Long-Term Efficacy of Selective Laser Trabeculoplasty in Primary Angle-Closure Disease After Laser Peripheral Iridotomy.

PURPOSE: To evaluate the long-term efficacy of selective laser trabeculoplasty (SLT) in eyes with primary angle-closure (PAC) and primary angle-closure glaucoma (PACG) following a laser peripheral iridotomy (LPI). METHOD: In this prospective cross-sectional study, 45 eyes of 34 patients with PAC/PACG diagnosis, uncontrolled intraocular pressure (IOP), and visible pigmented trabecular-meshwork (TM) at least 180° on gonioscopy following a LPI were recruited. Following a detailed baseline ophthalmic evaluation, all eligible eyes underwent SLT, and the patients were examined on day1, at 1 week, 1-, 3-, and 6-months, and 1-, 2-, 3-, 4-, and 5-year subsequently. The main outcomes measured were IOP, number of IOP-lowering agents, and complications. RESULTS: The mean age of the cohort was 57.80 ± 6.44 years, the male-female ratio was 8:26, and 17 eyes were PACG, and 28 were PAC. The baseline IOP was 23.81 ± 1.78 mm Hg, and was significantly declined at all follow-ups (p < .0001). The cumulative probability of overall success was 91% and 84% at 2-, and 5-year, respectively. At 5-year SLT provided drug-freedom in 80% of PAC and 23% of PACG eyes. Six eyes had IOP spike at 1-week and two patients underwent repeat SLT after 1-year. No other complications, such as pain/discomfort, inflammation, an increase in peripheral anterior synechiae and cystoid-macular-edema, were noted. CONCLUSIONS: SLT appears a safe and cost-effective procedure in PAC/mild- moderate PACG eyes with uncontrolled IOP after laser iridotomy. The long-term effectiveness of SLT as adjuvant treatment was good, but need large sized randomized studies for more validation.

The BET degrader ZBC260 suppresses stemness and tumorigenesis and promotes differentiation in triple-negative breast cancer by disrupting inflammatory signaling.

BACKGROUND: Breast cancer stem cells (BCSCs) are resistant to standard therapies, facilitate tumor dissemination, and contribute to relapse and progression. Super-enhancers are regulators of stemness, and BET proteins, which are critical for super-enhancer function, are a potential therapeutic target. Here, we investigated the effects of BET proteins on the regulation of breast cancer stemness using the pan-BET degrader ZBC260. METHODS: We evaluated the effect of ZBC260 on CSCs in TNBC cell lines. We assessed the effect of ZBC260 on cellular viability and tumor growth and measured its effects on cancer stemness. We used RNA sequencing and stemness index to determine the global transcriptomic changes in CSCs and bulk cells and further validated our findings by qPCR, western blot, and ELISA. RESULTS: ZBC260 potently inhibited TNBC growth both in vitro and in vivo. ZBC260 reduced stemness as measured by cell surface marker expression, ALDH activity, tumorsphere number, and stemness index while increasing differentiated cells. GSEA analysis indicated preferential downregulation of stemness-associated and inflammatory genes by ZBC260 in ALDH+ CSCs. CONCLUSIONS: The BET degrader ZBC260 is an efficient degrader of BET proteins that suppresses tumor progression and decreases CSCs through the downregulation of inflammatory genes and pathways. Our findings support the further development of BET degraders alone and in combination with other therapeutics as CSC targeting agents.

Natural killer cell regulation of breast cancer stem cells mediates metastatic dormancy.

