Postharvest handling of ethylene with oxidative and absorptive means.

Fruit ripening is an unfolding of a series of genetically-programmed modifications and tend to be highly orchestrated irrevocable phenomenon mediated by ethylene. Phytohormone ethylene also leads to over-ripening, senescence, loss of texture, microbial attack, reduced post-harvest life and other associated problems during storage and transportation of fruits. Its harmful impacts on fresh fruits, vegetables, and ornamentals result in substantial product losses even up to 80%. Curbing of this inevitable menace is therefore need of the hour. Accrual of ethylene in packaging system should fundamentally be ducked to extend the shelf-life and uphold an adequate superiority of perishables in visual and organoleptic terms. The current review discusses about properties, factors affecting and impact of ethylene, intimidation of its impact at gene vis-à-vis activity level using gene-modification/inhibition techniques, chemical/physical in conjunction with other suitable approaches. It also entails the most commercially cultivated approaches worldwide viz. KMnO4-based oxidation together with adsorption-based scrubbing of ethylene in thorough details. Future ethylene removal strategies should focus on systematic evaluation of KMnO4-based scavenging, exploring the mechanism of adsorption, adsorbent(s) behavior in the presence of other gases and their partial pressures, volatiles, temperature, relative humidity, development of hydrophobic adsorbents to turn-up under high RH, regeneration of adsorbent by desorption, improvement in photocatalytic oxidation etc. and further improvements thereof. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05777-1.

The role of susceptibility-weighted imaging & contrast-enhanced MRI in the diagnosis of primary CNS vasculitis: a large case series.

Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.

Natural flavonoid pectolinarin computationally targeted as a promising drug candidate against SARS-CoV-2.

Coronavirus disease-2019 (COVID-19) has become a global pandemic, necessitating the development of new medicines. In this investigation, we identified potential natural flavonoids and compared their inhibitory activity against spike glycoprotein, which is a target of SARS-CoV-2 and SARS-CoV. The target site for the interaction of new inhibitors for the treatment of SARS-CoV-2 has 82% sequence identity and the remaining 18% dissimilarities in RBD S1-subunit, S2-subunit, and 2.5% others. Molecular docking was employed to analyse the various binding processes used by each ligand in a library of 85 natural flavonoids that act as anti-viral medications and FDA authorised treatments for COVID-19. In the binding pocket of the target active site, remdesivir has less binding interaction than pectolinarin, according to the docking analysis. Pectolinarin is a natural flavonoid isolated from Cirsiumsetidensas that has anti-cancer, vasorelaxant, anti-inflammatory, hepatoprotective, anti-diabetic, anti-microbial, and anti-oxidant properties. The S-glycoprotein RBD region (330-583) is inhibited by kaempferol, rhoifolin, and herbacetin, but the S2 subunit (686-1270) is inhibited by pectolinarin, morin, and remdesivir. MD simulation analysis of S-glycoprotein of SARS-CoV-2 with pectolinarin complex at 100ns based on high dock-score. Finally, ADMET analysis was used to validate the proposed compounds with the highest binding energy.

Cortico-limbic disruption, material-specificity, and deficits in cognitive-affective theory of mind.

The Theory of Mind deficit due to cognitive-affective disintegration is a poorly understood cognitive consequence of cortical and subcortical disruption in right temporal lobe epilepsy. Following Marr's trilevel approach, we used the material-specific processing model to understand the Theory of Mind deficit in drug-resistant epilepsy (N = 30). We examined pre- and post-surgery changes in first-order (somatic-affective, non-verbal component) and second-order Theory of Mind (cognitive-verbal component) in three groups formed using: (i) seizure side (right versus left), (ii) right temporal epilepsy (right temporal lobe epilepsy versus non-right temporal lobe epilepsy), and (iii) right temporal lobe epilepsy with amygdalohippocampectomy (right temporal lobe epilepsy versus left temporal lobe epilepsy amygdalohippocampectomy versus non-amygdalohippocampectomy). We observed a marked deficit in the first-order Theory of Mind in the right temporal lobe amygdalohippocampectomy group; we mapped this deficit to decline in the non-verbal component of Theory of Mind (somatic-affective component). Preliminary results support using a material-specific processing model to understand the Theory of Mind deficits in right temporal lobe epilepsy amygdalohippocampectomy. Malleability of verbal processing in presence of deterioration of non-verbal processing might have clinical relevance for post-surgery recovery in right temporal lobe epilepsy amygdalohippocampectomy. Documenting the material-specific nature of deficits (verbal versus non-verbal) in non-western, linguistically, and socioeconomically diverse country enables us to understand the problem of heterogeneity in post-surgery cognitive consequences in the right amygdalohippocampectomy.

