Chronic thromboembolic pulmonary hypertension is an uncommon complication of COVID-19: UK national surveillance and observational screening cohort studies.

BACKGROUND: Pulmonary embolism (PE) is a well-recognised complication of coronavirus disease 2019 (COVID-19) infection, and chronic thromboembolic pulmonary disease with and without pulmonary hypertension (CTEPD/CTEPH) are potential life-limiting consequences. At present the burden of CTEPD/CTEPH is unclear and optimal and cost-effective screening strategies yet to be established. METHODS: We evaluated the CTEPD/CTEPH referral rate to the UK national multidisciplinary team (MDT) during the 2017-2022 period to establish the national incidence of CTEPD/CTEPH potentially attributable to COVID-19-associated PE with historical comparator years. All individual cases of suspected CTEPH were reviewed by the MDT for evidence of associated COVID-19. In a separate multicentre cohort, the risk of developing CTEPH following hospitalisation with COVID-19 was calculated using simple clinical parameters at a median of 5 months post-hospital discharge according to existing risk scores using symptoms, ECG and N-terminal pro-brain natriuretic peptide. RESULTS: By the second year of the pandemic, CTEPH diagnoses had returned to the pre-pandemic baseline (23.1 versus 27.8 cases per month; p=0.252). Of 334 confirmed CTEPD/CTEPH cases, four (1.2%) patients were identified to have CTEPH potentially associated with COVID-19 PE, and a further three (0.9%) CTEPD without PH. Of 1094 patients (mean age 58 years, 60.4% male) hospitalised with COVID-19 screened across the UK, 11 (1.0%) were at high risk of CTEPH at follow-up, none of whom had a diagnosis of CTEPH made at the national MDT. CONCLUSION: A priori risk of developing CTEPH following COVID-19-related hospitalisation is low. Simple risk scoring is a potentially effective way of screening patients for further investigation.

Investigation of excited states of BODIPY derivatives and non-orthogonal dimers from the perspective of singlet fission.

We report state of the art electronic structure calculations RICC2 and XMCQDPT of BODIPY nonorthogonal dimers to understand the photophysical processes from the intramolecular singlet fission (iSF) perspective. We have calculated singlet, triplet and quintet states at the XMCQDPT(8,8)/cc-pVDZ level of theory and diabatic singlet states at the XMCQDPT(4,4)/cc-pVDZ level of theory. In all the systems studied, charge transfer states (1(CA) and 1(AC)) couple strongly with locally excited (1(S1S0)) and multiexcitonic (1(T1T1)) states. The rates of formation of the multiexcitonic state from the locally excited state are very low on account of large activation energy (E(1(T1T1)) - E(1(S1S0))). A relaxed scan along the torsional angle revealed contrasting results for axial and orthogonal conformers. We proposed a probable mechanism for contrasting photophysical properties of dimers B[3,3] and B[2,8]. We also found that substitution of CN, NH2 and BH2 at meso, ß and α positions reduces the energy gap (ΔSF = 2E(T1) - E(S1)) significantly, making iSF a competing process in triplet state generation. Intrigued by the success of the CN group at the meso position in reducing the energy gap, we also studied the azaBODIPY monomer and its derivatives using the same methodology. The iSF is slightly endoergic with ΔSF ∼ 0.2 eV in these systems and iSF may play an important role in their photophysical responses.

Intramolecular singlet fission: Quantum dynamical simulations including the effect of the laser field.

In the previous work [Reddy et al., J. Chem. Phys. 151, 044307 (2019)], we have analyzed the dynamics of the intramolecular singlet fission process in a series of prototypical pentacene-based dimers, where the pentacene monomers are covalently bonded to a phenylene linker in ortho, meta, and para positions. The results obtained were qualitatively consistent with the experimental data available, showing an ultrafast population of the multiexcitonic state that mainly takes place via a mediated (superexchange-like) mechanism involving charge transfer and doubly excited states. Our results also highlighted the instrumental role of molecular vibrations in the process as a sizable population of the multiexcitonic state could only be obtained through vibronic coupling. Here, we extend these studies and investigate the effect of the laser field on the dynamics of intramolecular singlet fission by explicitly including the coupling to the laser field in our model. In this manner, and by selectively tuning the laser field to the different low-lying absorption bands of the systems investigated, we analyze the wavelength dependence of the intramolecular singlet fission process. In addition, we have also analyzed how the nature of the initially photoexcited electronic state (either localized or delocalized) affects its dynamics. Altogether, our results provide new insights into the design of intramolecular singlet fission-active molecules.

