Acute effects of caffeine and glucose intake on retinal vessel calibres in healthy volunteers.

PURPOSE: To evaluate the acute effects of caffeine and glucose intake on retinal vascular calibre of healthy adults. METHODS: This prospective crossover study was conducted at the Centre for Eye Research Australia (Melbourne, Australia). Standardized doses of 300 mg caffeine (approximately 3 cups coffee), 30 g glucose or 300 ml of water, were each given to 19 healthy subjects on separate days. Retinal photographs and blood pressure measurements were taken at baseline, 30-, 60- and 120-min after ingestion of each solution. Central retinal artery and vein equivalents (CRAE, CRVE) and the arterio-venule ratio were measured using computer-assisted software. The mean retinal vascular calibre measurements were compared between pre- and post-ingestion images. RESULTS: After caffeine intake, significant reductions were observed in mean CRAE of - 9.3 µm, - 10.4 µm and - 8.5 µm and CRVE of - 16.9 µm, - 18.7 µm and - 16.1 µm at 30-, 60- and 120-min after intake when compared with baseline (p ≤ 0.002 for all; paired t test). No significant changes were observed in mean retinal vascular calibre measurements after intake of either glucose or water when compared to baseline (p ≥ 0.072 for all). When controlling for baseline characteristics and blood pressure measurements, only caffeine intake had a significant effect on reducing both CRAE and CRVE at all time points post ingestion (p ≤ 0.003 for all, multiple linear regression model). CONCLUSION: Caffeine is associated with an acute vasoconstrictive effect on retinal arterioles and venules in healthy subjects. Factors other than blood pressure-induced autoregulation play a significant role in caffeine-associated retinal vasoconstriction.

Taurine alleviates kidney injury in a thioacetamide rat model by mediating Nrf2/HO-1, NQO-1, and MAPK/NF-κB signaling pathways.

This study investigated the molecular mechanisms by which taurine exerts its reno-protective effects in thioacetamide (TAA) - induced kidney injury in rats. Rats received taurine (100 mg/kg daily, intraperitoneally) either from day 1 of TAA injection (250 mg/kg twice weekly for 6 weeks) or after 6 weeks of TAA administration. Taurine treatment, either concomitant or later as a therapy, restored kidney functions, reduced blood urea nitrogen (BUN), creatinine, and malondialdehyde (MDA), increased renal levels of superoxide dismutase (SOD), and reversed the increase of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) caused by TAA. Taurine treatment also led to a significant rise in nuclear factor erythroid 2-related factor 2 (Nrf2), hemoxygenase-1 (HO-1), and NADPH quinone oxidoreductase-1 (NQO-1) levels, with significant suppression of extracellular signal-regulated kinase (ERK) 1/2, nuclear factor kappa B (NF-κB), and tumor necrosis factor α (TNF-α) gene expressions, and interleukin-18 (IL-18) and TNF-α protein levels compared with those in TAA kidney-injured rats. Taurine exhibited reno-protective potential in TAA-induced kidney injury through its antioxidant and anti-inflammatory effects. Taurine antioxidant activity is accredited for its effect on Nrf-2 induction and subsequent activation of HO-1 and NQO-1. In addition, taurine exerts its anti-inflammatory effect via regulating NF-κB transcription and subsequent production of pro-inflammatory mediators via mitogen-activated protein kinase (MAPK) signaling regulation.

Clinical and microbiological effects of ultrasonically activated irrigation versus syringe irrigation during endodontic treatment: a systematic review and meta-analysis of randomized clinical trials.

This study aimed to systematically review clinical and microbiology-related effects of ultrasonically activated irrigation (UAI) compared to syringe irrigation (SI) during endodontic treatment. Electronic databases searching and manual searching were conducted. Only randomized clinical trials (RCTs) were included comparing UAI to SI. The RoB 2.0 Cochrane tool was used for risk-of-bias (RoB) assessment. The main outcomes were postoperative pain, treatment failure, and microbiology-related outcomes. Qualitative and quantitative analyses, wherever applicable, were performed. Risk ratios (RR) and [standardized] mean differences {[S]MD} were calculated for dichotomous and continuous outcomes, respectively. Certainty of evidence (CoE) was assessed using GRADE tool. Ten RCTs were included. UAI reduced pain incidence within the first 24 h (RR 0.50, 95% CI 0.35-0.71, 308 teeth) and microbial counts (SMDpooled - 0.40, 95% CI [- 0.78, - 0.02], I2 = 0%, 126 teeth) than SI in non-vital teeth with apical periodontitis (AP). Both groups, however, had similar effects regarding pain intensity, lipopolysaccharide amounts, and the incidence of rescue-analgesic intake, treatment failure, and microbial presence (p > 0.05). CoE ranged from low to very low. Very limited evidence suggests that UAI could reduce postoperative-pain risk within the first 24 h and microbial counts for non-vital teeth with AP compared to SI. Most meta-analyses, however, are based on very few studies, mostly low-powered, with an overall very-low-to-low CoE. Further well-designed, larger RCTs are, thus, required.

