Porous n-type Si and porous p-type GaN nanostructures were fabricated using alternating current photo-assisted electrochemical (ACPEC) etching in 1:4 volume ratio of hydrofluoric acid (HF) and ...ethanol (C2H5OH) for a duration of 30 min. The proposed approach to this work was to study pore formation on the Si and p-GaN substrates in the aspects of morphological and structural changes. The morphological and structural properties of porous Si and porous p-type GaN samples have been studied using field emission scanning electron microscopy (FESEM) measurement, energy-dispersive X-ray spectroscopy (EDX), atomic force microscopy (AFM), and high-resolution X-ray diffraction (HR-XRD) in comparison to the respective as-grown sample. FESEM analysis revealed that uniform pore size with triangular-like shape was formed in porous Si sample while circular-like shape pores were formed in the porous p-type GaN sample. AFM measurement revealed that the root-mean-square surface roughness of porous Si and porous p-type GaN was 6.15 nm and 5.90 nm, respectively. Detailed investigation will be presented in this work to show that ACPEC etching technique is a viable technique to produce porous nanostructures in different substrates.
To describe first dose and steady state antiretroviral drug exposure in the female genital tract.
Non-blinded, single center, open-label pharmacokinetic study in HIV-infected women.
Twenty-seven ...women initiating combination antiretroviral therapy underwent comprehensive blood plasma and cervicovaginal fluid sampling for drug concentrations during the first dose of antiretroviral therapy and at steady-state. Drug concentrations were measured by validated HPLC/UV or HPLC-MS/MS methods. Pharmacokinetic parameters were estimated for 11 drugs by non-compartmental analysis. Descriptive statistics and 95% confidence intervals were generated using Intercooled STATA Release 8.0 (Stata Corporation, College Station, Texas, USA).
For all antiretroviral drugs, genital tract concentrations were detected rapidly after the first dose. Drugs were stratified according to the genital tract concentrations achieved relative to blood plasma. Median rank order of highest to lowest genital tract concentrations relative to blood plasma at steady state were: lamivudine (concentrations achieved were 411% greater than blood plasma), emtricitabine (395%), zidovudine (235%) tenofovir (75%), ritonavir (26%), didanosine (21%), atazanavir (18%), lopinavir (8%), abacavir (8%), stavudine (5%), and efavirenz (0.4%).
This is the first study to comprehensively evaluate antiretroviral drug exposure in the female genital tract. These findings support the use of lamivudine, zidovudine, tenofovir and emtricitabine as excellent pre-exposure/post-exposure prophylaxis (PrEP/PEP) candidates. Atazanavir and lopinavir might be useful agents for these applications due to favorable therapeutic indices, despite lower genital tract concentrations. Agents such as stavudine, abacavir, and efavirenz that achieve genital tract exposures less than 10% of blood plasma are less attractive PrEP/PEP candidates.
A series of 1,2,3-triazole, oxadiazole and aza-β-lactam derivatives were synthesized through consecutive reaction began from o-(N-propargyl) sulfonamido benzoic acid (1a). The reaction of (1a) with ...absolute ethanol in the presence of concentrated H2SO4 resulted in the formation of ester derivative (2a). The product of the previous reaction was reacted with 80% hydrazine hydrate to prepare benzohydrazide derivative (3a). 1,3,4-oxadiazole compound (4a) was obtained by condensation of compound (3a) with CS2 in presence KOH . Compound (3a) react with Phenyl isocyanates to give Carboxamide derivative (5a), that Condensation either with 2,4-dimethoxybenzaldhyde and p-hydroxybenzaldehyde to prepare the Schiff bases (6a-b). The cycloaddotion of Schiff-bases (6a-b) with phenyl isocyanate gave aza-β-lactams (7a-b). Benzamide derivatives (8a-c) were prepared via the reaction of compound (1a) with aniline derivatives, such as (p-toluidine, o-nitroaniline and m-nitroaniline). In a regioselective reaction 1,4-disubstituted-1,2,3-triazole derivative (9a-j) were synthesized via the click reaction of compounds 4a,5a and (8a-c) with benzyl azide and p-bromobenzyl azide. The compounds were identified using the spectral methods shown in the work. Cytotoxic effects of some final prepared compounds were studied in one cultured cellular models (MCF7 cell line) breast cancer (at various concentrations) by MTT assay, compound (9j) showed the better cytotoxic activity among the tested compounds.