A predictable electrocardiogram.

An electrocardiogram of an uncommon congenital heart disease is presented to highlight the unique findings in diagnosis with its clinical implications and predictive value.

Cyperus rotundus L.: Invasive weed plant with insecticidal potential against Aphis craccivora Koch and Planococcus lilacinus (Cockerell).

Cyperus rotundus L. is a widely distributed invasive weed plant with vast traditional medicinal uses. Herein, the methanolic root extract of C. rotundus and its fractions (n-hexane, chloroform, n-butanol, and aqueous) were evaluated for insecticidal activity against nymphs of Aphis craccivora Koch and crawlers of Planococcus lilacinus (Cockerell) to find promising lead (s). In contact topical assay, among extract/fractions, n-hexane fraction exhibited more toxicity against A. craccivora (LD50 = 1.12 µg/insect) and P. lilacinus (LD50 = 0.94 µg/insect). The chemical analysis of n-hexane fraction revealed a volatile composition similar to that of the essential oil (EO) of C. rotundus roots. Hence, EO was extracted using water and deep eutectic solvents (DESs) as cosolvent, which revealed enhancement in EO yield (from 0.28 to 0.46% w/w) on implementing DESs. A total of 35 diverse volatile metabolites were identified in all EO samples, accounting for 85.0 to 91.8% of chemical composition, having cyperotundone, cyperene mustakone, isolongifolen-5-one, boronia butenal as major constituents. The EO obtained with DES-7 [choline chloride: ethylene glycol (1:4)] and DES-6 [choline chloride: lactic acid (1:3)] were found effective against A. craccivora (LD50 = 0.62-0.87 µg/insect) and P. lilacinus (LD50= 0.59-0.67 µg/insect) after 96 h. NMR analysis of EO revealed cyperotundone as a major compound, which was isolated along with cyperene and cyperene epoxide. All the molecules were found effective against P. lilacinus, whereas against A. craccivora cyperotundone, cyperene and cyperene epoxide showed promising toxicity (LD50 = 0.74-0.86 µg/insect). Extract/fractions, EO, and isolated molecules showed a significant reproductive inhibition rate of A. craccivora at higher concentrations. All the tested concentrations of cyperotundone showed significant inhibition of acetylcholinesterase (AChE) and glutathione-S-transferase (GST) in A. craccivora and P. lilacinus. Based upon the present study, C. rotundus can be recommended to control targeted insects in the greenhouse/field conditions after performing bio-efficacy and phytotoxicity studies.

Acyl Transfer-Driven Rauhut-Currier Dimerization of Morita-Baylis-Hillman Ketones.

A serendipitous Rauhut-Currier dimerization of 1,1-disubstituted activated olefins derived from Morita-Baylis-Hillman adducts was observed in the presence of DABCO. The reaction is driven by the migration of an acyl group and produces multifunctionalized enol esters in yields greater than 90% in most cases, without necessitating column chromatographic purification. The acyl transfer is thought to proceed via a transition state typical of a Morita-Baylis-Hillman (MBH) reaction, supported by a brief mechanistic study involving computational calculations.

Rapid sub-nanomolar protein determination in serum using electropolymerized molecularly imprinted polymers (E-MIPs).

