Acceptable Yields Research Articles

Twisted Benzothieno-Fused BOPHY Dyes as Triplet Photosensitizers with Long-Lived Triplet Excited States.

The synthesis of a series of photostable [b]-benzothieno-fused BOPHY derivatives is reported via one-pot condensation of formylated isoindoles or formylindoles with hydrazine and subsequent boron complexation. These dyes show strong absorption in the deep red region and acceptable fluorescence quantum yields (∼30%). The two fused benzothiophene moieties are slightly deviated from the BOPHY core (with dihedral angles of 6.1 and 10.2°). This slightly twisted conformation brings an enhanced spin-orbit coupling and a reduced energy band gap between singlet and triplet states. The enhanced intersystem cross process endows these series of dyes with a good singlet oxygen quantum yield (up to 63%), a high triplet-state quantum yield (up to 78%), and a long lifetime value (up to 127 μs). Density functional theory calculations indicate that the transition from S1 to T2 states is crucial for triplet-state formation, highlighting their high efficiency in intersystem crossing. The calculated triplet electron spin surface reveals a widespread distribution of triplet states across the conjugated molecular structure, which enhances the Dexter mechanism for triplet energy transfer in these BOPHY photosensitizers. These findings are helpful for thorough understanding of the fundamental ISC process and developing triplet photosensitizers.

Elemental Sulfur Promoted Cyclization of o‐Chloronitrobenzenes and Aryl Isothiocyanates to Furnish 2‐Aminobenzothiazoles

Methods to afford 2‐aminobenzothiazoles often involve the use of o‐aminothiophenols or aniline‐typed precursors. Herein we describe a method to furnish 2‐aminobenzothiazoles through the cyclization of o‐chloronitrobenzenes and aryl isothiocyanates with the assistance of elemental sulfur. From the perspective of step economy, our strategy allows for the direct use of nitroarene precursors without further reduction to anilines. The scope of the reaction with respect to both substrates was investigated, and it was found that electronic properties of the aryl isothiocyanate was important for obtaining acceptable yields.

Optimum Determination of NPSB Fertilizer Rates on Bread Wheat (Triticum asetivum L.) Varieties

The field experiment was conducted at Degam district during main cropping season to investigate the response of bread wheat varieties to NPSB fertilizer rates and identify its economic benefit. Factorial combination of three improved bread wheat varieties (Danda’a, Hidase and Kakaba) and six fertilizer rates [Control, 50, 100, 150, 200 kg ha-1 NPSB fertilizer each supplemented with 92 kg N ha-1 and 64/20 kg NP ha-1 (Blanket recommendation) were laid out in randomized complete block design with three replications. The highest NKS (54.9), AGBM (13.8 tons ha-1), SY (9.4 tons ha-1) and GY (4549kg ha-1) were recorded from 200 kg NPSB fertilizer. Among the varieties the highest NKS (54.3) from Danda’a, TKW (49.3 g) and GY (3351kg ha-1) were recorded from Hidase variety. Variety Kakaba score the highest PH (102.5 cm) and PNT (5 per plant) with combination of 200 kg and 150 kg NPSB fertilizer respectively and reached days to heading and maturity earlier than Danda’a and Hidase. In general, the economic feasibility of the fertilizer over varieties combination indicated that application of 200 kg NPSB ha-1to all varieties Hidase, Danda’a and Kakaba resulted in maximum marginal rates of return 640.14 %, 604.81% and 481.47%, with a net benefit of 97993, 88596, and 82996 ETB respectively. Although, application of 200 kg NPSB ha-1 led to the highest MRR for the Hidase variety as compared to all other treatments and with about a total of 9397 ETB net benefit increment. Therefore, application of 200 kg of NPSB in supplement of 92 kg N ha-1 fertilizer with Hidase variety was the best producing economically profitable with acceptable grain yield.