Phosphomevalonate kinase regulates the MVA/MEP pathway in mango during ripening.

Mango is a popular tropical fruit with a great diversity in taste and aroma, contributed primarily by terpenoids. Phosphomevalonate kinase (PMK) is a key enzyme for isoprenoid biosynthesis in the mevalonic acid (MVA) pathway responsible for terpenoids. In this study, two cultivars of mango, "Dashehari" and "Banganpalli", showing opposite spatio-temporal patterns of ripening polarity, were investigated for studying the role of MiPMK in aroma production. MiPMK transcription and enzyme activity increased during ripening in both varieties. Expression in the early-ripening inner zones preceded that in the later-ripening outer zones of "Dashehari" while it was higher in the early ripening outer zones in "Banganpalli". Polypeptide sequences of the two enzymes showed differences in a few amino acids that were also reflected in kinetic properties such as specific activity and pH optima. Silencing of MiPMK in "Dashehari" fruit by VIGS suppressed the kinase activity and led to changes in relative contributions of the mevalonic acid (MVA) and methylerythritol 4-phosphate (MEP) pathways. This also altered the fruit metabolite profile with a reduction/disappearance of sesquiterpenes such as geranyl geraniol, trans-farnesol, ß-caryophyllene, ß-pinene, bisabolene and guaiane but the appearance of menthol and d-limonene in silenced fruit. The study shows that MiPMK levels may control downstream metabolite flux of the MVA pathway in mango.

Clinical and radiological spectrum of anti-myelin oligodendrocyte glycoprotein (MOG) antibody encephalitis: single-center observational study.

OBJECTIVE: The objective was to describe the clinical presentations, radiologic features, and outcomes of patients with autoimmune encephalitis associated with myelin oligodendrocyte glycoprotein antibody (MOG). BACKGROUND: During the past decade, the spectrum of the myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD) has expanded. Recently, patients with MOG antibody encephalitis (MOG-E) who do not fulfill the criteria for ADEM have been reported. In this study, we aimed to describe the spectrum of MOG-E. METHODS: Sixty-four patients with MOGAD were screened for encephalitis-like presentation. We collected the clinical, radiological, laboratory, and outcome data of the patients who presented with encephalitis and compared it with the non-encephalitis group. RESULTS: We identified sixteen patients (nine males and seven females) with MOG-E. The median age of the encephalitis population was significantly lower than the non-encephalitis group (14.5 years (11.75-18) vs. 28 years (19.75-42), p = 0.0004). Twelve out of sixteen patients (75%) had fever at the time of encephalitis. Headache and seizure were present in 9/16 (56.2%) and 7/16 (43.75%) patients, respectively. FLAIR cortical hyperintensity was present in 10/16 (62.5%) patients. Supratentorial deep gray nuclei were involved in 10/16 (62.5%) patients. Three patients had tumefactive demyelination, and one patient had a leukodystrophy-like lesion. Twelve of 16 (75%) patients had a good clinical outcome. Patient with leukodystrophy pattern and other with generalized CNS atrophy showed a chronic progressive course. CONCLUSION: MOG-E can have heterogeneous radiological presentations. FLAIR cortical hyperintensity, tumefactive demyelination, and leukodystrophy-like presentations are novel radiological presentations associated with MOGAD. Though majority of MOG-E have a good clinical outcome, few patients can have chronic progressive disease even on immunosuppressive therapy.

In Silico Quantification of Intersubject Variability on Aerosol Deposition in the Oral Airway.

