Profile of patients with ocular infections attending the out-patient department of a tertiary care centre in south India

Background: Bacterial and viral etiologies are most commonly blamed for ocular infections. Studies have shown that gram positive cocci are responsible for maximum number of infections, followed by anaerobic bacteria and gram negative bacilli. Infections of the ocular adnexa, ocular surface and orbit usually present as conjunctivitis, keratitis, scleritis, orbital cellulitis and periorbital necrotising fascitis. The intra-ocular infections usually occur subsequently to a corneal ulcer, penetrating eye injury or a severe blood stream infection, and presents as iritis, uveitis, chorioretinitis or endophthalmitis. The aim of the study was to find out the clinico-demographic profile of patients who were diagnosed to have ocular infections at a large tertiary care teaching hospital in south India.Methods: A retrospective study was designed to include all patients who came with suspected ocular infections to the out-patient department (OPD) of Pushpagiri Medical College Hospital, Thiruvalla, Kerala, India, from July 2015 to December 2015.Results: More than 50% of the participants reported ocular pain and around 60% has redness of the affected eye. Twenty five percent of the participants had discharge from the eyes and 56.7% reported persistent watering. Around 60% of the patients had irritation of the eye, while only 16.7% said that they feel blurring of vision. The final diagnosis was formed after careful examination by the senior most consultants available at the OPD and relevant investigations. Among the participants, 36.6% had conjunctivitis and 16.6% had corneal ulceration due to an infective cause. Around 13% has corneal abrasion, 11.6% had foreign body, 3% had dry eye and 3% had dacrocystitis.Conclusions: Only around 55% of the patients with suspected eye infections turned out to be actual infections and a vast majority of that was due to conjunctivitis. Though majority of the patients presented with pain, redness, watering and discharge, these symptoms/signs cannot be used to differentiate infective etiology from a non-infective one.

Universal cloning of continuous quantum variables

The cloning of quantum variables with continuous spectra is analyzed. A universal - or Gaussian - quantum cloning machine is exhibited that copies equally well the states of two conjugate variables such as position and momentum. It also duplicates all coherent states with a fidelity of 2/3. More generally, the copies are shown to obey a no-cloning Heisenberg-like uncertainty relation.Comment: 4 pages, RevTex. Minor revisions, added explicit cloning transformation, added reference

A new Suzuki synthesis of triphenylethylenes that inhibit aromatase and bind to estrogen receptors α and β

The design and synthesis of dual aromatase inhibitors/selective estrogen receptor modulators (AI/SERMs) is an attractive strategy for the discovery of new breast cancer therapeutic agents. Previous efforts led to the preparation of norendoxifen (4) derivatives with dual aromatase inhibitory activity and estrogen receptor binding activity. In the present study, some of the structural features of the potent AI letrozole were incorporated into the lead compound (norendoxifen) to afford a series of new dual AI/SERM agents based on a symmetrical diphenylmethylene substructure that eliminates the problem of E,Z isomerization encountered with norendoxifen-based AI/SERMs. Compound 12d had good aromatase inhibitory activity (IC50 = 62.2 nM) while also exhibiting good binding activity to both ER-α (EC50 = 72.1 nM) and ER-β (EC50 = 70.8 nM). In addition, a new synthesis was devised for the preparation of norendoxifen and its analogues through a bis-Suzuki coupling strategy.

Reduced Time to Admit Emergency Department Patients to Inpatient Beds Using Outflow Barrier Analysis and Process Improvement