Long-term investigation of the irrigation intervals and supplementary irrigation strategies effects on winter wheat in the U.S. Central High Plains based on a combination of crop modeling and field studies

Implementing optimized irrigation strategies to achieve acceptable wheat yield while conserving groundwater resources is critical for extensively irrigated regions. Field experiments regarding winter wheat irrigation management were conducted for two growing seasons (2013–2014 and 2014–2015) to calibrate and validate the AquaCrop model. To determine proper parameterization of the AquaCrop model for various data availability conditions, the model performance was tested for calibration based on three different datasets, including a) calibration based on a full irrigation condition (CA 1), b) calibration based on a dryland condition (CA 2), and c) calibration based on diverse irrigation conditions, which included full irrigation, different deficit irrigation levels, and dryland (CA 3). The CA 3 calibration scenario resulted in the model's highest accuracy in simulating biomass, grain yield, total soil water, and seasonal evapotranspiration during the calibration and validation process. However, the model performance was also convenient when calibration based on full irrigation conditions was pursued. The calibrated and validated AquaCrop model based on the CA3 was used to analyze long-term (36-year) irrigation management scenarios for identifying the optimized water-conservative winter wheat irrigation strategies. The long-term analysis emphasized that increasing irrigation intervals from 7 to 15 or 20 days could reduce groundwater withdrawal by 52–64 % while expecting a 14–19 % reduction in grain yield. By implementing one 25 mm irrigation after planting and two 25 mm depth irrigation events at jointing or leaf growth stages, 91 % of Kansas's average winter wheat yield (2.88 tons/ha) could be achieved. During wet years, the 1.2 ton/ha reduction in biomass and 0.27–0.62 ton/ha reduction in grain yield is expected irrespective of irrigation management strategies. Considerable uncertainty was detected in grain yield production during dry years under dryland (rainfed) conditions. The maximum winter wheat production could be achieved under normal years, establishing a balance between precipitation and heat units. Our agro-hydrological analysis revealed that the highest irrigation water use efficiency could be attained by the application of two 25 mm irrigation events at jointing or flag leaf growth stages during normal years, the application of two irrigation events during jointing or heading during wet years, and two 25 mm irrigations at heading or flowering during dry years. The results of this research could be used as a baseline for producers of the U.S. Central High Plains and semi-arid regions with similar climate characteristics to cope with water scarcity in winter wheat production.

Phosphomolybdic Acid‐Catalyzed One‐Pot Multicomponent Synthesis of 1,2,5,6‐Tetrahydropyridine Derivatives

AbstractWe report the synthesis of alkyl 1,2,6‐triaryl‐4‐arylaminopiperidine‐3‐ene‐3‐carboxylates in acceptable yields (42%–71%) and high trans‐diastereoselectivity (69:31 to 100:0) through a one‐pot multicomponent reaction of aromatic aldehydes, aromatic amines, and β‐ketoesters catalyzed by phosphomolybdic acid in methanol at room temperature. The structure and stereochemistry of tetrahydropyridines were confirmed by X‐ray crystallography. This protocol stands out for its operational simplicity, the use of an inexpensive and commercially available heteropolyacid catalyst, low catalyst loading, and purification via simple filtration, resulting in acceptable yields and high diastereoselectivity.

Heteroleptic Complexes of Ruthenium Nitrosyl with Pyridine and Bypiridine-Synthesis and Photoisomerization.

