivery of AmB can be a better, cheaper, and safer alternative than available AmB formulations.

Chronic Otitis Media and its Correlation with Unilateral Sensorineural Hearing Loss in a Tertiary Care Centre of North India.

Relation between chronic otitis media and sensorineural hearing loss is controversial. Otitis media can cause threshold shift in high frequency range. Also this correlation with patient's age, disease duration and normal ear is of importance for early prevention of hearing loss. The aim of this study was to evaluate relationship between sensorineural hearing loss and chronic otitis media. We also studied association of bone conduction between diseased ear and contralateral normal ear. In this study, 840 patients of unilateral COM were included. Audiometry was done and data analyzed. Majority of patients showing SNHL had COM for over a period of 5 years. Squamosal disease showed early progression to SNHL than mucosal disease. Higher frequencies were found to be more affected and maximum bone gap was seen at 4000 Hz. There was significant difference in mean bone conduction threshold between diseased ear and normal ear at all frequencies (p value < 0.001). Contradicting studies have emerged about association of SNHL with COM. Studies suggest that SNHL does not change with age but with duration. Bone conduction threshold tends to increase with increasing frequency. Few authors also pointed that this may be due to Carhart's effect and not due to disease damaging inner ear.

Bovine Serum Albumin Amplified Reactive Oxygen Species Generation from Anthrarufin-Derived Carbon Dot and Concomitant Nanoassembly for Combination Antibiotic-Photodynamic Therapy Application.

Amplification of reactive oxygen species (ROS) generation through covalent conjugation of bovine serum albumin (BSA) with newly synthesized, ROS-producing carbon dots (CDs) upon visible light irradiation is reported for the first time. Derivatization of surface carboxyl functional groups of Anthrarufin-derived, green-emitting CD with the amine functionality of BSA ushers distinct changes in the photophysics of CD including an unprecedented ∼50 nm shift in its excitation maxima, decrease in fluorescence lifetime, and concomitant increase in ROS generation. Substantial conformational changes of BSA were witnessed upon conjugation with CD, rendering the BSA-CD conjugate resistant to pepsinolysis. A protease-proof nanoassembly was derived from the BSA-CD conjugate through desolvation that simultaneously hosts a prototype antibiotic and generates ROS with excellent efficiency, making it an attractive platform for antibacterial photodynamic therapy (A-PDT) applications. Systemic annihilation of both Gram-positive and -negative bacteria was achieved with the BSA-CD nanoassembly and envisioned as alternatives to traditional photosensitizers.