Cloning of human cord blood-mesenchymal stem cells for isolation of enriched cell population of higher proliferation and differentiation potential.

Heterogeneity of Mesenchymal stem cells (MSCs) imposes limitations for their in vitro expansion and accounts for the lack of reproducibility in some clinical studies. So, this study was designed to isolate and enrich clones of multipotent and self-renewing MSCs from cord blood (CB). Enriched clones with higher proliferation and differentiation potential provide regenerative cells suitable for various clinical demands. MSCA and MSCB original (progenitor) cells were isolated from CB samples, and single cells were cloned by limiting dilution method, in mouse embryonic fibroblast conditioned media. Original MSCs and their single-cell derived clones were characterized by identifying their proliferation rate, immunophenotyping of surface antigens, expression of pluripotency and proliferation genes (Oct4, Sox2, Nanog, KLF4, c-Myc, and PDGFRA), and differentiation potential into multiple lineages (osteogenic, adipogenic, and chondrogenic). Some single-cell clones of MSCA showed a higher proliferation rate and greater differentiation potential than their original cells. However, original MSCB cells were of greater proliferation and differentiation potential than their derived single-cell clones, except for one clone which had comparable results. Cloning of MSCs was attainable when cultured in mouse embryonic fibroblast conditioned media. Single clones with higher proliferation and differentiation potential than their original progenitor cells were obtained by cloning of poorly functioning MSCs progenitor cells, enabling the selection of more therapeutically efficacious MSCs with better performance in clinical applications. Moreover, this study draws attention to the importance of CD105 as a possible MSCs biomarker associated with the multilineage commitment of MSCs.

A treat and extend protocol with Aflibercept for cystoid macular oedema secondary to central retinal vein occlusion - an 18-month prospective cohort study.

BACKGROUND: To evaluate the safety and efficacy of a treat-and-extend protocol of aflibercept for cystoid macular oedema (CMO) secondary to central retinal vein occlusion (CRVO). METHODS: Twenty patients with CMO secondary to CRVO were included in this prospective cohort study. After 3 loading 4-weekly injections, treatment intervals were increased by 2 weeks if there was no clinical activity, to a maximum of 12 weeks. If clinical activity recurred or persisted, the interval between injections was shortened by 2 weeks, to a minimum of 4 weeks. Main outcome measures were change in visual acuity and the proportion of patients gaining 15 or more Early Treatment of Diabetic Retinopathy Study (ETDRS) letters from baseline at 6, 12 and 18 months. RESULTS: Mean BCVA gain from baseline was 19.7 ± 13.8, 22.2 ± 13.9 and 21.9 ± 15.8 ETDRS letters at 6, 12 and 18 months, respectively. Sixty-five percent of patients gained 15 or more ETDRS letters at 6 months, increasing to 70.6% at 12 and 18 months. Patients received 5.0 [4.0 to 6.0], 8.5 [8.0 to 10.3] and 11.0 [9.0 to 12.5] injections by 6, 12 and 18 months, respectively. CONCLUSIONS: The visual outcomes achieved with a treat-and-extend protocol in this study were similar to the pivotal trials of aflibercept for CMO secondary to CRVO, which used monthly and then as-needed protocols. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, registration number ACTRN12615000417583, 01/05/2015.

Clinical validation of the RTVue optical coherence tomography angiography image quality indicators.

IMPORTANCE: All automated image quality indicators for en face optical coherence tomography angiography (OCTA) images require gold standard validation for determining optimum thresholds. BACKGROUND: A manual grading system (gold standard) for OCTA images was validated and compared to two automated image quality indicators: signal strength index (SSI) and scan quality index (SQI) generated by different software versions of the Optovue OCTA device. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: A total of 52 eyes of 52 healthy individual and 77 eyes of 51 patients with retinal vascular diseases. METHODS: A total of 129 OCTA images of the superficial vascular plexus were graded manually by three independent examiners. Each image was assigned grades 1 to 4 (1-2, unacceptable; 3-4, acceptable) masked to the software-generated quality indicators. MAIN OUTCOME MEASURES: Inter-grader agreement and comparison of the utility of SSI and SQI in discriminating between acceptable and unacceptable OCTA images. RESULTS: There was a substantial agreement between the three graders (κ = 0.63). Mean SSI and SQI was significantly different between acceptable and unacceptable images (P < .001). SQI outperformed SSI in separating acceptable from unacceptable images (areas under the receiver operating characteristic curve: 0.87 vs 0.80) and the optimum cut-off was ≥7 for SQI and ≥70 for SSI for acceptable images. Up to 30% of images with quality indicators reaching the optimum SQI and SSI cut-off thresholds still had unacceptable quality on manual grading. Unacceptable images were found in 33% and 66% of healthy and diseased eyes, respectively. CONCLUSIONS AND RELEVANCE: SQI is closely related to manual grading but we caution reliance on the optimized threshold to determine image quality. SQI is superior to SSI in discriminating between acceptable and unacceptable images.

