Aflibercept monotherapy versus aflibercept with targeted retinal laser to peripheral retinal ischemia for diabetic macular oedema (LADAMO).

OBJECTIVE: We tested the hypothesis that targeted retinal laser photocoagulation (TPRP) to peripheral retinal ischaemia reduces the overall burden of aflibercept injections when treating diabetic macular oedema (DMO) over a 24-month period. METHODS: Prospective, double-masked, multicentre, randomised controlled trial in Australia comparing aflibercept monotherapy, following a treat-and-extend protocol, or combination therapy of aflibercept and TPRP for DMO. The aflibercept monotherapy group received placebo laser. The primary outcome measure was the mean number of intravitreal aflibercept injections for each group at 24 months. Secondary outcome included: mean change in central macular thickness (CMT) and vision at trial completion, the proportion of eyes whose DMO resolved and the mean injection treatment interval. Ocular and systemic adverse events were recorded. RESULTS: We enrolled 48 eyes of 47 patients; 27 eyes were randomised to combination therapy (aflibercept and TPRP) and 21 to aflibercept monotherapy. Thirty-two eyes (67%) completed the 2-year study. The number of intravitreal treatments given were similar for combination therapy (10.5 (SD 5.8) and monotherapy (11.8 (SD5.6)) (P = 0.44). The mean visual improvement (+4.0 (-1.8, 9.8) and +7.8 (2.6, 12.9) letters, P = 0.32), mean decrease in CMT (-154 (-222,-87) µm and -152 (-218,-86) µm, P = 0.96), proportion of eyes with CMT < 300 µm (48% and 67%; P = 0.50) and safety outcomes were similar in both the combination and monotherapy treatment groups (respectively). CONCLUSIONS: Laser to areas of ischaemic peripheral retina does not reduce the burden of intravitreal aflibercept injections when treating diabetic macular oedema.

Microwave-assisted organic synthesis, antimycobacterial activity, structure-activity relationship and molecular docking studies of some novel indole-oxadiazole hybrids.

Multidrug-resistant tuberculosis (MDR-TB) is a severe threat to mankind because most drugs are ineffective in inhibiting tubercular strains. Due to the increase of MDR-TB, many first and second-line drugs are ineffective against tubercular strains. To combat the resistance of currently accessible drugs, structural changes must be made on a regular basis. Thus, in the search for new antimycobacterial drugs, a series of 1-(2-(1H-indol-3-yl)-5-phenyl-1,3,4-oxadiazol-3(2H)-yl)-3-phenylprop-2-en-1-ones (5a-o) have been developed, synthesized, characterized, and screened for antimycobacterial activity. The synthetic approach includes imine generation and cyclization using both conventional and microwave methods to create hybrid molecules with indole and oxadiazole motifs. The set of synthesized compounds have demonstrated some promising activity against tubercular strains of Mycobacterium tuberculosis (ATCC 25177) and M. bovis (ATCC 35734). Compound 5l inhibited M. bovis strain 100% in 10 µg/mL concentration, while compound 5m inhibited M. tuberculosis strain 90.4% in 30 µg/mL concentration. Molecular docking study against mycobacterial enoyl reductase (InhA) could provide well-clustered solutions to the binding modes and affinity for these molecules as compound 5l showed glide score of -12.275 and glide energy of -54.937 kcal/mol.

Distribution of soil carbon fractions under different bamboo species in northwest Himalayan foothills, India.