Objective: Because admitted emergency department (ED) patients waiting for an inpatient bed contribute to dangerous ED crowding, we conducted a patient flow investigation to discover and solve outflow delays. After solution implementation, we measured whether the time admitted ED patients waited to leave the ED was reduced. Methods: In June 2022, a team using Lean Healthcare methodologies identified flow delays and underlying barriers in a Midwest, mid-sized hospital. We calculated barriers’ magnitudes of burden by the frequency of involvement in delays. During October–December 2022, solutions targeting barriers were implemented. In October 2023, we tested whether waiting time, defined as daily median time in minutes from admission disposition to departure (ADtoD), declined by conducting independent sample, single-tailed t-test comparing pre- to post-intervention time periods, January 1–September 30, 2022 (273 days) to January 1–September 30, 2023 (273 days). Additionally, we regressed ADtoD onto pre-/post period while controlling for ED volume (total daily admissions and ED daily encounters) and hospital occupancy. A run chart analysis of monthly median ADtoD assessed improvement sustainability. Results: Process mapping revealed that three departments (ED, environmental services [EVS], and transport services) co-produced the outflow of admitted ED patients wherein 18 delays were identified. The EVS-clinical care collaboration failures explained 61% (11/18) of delays. Technology contributed to 78% (14/18) of delays primarily because staff’s technology did not display needed information, a condition we coined “digital blindness.” Comparing pre- and post-intervention days (3,144 patients admitted pre-intervention and 3,256 patients post), the median minutes a patient waited (ADtoD) significantly decreased (96.4 to 87.1 minutes, P = 0.04), even while daily ED encounter volume significantly increased (110.7 to 117.3 encounters per day, P < 0.001). After controlling in regression for other factors associated with waiting, the intervention reduced ADtoD by 12.7 minutes per patient (standard error 5.10, P = 0.01; 95% confidence interval −22.7, −2.7). We estimate that the intervention translated to ED staff avoiding 689 hours of admitted patient boarding over nine months (ADtoD coefficient [−12.7 minutes] multiplied by post-intervention ED admissions [3,256] and divided by 60). Run chart analysis substantiated the intervention’s sustainability over nine months. Conclusion: After systemwide patient flow investigation, solutions resolving digital blindness and environmental services-clinical care collaboration failures significantly reduced ED admitted patient boarding.&nbsp

Complete Genome Sequence of Serotype III Streptococcus agalactiae Sequence Type 17 Strain 874391.

Here we report the complete genome sequence of Streptococcus agalactiae strain 874391. This serotype III isolate is a member of the hypervirulent sequence type 17 (ST-17) lineage that causes a disproportionate number of cases of invasive disease in humans and mammals. A brief historical context of the strain is discussed

Elevated acute phase proteins affect pharmacokinetics in COVID-19 trials: Lessons from the CounterCOVID - imatinib study.

This study aimed to determine whether published pharmacokinetic (PK) models can adequately predict the PK profile of imatinib in a new indication, such as coronavirus disease 2019 (COVID-19). Total (bound + unbound) and unbound imatinib plasma concentrations obtained from 134 patients with COVID-19 participating in the CounterCovid study and from an historical dataset of 20 patients with gastrointestinal stromal tumor (GIST) and 85 patients with chronic myeloid leukemia (CML) were compared. Total imatinib area under the concentration time curve (AUC), maximum concentration (C <sub>max</sub> ) and trough concentration (C <sub>trough</sub> ) were 2.32-fold (95% confidence interval [CI] 1.34-3.29), 2.31-fold (95% CI 1.33-3.29), and 2.32-fold (95% CI 1.11-3.53) lower, respectively, for patients with CML/GIST compared with patients with COVID-19, whereas unbound concentrations were comparable among groups. Inclusion of alpha1-acid glycoprotein (AAG) concentrations measured in patients with COVID-19 into a previously published model developed to predict free imatinib concentrations in patients with GIST using total imatinib and plasma AAG concentration measurements (AAG-PK-Model) gave an estimated mean (SD) prediction error (PE) of -20% (31%) for total and -7.0% (56%) for unbound concentrations. Further covariate modeling with this combined dataset showed that in addition to AAG; age, bodyweight, albumin, CRP, and intensive care unit admission were predictive of total imatinib oral clearance. In conclusion, high total and unaltered unbound concentrations of imatinib in COVID-19 compared to CML/GIST were a result of variability in acute phase proteins. This is a textbook example of how failure to take into account differences in plasma protein binding and the unbound fraction when interpreting PK of highly protein bound drugs, such as imatinib, could lead to selection of a dose with suboptimal efficacy in patients with COVID-19

RegSNPs-intron: a computational framework for predicting pathogenic impact of intronic single nucleotide variants

Single nucleotide variants (SNVs) in intronic regions have yet to be systematically investigated for their disease-causing potential. Using known pathogenic and neutral intronic SNVs (iSNVs) as training data, we develop the RegSNPs-intron algorithm based on a random forest classifier that integrates RNA splicing, protein structure, and evolutionary conservation features. RegSNPs-intron showed excellent performance in evaluating the pathogenic impacts of iSNVs. Using a high-throughput functional reporter assay called ASSET-seq (ASsay for Splicing using ExonTrap and sequencing), we evaluate the impact of RegSNPs-intron predictions on splicing outcome. Together, RegSNPs-intron and ASSET-seq enable effective prioritization of iSNVs for disease pathogenesis

PEG Branched Polymer for Functionalization of Nanomaterials with Ultralong Blood Circulation