Rapid detection of biologicals is important for a range of applications such as medical screening and diagnostics. Antibodies are typically employed for biosensing with high sensitivity and selectivity but can take months to prepare. Here, we investigate electropolymerized molecularly imprinted polymers (E-MIPs), which are produced in minutes as alternative-antibody rapid biosensors for the selective recognition of model proteins bovine haemoglobin (BHb) and bovine serum albumin (BSA). We evaluated two disposable screen-printed electrodes (SPE) designated AT-Au and BT-Au based on their different annealing temperatures. E-MIPs for BHb demonstrated an imprinting factor of 146 : 1 at 1 nM and 12 : 1 at 0.1 nM, showing high effectiveness of E-MIPs compared to their control non-imprinted polymers. The BHb imprinted E-MIP, when tested against BSA as a non-target protein, gave a selectivity factor of 6 : 1 for BHb. Sensor sensitivity directly depended on the nature of the SPE, with AT-Au SPE demonstrating limits of detection in the sub-micromolar range typically achieved for MIPs, while BT-Au SPE exhibited sensitivity in the sub-nanomolar range for target protein. We attribute this to differences in electrode surface area between AT-Au and BT-Au SPEs. The E-MIPs were also tested in calf serum as a model biological medium. The BT-Au SPE MIPs detected the presence of target protein in <10 min with an LOD of 50 pM and LOQ of 100 pM, suggesting their suitability for protein determination in serum with minimal sample preparation. Using electrochemical impedance spectroscopy, we determine equilibrium dissociation constants (KD) for E-MIPs using the Hill-Langmuir adsorption model. KD of BHb E-MIP was determined to be 0.86 ± 0.11 nM.

Perioperative Management in Pulmonary Endarterectomy.

Pulmonary endarterectomy (PEA) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (PH), provided lesions are proximal enough in the pulmonary vasculature to be surgically accessible and the patient is well enough to benefit from the operation in the longer term. It is a major cardiothoracic operation, requiring specialized techniques and instruments developed over several decades to access and dissect out the intra-arterial fibrotic material. While in-hospital operative mortality is low (<5%), particularly in high-volume centers, careful perioperative management in the operating theater and intensive care is mandatory to balance ventricular performance, fluid balance, ventilation, and coagulation to avoid or treat complications. Reperfusion pulmonary edema, airway hemorrhage, and right ventricular failure are the most problematic complications, often requiring the use of extracorporeal membrane oxygenation to bridge to recovery. Successful PEA has been shown to improve both morbidity and mortality in large registries, with survival >70% at 10 years. For patients not suitable for PEA or with residual PH after PEA, balloon pulmonary angioplasty and/or PH medical therapy may prove beneficial. Here, we describe the indications for PEA, specific surgical and perioperative strategies, postoperative monitoring and management, and approaches for managing residual PH in the long term.

Individual and area-level socioeconomic correlates of hypertension prevalence, awareness, treatment, and control in uMgungundlovu, KwaZulu-Natal, South Africa.

BACKGROUND: Hypertension is the second leading risk factor for death in South Africa, and rates have steadily increased since the end of Apartheid. Research on the determinants of hypertension in South Africa has received considerable attention due to South Africa's rapid urbanization and epidemiological transition. However, scant work has been conducted to investigate how various segments of the Black South African population experience this transition. Identifying the correlates of hypertension in this population is critical to the development of policies and targeted interventions to strengthen equitable public health efforts. METHODS: This analysis explores the relationship between individual and area-level socioeconomic status and hypertension prevalence, awareness, treatment, and control within a sample of 7,303 Black South Africans in three municipalities of the uMgungundlovu district in KwaZulu-Natal province: the Msunduzi, uMshwathi, and Mkhambathini. Cross-sectional data were collected on participants from February 2017 to February 2018. Individual-level socioeconomic status was measured by employment status and educational attainment. Ward-level area deprivation was operationalized by the most recent (2011 and 2001) South African Multidimensional Poverty Index scores. Covariates included age, sex, BMI, and diabetes diagnosis. RESULTS: The prevalence of hypertension in the sample was 44.4% (n = 3,240). Of those, 2,324 were aware of their diagnosis, 1,928 were receiving treatment, and 1,051 had their hypertension controlled. Educational attainment was negatively associated with hypertension prevalence and positively associated with its control. Employment status was negatively associated with hypertension control. Black South Africans living in more deprived wards had higher odds of being hypertensive and lower odds of having their hypertension controlled. Those residing in wards that became more deprived from 2001 to 2011 had higher odds of being aware of their hypertension, yet lower odds of receiving treatment for it. CONCLUSIONS: Results from this study can assist policymakers and practitioners in identifying groups within the Black South African population that should be prioritized for public health interventions. Black South Africans who have and continue to face barriers to care, including those with low educational attainment or living in deprived wards had worse hypertension outcomes. Potential interventions include community-based programs that deliver medication to households, workplaces, or community centers.