Why are there so few biomarkers accepted by health authorities and implemented in clinical practice, despite the high and growing number of biomaker studies in medical research ? In this ...meta-epidemiological study, including 804 studies that were critically appraised by expert reviewers, the authors have identified all prognostic kidney transplant biomarkers and showed overall suboptimal study designs, methods, results, interpretation, reproducible research standards, and transparency. The authors also demonstrated for the first time that the limited number of studies challenged the added value of their candidate biomarkers against standard-of-care routine patient monitoring parameters. Most biomarker studies tended to be single-center, retrospective studies with a small number of patients and clinical events. Less than 5% of the studies performed an external validation. The authors also showed the poor transparency reporting and identified a data beautification phenomenon. These findings suggest that there is much wasted research effort in transplant biomarker medical research and highlight the need to produce more rigorous studies so that more biomarkers may be validated and successfully implemented in clinical practice.
Despite the increasing number of biomarker studies published in the transplant literature over the past 20 years, demonstrations of their clinical benefit and their implementation in routine clinical practice are lacking. We hypothesized that suboptimal design, data, methodology, and reporting might contribute to this phenomenon.
We formed a consortium of experts in systematic reviews, nephrologists, methodologists, and epidemiologists. A systematic literature search was performed in PubMed, Embase, Scopus, Web of Science, and Cochrane Library between January 1, 2005, and November 12, 2022 (PROSPERO ID: CRD42020154747). All English language, original studies investigating the association between a biomarker and kidney allograft outcome were included. The final set of publications was assessed by expert reviewers. After data collection, two independent reviewers randomly evaluated the inconsistencies for 30% of the references for each reviewer. If more than 5% of inconsistencies were observed for one given reviewer, a re-evaluation was conducted for all the references of the reviewer. The biomarkers were categorized according to their type and the biological milieu from which they were measured. The study characteristics related to the design, methods, results, and their interpretation were assessed, as well as reproducible research practices and transparency indicators.
A total of 7372 publications were screened and 804 studies met the inclusion criteria. A total of 1143 biomarkers were assessed among the included studies from blood ( n =821, 71.8%), intragraft ( n =169, 14.8%), or urine ( n =81, 7.1%) compartments. The number of studies significantly increased, with a median, yearly number of 31.5 studies (interquartile range IQR, 23.8-35.5) between 2005 and 2012 and 57.5 (IQR, 53.3-59.8) between 2013 and 2022 ( P < 0.001). A total of 655 studies (81.5%) were retrospective, while 595 (74.0%) used data from a single center. The median number of patients included was 232 (IQR, 96-629) with a median follow-up post-transplant of 4.8 years (IQR, 3.0-6.2). Only 4.7% of studies were externally validated. A total of 346 studies (43.0%) did not adjust their biomarker for key prognostic factors, while only 3.1% of studies adjusted the biomarker for standard-of-care patient monitoring factors. Data sharing, code sharing, and registration occurred in 8.8%, 1.1%, and 4.6% of studies, respectively. A total of 158 studies (20.0%) emphasized the clinical relevance of the biomarker, despite the reported nonsignificant association of the biomarker with the outcome measure. A total of 288 studies assessed rejection as an outcome. We showed that these rejection studies shared the same characteristics as other studies.
Biomarker studies in kidney transplantation lack validation, rigorous design and methodology, accurate interpretation, and transparency. Higher standards are needed in biomarker research to prove the clinical utility and support clinical use.
Virus outbreaks such as the current SARS-CoV-2 pandemic are challenging for health care workers (HCWs), affecting their workload and their mental health. Since both, workload and HCW's well-being are ...related to the quality of care, continuous monitoring of working hours and indicators of mental health in HCWs is of relevance during the current pandemic. The existing investigations, however, have been limited to a single study period. We examined changes in working hours and mental health in Swiss HCWs at the height of the pandemic (T1) and again after its flattening (T2).