Soil carbon and its fractions are important in understanding the mechanism of soil carbon sequestration. The present study evaluated the impact of seven commercial bamboo species, viz., Bambusa balcooa, B. bambos, B. vulgaris, B. nutans, Dendrocalamus hamiltonii, D. stocksii, and D. strictus, on labile and non-labile carbon fractions. In the 0-15-cm layer, B. nutans had the highest very labile C (7.65 g kg-1) followed by B. vulgaris > B. balcooa > D. stocksii > D. hamiltonii > B. bambos > D. strictus > open. The active carbon pool was significantly low under the control plot (i.e. the open) indicating the positive influence of bamboo in soil C build-up in the top 0-15 cm soil layer. Amongst the different species of bamboo evaluated in this study, D. strictus accumulated the highest active C pool in 0-30-cm soil layer followed by B. vulgaris. Of the total organic C in the 0-30 cm soil depth, majority (55-60%) was contributed by the passive C pool comprising the less labile and the non-labile fraction of SOC. A high value of carbon stratification ratio (> 2) was observed for D. strictus, B. bambos, and D. hamiltonii which proves their potential for restoration of the degraded lands. The majority of bamboo species except for B. balcooa and D. stocksii showed a higher carbon management index than open systems, thereby indicating higher rates of soil C rehabilitation. Of the seven bamboo species, B. vulgaris, D. strictus, and B. nutans can be adopted for cultivation in the northwest Himalayas given their ability to positively impact the SOC and its fractions in both surface and sub-surface soil.

Assessment of eco-hydrological parameters for important sympodial bamboo species in Himalayan foothills.

Bamboos due to high soil water conservation potential are gaining increased attention in plantation programs across the globe. Large-scale plantation of fast-growing bamboo, however, can have important hydrological consequences. The study aims to quantify the eco-hydrological parameters, viz., throughfall (TF), stemflow (SF), and interception (I) in seven important sympodial bamboo species in north western Himalayan foothills of India. The species selected include Bambusa balcooa, Bambusa bambos, Bambusa vulgaris., Bambusa nutans, Dendrocalamus hamiltonii, Dendrocalamus stocksii, and Dendrocalamus strictus. Throughfall versus gross rainfall (GR) relationship in different species indicated high throughfall production during high rainfall events with r2 > 0.90. Average throughfall was lowest (62.1%) in D. hamiltonii and highest in B. vulgaris (74.6%). SF ranged from 1.32% in B. nutans to 3.39% in D. hamiltonii. The correlation coefficient (r) between leaf area index (LAI), number of culms, and crown area with the interception were 0.746, 0.691, and 0.585, respectively. The funneling ratio (F) was highest (27.0) in D. hamiltonii and least in B. nutans. Canopy storage capacity was highest in D. strictus (3.57 mm) and least in D. hamiltonii (1.09 mm). Interception loss was highest (34.4%) in D. hamiltonii and lowest in B. vulgaris (23.5%) and D. strictus (23.6%). Higher interception in bamboos make them suitable for soil conservation, but careful selection of species is required in low rainfall areas.

MRI Brain Findings in 126 Patients with COVID-19: Initial Observations from a Descriptive Literature Review.

BACKGROUND AND PURPOSE: Recently, numerous investigational studies, case series, and case reports have been published describing various MR imaging brain findings in patients with COVID-19. The purpose of this literature review was to compile and analyze brain MR imaging findings in patients with COVID-19-related illness. MATERIALS AND METHODS: Literature searches of PubMed, publicly available Internet search engines, and medical journal Web sites were performed to identify articles published before May 30, 2020 that described MR imaging brain findings in patients with COVID-19. RESULTS: Twenty-two articles were included in the analysis: 5 investigational studies, 6 case series, and 11 case reports, encompassing MR imaging of the brain in 126 patients. The articles originated from 7 different countries and were published in 14 medical journals. MR imaging brain findings included specific diagnoses (such as acute infarct, posterior reversible encephalopathy syndrome) or specific imaging features (such as cortical FLAIR signal abnormality, microhemorrhages). CONCLUSIONS: The most frequent diagnoses made on brain MR imaging in patients with COVID-19 were acute and subacute infarcts. Other common findings included a constellation of leukoencephalopathy and microhemorrhages, leptomeningeal contrast enhancement, and cortical FLAIR signal abnormality.

Vessel Wall Enhancement and Focal Cerebral Arteriopathy in a Pediatric Patient with Acute Infarct and COVID-19 Infection.