Breast cancer patients with estrogen receptor positive tumors face a constant risk of disease recurrence for the remainder of their lives. Dormant tumor cells residing in tissues such as the bone marrow may generate clinically significant metastases many years after initial diagnosis. Previous studies suggest that dormant cells display "stem like" properties (CSCs), which may be regulated by the immune system. Although many studies have examined tumor cell intrinsic characteristics of dormancy, the role of the immune system in controlling dormancy and its escape is not well understood. This scientific gap is due, in part, to a lack of immunocompetent mouse models of breast cancer dormancy with many studies involving human xenografts in immunodeficient mice. To overcome this limitation, we studied dormancy in immunocompetent, syngeneic mouse breast cancer models. We find that PyMT, Met-1 and D2.0R cell lines contain CSCs that display both short- and long-term metastatic dormancy in vivo, which is dependent on the host immune system. Natural killer cells were key for the metastatic dormancy phenotype observed for D2.0R and the role of NK cells in regulating CSCs was further investigated.Quiescent D2.0R CSC are resistant to NK cytotoxicity, while proliferative D2.0R CSC were sensitive to NK cytotoxicity both in vitro and in vivo. This resistance was mediated, in part, by the expression of Bach1 and Sox2 transcription factors. NK killing was enhanced by the STING agonist MSA-2. Collectively, our findings demonstrate the important role of immune regulation of breast tumor dormancy and highlight the importance of utilizing immunocompetent models to study this phenomenon.

Assessment of Quality of Life after Hysterectomy using European Quality of Life Five Dimension Scale (EQ5D).

In several regions throughout the globe, caesarean sections constitute the most common nonobstetric surgery, followed by hysterectomy, which is the surgical excision of the uterus. While it is not the only solution for reproductive organ issues, it is the most effective technique to treat many illnesses over the long term. The uterus is a very critical reproductive organ for all age groups as this is not only essential for giving birth but also for hormonal-related physiology in women's life. The quality of life is impacted by a number of hysterectomy-related effects on females. Physical, psychological, environmental, and social relations are some of these impacts. All EuroQol five-dimensions (EQ5D) subscales significantly improved, as per the research 's findings. Preoperative psychosocial status, perioperative pain, indication of hysterectomy, complications occur during surgery, and mode of hysterectomy postoperative infection had been discovered as determinants of quality of life outcome following hysterectomy. In most of the subjects we noticed small, however, noticable improvements in all component of EQ5D Scale. The strengths of EQ5D questionnaire lie in its simplicity and moreover it is available in several languages.

Predictors of participant retention in a community-based HIV prevention cohort: perspectives from the HPTN 071 (PopART) study.

INTRODUCTION: In 2021, there were 38.4 million people living with HIV (PLHIV) globally, of which 20.6 million (54%) were living in Eastern and Southern Africa. Longitudinal studies, inclusive of community randomized trials (CRTs), provide critical evidence to guide a broad range of health care interventions including HIV prevention. In this study, we have used an individual-level cohort study design to evaluate the association between sex and other baseline characteristics and participant retention in the HPTN 071 (PopART) trial in Zambia and South Africa. METHODS: HPTN 071 (PopART) was a community randomized trial (CRT) conducted from 2013 to 2018, in 21 communities. The primary outcome was measured in a randomly selected population cohort (PC), followed up over 3 to 4 years at annual rounds. PC retention was defined as completion of an annual follow-up questionnaire. Baseline characteristics were described by study arm and Poisson regression analyses used to measure the association between baseline factors and retention. In addition, we present a description of researcher-documented reasons for study withdrawal by PC participants. RESULTS: Of the 38,474 participants enrolled during the first round of the trial (PC0), most were women (27,139, 71%) and 73% completed at least one follow-up visit. Retention was lower in men (adj RR: 0.90; 95% CI: 0.88, 0.91) and higher among older participants (adj RR: 1.23; 95% CI 1.20, 1.26) when comparing ages 35-44 to 18-24 years. Retention was higher among individuals with high socioeconomic status (SES) (adj RR 1.16; 95% CI 1.14, 1.19) and medium SES (adj RR 1.12; 95% CI 1.09, 1.14) compared to low SES. The most common reasons for study withdrawal were study refusal (23%) and relocation outside the CRT catchment area (66%). CONCLUSION: Despite challenges, satisfactory retention outcomes were achieved in PopART with limited variability across study arms. In keeping with other studies, younger age, male sex, and lower SES were associated with lower levels of retention. Relocation outside of catchment area was the most common reason for non-retention in this CRT.

A photonic artificial synapse with a reversible multifaceted photochromic compound.