The reaction of [RuNO(Py)2Cl2OH] with bipyridine in water-ethanol media results in trans-(NO, OH)-[RuNO(Py)(Bpy)ClOH]+ with an acceptable yield (60-70%) as hexafluorophosphate salt. Further treatment of the hydroxy-complex with concentrated HF quantitatively leads to trans-(NO, F)-[RuNO(Py)(Bpy)ClF]+. Despite the chirality of both coordination spheres, the hexafluorophosphate salts crystallized as racemates. A NO-linkage isomerism study of the obtained complexes was performed at 80 K with different excitation wavelengths (405, 450, 488 nm). The most favorable wavelengths for the MS1 isomer (Ru-ON) formation were 405 and 450 nm, where the linkage isomer populations were 17% and 1% for [RuNO(Py)(Bpy)ClOH]PF6 and [RuNO(Py)(Bpy)ClF]PF6. The shift of the excitation wavelength to the green (488 nm) sharply decreased the MS1 population. The IR-spectral signatures of MS1 were registered. Reverse-transformation Ru-ON (MS1)-Ru-NO (GS) was investigated for [RuNO(Py)(Bpy)ClOH]PF6 using IR and DSC techniques that made it possible to determine the kinetic parameters (Ea and k0) and decay temperature.

Assessment of sediment yield and accumulation in reservoir: The case of Gibe One Reservoir, Southwestern Ethiopia

Soil erosion and sediment buildup are the factors that speed up the decline in capacity and function of reservoirs, agricultural products, and water resources. In order to simulate sediment and runoff and map high sediment-yielding sub-basins in the Gibe Gojeb catchment in southwest Ethiopia, this study used the Soil and Water Assessment Tool (SWAT) model. Using data on sediment and river flow, calibration and validation were carried out. Between 2003 and 2016, the catchment produced an average annual sediment loading of 62.5 tons ha−1 yr−1, with loading fluctuations ranging from 0.2 to 108.4 tons ha−1 yr−1. The acceptable sediment yield threshold value ranges from 12.3 to 108.4 tons ha−1 yr−1 for 56 sub-basins, and from 0.2 to 10 tons ha−1 yr−1 for 5 sub-basins. The most significant sub-basins with very high to extremely severe sediment yields were sub-basins 1 to 30, 32 to 44, 47, 48, 50, 51, and 53 to 61. After thirteen years of operation, the yearly amount of 58,802 tons of sediment transferred from the catchment and deposited into Gibe One reservoir has decreased the capacity by 5.7 %. The accumulation of sediment in a reservoir has an impact on its functionality, power production, and capacity, affecting the safety of dams and the environment. The study's findings enhanced our comprehension of sediment accumulation in reservoirs and furnished us with the necessary information regarding reservoir safety, integrated soil, and water management.

A Novel Synthesis and Quantitation Route of Belinostat

Introduction: This research article describes the production, quantification, and purification of belinostat from 3-nitrobenzaldehyde as the starting material. A cascade-step process produces higher yields when compared to all previous existing methodologies. Method: The procedure involved the following: Horner–Wadsworth–Emmons (HWE) reaction of aromatic aldehydes with triethylphosphonoacetate in the presence of potassium carbonate, reduction of the nitro group to the amino group, sulfochlorination by thionyl chloride, aniline-mediated sulfonamidation, and hydroxylamine amidation as the last step. Results: The prepared solid belinostat was purified, and an acceptable yield of 56-60% was obtained. Conclusion: The approach has several key benefits, including low-cost beginning materials, straightforward techniques, safer and more reliable results, and substantial environmental advantages.

Diels-Alder Cycloaddition of 2,5-Bis(hydroxymethyl)furan (BHMF) and N-Phenylmaleimide Derivatives.