Herein, we report the findings of intracranial arterial wall enhancement, consistent with focal cerebral arteriopathy-inflammatory type, in a child presenting with acute infarct in the setting of coronavirus disease 2019 (COVID-19) infection. To our knowledge, this report provides the first description of vessel wall imaging findings in COVID-19-associated acute stroke.

A multi-wavelength streaked optical pyrometer for dynamic shock compression measurements above 2500 K.

This article presents a concept and implementation of a calibrated streaked spectral pyrometer (SSP) temperature diagnostic used in dynamically driven shock experiments on a two-stage gas gun. This system relies upon measuring the total system response using a tunable monochromator, a NIST-traceable calibrated power meter, and a SSP. The diagnostic performance is validated against previously measured temperatures of shock driven z-cut quartz at 99 GPa and 93 GPa. The results are found to agree with the literature to within 5% and are discussed in this manuscript. The experimental setup utilizes measurements from multiple SSP systems per sample, providing several independent measurements and substantially increasing confidence in the extrapolated shock driven sample temperature.

Rooting behaviour and soil properties in different bamboo species of Western Himalayan Foothills, India.

Due to extensive root system, connected rhizome bamboos are considered suitable for improving soil properties within a short period, though most of the claims are anecdotal and need to be supported with quantified data. The study evaluates seven bamboo species viz., Bambusa balcooa, Bambusa bambos, Bambusa vulgaris, Bambusa nutans, Dendrocalamus hamiltonii, Dendrocalamus stocksii and Dendrocalamus strictus for their rooting pattern and impact on soil health properties. Coarse and fine root intensity was maximum in B. vulgaris. Coarse root biomass ranged from 0.6 kg m-3 in B. nutans to 2.0 kg m-3 in B. vulgaris and B. bambos. Fine root biomass ranged from 1.1 kg m-3 in B. nutans to 4.5 kg m-3 in D. hamiltonii. Contribution of fine roots in terms of intensity and biomass was much higher than coarse roots. Fine root biomass showed declining trend with increase in soil depth in all the species. During sixth year, the litter fall ranged from 8.1 Mg ha-1 in D. stocksii to 12.4 Mg ha-1 in D. hamiltonii. Among soil physical properties significant improvement were recorded in hydraulic conductivity, water stable aggregates and mean weight diameter. Soil pH, organic carbon and available phosphorus under different species did not reveal any significant changes, while significant reduction was observed in total nitrogen and potassium. Significant positive correlation was observed between WSA and iron content. Soil microbial population and enzyme activities were higher in control plot. Considering root distribution, biomass, soil hydraulic conductivity and water stable aggregates, B. bambos, B. vulgaris and D. hamiltonii are recommended for rehabilitation of degraded lands prone to soil erosion.

Pathogenic Nocardia cyriacigeorgica and Nocardia nova Evolve To Resist Trimethoprim-Sulfamethoxazole by both Expected and Unexpected Pathways.

Nocardia spp. are Gram-positive opportunistic pathogens that affect largely immunocompromised patients, leading to serious pulmonary or systemic infections. Combination therapy using the folate biosynthesis pathway inhibitors trimethoprim (TMP) and sulfamethoxazole (SMX) is commonly used as an antimicrobial therapy. Not surprisingly, as antibiotic therapies for nocardiosis can extend for many months, resistance to TMP-SMX has emerged. Using experimental evolution, we surveyed the genetic basis of adaptation to TMP-SMX across 8 strains of Nocardia nova and 2 strains of Nocardia cyriacigeorgica By employing both continuous experimental evolution to provide longitudinal information on the order of changes and characterization of resistant endpoint isolates, we observe changes that are consistent with modifications of two enzymes of the folate biosynthesis pathway: dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) (FolP), with the mutations often being clustered near the active site of the enzymes. While changes to DHFR and DHPS might be expected, we also noted that mutations in a previously undescribed homolog of DHPS (DHPS2 or FolP2) that was annotated as being "nonfunctional" were also sufficient to generate TMP-SMX resistance, which serves as a cautionary tale for the use of automated annotation by investigators and for the future discovery of drugs against this genus. Additionally, folP2 overlapped glucosyl-3-phosphoglycerate synthase. Remarkably, an adaptive frameshift mutation within the overlapping region resulted in a new in-frame fusion to the downstream gene to produce a potentially new bifunctional enzyme. How a single potentially bifunctional DHPS2 enzyme might confer resistance is unclear. However, it highlights the unexpected ways in which adaptive evolution finds novel solutions for selection.