Nanomaterials have been actively pursued for biological and medical applications in recent years. Here, we report the synthesis of several new poly(ethylene glycol) grafted branched-polymers for functionalization of various nanomaterials including carbon nanotubes, gold nanoparticles (NP) and gold nanorods (NRs), affording high aqueous solubility and stability for these materials. We synthesize different surfactant polymers based upon poly-(g-glutamic acid) (gPGA) and poly(maleic anhydride-alt-1-octadecene) (PMHC18). We use the abundant free carboxylic acid groups of gPGA for attaching lipophilic species such as pyrene or phospholipid, which bind to nanomaterials via robust physisorption. Additionally, the remaining carboxylic acids on gPGA or the amine-reactive anhydrides of PMHC18 are then PEGylated, providing extended hydrophilic groups, affording polymeric amphiphiles. We show that single-walled carbon nanotubes (SWNTs), Au NPs and NRs functionalized by the polymers exhibit high stability in aqueous solutions at different pHs, at elevated temperatures and in serum. Morever, the polymer-coated SWNTs exhibit remarkably long blood circulation (t1/2 22.1 h) upon intravenous injection into mice, far exceeding the previous record of 5.4 h. The ultra-long blood circulation time suggests greatly delayed clearance of nanomaterials by the reticuloendothelial system (RES) of mice, a highly desired property for in vivo applications of nanomaterials, including imaging and drug delivery

Interaction of Water-Soluble CdTe Quantum Dots with Bovine Serum Albumin

Semiconductor nanoparticles (quantum dots) are promising fluorescent markers, but it is very little known about interaction of quantum dots with biological molecules. In this study, interaction of CdTe quantum dots coated with thioglycolic acid (TGA) with bovine serum albumin was investigated. Steady state spectroscopy, atomic force microscopy, electron microscopy and dynamic light scattering methods were used. It was explored how bovine serum albumin affects stability and spectral properties of quantum dots in aqueous media. CdTe–TGA quantum dots in aqueous solution appeared to be not stable and precipitated. Interaction with bovine serum albumin significantly enhanced stability and photoluminescence quantum yield of quantum dots and prevented quantum dots from aggregating

Type 2 NADH dehydrogenase is the only point of entry for electrons into the Streptococcus agalactiae respiratory chain and is a potential drug target

The opportunistic pathogen Streptococcus agalactiae is the major cause of meningitis and sepsis in a newborn’s first week, as well as a considerable cause of pneumonia, urinary tract infections, and sepsis in immunocompromised adults. This pathogen respires aerobically if heme and quinone are available in the environment, and a functional respiratory chain is required for full virulence. Remarkably, it is shown here that the entire respiratory chain of S. agalactiae consists of only two enzymes, a type 2 NADH dehydrogenase (NDH-2) and a cytochrome bd oxygen reductase. There are no respiratory dehydrogenases other than NDH-2 to feed electrons into the respiratory chain, and there is only one respiratory oxygen reductase to reduce oxygen to water. Although S. agalactiae grows well in vitro by fermentative metabolism, it is shown here that the absence of NDH-2 results in attenuated virulence, as observed by reduced colonization in heart and kidney in a mouse model of systemic infection. The lack of NDH-2 in mammalian mitochondria and its important role for virulence suggest this enzyme may be a potential drug target. For this reason, in this study, S. agalactiae NDH-2 was purified and biochemically characterized, and the isolated enzyme was used to screen for inhibitors from libraries of FDA-approved drugs. Zafirlukast was identified to successfully inhibit both NDH-2 activity and aerobic respiration in intact cells. This compound may be useful as a laboratory tool to inhibit respiration in S. agalactiae and, since it has few side effects, it might be considered a lead compound for therapeutics development. IMPORTANCE S. agalactiae is part of the human intestinal microbiota and is present in the vagina of ~30% of healthy women. Although a commensal, it is also the leading cause of septicemia and meningitis in neonates and immunocompromised adults. This organism can aerobically respire, but only using external sources of heme and quinone, required to have a functional electron transport chain. Although bacteria usually have a branched respiratory chain with multiple dehydrogenases and terminal oxygen reductases, here we establish that S. agalactiae utilizes only one type 2 NADH dehydrogenase (NDH-2) and one cytochrome bd oxygen reductase to perform respiration. NADH-dependent respiration plays a critical role in the pathogen in maintaining NADH/NAD+ redox balance in the cell, optimizing ATP production, and tolerating oxygen. In summary, we demonstrate the essential role of NDH-2 in respiration and its contribution to S. agalactiae virulence and propose it as a potential drug target