First report of Cephalerous virescens causing Algal leaf spot of Averrhoa carambola in India.

Averrhoa carambola (Star fruit) is a drought resistant edible fruit belongs to family Oxalidaceae. It is native of Malaysia and further cultivation is extended to China, Southeast Asia, India and Northern South America. Star fruit has juicy texture and used in salads, beverages and traditionally it has been used for ayurvedic medicines in India, Brazil and China (Abduh et al. 2023). In early January 2023, we observed the symptoms of raised, more or less circular, orange to dark brown, velvet textured, scattered algal leaf spots (1-4 mm) on the upper surface of A. carambola leaves at College farm, Agricultural College, Aswaraopet (17.252039 latitude, 81.109573 longitude) (Supplementary Fig 1). The disease was observed in 2 hectare model orchard with incidence of 45% causing leaf defoliation and thereby reducing the yield and quality of fruits. Transverse section cutting of algal spots revealed the algal thalli at subcuticular region and causing necrosis of epidermal cells. Sporangiophores (n=20) raised from algal leaf spot were cylindrical, 4 to 5 celled, 200-450 µm long x 8-20 µm wide, and forming a head cell with suffultory cells and sporangia on the top. Sporangia (n=20) were spherical to elliptical, rusty brown and 17.5-29 µm long × 18-23.6 µm wide and the total number of sporangia produced by each sporangiophores varies from 1 to 6. Setae (n=20) were filamentous with three to six celled, 17.5-50 µm long × 2.5-7.5 µm wide (Supplementary Figure 2). In our collection, mature gametangia were not observed. Morphological characters were studied on 20 diseased leaf samples collected from randomly selected five plants. To isolate pathogen, fresh algal thalli (n=5) were scraped from host tissue, surface sterilized (70% alcohol (30 s), 1% sodium hypochlorite (30 s) and sterile distilled water (3 × 60 s), inoculated to trebouxia liquid media and incubated at 25 ± 2 °C with a 12 hours photoperiod for 72 hours (Vasconcelos et al. 2018). The resultant five algal filaments were subjected to PCR amplification. The primer pair PNS1/NS41 was used in a PCR to amplify a fragment of 18S rRNA (Davis and Kaur 2019). The 18S rRNA gene sequences of the algae were compared using the Basic Local Alignment Search Tool (BLAST; http://www.ncbi.nlm.nih.gov/Blast/Blast.cgi) showed that our partial sequence had 99.5% similarity to C. virescens (KM020142.1). Hence, it was classified as C. virescens and sequences was deposited in NCBI-GenBank with accession numbers (OR053653, OR243777, OR429406, OR429407 and OR243779). For proving pathogenicity, algal filaments obtained from trebouxia liquid media were inoculated to 6 months old healthy A. carambola plant. Pathogenicity test was negative and typical symptoms could not be produced even up to 150 days of inoculation. In previous studies also, due to difficulty with production of zoospores in synthetic media, Koch's postulates of C. virescens as a plant pathogen has not been demonstrated experimentally (Sunpapao et al. 2017; Sanahuja et al. 2018; Kumar et al. 2019). In the second experiment, zoosporangia spore suspension were prepared from small pieces of algal leaf spot tissue processed in a sterile pestle and mortar and filtered through sterile cheesecloth (Sunpapao et al. 2017). A total of five isolates of zoosporangia spore suspension (1 x 102 to 1 x 104/ml of water) was sprayed on healthy, surface sterilized leaves of A. carambola plants (n=5) until runoff with a handheld airpump sprayer and incubated in green house (T: 25 oC, H: 80%). During the experiment leaves were remain attached to plant (5 days old) and plants were 6 months old grown in plastic pots under controlled conditions. Two plants were inoculated with each isolate and three non inoculated control plants were included. Non inoculated controls were sprayed with sterile distilled water. The pathogenicity experiment was repeated. The initial symptoms were produced 60 days after inoculation and complete algal thalli was observed on 90 days after inoculation, control plants were without any symptoms upto 150 days. Reisolated algal thalli from symptomatic plants were morphologically similar to original algal thalli and molecularly identified as C. virescens (accession number OR067193 and OR243810). Red rust caused by C. virescens is a major algal disease in the world and causing severe leaf defoliation in various horticultural crops viz., Mangifera indica (Vasconcelos et al. 2018), Manilkara zapota (Sunpapao et al. 2017), Psidium guajava (Rajbongshi et al. 2022), Ziziphus mauritiana (Shareefa et al. 2022) and Anacardium occidentale (Dooh et al. 2022). The available literature suggest that, this is the first report of algal leaf spot on A. carambola caused by C. virescens in India. This report extends the range of known pathogens associated with A. carambola plant and serves as a basis for development and implementing disease management strategies.