Currently, amidst atmospheric menace where natural calamities such as wildfire and floods are becoming more frequent than ever, biobased derivatives offer a sustainable alternative to conventional ways, for instance, petrochemical commodities. Biobased products, obtained from agricultural waste, including 5-(hydroxymethyl)furfural (HMF), 2,5-bis(hydroxymethyl)furan (BHMF), and 2,5-furandicarboxylic acid (FDCA) are promising chemical platforms in the biorefinery, which is yet to be explored. The Diels-Alder cycloaddition of BHMF and N-phenylmaleimide derivatives under optimal reaction conditions is investigated in this report. First, HMF is reduced to BHMF in the presence of NaBH4, and then the Diels-Alder reaction of BHMF and N-phenylmaleimide derivatives is investigated to produce Diels-Alder adducts. All novel compounds are synthesized in acceptable yields and effectively characterized by employing important techniques such as one-dimensional (1D) NMR spectroscopy (1H, 13C, DEPT-90, and DEPT- 135), two-dimensional (2D) NMR spectroscopy (1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC), IR spectroscopy, elemental analysis, mass spectrum (QTOF), and single-crystal X-ray diffraction (SC-XRD). Furthermore, this study underlines the necessity of sustainable synthetic methodologies and gives critical insights into the progress of ecologically friendly methodologies, providing a new avenue as a tunable precursor for the challenging functionalized polymer in the future.

Deciphering the genetic basis of agronomic, yield, and nutritional traits in rice (Oryza sativa L.) using a saturated GBS-based SNP linkage map

Developing high-yielding rice varieties that possess favorable agronomic characteristics and enhanced grain Zn content is crucial in ensuring food security and addressing nutritional needs. This research employed ICIM, IM, and multi-parent population QTL mapping methods to identify important genetic regions associated with traits such as DF, PH, NT, NP, PL, YLD, TGW, GL, GW, Zn, and Fe. Two populations of recombinant inbred lines consisting of 373 lines were phenotyped for agronomic, yield and grain micronutrient traits for three seasons at IRRI, and genotyped by sequencing. Most of the traits demonstrated moderate to high broad-sense heritability. There was a positive relationship between Zn and Fe contents. The principal components and correlation results revealed a significant negative association between YLD and Zn/Fe. ICIM identified 81 QTLs, while IM detected 36 QTLs across populations. The multi-parent population analysis detected 27 QTLs with six of them consistently detected across seasons. We shortlisted eight candidate genes associated with yield QTLs, 19 genes with QTLs for agronomic traits, and 26 genes with Zn and Fe QTLs. Notable candidate genes included CL4 and d35 for YLD, dh1 for DF, OsIRX10, HDT702, sd1 for PH, OsD27 for NP, whereas WFP and OsIPI1 were associated with PL, OsRSR1 and OsMTP1 were associated to TGW. The OsNAS1, OsRZFP34, OsHMP5, OsMTP7, OsC3H33, and OsHMA1 were associated with Fe and Zn QTLs. We identified promising RILs with acceptable yield potential and high grain Zn content from each population. The major effect QTLs, genes and high Zn RILs identified in our study are useful for efficient Zn biofortification of rice.

Sonochemical thiocyanation of pyrrolo[1,2-a]quinoxalines: Identification of potential inhibitors of SIRT1

A series of compounds based on the 1-thiocyanatopyrrolo[1,2-a]quinoxaline framework were designed and assessed as potential inhibitors of SIRT1. A convenient access to this class of compounds was achieved via the sonochemical thiocyanation of pyrrolo[1,2-a]quinoxalines. The methodology involved use of N-thiocyanatosaccharin as a key agent under mild reaction conditions. The reaction proceeded with high regioselectivity affording the desired compounds in good to acceptable yields. The in silico docking studies suggested good interactions of these compounds with SIRT1 when majority of them formed an H-bond with GLN 345 though the most promising 3h formed H-bond with ILE347. The thiocyanato (NCS-) group of these compounds seemed to have played a key role in their interactions that formed either an H-bond through its nitrogen atom and/or participated in a pi-sulfur interaction via its sulfur atom. Moreover, the analysis of in silico structure-interaction of all the 1-thiocyanatopyrrolo[1,2-a]quinoxalines suggested that compound with –CN, -Cl (dichloro) and –OH substitutions had better binding interactions with SIRT1. Accordingly, 3h, 3i and 3j were identified as top molecules that also showed probable selectivity towards SIRT1 over SIRT2 in silico. Correlating the outcome of in silico studies, these compounds displayed encouraging inhibition of SIRT1 in vitro with IC50 ∼2.6–3.4 µM when 3h appeared as the most active molecule. The SAR (Structure-Activity-Relationship) analysis indicated good inhibition of compounds possessing the C-4 aryl group represented by the phenyl ring containing a 4-cyano or 2,4-dichloro or 2‑hydroxy group. Based on in silico and in vitro studies along with ADME predictions the 1-thiocyanatopyrrolo[1,2-a]quinoxaline 3h, 3i and 3j were selected as initial hits for further pharmacological evaluation.