Comparative effectiveness of chemotherapy vs resection of the primary tumour as the initial treatment in older patients with Stage IV colorectal cancer.

AIM: The objectives were to determine trends in the use of chemotherapy as the initial treatment and to evaluate the comparative effectiveness of initial chemotherapy vs resection of the primary tumour on survival (intention-to-treat analysis) in Stage IV colorectal cancer (CRC). METHOD: This cohort study used 2000-2011 data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, including patients ≥ 66 years of age presenting with Stage IV CRC. Cox proportional hazards models and instrumental variable analysis were used to compare the effectiveness of chemotherapy as the initial treatment with resection of the primary tumour as the initial treatment, with 2-year survival as the end point. RESULTS: The use of chemotherapy as the first treatment increased over time, from 26.8% in 2001 to 46.9% in 2009 (P < 0.0001). The traditional Cox model showed that chemotherapy as the initial treatment was associated with a higher risk of mortality [hazard ratio (HR) = 1.35; 95% CI: 1.27-1.44]. When accounting for known and unknown confounders in an instrumental variable analysis, chemotherapy as the initial treatment suggested benefit on 2-year survival (HR = 0.68; 95% CI: 0.44-1.04); however, the association did not reach statistical significance. The study findings were similar in six subgroup analyses. CONCLUSION: The use of chemotherapy as the initial therapy for CRC increased substantially from 2001 to 2009. Instrumental variable analysis found that, compared with resection, chemotherapy as the initial treatment offers similar or better 2-year survival in patients with Stage IV CRC. Given the morbidity and mortality associated with colorectal resection in elderly patients, chemotherapy provides an option to patients who are not good candidates for resection.

Minimizing Radiation Exposure in Evaluation of Pediatric Head Trauma: Use of Rapid MR Imaging.

BACKGROUND AND PURPOSE: With >473,000 annual emergency department visits for children with traumatic brain injuries in the United States, the risk of ionizing radiation exposure during CT examinations is a real concern. The purpose of this study was to assess the validity of rapid MR imaging to replace CT in the follow-up imaging of patients with head trauma. MATERIALS AND METHODS: A retrospective review of 103 pediatric patients who underwent initial head CT and subsequent follow-up rapid MR imaging between January 2010 and July 2013 was performed. Patients had minor head injuries (Glasgow Coma Scale, >13) that required imaging. Initial head CT was performed, with follow-up rapid MR imaging completed within 48 hours. A board-certified neuroradiologist, blinded to patient information and scan parameters, then independently interpreted the randomized cases. RESULTS: There was almost perfect agreement in the ability to detect extra-axial hemorrhage on rapid MR imaging and CT (κ = 0.84, P < .001). Evaluation of hemorrhagic contusion/intraparenchymal hemorrhage demonstrated a moderate level of agreement between MR imaging and CT (κ = 0.61, P < .001). The ability of MR imaging to detect a skull fracture also showed a substantial level of agreement with CT (κ = 0.71, P < .001). Detection of diffuse axonal injury demonstrated a slight level of agreement between MR imaging and CT (κ = 0.154, P = .04). However, the overall predictive agreement for the detection of an axonal injury was 91%. CONCLUSIONS: Rapid MR imaging is a valid technique for detecting traumatic cranial injuries and an adequate examination for follow-up imaging in lieu of repeat CT.

Structural changes of the choroid in sarcoid- and tuberculosis-related granulomatous uveitis.