Modern computational technology based on the von Neumann architecture physically partitions memory and the central processing unit, resulting in fundamental speed limitations and high energy consumption. On the other hand, the human brain is an extraordinary multifunctional organ composed of more than a billion neurons capable of simultaneously thinking, processing, and storing information. Neurons are interconnected with synapses that control information flow from pre-synaptic-to-post-synaptic neurons. Therefore, emulating synaptic functionalities and developing neuromorphic computational architecture has recently attracted much interest. Due to their high-speed, large bandwidth, and no interconnect-related power loss, photonic (all-optical) synapses can overcome the existing hurdles with electronic synapses. Here, we show an artificial photonic synapse by utilizing the well-established reversible, high-contrast photochromic organic compound, spiropyran, stimulated by optical pulses. Optical transmission of spiropyran significantly changes during spiropyran-merocyanine isomerization driven by UV-visible optical pulses. Such changes are equivalent to the biological synapses' inhibitory and excitatory synaptic actions. The slow relaxation to the initial state is considered as synaptic plasticity responsible for learning and memory formation. Short-term memory (STM), long-term memory (LTM), and transition from the STM to the LTM are demonstrated in all-optical synapses by modulating the stimuli's strength. The solvatochromic properties of spiropyran are further utilized to augment memory in synapses. Our work shows that photochromic organic compounds are excellent hosts for artificial photonic synapses and can be implemented in neuromorphic applications.

Consequences of Arsenic Contamination on Plants and Mycoremediation-Mediated Arsenic Stress Tolerance for Sustainable Agriculture.

Arsenic contamination in water and soil is becoming a severe problem. It is toxic to the environment and human health. It is usually found in small quantities in rock, soil, air, and water which increase due to natural and anthropogenic activities. Arsenic exposure leads to several diseases such as vascular disease, including stroke, ischemic heart disease, and peripheral vascular disease, and also increases the risk of liver, lungs, kidneys, and bladder tumors. Arsenic leads to oxidative stress that causes an imbalance in the redox system. Mycoremediation approaches can potentially reduce the As level near the contaminated sites and are procuring popularity as being eco-friendly and cost-effective. Many fungi have specific metal-binding metallothionein proteins, which are used for immobilizing the As concentration from the soil, thereby removing the accumulated As in crops. Some fungi also have other mechanisms to reduce the As contamination, such as biosynthesis of glutathione, cell surface precipitation, bioaugmentation, biostimulation, biosorption, bioaccumulation, biovolatilization, methylation, and chelation of As. Arsenic-resistant fungi and recombinant yeast have a significant potential for better elimination of As from contaminated areas. This review discusses the relationship between As exposure, oxidative stress, and signaling pathways. We also explain how to overcome the detrimental effects of As contamination through mycoremediation, unraveling the mechanism of As-induced toxicity.

Multiple Infection and Human Immunodeficiency Virus Superinfection Among Persons who Inject Drugs in Indonesia and Ukraine.

BACKGROUND: The HIV Prevention Trials Network (HPTN) 074 study evaluated an integrated human immunodeficiency virus (HIV) treatment and prevention strategy among persons who inject drugs (PWID) in Indonesia, Ukraine, and Vietnam. We previously detected multiple HIV infection in 3 of 7 (43%) of seroconverters with 3-8 HIV strains per person. In this report, we analyzed multiple HIV infection and HIV superinfection (SI) in the HPTN 074 cohort. METHODS: We analyzed samples from 70 participants in Indonesia and Ukraine who had viral load >400 copies/mL at enrollment and the final study visit (median follow-up, 2.5 years). HIV was characterized with Sanger sequencing, next-generation sequencing, and phylogenetic analysis. Additional methods were used to characterize a rare case of triple-variant SI. RESULTS: At enrollment, multiple infection was detected in only 3 of 58 (5.2%) participants with env sequence data. SI was detected in only 1 of 70 participants over 172.3 person-years of follow-up (SI incidence, 0.58/100 person-years [95% confidence interval, .015-3.2]). The SI case involved acquisition of 3 HIV strains with rapid selection of a strain with a single pol region cluster. CONCLUSIONS: These data from a large cohort of PWID suggest that intrahost viral selection and other factors may lead to underestimation of the frequency of multiple HIV infection and SI events.

