Photophysical and structural characterisation of in situ formed quantum dots.

Conjugated polymer-semiconductor quantum dot (QD) composites are attracting increasing attention due to the complementary properties of the two classes of materials. We report a convenient method for in situ formation of QDs, and explore the conditions required for light emission of nanocomposite blends. In particular we explore the properties of nanocomposites of the blue emitting polymer poly[9,9-bis(3,5-di-tert-butylphenyl)-9H-fluorene] together with cadmium sulphide (CdS) and cadmium selenide (CdSe) precursors. We show the formation of emissive quantum dots of CdSe from thermally decomposed precursor. The dots are formed inside the polymer matrix and have a photoluminescence quantum yield of 7.5%. Our results show the importance of appropriate energy level alignment, and are relevant to the application of organic-inorganic systems in optoelectronic devices.

Solubility advantage from amorphous etoricoxib solid dispersions.

OBJECTIVE: This study aimed to evaluate kinetic solubility advantage of amorphous etoricoxib solid dispersions prepared with three water soluble polymers and correlate it with solid state and supersaturated drug solution stabilization potential of these polymers. METHODS: Amorphous solid dispersions (ASDs) of etoricoxib were prepared with polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP) and hydroxyethyl cellulose (HEC) at 70:30w/w ratio and characterized for glass transition temperature (Tg), miscibility and intermolecular interactions. Kinetic solubility profiles of amorphous etoricoxib and its ASDs were determined in water at 37 °C. Solid-state stability was assessed by enthalpy relaxation studies at a common degree of undercooling of around 19.0 °C at 0% RH. Recrystallization behavior of supersaturated drug solution was evaluated in the absence and presence of pre-dissolved polymer at 37 °C. RESULTS: Amorphous etoricoxib exhibited rapid solid-to-solid transition to yield a solubility advantage of merely 1.5-fold in water. Among the ASDs, etoricoxib-PVP dispersion exhibited maximal "peak" (2-fold) and "plateau" (1.8-fold) solubility enhancement, while etoricoxib-PVA dispersion could only sustain the "peak" solubility achieved by amorphous etoricoxib. In contrast, etoricoxib-HEC dispersion displayed no solubility advantage. The rank order for solid state and supersaturated solution stabilization followed a similar trend of amorphous etoricoxib < HEC < PVA < PVP. CONCLUSION: Dissolution behavior of ASDs is influenced by concomitantly occurring solid phase changes, thus understanding these processes independently can enable assessment of the predominant route of drug crystallization and stabilization by the polymer.

Added value of the measles-rubella supplementary immunization activity in reaching unvaccinated and under-vaccinated children, a cross-sectional study in five Indian districts, 2018-20.

INTRODUCTION: Supplementary immunization activities (SIAs) aim to interrupt measles transmission by reaching susceptible children, including children who have not received the recommended two routine doses of MCV before the SIA. However, both strategies may miss the same children if vaccine doses are highly correlated. How well SIAs reach children missed by routine immunization is a key metric in assessing the added value of SIAs. METHODS: Children aged 9 months to younger than 5 years were enrolled in cross-sectional household serosurveys conducted in five districts in India following the 2017-2019 measles-rubella (MR) SIA. History of measles containing vaccine (MCV) through routine services or SIA was obtained from documents and verbal recall. Receipt of a first or second MCV dose during the SIA was categorized as "added value" of the SIA in reaching un- and under-vaccinated children. RESULTS: A total of 1,675 children were enrolled in these post-SIA surveys. The percentage of children receiving a 1st or 2nd dose through the SIA ranged from 12.8% in Thiruvananthapuram District to 48.6% in Dibrugarh District. Although the number of zero-dose children prior to the SIA was small in most sites, the proportion reached by the SIA ranged from 45.8% in Thiruvananthapuram District to 94.9% in Dibrugarh District. Fewer than 7% of children remained measles zero-dose after the MR SIA (range: 1.1-6.4%) compared to up to 28% before the SIA (range: 7.3-28.1%). DISCUSSION: We demonstrated the MR SIA provided considerable added value in terms of measles vaccination coverage, although there was variability across districts due to differences in routine and SIA coverage, and which children were reached by the SIA. Metrics evaluating the added value of an SIA can help to inform the design of vaccination strategies to better reach zero-dose or undervaccinated children.