AIM: The aim of this study is to characterise the choroidal features of patients diagnosed with sarcoid- and tuberculosis (TB)-associated granulomatous uveitis using spectral domain optical coherence tomography (OCT). METHODS: Twenty-seven patients (27 eyes) diagnosed with sarcoid- (13 eyes) and TB (14 eyes)-related uveitis were included in this retrospective, cross-sectional study. Over a six-month period, patients diagnosed with sarcoid and TB granulomatous uveitis were scanned using enhanced depth imaging OCT. Clinical and demographical characteristics were recorded, including the method of diagnosis, disease activity, site of inflammation (anterior or posterior), treatments, and visual acuity (VA). Manual segmentation of the choroidal layers was performed using custom image analysis software. RESULTS: The main outcome measure was OCT-derived thickness measurements of the choroid and choroidal sublayers (Haller's large vessel and Sattler's medium vessel layers) at the macula region. The ratio of Haller's large vessel to Sattler's medium vessel layer was significantly different at the total macula circle in eyes diagnosed with TB uveitis (1.47 (=140.71/95.72 µm)) compared with sarcoid uveitis (1.07 (=137.70/128.69 µm)) (P=0.001). A thinner choroid was observed in eyes with a VA ≥0.3 LogMAR (Snellen 6/12; 198.1 µm (interquartile range (IQR)=147.0-253.4 µm) compared with those with VA <0.3 LogMAR (292.4 µm (IQR=240.1-347.6 µm)) at the total macula circle (P=0.004). At the foveal central subfield, the median choroidal thickness was 336.8 µm (IQR=272.3-375.4 µm) in active compared with 239.3 µm (IQR=195.3-330.9 µm) in quiescent disease (P=0.04). CONCLUSION: A disproportionately enlarged Sattler's layer may indicate a diagnosis of sarcoid-related uveitis, and choroidal thickening may be a feature of active granulomatous uveitis.

Observation and quantification of nanoscale processes in lithium batteries by operando electrochemical (S)TEM.

An operando electrochemical stage for the transmission electron microscope has been configured to form a "Li battery" that is used to quantify the electrochemical processes that occur at the anode during charge/discharge cycling. Of particular importance for these observations is the identification of an image contrast reversal that originates from solid Li being less dense than the surrounding liquid electrolyte and electrode surface. This contrast allows Li to be identified from Li-containing compounds that make up the solid-electrolyte interphase (SEI) layer. By correlating images showing the sequence of Li electrodeposition and the evolution of the SEI layer with simultaneously acquired and calibrated cyclic voltammograms, electrodeposition, and electrolyte breakdown processes can be quantified directly on the nanoscale. This approach opens up intriguing new possibilities to rapidly visualize and test the electrochemical performance of a wide range of electrode/electrolyte combinations for next generation battery systems.

A biofilm microreactor system for simultaneous electrochemical and nuclear magnetic resonance techniques.

Nuclear magnetic resonance (NMR) techniques are ideally suited for the study of biofilms and for probing their microenvironments because these techniques allow for noninvasive interrogation and in situ monitoring with high resolution. By combining NMR with simultaneous electrochemical techniques, it is possible to sustain and study live biofilms respiring on electrodes. Here, we describe a biofilm microreactor system, including a reusable and a disposable reactor, that allows for simultaneous electrochemical and NMR techniques (EC-NMR) at the microscale. Microreactors were designed with custom radio frequency resonator coils, which allowed for NMR measurements of biofilms growing on polarized gold electrodes. For an example application of this system we grew Geobacter sulfurreducens biofilms on electrodes. EC-NMR was used to investigate growth medium flow velocities and depth-resolved acetate concentration inside the biofilm. As a novel contribution we used Monte Carlo error analysis to estimate the standard deviations of the acetate concentration measurements. Overall, we found that the disposable EC-NMR microreactor provided a 9.7 times better signal-to-noise ratio over the reusable reactor. The EC-NMR biofilm microreactor system can ultimately be used to correlate extracellular electron transfer rates with metabolic reactions and explore extracellular electron transfer mechanisms.