FAST-IT: Find A Simple Test - In TIA (transient ischaemic attack): a prospective cohort study to develop a multivariable prediction model for diagnosis of TIA through proteomic discovery and candidate lipid mass spectrometry, neuroimaging and machine learning-study protocol.

INTRODUCTION: Transient ischaemic attack (TIA) may be a warning sign of stroke and difficult to differentiate from minor stroke and TIA-mimics. Urgent evaluation and diagnosis is important as treating TIA early can prevent subsequent strokes. Recent improvements in mass spectrometer technology allow quantification of hundreds of plasma proteins and lipids, yielding large datasets that would benefit from different approaches including machine learning. Using plasma protein, lipid and radiological biomarkers, our study will develop predictive algorithms to distinguish TIA from minor stroke (positive control) and TIA-mimics (negative control). Analysis including machine learning employs more sophisticated modelling, allowing non-linear interactions, adapting to datasets and enabling development of multiple specialised test-panels for identification and differentiation. METHODS AND ANALYSIS: Patients attending the Emergency Department, Stroke Ward or TIA Clinic at the Royal Adelaide Hospital with TIA, minor stroke or TIA-like symptoms will be recruited consecutively by staff-alert for this prospective cohort study. Advanced neuroimaging will be performed for each participant, with images assessed independently by up to three expert neurologists. Venous blood samples will be collected within 48 hours of symptom onset. Plasma proteomic and lipid analysis will use advanced mass spectrometry (MS) techniques. Principal component analysis and hierarchical cluster analysis will be performed using MS software. Output files will be analysed for relative biomarker quantitative differences between the three groups. Differences will be assessed by linear regression, one-way analysis of variance, Kruskal-Wallis H-test, χ2 test or Fisher's exact test. Machine learning methods will also be applied including deep learning using neural networks. ETHICS AND DISSEMINATION: Patients will provide written informed consent to participate in this grant-funded study. The Central Adelaide Local Health Network Human Research Ethics Committee approved this study (HREC/18/CALHN/384; R20180618). Findings will be disseminated through peer-reviewed publication and conferences; data will be managed according to our Data Management Plan (DMP2020-00062).

Terapia a laser de alta intensidade (Class IV) e fonoforese em gel de ibuprofeno para o tratamento de osteoartrite de joelho entre pessoas que vivem em terreno montanhoso: um protocolo de ensaio multicêntrico, duplo-cego randomizado / High-intensity laser therapy (Class IV) and ibuprofen gel phonophoresis for treating knee osteoarthritis among people living in hilly terrain: A randomized, double blind, multi-centre trial protocol

INTRODUÇÃO: Pessoas que vivem em terrenos íngremes com carga cíclica anormal podem levar à degeneração da cartilagem óssea. A terapia a laser de alta intensidade (TLAI) e a fonoforese trazem inúmeros benefícios aos pacientes com osteoartrite de joelho (OAJ). No entanto, ainda não está claro qual tratamento é eficaz entre eles na reabilitação de pacientes com OAJ. OBJETIVO: Verificar se a TLAI de 8 semanas não é pior que a fonoforese em gel de ibuprofeno (FGI) no tratamento de pacientes com osteoartrite de joelho que vivem em terreno montanhoso. MATERIAIS E MÉTODOS: Um total de 108 indivíduos com OAJ serão recrutados por amostragem aleatória simples para participar de um estudo randomizado, duplo-cego e controlado. Os indivíduos recrutados com OAJ serão divididos aleatoriamente em dois grupos, grupo TLAI (grupo experimental) e grupo FGI (grupo controle). A duração do tratamento de TLAI e FGI será de 8 minutos em uma sessão/articulação do joelho para cada dia, por 3 dias/semana até 8 semanas, além de seus exercícios convencionais por 30 minutos. O Western Ontario and Mc Master Universities Osteoarthritis Index, o algômetro digitalizado de pressão de dor e o questionário de 36 itens Short-Form Health Survey são as medidas de resultado que serão registradas ao término, no final do período pós-intervenção de 8 semanas. PERSPECTIVAS: Os resultados deste ensaio contribuirão para recomendações baseadas em evidências para a implicação clínica de que o TLAI não é pior que o FGI juntamente com a intervenção de exercício para tratar indivíduos com OAJ que vivem em terreno íngreme.