Assessment of Roof Tilt and Building Azimuth for Off-Grid Photovoltaic Power for Buildings in Metropolitan Lagos, Nigeria

The study determined optimum roof tilt and building azimuth for rooftop-based distributed photovoltaic (PV) energy generation in Ikeja, Lagos State, Nigeria as strategic technological input to alternative power generation and new housing development in Metropolitan Lagos. The energy planning & foresight analysis methodology was used. The data were obtained via literature, Global Positioning System (GPS) systems, energy models and site visits; and comprised manual and satellite imagery, dimensions, roof angles and coordinates of the building structures in the study area (Rows between 0 – 60o, Columns between 0 – 180o; System sizes: 533 kW, 110 kW and 0.547 kW). The results showed solar array yield varied from 768,944 kWh per annum for a 500 kVA system to 780 kWh per annum for a 500 VA system. A five tier rooftop generation template of 245 MWp was consequently developed. Optimal roof tilt and building azimuth angles for the systems were estimated to be 5o and 180o respectively though combinations of azimuth and tilt angles not exceeding 30o tilt and 90o azimuth gave acceptable yields. The study concluded that the optimum roof tilt and building azimuth for rooftop-based distributed photovoltaic (PV) energy generation in the study area were strategic policy intelligence inputs for the renewable power generation and new housing development programmes of the Federal and Lagos State Governments.

Exonuclease III assisted exponential amplification reaction (EXPAR) for specific miRNA-155 analysis during post-anesthetic nursing

The persistent obstacle in precise and sensitive identification of microRNAs (miRNAs) pertains to the advancement of expeditious and effective isothermal amplification methodologies suitable for point-of-care environments and monitoring the cancer prognosis in patients receiving post-anesthetic nursing. The exponential amplification reaction (EXPAR) has attracted considerable interest due to its simplicity and ability to rapidly amplify signals. The practical application of the EXPAR is, nevertheless, severely hampered by the inability to differentiate closely related homologous sequences and to modify the designed templates to suit other targets. A loop-stem template for the EXPAR system was developed in this study to facilitate specific target recognition with the aid of exonuclease III (Exo III). This innovation effectively eliminated non-specific hybridization that could occur between the template and interfering sequences, thereby ensuring minimal background amplification of EXPAR. By modulating Exo III-based target recycling, EXPAR based chain amplification and G4/hemin based color reaction, this method facilitated the precise and sensitive examination of miRNA-155, yielding acceptable yields and a minimal detection limit of 0.43 fM. The approach expedites simple and expeditious molecular diagnostic applications involving short nucleic acids and offers an innovative method for enhancing the selectivity of EXPAR-based techniques, providing a robust tool for monitoring the expression level from patients receiving post-anesthetic nursing and guiding the treatment strategy.

Dura mater and survival time determination in individuals who died after traumatic brain injury: a preliminary study.

Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality among young people and is a matter of concern for forensic pathologists. Many authors have tried to estimate a person's survival time (ST) after TBI using different approaches. The present study aimed to present an innovative workflow to estimate the ST after TBI by observing the inflammatory reaction of the dura mater (DM). The authors collected DM samples from 36 cadavers (20 with TBI and 16 with no history or signs of TBI). Each sample was labelled via immunohistochemistry with three different primary antibodies, CD15, CD68, and CD3, yielding 108 slides in total. The slides were digitalized and analysed using QuPath software. The DM is involved in the inflammatory response after TBI. CD15 immunoreactivity allowed us to distinguish between subjects who died immediately after TBI and those with an ST of minutes or hours. CD3 immunoreactivity can be used to differentiate subjects with an ST of days from those with other STs. Moreover, the DM samples showed an acceptable diagnostic yield even in samples with signs of putrefaction.