We conducted two cross-sectional online studies among Swiss HCWs assessing working hours, depression, anxiety, and burnout. From each study, 812 demographics-matched participants were included into the analysis. Working hours and mental health were compared between the two samples.
Compared to prior to the pandemic, the share of participants working less hours was the same in both samples, whereas the share of those working more hours was lower in the T2 sample. The level of depression did not differ between the samples. In the T2 sample, participants reported more anxiety, however, this difference was below the minimal clinically important difference. Levels of burnout were slightly higher in the T2 sample.
Two weeks after the health care system started to transition back to normal operations, HCWs' working hours still differed from their regular hours in non-pandemic times. Overall anxiety and depression among HCWs did not change substantially over the course of the current SARS-CoV-2 pandemic.
RP2-Associated X-linked Retinopathy Georgiou, Michalis; Robson, Anthony G.; Jovanovic, Katarina ...
Ophthalmology (Rochester, Minn.),
April 2023, Letnik:
130, Številka:
4
Journal Article
Recenzirano
Odprti dostop
To review and describe in detail the clinical course, functional and anatomic characteristics of RP2-associated retinal degeneration.
Retrospective case series.
Male participants with disease-causing ...variants in the RP2 gene.
Review of all case notes and results of molecular genetic testing, retinal imaging (fundus autofluorescence FAF imaging, OCT), and electrophysiology assessment.
Molecular genetic testing, clinical findings including best-corrected visual acuity (BCVA), qualitative and quantitative retinal imaging analysis, and electrophysiology parameters.
Fifty-four molecularly confirmed patients were identified from 38 pedigrees. Twenty-eight disease-causing variants were identified, with 20 not previously clinically characterized. Fifty-three patients (98.1%) presented with retinitis pigmentosa. The mean age of onset (range ± standard deviation SD) was 9.6 years (1–57 ± 9.2 years). Forty-four patients (91.7%) had childhood-onset disease, with mean age of onset of 7.6 years. The most common first symptom was night blindness (68.8%). Mean BCVA (range ± SD) was 0.91 logarithm of the minimum angle of resolution (logMAR) (0–2.7 ± 0.80) and 0.94 logMAR (0–2.7 ± 0.78) for right and left eyes, respectively. On the basis of the World Health Organization visual impairment criteria, 18 patients (34%) had low vision. The majority (17/22) showed electroretinogram (ERG) evidence of a rod-cone dystrophy. Pattern ERG P50 was undetectable in all but 2 patients. A range of FAF findings was observed, from normal to advanced atrophy. There were no statistically significant differences between right and left eyes for ellipsoid zone width (EZW) and outer nuclear layer (ONL) thickness. The mean annual rate of EZW loss was 219 μm/year, and the mean annual decrease in ONL thickness was 4.93 μm/year. No patient with childhood-onset disease had an identifiable ellipsoid zone (EZ) after the age of 26 years at baseline or follow-up. Four patients had adulthood-onset disease and a less severe phenotype.
This study details the clinical phenotype of RP2 retinopathy in a large cohort. The majority presented with early-onset severe retinal degeneration, with early macular involvement and complete loss of the foveal photoreceptor layer by the third decade of life. Full-field ERGs revealed rod-cone dystrophy in the vast majority, but with generalized (peripheral) cone system involvement of widely varying severity in the first 2 decades of life.
Proprietary or commercial disclosure may be found after the references.
UV sensing of twinned ZnO–PANI composite Talib, Rawnaq A.; Abdullah, M. J.; Ahmed, Naser M. ...