Chronic stress, sense of coherence and risk of type 2 diabetes mellitus.

AIMS: The study was conducted to ascertain whether chronic stress and sense of coherence are associated with risk of type 2 diabetes mellitus. METHODS: Stress questionnaires - Presumptive Stressful Life Events Scale (PSLES), Perceived Stress Scale (PSS) and Sense of Coherence (SOC) - were administered to 500 Newly Detected Diabetes Mellitus (NDDM) cases and 500 Normal Glucose Tolerance (NGT) controls recruited following 75 g OGTT. Assessment of stress was completed before the diagnosis of diabetes was revealed to them. RESULTS: PSLES and PSS scores were significantly higher and SOC score was significantly lower in NDDM subjects compared to those with NGT. PSLES and PSS correlated positively with anthropometric parameters (waist circumference, BMI), glycemic parameters (FPG, 2 hPG, A1C) and HOMA-IR and inversely with HOMA-ß whereas SOC correlated inversely with glycemic parameters (FPG, 2 hPG, A1C) and HOMA-IR and positively with HOMA-ß. In stepwise logistic regression analysis, SOC emerged as the strongest independent predictor of diabetes (OR: 0.774) after HOMA-IR (OR: 1.621) and BMI (OR: 1.288). Other significant predictors included PSS (OR:1.153), PSLES-LT (OR: 1.005) and HOMA-ß (OR: 0.894). CONCLUSION: Chronic stress and low sense of coherence are associated with a higher risk of type 2 diabetes mellitus.

Co-relationship of physical stability of amorphous dispersions with enthalpy relaxation.

Physical stability studies of valdecoxib (VLB) and its solid dispersions with PVP (1, 2, 5, 10, 15 and 20% w/w) were carried out by Differential Scanning Calorimetry (DSC). Change in specific heat with time was measured to determine the degree of crystallinity of amorphous drug and its binary dispersions after storage at 40 degrees C and 75% RH. The rate of crystallization was found to decrease with increasing PVP concentration and time for 10% crystallization (t90%) was found to increase significantly for the amorphous drug when formulated as PVP dispersions. Enthalpy relaxation was found to be inversely correlated with t90% (min) values and was found to be a good predictor of devitrification tendency and hence stability of amorphous VLB.

Characterization of solid-state forms of mebendazole.

This study deals with the generation and characterization of various solid-state forms of mebendazole (MBZ), a benzimidazole antihelmentic. The drug was subjected to polymorphic screen using different solvents to explore the possibility of existence of different solid forms. Different reported polymorphic forms of MBZ, i.e. form A, B and C were found to be recrystallized from acetic acid:methanol mixture (1:1), ethyl acetate and methanol, respectively. N,N-Dimethyl acetamide (DMA) and N,N-dimethyl formamide (DMF) yielded two new solvates of MBZ. These solid-state forms were characterized by thermoanalytical (DSC, TGA, HSM), crystallographic (XRD), microscopic (optical, polarized), and spectroscopic (FTIR) techniques. Solubility studies were carried out for the solvates to identify the solubility advantage. Molecular modeling studies revealed moderately strong hydrogen bonding between the solvent molecules and MBZ.

A 31-kDa seminal plasma heparin-binding protein reduces cold shock stress during cryopreservation of cross-bred cattle bull semen.