Assessing the effects of plant density and nitrogen on millet yield in Southern Niger using the CERES-millet model

BackgroundThe dryland production environments in Niger Republic (Niger) generate variable crop production risks that reduce crop yields and increase regional food insecurity. Optimal combinations of crop varieties and management are needed to maximize crop water-limited yields in these environments.MethodsIn this study, we calibrated and validated the CERES-Millet model using data from field experiments. Seasonal analysis (1984–2020) was carried out in 18 selected sites across the three agroecological zones (AEZs) to test the effects of plant density and N fertilization on grain yield. The treatment included five different plant densities (1.5, 3, 6, 9, and 12 plants m−2) and four N rates (0, 20, 40, and 60 kg N ha−1). Three millet varieties (CHAKTI, HKP, and SOSAT-C88) were compared. Millet production risk was assessed at each AEZ using cumulative probability distribution graphs. The acceptable grain yield required to compensate for the minimum production cost of millet in Niger was set to 975 kg ha−1 (75th percentile of the simulated data).ResultsThe CERES-Millet model reasonably reproduced number of days to flowering (d-index > 0.50; RMSE < 2 days), number of days to maturity (d-index > 0.50; RMSE < 2 days), and grain yield d-index > 0.78; RMSE < 100 kg ha−1) for all the three varieties. The results showed that there was significant response to N (40 – 110% yield increase following N application) and plant density (30–80% yield increase by increasing density above 1.5 plants m−2) in all the AEZs depending on variety. The SOSAT was the most responsive variety to N application and plant density in all AEZs. Under low N application (0–20 kg ha−1) and low (1.5—3 plants m−2) to moderate plant density (6 plants m−2), CHAKTI and HKP had the highest production risks. Increasing N application above 20 kg ha−1 mitigate these risks where grain yield was above the 975 kg ha−1 threshold representing the minimum production cost for millet in more than 50% of the years under all plant densities except in Sahel where this threshold was only achieved in < 20% of the years. In all AEZs, increasing plant density above 6 plants m−2 increases this risk under low to moderate N application, but the downside risk was mitigated when N was applied at high rates.ConclusionThis study demonstrated N application rate and plant density recommendations must be tailored to specific variety and AEZs to maximize grain yield and reduce volatility in Niger.

Synthesis, Characterization, and Optimization of Novel Furan-ring Fused Chalcones via Radical Cyclization of α,β-Unsaturated Ketones and Cyclic Ketone

Abstract: Novel Furan-ring Fused Chalcones (FFC) were synthesized using a radical cyclization reaction of α,β-unsaturated ketones with cyclic ketone as the model reaction to attain this goal. In this study, traditional and microwave-assisted methods for the efficient and cost-effective synthesis of furan-ring fused chalcones in mild reaction conditions are compared and optimized. The goal is to develop a reliable and adaptable synthetic technique that may be used to produce these useful chalcone derivatives quickly and effectively. The optimal experimental conditions for these reactions were carefully determined using two independent methodologies: conventional (Method A) and microwave (Method B). The results indicated that the proposed method B could be used effectively in the future to synthesize novel furans with short reaction times and acceptable yields (87-94 %), and products were purified by column chromatography and preparative thin layer chromatography (PTLC). All new compounds were characterized by 1H-NMR, 13C-NMR, LC-MS, and elemental analyses.