Insecticidal and Detoxification Enzyme Inhibition Activities of Essential Oils for the Control of Pulse Beetle, Callosobruchus maculatus (F.) and Callosobruchus chinensis (L.) (Coleoptera: Bruchidae).

Pulse beetle is the most harmful pest attacking stored grains and affecting quality and marketability. Continuous use of chemical-based pesticides against pulse beetle led to the development of insecticidal resistance; essential oils (EOs) can be an effective natural alternative against this pest. The main objective was to study the chemical composition of seven EOs viz., Acorus calamus, Hedychium spicatum, Lavandula angustifolia, Juniperus recurva, Juniperus communis, Cedrus deodara and Pinus wallichiana, their insecticidal and enzyme inhibition activities against pulse beetle. The primary compounds present in these EOs were cis-asarone, 1,8-cineole, linalyl isobutyrate, 2-ß-pinene, camphene, α-dehydro-ar-himachalene and camphene. A. calamus oil showed promising fumigant toxicity to Callosobruchus maculatus and C. chinensis (LC50 = 1357.86 and 1379.54 µL/L, respectively). A combination of A. calamus + L. angustifolia was effective against C. maculatus and C. chinensis (LC50 = 108.58 and 92.18 µL/L, respectively). All the combinations of EOs showed synergistic activity. In the repellency study, A. calamus showed more repellence to C. maculatus and C. chinensis (RC50 = 53.98 and 118.91 µL/L, respectively). A. calamus and L. angustifolia oil at 2500, 5000 and 10,000 µL/L significantly inhibited the AChE and GST enzymes in C. maculatus and C. chinensis after 24 and 48 h.

Anti-inflammatory potential of turmeric, amla, and black pepper mixture against sepsis-induced acute lung injury in rats.

Acute lung injury (ALI), is a severe inflammatory lung disease. We tested the prophylactic effect of a functional food mix comprising three anti-inflammatory plant products: turmeric, amla, and black pepper (TAB) against lipopolysaccharide (LPS)-induced ALI in rats. Two-month-old male Wistar rats were randomly divided into three groups: control (C), LPS (5 mg/kg), and LPS with TAB (TAB). After 6 h of LPS injection, the rats were sacrificed by cervical decapitation to collect the lung tissue. Results showed that TAB partially ameliorated LPS-induced increase in circulating inflammatory cytokines (TNFα and IL6) and significantly prevented lung histopathological changes. TAB also suppressed LPS-activated ER stress markers (GRP78, pIRE1, and CHOP) and apoptotic markers (caspase-3 and - 12) in the lung. The anti-inflammatory effects of the TAB support its potential use as an adjuvant to mitigate ALI. Importantly, TAB's ingredients have been used for centuries as part of the diet with limited or no toxic effects.