Correlation between JAK2 allele burden and pulmonary arterial hypertension and hematological parameters in Philadelphia negative JAK2 positive myeloproliferative neoplasms. An Egyptian experience.

Myeloproliferative neoplasms are characterized by a common stem cell-derived clonal proliferation, but are phenotypically diverse. JAK2 is mutated (V617F) in more than 90 % of patients with polycythemia vera (PV) and approximately 60 % of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). Pulmonary arterial hypertension (PAH) is a major complication of several hematological disorders. Chronic myeloproliferative disorders associated with PAH have been included in group five for which the etiology is unclear and/or multifactorial. The aim of this study is to screen Egyptian Philadelphia negative JAK2 positive myeloproliferative neoplasm patients for the presence of PAH and its correlation with JAK2 allele burden. We also made a review for correlation of JAK2 allele with hematological parameters comparing our results to others. We enrolled 60 patients with Philadelphia negative myeloproliferative neoplasms. All patients enrolled in the study were subjected to laboratory and imaging workup in the form of CBC, liver, kidney profile, bone marrow examination, abdominal ultrasonography, and transthoracic echocardiography. Our results revealed that 7 patients out of 60 (11.67 %) had pulmonary arterial hypertension, 3 patients with PMF, 2 patients with PRV, and 2 patients with ET, and its correlation with JAK2 allele burden was not statistically significant. Correlation analysis between JAK2 V617F allele burden and other parameters revealed: statistical significant correlation with age, HB, HCT, PLT, UA, LDH, and splenic diameter but insignificant correlation with WBCs and PAH. Pulmonary arterial hypertension prevalence in our study was 11.67 % and no significant correlation with JAK 2 allele burden. Our study is the largest one up to our knowledge that studies the association between its prevalence and JAK2 burden.

Gold conjugated nanobodies in a signal-enhanced lateral flow test strip for rapid detection of SARS-CoV-2 S1 antigen in saliva samples.

Despite the transfer of COVID-19 from the pandemic to control, we are still in a state of uncertainty about long-term success. Therefore, there is a great need for rapid and sensitive diagnostics to sustain the control status. After several optimization trials, we developed lateral flow test (LFT) strips for rapid detection of SARS-CoV-2 spike 1 (S1) antigen in saliva samples. For signal enhancement of our developed strips, we applied dual gold conjugates. Gold-labeled anti-S1 nanobodies (Nbs) were employed as S1 detector conjugate, while gold-labeled angiotensin-converting enzyme 2 (ACE2) was used as S1 capturing conjugate. In a parallel strip design, we used an anti-S1 monoclonal antibody (mAb) as an antigen detector instead of anti-S1 Nbs. Saliva samples were collected from 320 symptomatic subjects (180 RT-PCR confirmed positive cases and 140 confirmed negative cases) and were tested with the developed strips. In early detection for positive samples with cycle threshold (Ct ≤ 30), Nbs-based LFT strips showed higher sensitivity (97.14%) and specificity (98.57%) than mAb-based strips which gave 90.04% sensitivity and 97.86% specificity. Moreover, the limit of detection (LoD) for virus particles was lower for Nbs-based LFT (0.4 × 104 copies/ml) than for the mAb-based test (1.6 × 104 copies/ml). Our results are in favor of the use of dual gold Nbs and ACE2 conjugates in LFT strips. These signal-enhanced strips offer a sensitive diagnostic tool for rapid screening of SARS-CoV-2 S1 antigen in the easily collected saliva samples.

How the COVID-19 Pandemic Contributed to Diagnostic Bias.

Diagnosis bias in the medical field is a recognized entity that can contribute to misdiagnoses and incorrect management. It remains a constant challenge that must be recognized and addressed. Several factors play a role in the formation of preconceptions which influence the physicians' decision-making process. The aim of this paper is to present a case that was misdiagnosed and mistakenly managed due to diagnosis bias during the coronavirus disease 2019 (COVID-19) pandemic. We also suggest two ways to reduce the risk of diagnosis bias. Multi-inflammatory syndrome of children (MIS-C) was described during the COVID-19 pandemic. The rise in the incidence of MIS-C masked the diagnosis of other diseases that present in a similar fashion. In this paper, we describe the case of a seven-year-old girl, who presented in 2020, with acute onset respiratory distress. Her chest images were suggestive of COVID-19 pneumonitis which prompted the physicians to complete the MIS-C workup by performing an echocardiogram. A large aneurysm of the left main artery was seen which led to a preliminary diagnosis of MIS-C. A repeat echocardiography, 48 hours after the initiation of MIS-C treatment, was suggestive of a large coronary fistula complicated by infective endocarditis and multiple septic pulmonary emboli. It can be inferred that the misdiagnosis occurred as a result of availability and premature-closure biases. Efforts to decrease such biases include group decision-making and using checklists during the assessment of a patient.