INTRODUCTION: People living in hilly terrain with abnormal cyclic loading could lead to bone cartilage degeneration. High-intensity laser therapy (HILT) and Ibuprofen gel phonophoresis (IGP) have innumerable benefits for patients with knee osteoarthritis (KOA). However, it is still unclear which treatment is effective among them in rehabilitating patients with KOA. OBJECTIVE: To verify whether 8-week HILT is no worse than the IGP in treating patients with knee osteoarthritis living in hilly terrain. MATERIALS AND METHODS: A total of 108 individuals with KOA will be recruited by simple random sampling to participate in a randomized, double-blind, controlled study. Recruited individuals with KOA will be randomly divided into two groups, the HILT group (experimental group) and the IGP group (active control group). The treatment duration of HILT and IGP will be 8 minutes in one session/knee joint for each day for 3 days/week up to 8 weeks in addition to their conventional exercises for 30 minutes. The Western Ontario and McMaster Universities Osteoarthritis Index, Digitalized pain pressure algometer, and 36-Item Short-Form Health Survey questionnaire are the outcome measures that will be recorded at baseline, end of the 8-week post-intervention period. PERSPECTIVES: The results from this trial will contribute to evidencebased recommendations for the clinical implication of whether HILT is no worse than IGP, along with exercise intervention for treating individuals with KOA living in hilly terrain.

Organochlorine pesticide dieldrin upregulate proximal promoter (PII) driven CYP19A1 gene expression and increases estrogen production in granulosa cells.

Organochlorine pesticides are highly persistent environmental pollutants, generally shown to act through estrogen receptor alpha and alter estrogen biosynthesis. However, the molecular mechanism of regulation of estrogen biosynthesis by these pesticides is not clear. Estrogen is main female fertility hormone regulated by rate-limiting enzyme aromatase. It is encoded by the CYP19A1 gene, which is expressed using specific promoters. In the present study, the attempt has been made to elucidate the effect of dieldrin on the promoter-specific CYP19A1 gene expression and estrogen hormone production in buffalo granulosa cells. The buffalo granulosa cells were cultured and treated with dieldrin in a dose (100,150 and 200 ng/mL) and time (6, 12, and 24 h) dependent manner, followed by analysis of CYP19A1, promoter-specific CYP19A1 transcript expression, and estrogen production. Results showed that dieldrin significantly increased the expression of the CYP19A1 gene after 6 and 12 h while its expression was decreased after 24 h. To understand the upregulation of CYP19A1 gene, promoters' specific CYP19A1 transcript analysis was done. The finding showed that dieldrin significantly increased the proximal promoter specific CYP19A1 transcript while there was no effect on distal promoter specific CYP19A1 transcripts. This specific-promoter activity was quantified by chromatin immunoprecipitation assay (ChIP). Results confirmed the involvement of the proximal promoter in the overexpression of CYP19A1 gene. Furthermore, a significant increase in estradiol-17ß level was also observed. Overall, the present study demonstrated the stimulatory effect of dieldrin on the CYP19A1 gene and will help to understand the toxicological role of dieldrin on the reproductive system.

Intranasal delivery of Naloxone-loaded solid lipid nanoparticles as a promising simple and non-invasive approach for the management of opioid overdose.