In the present study, a 31-kDa protein, purified from cattle bull seminal plasma heparin-binding proteins (SP-HBP), was characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry. Raw semen of six cross-bred bulls was treated with 31-kDa HBP before cryopreservation to observe its effect on motility, viability, hypo-osmotic swelling test, acrosome integrity, in vitro capacitation/acrosome reaction, and oxidative stress at pre-freeze and frozen-thawed phases of cryopreservation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 31-kDa protein eluted and purified from SP-HBP (separated on acrylamide gels) resulted in a single band of 40 kDa. In matrix-assisted laser desorption/ionization-time of flight analysis, 12 peptides were identified with matching significantly (P < 0.05) to interlukin-6 of bovine with a top score of 55. Addition of 25 µg/mL of fluorescein isothiocyanate-conjugated 31-kDa protein to raw semen and incubation at 37 °C for 20 minutes before cryopreservation resulted in its binding mainly to head region. Treatment of semen with 31-kDa HBP resulted in a significant (P < 0.05) average increase of 9.2%, 6.8%, and 11.7% and 5.5%, 6.5%, and 11.0% in motile, viable, hypo-osmotic swelling-responsive spermatozoa in six bulls at pre-freeze and frozen-thawed phases of cryopreservation, respectively. Percentage of spermatozoa with intact acrosomes nonsignificantly enhanced in the semen treated with 31-kDa HBP at both phases of cryopreservation. An average nonsignificant increase of 3.1% in in vitro capacitated and acrosome-reacted spermatozoa was obtained in semen supplemented with 31-kDa HBP. Addition of 31-kDa HBP also nonsignificantly reduced Malonadialdehyde (MDA) level by 10.7 and 19.3 µM/10(9) spermatozoa in prefrozen and frozen-thawed semen, respectively. The results obtained here indicate to conclude that treatment of cross-bred cattle bull semen with 31-kDa HBP protects the spermatozoa from cold shock effect by coating the sperm surface.

Modulation of N-nitrosodiethylamine (NDEA) induced oxidative stress by vitamin E in rat erythrocytes.

Nitrosamines, such as N-nitrosodiethylamine (NDEA), induced oxidative stress due to the generation of reactive oxygen species, which are capable of initiating peroxidative damage to the cell. The present study was designed to establish whether pre-treatment with vitamin E (40 mg/kg body wt, intraperitoneally (ip), twice a week for 4 weeks) to NDEA induced rats provides protection against oxidative stress caused by NDEA. A single necrogenic dose of NDEA (200 mg/kg body wt) was administered intraperitoneally (ip) to the rats with or without vitamin E pre-treatment and the animals were sacrificed on Day 7, 14 or 21 after NDEA administration. Lipid peroxidation (LPO) and the activities of antioxidant enzymes were determined in erythrocytes as indices of oxidative damage. The result showed elevated levels of LPO in erythrocytes with NDEA treatment, however, vitamin E pre-treated rats administered NDEA showed decreased LPO (Day 14 and 21). Superoxide dismutase (SOD) enzyme activity and the glutathione (GSH) content increased with NDEA treatment and remained high in vitamin E pre-treated group. Catalase (CAT), glutathione reductase (GSH-R) and glutathione-S-transferase (GST) enzyme activities declined with NDEA treatment; however, vitamin E pre-treated rats administered NDEA, showed elevation in the enzyme activities. Glutathione peroxidase (GSH-Px) activity increased in erythrocytes in vitamin E pre-treated rats administered NDEA, while Se-GSH-Px activity was not affected significantly. This study demonstrates that the pre-treatment with vitamin E prior to the administration of NDEA was effective in counteracting and modulating oxidative stress in rat erythrocytes in a time-dependent manner.

Ternary amorphous composites of celecoxib, poly(vinyl pyrrolidone) and meglumine with enhanced solubility.

The present study highlights the development of ternary amorphous composites to enhance the solubility of a poorly soluble crystalline drug, celecoxib (CEL). These systems comprised of an 'amorphous drug,' and its 'stabilizer' and 'solubilizer.' The ternary amorphous system of CEL, poly(vinyl pyrrolidone) (PVP) and meglumine (MEG) (7:2:1 w/w) enhanced CEL solubility by approximately equal to 10.2-fold over that for the crystalline drug, and maintained the thermodynamic stability of the amorphous drug. However, MEG alone was unable to stabilize the amorphous CEL against thermally-induced crystallization, and so gave no solubility advantage. The PVP-MEG combination provided a 'synergistic' enhancement of CEL solubility, as compared to their use alone in the amorphous systems. Phase-solubility studies provided greater insight into molecular mechanisms underlying stability and solubility of these amorphous systems. MEG exhibited phase-specific interaction with CEL molecules, when stabilized by PVP in the amorphous state. The higher solubility of CEL from ternary amorphous systems was also thermodynamically favored, as analyzed by van't Hoff plots. A possible molecular level interaction of MEG with PVP-stabilized amorphous CEL seems to be responsible for the solubility advantage of the CEL-PVP-MEG ternary amorphous system.