Desidustat in Anemia due to Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-D).

BACKGROUND: A phase 3 study to assess the efficacy and safety of the desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, against the epoetin alfa for the treatment of anemia in patients with chronic kidney disease (CKD) with dialysis dependency. METHODS: DREAM-D was a phase 3, multicenter, open-label, randomized, active-controlled clinical study conducted across 38 centers in India. A total of 392 patients with clinical diagnosis of anemia due to CKD with dialysis need (Erythrocyte Stimulating Agent [ESA] naïve or prior ESA users) and with baseline hemoglobin levels of 8.0-11.0 g/dL (inclusive) were randomized in a 1:1 ratio to receive either desidustat oral tablets (thrice a week) or epoetin alfa subcutaneous injection for 24 weeks to maintain a hemoglobin level of 10-12 g/dL. The primary endpoint was to assess the change in the hemoglobin level between the desidustat and the epoetin alfa groups from the baseline to evaluation period week 16-24. The key secondary efficacy endpoint was the number of patients with hemoglobin response. RESULTS: The least square mean (standard error) change in hemoglobin from the baseline to week 16-24 was 0.95 (0.09) g/dL in the desidustat group and 0.80 (0.09) g/dL in the epoetin alfa group (difference: 0.14 [0.14] g/dL; 95% confidence interval: -0.1304, 0.4202), which met the prespecified noninferiority margin. The number of hemoglobin responders was significantly higher in the desidustat group (106 [59.22%]) when compared to the epoetin alfa group (89 [48.37%]) (p = 0.0382). The safety profile of the desidustat oral tablet was comparable with the epoetin alfa injection. There were no new risks or no increased risks seen with the use of desidustat compared to epoetin alfa. CONCLUSION: In this study, desidustat was found to be noninferior to epoetin in the treatment of anemia in CKD patients on dialysis and it was well-tolerated. Clinical Trial Registry Identifier: CTRI/2019/12/022312 (India).

Base-triggerable lauryl sarcosinate-dodecyl sulfate catanionic liposomes: structure, biophysical characterization, and drug entrapment/release studies.

Equimolar mixtures of oppositely charged single-chain amphiphiles form a variety of phases, including vesicles. Such catanionic mixed lipid systems show high stability and exhibit versatile physicochemical properties. In the present study we have investigated the aggregation behaviour of lauryl sarcosinate hydrochloride (LS·HCl) in aqueous dispersion as well as its interaction with the anionic surfactant sodium dodecyl sulfate (SDS). The CMC of LS·HCl was estimated to be ∼5 mM by isothermal titration calorimetry (ITC) and fluorescence spectroscopy using pyrene as the fluorescent probe. Turbidimetric and ITC studies on the interaction of LS·HCl with SDS demonstrated that the two surfactants form an equimolar catanionic complex. The crystal structure of the lauryl sarcosinate-dodecyl sulfate (LS-DS) complex revealed that the complex is stabilized by classical N-H⋯O as well as C-H⋯O hydrogen bonds, besides the electrostatic attraction between LS (cation) and DS (anion) and dispersion interactions between the hydrocarbon chains. Differential scanning calorimetry studies revealed that the phase transition of the equimolar LS-DS complex is significantly reduced compared to the analogous LG-DS and LA-DS complexes in the fully hydrated state. Dynamic light scattering, atomic force microscopy and transmission electron microscopy studies demonstrated that the LS-DS catanionic complex forms stable medium-sized vesicles (diameter of ∼300-500 nm). In vitro studies with 5-fluorouracil and rhodamine 6G showed efficient entrapment and release of these two anti-cancer drugs in the physiologically relevant pH range of 6.0-8.0, but with contrasting pH dependences. These observations indicate that LS-DS catanionic vesicles may find application in designing drug delivery systems.

Coronary imaging of cardiac allograft vasculopathy predicts current and future deterioration of left ventricular function in patients with orthotopic heart transplantation.