Naloxone is an opioid receptor antagonist that can eradicate all pre-indications of the toxicity and inverse the opioid overdose. However, oral administration of naloxone offers limitations such as its extensive first-pass metabolism that results in poor therapeutic effects. In order to resolve this issue, we developed intranasal solid-lipid nanoparticles in which naloxone was incorporated for the higher brain disposition of naloxone with superior therapeutic effects for the reversal of toxicity of opioid overdose. The preparation of naloxone loaded solid-lipid nanoparticles was done by employing the solvent evaporation method. Later, the designed formulation was optimized by Quality by Design approach, specifically, Box-Behnken method. The composition of optimized formulation was Glyceryl monostearate as a solid lipid (40 mg), Pluronic127 (0.5%) and Tween 80 (0.1%) as a surfactant and co-surfactant, respectively. Furthermore, the characterization of optimized formulation was achieved in terms of particle size, PDI, zeta potential, entrapment efficiency, and drug loading which were 190.2 nm, 0.082, -16 mV, 95 ± 0.532% and 19.08 ± 0.106%, respectively. Afterwards, in vitro, ex vivo and in vivo experiments were performed in which higher drug release and superior drug uptake by nasal membrane were observed for naloxone-loaded solid-lipid nanoparticles, later it was confirmed by confocal microscopy of ex vivo nasal membrane tissue. The findings of gamma scintigraphy investigation exhibited better deposition of naloxone-loaded solid-lipid nanoparticles as compared to naloxone solution. Also, the better deposition of naloxone by gamma scintigraphy was further validated by the investigation through the biodistribution study. Additionally, the key findings of the pharmacokinetic study revealed Cmax, Tmax, AUC0-t, AUC0-∞, T1/2 and Ke was found to be 163.95 ± 2.64 ng/ml, 240 ± 2.1 min, 17.75 ± 1.08 ng.hr/ml, 18.82 ± 2.51 ng.hr/ml, 70.71 ± 0.115 min, 0.098 ± 0.01 h-1 respectively. Lastly, investigations such as weight variation and histopathological proved the plausible potential of naloxone-loaded solid-lipid nanoparticles in terms of safety as no toxicity was noticed even after the administration of the three-folds dose of the normal dose. Therefore, considering all these findings, it could be easy to say that these developed naloxone-loaded solid-lipid nanoparticles could be administrated via intranasal route and can act as successful novel nanoformulation for the effective treatment of opioid overdose.

Reverse transcription-loop mediated isothermal amplification (RT-LAMP) assay for detection of AhR receptor responsive xenobiotics.

Dioxins are a group of highly toxic environmental persistent organic pollutants, which are lipophilic in nature. 2, 3, 7, 8- tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic representative of this class. TCDD causes several human health effects like endocrine disruption, carcinogenesis and reproductive toxicity mediated by aryl-hydrocarbon receptor. Current detection methods of dioxins like gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry etc. are costly and time consuming. Therefore, the present study aims to develop a relatively faster and cheaper technique called reverse transcription-loop mediated isothermal amplification (RT-LAMP) assay to detect dioxins. Cultured granulosa cells used as a model system were treated with different doses (5, 10 and 15 pg/mL) of aryl hydrocarbon receptor (AhR)responsive xenobiotic, TCDD, in accordance with maximum residue limit values. Cells were treated for 6, 12 and 24 h, respectively to study the gene expression of TCDD receptor called AhR and AhR responsive genes, CYP1A1 and CYP1B1, in a dose and time dependent manner. All targeted genes expression significantly increased after 6 and 12 h by 1.3-8 folds. For the development of RT-LAMP assay, CYP1A1 gene was used with 6 h TCDD treatment. RT-LAMP assay was standardized with optimal color change at 30 min using 50 ng of cellular RNA. In all the cases, we could distinguish RT-LAMP-positive condition from one sample to another sample due to intensity of color. The method was also validated by spectrometric method. In conclusion, the developed method will be used to screen AhR receptor responsive xenobiotics by observing the color change in RT-LAMP assay like dioxin used in the present study.

BACILLARY LAYER DETACHMENT IN ACUTE VOGT-KOYANAGI-HARADA DISEASE: A Novel Swept-Source Optical Coherence Tomography Analysis.