Hypofractionated stereotactic body radiotherapy in spinal metastasis - with or without epidural extension.

AIMS: To evaluate clinical outcome and the effect of malignant epidural compression (MEC) in the treatment of spine metastasis with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Seventy-six lesions in 52 patients with spinal metastasis received SBRT during the period July 2010 to December 2012. MEC was detected in 20 patients (38.4%) and was separately contoured. The median dose prescribed to involved vertebra (planning target volume) was 24 Gy (range 24-27 Gy) in a median of three fractions (range 1-3). Uninvolved elements were prescribed 21 Gy in three fractions. In 59 lesions (77.6%), the entire vertebra was treated and in 17 lesions (22.4%) only the anterior elements were treated. All patients were treated with volumetric modulated arc therapy with image guidance on a Novalis Tx linear accelerator with the ExacTrac system. Dosimetric and clinical outcomes were compared in patients with or without MEC. RESULTS: At a median follow-up of 8.48 months (range 3-40 months), 1 year local control and overall survival was 94 and 68%, respectively. In patients with or without epidural extension, the median dose to the gross tumour volume (GTV; 95%) was 23.48 Gy (range 13.70-25.75) and 22.99 Gy (range 13.55-26.84), the median spinal cord Dmax was 17.36 Gy (range 8.47-21.63) and 15.71 Gy (range 8.39-23.33). The median GTV epidural (D95%) was 21.16 Gy (range 15.43-23.92). Complete pain relief was seen in 90% of patients with MEC and 93.75% without MEC (P=NS) and neurological improvement was seen in 60% of patients in both groups of patients. CONCLUSION: It is feasible to deliver a high dose of radiation (∼90% of the prescription dose) to the epidural component with volumetric modulated arc therapy SBRT and image guidance. It yielded high rates of pain control and local control in patients with spine metastases with or without MEC.

Neurotoxicity of HIV-1 proteins gp120 and Tat in the rat striatum.

HIV-associated dementia complex is a serious disabling disease characterized by cognitive, behavioral and motor dysfunction. Basal ganglia involvement in HIV-1 infection may be responsible for some of the psychomotor symptoms associated with HIV dementia. The objectives of the present study were to determine: (1) whether gp120 and Tat produce striatal toxicity, and (2) whether gp120 and Tat show synergistic toxicity in the striatum. In these studies, the recombinant proteins gp120, Tat, or saline (0.9%) were stereotaxically injected in the striatum of adult male rats. The striatal sections were evaluated for area of tissue loss (Cresyl-violet stained sections) and the number of GFAP immunoreactive cells 7 days after the injections. Doses of gp120 250 ng/microl or higher and Tat 5 microg/microl or higher produced a significant area of tissue loss and significantly increased the number of GFAP reactive cells. We found no toxicity in animals treated with immunoabsorbed gp120 or Tat. Combined gp120 (100 ng/microl)+Tat (1 microg/microl) injections into the rat striatum significantly increased the area of tissue loss and altered morphology and increased number of GFAP reactive cells, as compared to controls. Thus, the present results suggest the involvement of gp120 and Tat in striatal toxicity and provide a model for further studies to fully characterize their role in HIV-1 toxicity and to develop therapeutic strategies for HIV-1 associated dementia complex.

Oxidative damage induced by the injection of HIV-1 Tat protein in the rat striatum.

Oxidative stress has been hypothesized to play a role in the pathogenesis of different neurodegenerative disorders, including HIV-related dementia. Tat, a nonstructural protein of HIV, is implicated in potentiation of neuronal apoptosis by mechanisms involving the disruption of calcium homeostasis and oxidative stress. The injection of Tat caused an increase of protein carbonyl formation in the rat striatum. Increased oxidative modification of proteins occurred early after Tat injection and preceded Tat-mediated astrogliosis. Immunostaining of brain sections demonstrated that an area of prominent protein carbonyl immunoreactivity surrounded an injection site in the striatum of Tat-injected rats. Intense protein carbonyl immunoreactivity was localized in cell bodies. Our study suggests that increased protein oxidation may be an important part of the mechanism of Tat neurotoxicity.