BACKGROUND: Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) improve sensitivity of cardiac allograft vasculopathy (CAV) detection compared to invasive coronary angiography (ICA), but their ability to predict clinical events is unknown. We determined whether severe CAV detected with ICA, IVUS, or OCT correlates with graft function. METHODS: Comparison of specific vessel parameters between IVUS and OCT on 20 patients attending for angiography 12-24 months post-orthotopic heart transplant. Serial left ventricular ejection fraction (EF) was recorded prospectively. RESULTS: Analyzing 55 coronary arteries, OCT and IVUS correlated well for vessel CAV characteristics. A mean intimal thickness (MIT)OCT  > .25 mm had a sensitivity of 86.7% and specificity of 74.3% at detecting Stanford grade 4 CAV. Those with angiographically evident CAV had significant reduction in graft EF over 7.3 years follow-up (median ΔEF -2% vs +1.5%, P = .03). Patients with MITOCT  > .25 mm in at least one vessel had a lower median EF at time of surveillance (57% vs 62%, P = .014). Two MACEs were noted. CONCLUSION: Imaging with OCT correlates well with IVUS for CAV detection. Combined angiography and OCT to screen for CAV within 12-24 months of transplant predicts concurrent and future deterioration in graft function.

American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.

OBJECTIVE: The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers. METHODS: The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RESULTS: This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes. CONCLUSIONS: This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.

Detection of SARS-CoV-2 in the air in Indian hospitals and houses of COVID-19 patients.

To understand the transmission characteristics of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) through air, samples from different locations occupied by coronavirus disease (COVID-19) patients were analyzed. Three sampling strategies were used to understand the presence of virus in the air in different environmental conditions. In the first strategy, which involved hospital settings, air samples were collected from several areas of hospitals like COVID-intensive-care units (ICUs), nurse-stations, COVID-wards, corridors, non-COVID-wards, personal protective equipment (PPE) doffing areas, COVID rooms, out-patient (OP) corridors, mortuary, COVID casualty areas, non-COVID ICUs and doctors' rooms. Out of the 80 air samples collected from 6 hospitals from two Indian cities- Hyderabad and Mohali, 30 samples showed the presence of SARS-CoV-2 nucleic acids. In the second sampling strategy, that involved indoor settings, one or more COVID-19 patients were asked to spend a short duration of time in a closed room. Out of 17 samples, 5 samples, including 4 samples collected after the departure of three symptomatic patients from the room, showed the presence of SARS-CoV-2 nucleic acids. In the third strategy, involving indoor settings, air samples were collected from rooms of houses of home-quarantined COVID-19 patients and it was observed that SARS-CoV-2 RNA could be detected in the air in the rooms occupied by COVID-19 patients but not in the other rooms of the houses. Taken together, we observed that the air around COVID-19 patients frequently showed the presence of SARS-CoV-2 RNA in both hospital and indoor residential settings and the positivity rate was higher when 2 or more COVID-19 patients occupied the room. In hospitals, SARS-CoV-2 RNA could be detected in ICUs as well as in non-ICUs, suggesting that the viral shedding happened irrespective of the severity of the infection. This study provides evidence for the viability of SARS-CoV-2 and its long-range transport through the air. Thus, airborne transmission could be a major mode of transmission for SARS-CoV-2 and appropriate precautions need to be followed to prevent the spread of infection through the air.

Characterization of Triadica sebifera (L.) Small Extracts, Antifeedant Activities of Extracts, Fractions, Seed Oil and Isolated Compounds against Plutella xylostella (L.) and Their Effect on Detoxification Enzymes.