Characterizing a learning curve for robotic-assisted bronchoscopy: Analysis of skills acquisition in a high-volume academic center

ObjectiveShape-sensing robotic-assisted bronchoscopy is an emerging technology for the sampling of pulmonary lesions. We seek to characterize the shape-sensing robotic-assisted bronchoscopy learning curve at an academic center. MethodsShape-sensing robotic-assisted bronchoscopy procedures performed by 9 proceduralists at a single institution were analyzed. Cumulative sum analyses were performed to examine diagnostic sampling and procedure time over each operator’s first 50 cases, with the acceptable yield threshold set to 73%. ResultsDuring the study period, 442 patients underwent sampling of 551 lesions. Each operator sampled 61 lesions (interquartile range, 60-63 lesions). Lesion size was 1.90 cm (interquartile range, 1.33-2.80 cm). The median procedure time for single-target cases decreased from 62 minutes during the first 10 cases to 39 minutes after case 40 (P < .001). The overall diagnostic yield was 72% (range, 58%-83%). Six of 9 operators achieved proficiency over the study period. An aggregated cumulative sum analysis of those who achieved competency demonstrated a steep improvement between lesions 1 and 21 and crossing of the competency threshold by lesion 25. Temporal analysis of yield-related lesion characteristics demonstrated that at approximately lesion 20, more challenging lesions were increasingly targeted, as evidenced by smaller target size, higher rates of unfavorable radial endobronchial ultrasound views, and a negative bronchus sign. ConclusionsSkills acquisition in shape-sensing robotic-assisted bronchoscopy is variable. Approximately half of proceduralists become facile with the technology within 25 lesions. After the initial learning phase, operators increasingly target lesions with more challenging features. Overall, these findings can inform certification and competency standards and provide new users with expectations related to performance over time.

#1966 Participation rate and yield of screening for albuminuria in the primary care setting for early identification of chronic kidney disease (SALINE)

Abstract Background and Aims Although guidelines recommend opportunistic screening for chronic kidney disease (CKD) in individuals with established risk factors, such as diabetes, hypertension, or cardiovascular disease, screening for CKD in these individuals remains suboptimal. This study aimed to evaluate the effectiveness of an additional systematic home-based albuminuria screening program in patients at risk for CKD in a primary care setting. Method A cross-sectional screening study was performed in 10 general practices and 5 pharmacies in the Netherlands between Nov 2021-Nov 2023. A random selection of patients aged 45-80 years with risk factors for CKD progression was invited for home-based albuminuria screening. These patients were registered at their general practitioner (GP) or at the pharmacy. Patients in the GP-group were identified based on the following risk factors: diabetes, cardiovascular disease, hypertension, hypercholesterolemia, or obesity. Patients were excluded in case of a normal albuminuria status (ACR (albumin-creatinine ratio) &amp;lt;3.0 mg/mmol) within 18 months prior to the screening. Patients in the pharmacy-group were identified based on drug prescriptions for the aforementioned risk factors in the last 6 months. Home-based albuminuria screening was performed using a urine collection device that was sent by post to a central laboratory for ACR measurement. If the test result was positive upon confirmation (i.e. ≥two tests ACR ≥3 mg/mmol), patients were invited for an elaborate visit in the general practice or pharmacy, to assess presence of CKD and cardiovascular risk factors. Main outcomes were participation rate and yield of the home-based albuminuria screening in the total study population and in both screening groups separately. Secondary outcomes were the yield of persistent albuminuria despite treatment with RAS-inhibition in both screening groups and the yield of previously undiagnosed albuminuria in the GP-group. Results We invited 6 380 patients (2 578 via pharmacy registries and 3 802 via GP registries), of whom 2 147 completed the home-based screening, corresponding to a participation rate of 33.7%. The participation rate among GP patients was 41.4% (1 575/3 802), compared to 22.2% (572/2 578) among pharmacy patients (P &amp;lt; .001). Albuminuria was confirmed in 8.5% (134/3 802) and 5.6% (32/2 578) of the participants in the GP- and pharmacy-group, respectively. Among participants in the GP-group, 59.7% (80/134) had a positive albuminuria test within one year prior to the screening; the remaining 40.3% either had no albuminuria test (or a normal albuminuria test within one year prior to the screening. Of those with increased albuminuria in the GP- and pharmacy-group, 85.8% (115/134) and 81.3% (26/32) attended the elaborate screening visit, respectively. In the GP-group, 72.2% (83/115) had an eGFR &amp;gt;60 and only 19.1% (22/115) an adequate blood pressure (&amp;lt;130/80 mmHg), compared to 69.2% (18/26) and 19.2% (5/26) in the pharmacy-group. Of the albuminuric participants in the GP- and pharmacy-group, respectively, 44.3% (51/115) and 23.1% (6/26) were not treated with RAS inhibition, and 94.8% (109/115) and 96.2% (25/26), respectively, were not treated with an SGLT2 inhibitor. Many patients were not aware of having albuminuria before participating in the systematic home-based screening program 42.6% (109/115) in the GP-group vs. 61.5% (16/26) in the pharmacy-group). Conclusion In conclusion, systematic albuminuria screening in the primary care setting when added to regular opportunistic screening has an acceptable participation rate and yield when performed via GPs, but is less effective when performed via pharmacies. It identifies patients with yet unknown albuminuria and most of the identified patients may benefit of initiation or optimization of albuminuria-lowering treatment. The introduction of such systematic albuminuria screening programs via GPs merits further study.