Aspergillus flavus keratitis after laser in situ keratomileusis.

PURPOSE: To report a case of fungal keratitis caused by Aspergillus flavus after laser in situ keratomileusis surgery. METHODS: Case report. A 24-year-old woman developed pain, redness, decreased vision, and an infiltrate posterior to the corneal flap in her right eye 3 days after laser in situ keratomileusis. On referral, approximately 3 weeks after laser in situ keratomileusis, examination of the right eye revealed light perception vision, a large full-thickness corneal infiltrate, and hypopyon. Corneal scrapings were taken for direct microscopic examination and culture. RESULTS: Corneal scraping revealed the presence of fungal filaments in smears and in culture. The fungus was identified as A. flavus. Intensive topical natamycin and systemic ketoconazole therapy was initiated. Despite intensive medical treatment, the infiltrate progressed and the patient was subjected to a therapeutic penetrating keratoplasty. There was no recurrence of infection after surgery. At last follow-up 4 months after surgery, the eye was quiet with graft edema. CONCLUSION: Fungal keratitis is a rare complication of laser in situ keratomileusis surgery. In a case that does not respond to medical treatment, early surgical intervention must be considered.

Amniotic membrane transplantation in acute chemical and thermal injury.

PURPOSE: To present a case of chemical injury and a case of thermal injury treated by amniotic membrane transplantation in acute phase. METHODS: Case reports. An eye with sodium hydroxide injury, opaque cornea, and limbal ischemia of more than 180 degrees and an eye with hot tea injury, opaque cornea, stromal edema, and scarring were treated by amniotic membrane transplantation within the first few weeks of injury. RESULTS: In the eye with sodium hydroxide injury, 4 months after amniotic membrane transplantation, the ocular surface is stable, superficial corneal scarring with vascularization is present, and visual acuity is 20/25. In the eye with thermal injury, 6 months after amniotic membrane transplantation, the ocular surface is stable, but there is superficial scarring and vascularization, and visual acuity is 20/20. CONCLUSIONS: Amniotic membrane transplantation can be considered in chemical injury with severe limbal ischemia and in severe thermal injury in acute phase. Long-term studies are warranted to evaluate further the efficacy of amniotic membrane transplantation in these clinical situations.

Photoastigmatic refractive keratectomy for correction of astigmatism after keratoplasty.

BACKGROUND: The efficacy and safety of photoastigmatic refractive keratectomy (PARK) to correct astigmatism after keratoplasty was evaluated. METHODS: PARK was performed using the Nidek EC-5000 excimer laser in 10 eyes of 10 patients (mean age: 49.5 +/- 11.5 years) with astigmatism after keratoplasty. RESULTS: The refractive cylinder decreased from 5.80 to 3.20 D, whereas at 6 months, topographic cylinder decreased from 7.40 to 5.90 D post-operatively. Five eyes (50%) had uncorrected visual acuity of 20/60 or better at 3 months. Stromal haze increased from 3 to 6 months postoperatively, and at 6 months, 5 eyes (50%) had a haze score of greater than or equal to 2.0. CONCLUSION: PARK is a moderately effective method of correcting astigmatism after keratoplasty.

Fungal keratitis after laser in situ keratomileusis.

A 22-year-old woman presented with pain, redness, watering, and decrease in vision in her left eye 15 days after laser in situ keratomileusis for myopia. Slitlamp examination showed a central full-thickness infiltrate with hyphate edges. Microscopic examination of corneal scrapings from the edge and underneath the flap showed fungal filaments, and the growth on culture media was identified as Scedosporium apiospermum.

Laser refractive surgery: technological advance and tissue response.

Photorefractive keratectomy (PRK) and laser assisted in situ keratomileusis (LASIK), using an excimer laser, are the currently popular techniques of correcting refractive errors. Since these techniques work by selective ablation of corneal stroma, the tissue healing response plays a great role in the ultimate outcome of surgery. Also, various methods of wound healing modulation can be used to achieve better results. While these procedures do lead to a decrease in dioptric power and increase in unaided visual acuity, higher visual functions like contrast sensitivity can sometimes be compromised after the surgery.