Plutella xylostella L. is one of the world's major pests of cruciferous crops. The indiscriminate use of synthetic insecticides has led to insecticide resistance and resurgence, and has been harmful to non-target organisms and the environment. Botanical insecticides are the best alternatives to synthetic pesticides for the management of pests in organic agriculture and integrated management. T. sebifera is an invasive species and has good potential as an insecticide due to the availability of plant material in some parts of India. The antifeedant activities of T. sebifera have not been reported against P. xylostella and other lepidopteron insects to date. Therefore, the current study targeted the characterization of leaf and bark extracts, feeding deterrence, synergistic and detoxification enzyme activities of leaf/bark ethanolic extracts/fractions, seed oil, and isolated compounds. UHPLC-QTOF-IMS analysis showed that shikimic acid, xanthoxylin, quercetin, kaempferol, methyl gallate, and stigmasterol are common metabolites identified in leaf and bark extracts. The combination of seed oil with bark extract showed higher deterrence (DC50 = 317.10 mg/L) as compared to leaf/bark extracts alone. Gallic acid showed higher deterrence (67.48%) than kaempferol and quercetin. The n-butanol fraction of bark was more repellent (RC50 = 414.61 mg/L). Based on DC50, the seed oil with leaf extract (1:1 ratio) alone with choice and seed oil with leaf and bark extract without choice showed synergistic interaction, but seed oil with bark extract with choice showed additive interaction. The ethanol extract of leaf, bark, and seed oil inhibited GST and AChE in P. xylostella. The leaf extract and seed oil or their combinations may be recommended as antifeedants to reduce damage by P. xylostella based on persistence, antifeedant, phytotoxicity, safety to predators/parasitoids, etc., under field conditions.

Chemical Composition and Insecticidal Activities of Essential Oils against the Pulse Beetle.

Pulse beetles, Callosobruchus chinensis and Callosobruchus maculatus, are essential pests of cowpea, gram, soybean and pulses. Application of synthetic insecticides against the pulse beetle has led to insect resistance; insecticide residues on grains affect human health and the environment. Essential oils (EOs) are the best alternatives to synthetics due to their safety to the environment and health. The main objective of the investigation was to study the chemical composition and insecticidal activities of EOs, their combinations and compounds against the pulse beetle under laboratory. Neo-isomenthol, carvone and ß-ocimene are the significant components of tested oils using GC-MS. Mentha spicata showed promising fumigant toxicity against C. chinensis (LC50 = 0.94 µL/mL) and was followed by M. piperita (LC50 = 0.98 µL/mL), whereas M. piperita (LC50 = 0.92 µL/mL) against C. maculatus. A combination of Tagetes minuta + M. piperita showed more toxicity against C. chinensis after 48 h (LC50 = 0.87 µL/mL) than T. minuta + M. spicata (LC50 = 1.07 µL/mL). L-Carvone showed fumigant toxicity against C. chinensis after 48 h (LC50 = 1.19 µL/mL). Binary mixtures of T. minuta +M. piperita and M. spicata showed promising toxicity and synergistic activity. EOs also exhibited repellence and ovipositional inhibition. The application of M. piperita can be recommended for the control of the pulse beetle.

Insecticidal Activity of Extracts, Fractions, and Pure Molecules of Cissampelos pareira Linnaeus against Aphid, Aphis craccivora Koch.

Aphis craccivora Koch is a polyphagous and major pest of leguminous crops causing significant damage by reducing the yield. Repeated application of synthetic insecticides for the control of aphids has led to development of resistance. Therefore, the present study aimed to screen the insecticidal activity of root/stem extracts/fractions, and pure molecules from Cissampelos pareira Linnaeus against A. craccivora for identification of lead(s). Among root extract/fractions, the n-hexane fraction was found most effective (LC50 = 1828.19 mg/L) against A. craccivora, followed by parent extract (LC50 = 2211.54 mg/L). Among stem extract/fractions, the n-hexane fraction (LC50 = 1246.92 mg/L) was more effective than the water and n-butanol fractions. Based on GC and GC-MS analysis, among different compounds identified in the n-hexane fraction of root and stem, ethyl palmitate (known to possess insecticidal activity) was present in the highest concentration (24.94 to 52.95%) in both the fractions. Among pure molecules, pareirarineformate was found most effective (LC50 = 1491.93 mg/L) against A. craccivora, followed by cissamine (LC50 = 1556.31 mg/L). Parent extract and fractions of C. pareira possess promising activity against aphid. Further, field bio-efficacy studies are necessary to validate the current findings for the development of botanical formulation.