PURPOSE: To report the frequency, optical coherence tomography (OCT) findings, and visual and anatomic outcomes of patients with acute Vogt-Koyanagi-Harada disease presenting with the bacillary layer detachment (BLD) (intraretinal split at the photoreceptor inner segment myoid). METHODS: This was a retrospective analysis of a consecutive series of patients with Vogt-Koyanagi-Harada disease having a minimum follow-up of 6 months. All patients had swept-source OCT, fluorescein angiography, and indocyanine green angiography performed at baseline. The characteristics of serial swept-source OCT were recorded and analyzed. RESULTS: Sixty-two subjects (42 women; age: 34.2 ± 12 years) with Vogt-Koyanagi-Harada disease were included. 118 eyes (95.2%) had serous retinal detachment at presentation. 112 eyes (94.9%) showed the BLD at baseline. In 8 of 112 (7.1%) eyes with the BLD, the external limiting membrane at the anterior aspect of the BLD showed focal discontinuity. The interdigitation zone at the base of the BLD showed discontinuity in 53 of 112 (47.3%) eyes with the BLD. The ellipsoid zone could not be identified as a separate hyperreflective line at the base of the BLD in 102 of 112 eyes (91.1%). Bacillary layer detachments resolved within 3.4 ± 1.3 days after intravenous methylprednisolone therapy with improvement in the best-corrected visual acuity from 0.96 to 0.4 logarithm of the minimum angle of resolution (20/184 Snellen's equivalent) (P < 0.001). Resolution of serous retinal detachment was observed after 5.9 ± 2.6 days. CONCLUSION: In eyes with acute Vogt-Koyanagi-Harada disease, the BLD is a common finding and represents a split in the photoreceptor layer at the inner segment myoid and can be differentiated from serous retinal detachment using swept-source OCT. In addition, resolution of the BLD and photoreceptor recovery can be evaluated using serial swept-source OCT.

Photophysics and Electronic Structure of Lateral Graphene/MoS2 and Metal/MoS2 Junctions.

Integration of semiconducting transition metal dichalcogenides (TMDs) into functional optoelectronic circuitries requires an understanding of the charge transfer across the interface between the TMD and the contacting material. Here, we use spatially resolved photocurrent microscopy to demonstrate electronic uniformity at the epitaxial graphene/molybdenum disulfide (EG/MoS2) interface. A 10× larger photocurrent is extracted at the EG/MoS2 interface when compared to the metal (Ti/Au)/MoS2 interface. This is supported by semi-local density functional theory (DFT), which predicts the Schottky barrier at the EG/MoS2 interface to be ∼2× lower than that at Ti/MoS2. We provide a direct visualization of a 2D material Schottky barrier through combination of angle-resolved photoemission spectroscopy with spatial resolution selected to be ∼300 nm (nano-ARPES) and DFT calculations. A bending of ∼500 meV over a length scale of ∼2-3 µm in the valence band maximum of MoS2 is observed via nano-ARPES. We explicate a correlation between experimental demonstration and theoretical predictions of barriers at graphene/TMD interfaces. Spatially resolved photocurrent mapping allows for directly visualizing the uniformity of built-in electric fields at heterostructure interfaces, providing a guide for microscopic engineering of charge transport across heterointerfaces. This simple probe-based technique also speaks directly to the 2D synthesis community to elucidate electronic uniformity at domain boundaries alongside morphological uniformity over large areas.

Enhancement in brain uptake of vitamin D3 nanoemulsion for treatment of cerebral ischemia: formulation, gamma scintigraphy and efficacy study in transient middle cerebral artery occlusion rat models.

AIM: For the treatment of cerebral ischaemia, vitamin-D3 loaded nanoemulsions were developed. METHOD: Tween 20 and polyethylene glycol were chosen as surfactant/co-surfactant, while oleic acid as the oil phase. The formulation was characterised for various in-vitro parameters. Targeting efficiency was investigated through radiometry, gamma scintigraphy and efficacy was studied in transient middle cerebral artery occlusion (MCAo) rat model. RESULT: Vitamin D3-nanoemulsion showed a mean size range of 49.29 ± 10.28 nm with polydispersity index 0.17 ± 0.04 and zeta potential 13.77 mV. The formulation was found stable during thermodynamic stability study and permeated within 180 min through sheep nasal mucosa (permeation coefficient 7.873 ± 0.884 cm/h). Gamma scintigraphy and radiometry assay confirmed better percentage deposition (2.53 ± 0.17%) of 99mTc-vitamin D3-nanoemulsion through nasal route compared to IV administered 99mTc-vitamin D3 solution (0.79 ± 0.03%). Magnetic Resonance Imaging (MRI) of the ischaemic model confirmed better efficacy of vitamin D3-nanoemulsion. CONCLUSION: This work demonstrated better permeation, deposition, and efficacy of vitaminD3-nanoemulsion through the intranasal route.