RTVue XR AngioVue Optical Coherence Tomography Angiography Software Upgrade Impacts on Retinal Thickness and Vessel Density Measurements.

Purpose: To determine the impact of an AngioVue software upgrade on total retinal thickness (RT) and inner retinal vessel density (VD) measurements derived from optical coherence tomography angiography (OCTA). Methods: Optovue OCTA images (3 × 3 mm) from 126 individuals (105 healthy eyes and 72 eyes with retinal disease) were acquired before an upgrade of the AngioVue software, which resulted in an inward shift of the outer boundary of the inner retinal vessels and improved Bruch's membrane segmentation. Total RT and inner retinal VD values were extracted before and after the software upgrade for comparison. Bias and limits of agreement (LA) were calculated. Results: The mean (SD) age of participants was 46 (17) years. Mean (LA) foveal RT increased by 3.0 (-11 to +17) and 3.7 (-11 to +18) µm (P < 0.001) and parafoveal RT increased by 9.7 (-3.8 to +23) and 6.4 (-2.5 to +15) µm (P < 0.001) in healthy and diseased retina, respectively. Mean (LA) foveal inner retinal VD decreased by 6.6 (2.5-11) and 7.7 (0.4-15) percentage units (P < 0.001) and parafoveal inner retinal VD decreased by 4.1 (1.2-7.0) and 4.7 (0.5-8.9) percentage units (P < 0.001) in healthy and diseased retina, respectively. Conclusions: The AngioVue software upgrade resulted in an unexpected increase in total RT and an expected reduction in inner retinal VD measurements in all regions due to altered segmentation. Translational Relevance: RT and VD measures derived from the newer AngioVue software version are not directly comparable to the reported normative data derived from the older software.

Accuracy of radiologic- laparoscopic peritoneal carcinomatosis categorization in the prediction of surgical outcome.

OBJECTIVE: To evaluate the agreement between multiple detector CT (MDCT) and laparoscopy in the preoperative categorization of peritoneal carcinomatosis, and to determine the impact of this categorization on the prediction of cytoreduction status. METHODS: This prospective study included 80 consecutive females with primary ovarian cancer eligible for cytoreductive surgery (CRS). MDCT and diagnostic laparoscopy were performed prior to surgery for assessment of peritoneal carcinomatosis extent. Based on PCI (peritoneal cancer index) score, carcinomatosis was categorized into three groups. Categorization agreement between CT and laparoscopy was assessed and compared with the intraoperative-histopathologically proven PCI. Impact of PCI categorization on cytoreduction status was also evaluated. RESULTS: The overall agreement between CT and laparoscopy in preoperative peritoneal carcinomatosis categorization was good (K =0.71-0.79) in low category group and excellent in both moderate and large group (interclass correlation coeeficient = 0.89-0.91). (p<0.01) Optimal cytoreduction was achieved in 62/80 (77.5%) patients, PCI < 20 was detected in 48/62 (77.4%), pre-operative PCI < 20 correctly predicted optimal cytoreductive surgery (OCS) in 40/48 (83.3%) cases. Suboptimal cytoreduction was performed in 18/80 (22.5%) patients. PCI > 20 was detected in (10/18) 55.6%, preoperative CT and laparoscopy PCI > 20 correctly predicted SCS in 8/10 (80%) cases. The area under receiver operating characteristic curve showed that PCI cut-off <20 was the best predictor of OCS with an accuracy 85%, sensitivity 97%, specificity 40%, negative predictive value 76%, and positive predictive value 93%. CONCLUSION: Both laparoscopy and CT are equally effective in pre-operative peritoneal carcinomatosis categorization. PCI < 20 is accurate in the prediction of optimal cytoreduction. More than half of patients with suboptimal cytoreduction had PCI > 20 and interval debulking surgery can be recommended. ADVANCES IN KNOWLEDGE: Both laparoscopy and CT are equally effective in pre-operative peritoneal carcinomatosis categorization. PCI < 20 is accurate in the prediction of optimal cytoreduction. More than half of patients with suboptimal cytoreduction had PCI > 20 and interval debulking surgery can be recommended.