Spray freeze dried cannabidiol with dipalmitoylphosphatidylcholine (DPPC) for inhalation and solubility enhancement

Pulmonary delivery is an efficient route of administration to deliver cannabidiol (CBD) due to the high bioavailability and fast onset of action. The major formulation challenge is the poor aqueous solubility of CBD. This study aimed to produce inhalable CBD powders with enhanced solubility and characterise their solid-state properties. CBD was spray freeze dried with mannitol or trehalose dihydrate with and without dipalmitoylphosphatidylcholine (DPPC). All four powders had acceptable yields at > 70 % with porous and spherical particles. The two crystalline mannitol powders contained less residual solvent than both amorphous trehalose ones. The addition of DPPC did not affect the crystallinity and residual solvent level of the powders. Instead, DPPC made the particles more porous, decreased the particle size from 19-23 µm to 11–13 µm, and increased CBD solubility from 0.36 µg/mL to over 2 µg/mL. The two DPPC powders were dispersed from a low resistance RS01 inhaler, showing acceptable aerosol performance with emitted fractions at 91–93 % and fine particle fractions < 5 µm at 34–43 %. These formulations can be used as a platform to deliver CBD and other cannabinoids by inhalation.

An inexpensive, metal-free and one-pot approach towards N-sulfonyl amidines: Identification of a chorismate mutase inhibitor with activities against S. aureus

The simple yet innovative synthetic approaches for the direct access to the diversity based unique class of compounds of potential biological interest are of considerable interest as that can greatly facilitate the efforts in bioorganic / medicinal chemistry and drug discovery. In our efforts, we have developed a metal-free, inexpensive and one-pot method for the facile and direct synthesis of N-sulfonyl amidines that were designed as inhibitors of chorismate mutase. The methodology involved POCl3-SOCl2 promoted reaction of amide with sulphonamide to afford an array of new and unique class of compounds in good to acceptable yields. The methodology is free from the use of additional organic reaction media and amenable for scale-up. Based on in vitro and in silico studies, 3g has been identified as a first example of chorismate mutase inhibitor with selective and promising activities on a range of S. aureus strains. Indeed, the docking of 3g into AlphaFold predicted structure S. aureus CM I (UniProt ID: A0A380DU97) revealed good interactions with stabilization mostly via π-anion interactions in addition to a halogen (fluorine) bond. Compound 3g is of further pharmacological interest.