Submental nalbuphine exhibits improved efficacy in ameliorating acute pain in prehospital emergent conditions; a comparative study with conventional intramuscular using gamma scintigraphy.

BACKGROUND: Nalbuphine (NLB) is a kappa-agonist and mu-partial antagonist, widely used for opioid withdrawal de-addiction, opioid-induced pruritis and as emergent analgesia. OBJECTIVE: The present study aimed to assess the safety and efficacy of NLB in pain sensitization, through a submental route so as to provide faster management in emergent situations. MATERIALS & METHODS: In-vivo efficacy and safety studies of NLB-submental injection were assessed in Sprague-Dawley(SD) rats. For eddy's hot plate study, animals were allocated into three groups, the first group served as normal control; group II received NLB (through submental route at 1.2 mg/kg); group III received NLB (through intramuscular route at 1.2 mg/kg). Response latency (in terms of response latency) was measured at 10, 30 & 60 min in all the experimental groups. Safety studies were carried out according to OECD 423. In-vitro release study was conducted using a cellulose dialysis membrane (12,000 KDa). The biodistribution and release kinetics studies were carried out using gamma scintigraphy studies in New Zealand rabbits and humans respectively. RESULTS: The response latency of NLB from the submental route was found to be 7.17 (SD 1.47) seconds and in the case of the intramuscular route it was calculated as 4.00 (SD 1.26) seconds at 10 min. The data depicts the better efficacy of submental injection in ameliorating pain than the intramuscular injection. Toxicity studies predict the safe profile through a submental route. The release kinetics in humans of submental NLB was 46% faster as compared to the intramuscular site of injection. The NLB injection through both routes was compared by non-invasive gamma scintigraphy technique and we found that submental injection has faster (within 10 min) onset of action & distributes rapidly. CONCLUSION: The submental route of NLB is faster, more efficacious than the intramuscular route. Thus, we conclude that in the case of emergent scenarios (i.v or i.m. route is compromised), where immediate relief is necessary, the submental route is a preferred choice.

A Comparative Study of Chitosan Gel and Soframycin in the Management of Wounds.

Wounds and related injuries remain a major cause of death and disability. Healing of wound is a complex, highly regulated process that includes cellular, molecular, biochemical, and physiological events that permit living organisms to repair accidental lesions. Therefore, dealing with wounds has always been a subject of concern to the world, and demand for products in wound management had increased to $9.3 trillion worldwide in the health care industry, affecting economic growth. The present work aimed to assess the wound healing effect of chitosan, and a comparative profile with soframycin is established in experimental animals. Enormous research reports, the wound healing properties of chitosan, but the protective mechanism implicated in wound healing activity of chitosan is unknown. In addition to this, we evaluated the anatomical, macroscopical, and histopathological alterations in wounds of experimental rats. Collagenase activity was performed to determine the granulation tissue formation and epithelialization of wounds treated with untainted chitosan. Wounds treated with glycerated chitosan gel, that is, GCG-3 (high degree of deacetylation), showed faster healing with highest percentage of contraction as compared with the soframycin-treated group. The healing of wounds was found to be 85% in GCG-3 on the sixth day of treatment, showing significant (P < .001) improvement in epithelial tissue. The collagenase activity in GCG-3 was 192 unit/mg of protein. Wound reepithelialization was found to be to 94 ± 4% in case of the GCG-3-treated group and 87 ± 5% in the soframycin-treated group. Higher degree of deacetylation in the chitosan, GCG-3, warrants its use in the treatment and management of dermal wounds.