Applied physics. A, Materials science & processing,
05/2016, Letnik:
122, Številka:
5
Journal Article
Recenzirano
A novel twinned ZnO–polyaniline (PANI) composite was fabricated through a chemical method using zinc acetate hexahydrate and ammonium hydroxide with the addition of 15 wt%PANI. Pure ZnO and composite ...were characterized by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), Raman spectroscopy, and UV–visible spectrophotometer. FESEM images revealed that ZnO–PANI composite has a twinned rod microstructure, with homogeneous size distribution; the average length of rods becomes shorter, while the average diameter becomes larger with the addition of PANI. XRD analysis confirms the formation of the hexagonal wurtzite ZnO structure. With the addition of PANI, the original structure of ZnO remains stable. Raman peaks were observed, which were associated with the interfacial interactions between ZnO and PANI molecular chains. The use of porous Si substrates is found to be very beneficial to favor the bonding strength between the as-grown composite and Si substrate. The optical bandgap estimated from absorbance decreases from 3.22 to 3.05 eV. The fabricated photodetector based on the newly synthesized twinned rod-like ZnO–PANI composite revealed high gain of 5.23 and better sensitivity than pure ZnO. This enhancement can be attributed to the presence of PANI, which absorbs more light in the visible region.
Cardiac implantable electronic devices (CIEDs) are commonly associated with transvenous lead-related thrombi that can cause pulmonary embolism (PE).
We retrospectively evaluated all patients with ...transvenous CIED leads implanted at Mayo Clinic Rochester between 1 January 2000, and 25 October 2010. Pulmonary embolism outcomes during follow-up were screened using diagnosis codes and confirmed with imaging study reports. Of 5646 CIED patients (age 67.3 ± 16.3 years, 64% men, mean follow-up 4.69 years) 88 developed PE (1.6%), incidence 3.32 95% confidence interval (CI) 2.68-4.07 per 1000 person-years men: 3.04 (95% CI 2.29-3.96) per 1000 person-years; women: 3.81 (95% CI 2.72-5.20) per 1000 person-years. Other than transvenous CIED lead(s), 84% had another established risk factor for PE such as deep vein thrombosis (28%), recent surgery (27%), malignancy (25%), or prior history of venous thromboembolism (15%). At the time of PE, 22% had been hospitalized for ≥ 48 h, and 59% had been hospitalized in the preceding 30 days. Pulmonary embolism occurred in 22% despite being on systemic anticoagulation therapy. Out of 88 patients with PE, 45 subsequently died, mortality rate 93 (95% CI 67-123) per 1000 person-years (hazard ratio 2.0, 95% CI 1.5-2.7, P < 0.0001).
Though lead-related thrombus is commonly seen in patients with transvenous CIED leads, clinical PE occurs with a low incidence. It is possible that embolism of lead thrombus is uncommon or emboli are too small to cause consequential pulmonary infarction.
To evaluate the impact of injection frequency on yearly visual outcomes of patients treated with intravitreal aflibercept for neovascular age-related macular degeneration (nAMD) over a period of 5 ...years in a tertiary ophthalmic centre.
Single centre, retrospective cohort study.
Consecutive treatment-naive nAMD patients initiated on aflibercept injections 5 years ago.
The Moorfields OpenEyes database was searched for consecutive patients who were initiated on intravitreal aflibercept for nAMD in 2013-14 and the visual acuity (VA) in Early Diabetic Retinopathy Study (ETDRS) letters and injection records per year were recorded for a period of 5 years. Analyses of the whole cohort and a sub-sample of 5-year completers were done. The cohort was further grouped into Group A (on continuous treatment), Group B (early cessation of treatment) and Group C (interrupted treatment) to evaluate the relation between treatment frequency and visual outcomes.
The primary end point was change in VA at 5 years; secondary outcomes included proportion of eyes that gained or maintained VA, number of injections received and the effect of treatment frequency.
Data were collected on 468 patients (512 eyes). Sixty-six percent of the patients completed 5-year follow-up. The mean age of the whole cohort was 79.5 ± 8.5 years and the mean baseline VA was 58.3 ± 15.4 letters. Amongst the completers, final VA change was -2.9 (SD 23.4) ETDRS letters and the cumulative number of injections over 5 years was 24.2 (10.6). Group A had three letter gain and received significantly higher cumulative number of injections over 5 years than Group B and C (31.8, 14.6 and 18.4 respectively, p = 0.001). After adjusting for age and baseline VA, on average, final VA was +8.0 letters higher in the ≥20 injections group than the <20 group (p = 0.001).
Aflibercept therapy results in sustained good visual outcome over 5 years in neovascular AMD eyes when early and persistent treatment is given.
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