Corneal triple procedure: indications, complications, and outcomes: a developing country scenario.

PURPOSE: We report the indications, complications, and outcomes of 104 corneal triple procedures in our institute. METHODS: Patient records of 104 consecutive cases of corneal triple procedure (penetrating keratoplasty with extracapsular cataract extraction and intraocular lens implantation) performed by experienced corneal surgeons between January 1992 and December 1997 were retrospectively reviewed. Relevant preoperative, operative, and postoperative data were collected. The outcome was assessed by the graft clarity and visual acuity at the last visit. Survival analysis of these grafts was determined by Kaplan-Meier method. RESULTS: Of 104 patients, 70 were men and 34 were women. Mean age of these patients was 48.5+/-17.1 years (range, 1-75 years). Corneal scarring with cataract was the reason for surgery in 69 (66.4%) cases. The intraoperative complications included vitreous upthrust in seven (6.9%) cases and posterior capsular dehiscence in three (2.9%) cases. The most common early postoperative complications were increased intraocular pressure in 19 (18.3%) and increased anterior chamber reaction in 25 (24%) cases. Posterior capsular opacification was seen in 26 (25%), graft reaction in 15 (14.4%), and secondary glaucoma in 15 (14.4%) cases. These formed the important late postoperative complications. The average postoperative follow-up was 23.7+/-17.6 months (range, 1.6-79.4 months); at which time 72% of the grafts remained clear. At last follow-up, 40% of patients had a visual acuity of > or = 20/40. CONCLUSIONS: Corneal scarring with cataract is the most common reason for triple procedure in this part of the world. This is a safe surgical procedure with good graft clarity and reasonable visual recovery.

Ipsilateral rotational autokeratoplasty: an alternative to penetrating keratoplasty in nonprogressive central corneal scars.

PURPOSE: To report the outcome of ipsilateral rotational autokeratoplasty performed for nonprogressive central corneal opacities. METHODS: Medical records of 27 patients who underwent ipsilateral rotational autokeratoplasty between June 1995 and December 1998 were retrospectively reviewed. The etiology of corneal opacity, preoperative visual acuity, and size of the trephine used was noted. Any intraoperative and early and late postoperative complications were noted in all patients. The final outcome, visual acuity, and astigmatism at final correction were analyzed. RESULTS: The main etiology of corneal opacity was trauma (44.4%), followed by resolved keratitis (29.6%). The size of the graft ranged from 6.5 to 9 mm. Fifteen patients underwent autokeratoplasty alone; additional procedures were combined in the remaining 12. Wound leak was the most common postoperative complication, which was seen in seven patients. The mean follow-up was 12.11 months (SD = 11.95 months). Five patients (18.5%) were lost to follow-up. Of the remaining 22, 19 (86.36%) had clear grafts and 3 (13.6%) had failed grafts. The mean astigmatism at final correction was 4.25 diopters cylinder (SD = 2.72). Final visual acuity of 20/80 or better was obtained in 13 cases (59.09%). CONCLUSIONS: Contrary to common belief, ipsilateral rotational autokeratoplasty is a safe and effective surgical procedure. It can be considered as an alternative procedure to penetrating keratoplasty in a scenario in which tissue scarcity exists, as well as in cases that have a high risk of developing immunologic allograft rejection. Further prospective studies with preoperative specular microscopy and postoperative corneal topography will provide greater insight into the usefulness of this procedure.

Co-occurring adenoviral keratitis and hemorrhagic cystitis. A case report.

Adenoviruses are ubiquitous viruses, commonly causing ocular infections. They are also known to cause multisystem infections. External ocular infections caused by adenovirus are most often due to contaminated secretions. We report a patient in whom genitourinary symptoms developed and subsided along with ocular symptoms. Adenovirus was isolated on ocular culture. This is the first reported case of concurrent adenoviral keratitis and hemorrhagic cystitis. Eliciting a history of genitourinary and respiratory symptoms is important in patients with ocular adenoviral infections.