The extrathoracic oral airway is not only a major mechanical barrier for pharmaceutical aerosols to reach the lung but also a major source of variability in lung deposition. Using computational fluid dynamics, deposition of 1−30 µm particles was predicted in 11 CT-based models of the oral airways of adults. Simulations were performed for mouth breathing during both inspiration and expiration at two steady-state flow rates representative of resting/nebulizer use (18 L/min) and of dry powder inhaler (DPI) use (45 L/min). Consistent with previous in vitro studies, there was a large intersubject variability in oral deposition. For an optimal size distribution of 1−5 µm for pharmaceutical aerosols, our data suggest that >75% of the inhaled aerosol is delivered to the intrathoracic lungs in most subjects when using a nebulizer but only in about half the subjects when using a DPI. There was no significant difference in oral deposition efficiency between inspiration and expiration, unlike subregional deposition, which shows significantly different patterns between the two breathing phases. These results highlight the need for incorporating a morphological variation of the upper airway in predictive models of aerosol deposition for accurate predictions of particle dosimetry in the intrathoracic region of the lung.

Pyrazoline scaffold: hit identification to lead synthesis and biological evaluation as antidiabetic agents.

Background: Mining of novel scaffolds as potential DPP-IV inhibitors for future development of potential candidates as antidiabetic agents to address global issues. Methodology: The identified hit KB-10 from a previously reported study was taken as a lead for designing a library of analogues and screened initially based on in silico parameters and docking score. A series of selected (2[4-(1-acetyl-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)phenoxy]-1-phenylethanone derivatives were synthesized and evaluated through in vitro studies. Compounds KB-23, KB-22 and KB-06 were found to be as potent, with IC50 values of 0.10 µM, 0.12 µM and 0.35 µM, respectively. They also showed promising antihyperglycemic potential in in vivo studies (oral glucose tolerance tests) in Wistar rats. Conclusion: This work establishes pyrazoline analogues KB-23, KB-22 and KB-06 as promising starting points for the development of potential antidiabetic agents.

Epidemiological and Time Series Analysis of Tuberculosis with Prediction during COVID-19 Pandemic using ARIMA Model: A Study from Churu District of Rajasthan.

As Tuberculosis (TB) is a major public health problem in India and to achieve the goal of TB elimination, it is important to assess the trend of TB cases and the impact of lockdowns and other restrictions imposed for control of COVID-19 in India on the National TB Elimination Programme. Hence, the present study aims to study the temporal trend of TB cases and assess the impact of lockdown on TB detection. A retrospective record-based study was conducted in a tertiary care institute of India. A time series analysis of TB cases from April 2018 to May 2020 was carried out. An Auto-Regressive Integrated Moving Averages (ARIMA) model was used to forecast TB cases during the lockdown period and the result was compared with actual cases detected. The statistical analysis was accomplished with R software. The time series analysis showed that the projected TB cases in April and May 2020 were 67 and 86, respectively, while the observed cases in these months were 35 and 76. The trend of TB cases during the study period showed no steady increase or decrease and the detection of TB has declined during the COVID-19 lockdown period. The TB cases peaked from April to June and males constitute the majority of TB cases.

Root system architecture for abiotic stress tolerance in potato: Lessons from plants.

The root is an important plant organ, which uptakes nutrients and water from the soil, and provides anchorage for the plant. Abiotic stresses like heat, drought, nutrients, salinity, and cold are the major problems of potato cultivation. Substantial research advances have been achieved in cereals and model plants on root system architecture (RSA), and so root ideotype (e.g., maize) have been developed for efficient nutrient capture to enhance nutrient use efficiency along with genes regulating root architecture in plants. However, limited work is available on potatoes, with a few illustrations on root morphology in drought and nitrogen stress. The role of root architecture in potatoes has been investigated to some extent under heat, drought, and nitrogen stresses. Hence, this mini-review aims to update knowledge and prospects of strengthening RSA research by applying multi-disciplinary physiological, biochemical, and molecular approaches to abiotic stress tolerance to potatoes with lessons learned from model plants, cereals, and other plants.

Primary CNS vasculitis (PCNSV): a cohort study.

Primary CNS Vasculitis (PCNSV) is a rare inflammatory disorder affecting the blood vessels of the central nervous system. Patients present with a combination of headaches, seizures, and focal neurological deficits. There is usually a diagnostic delay. Treatment is based on observational studies and expert opinion. Our objective was to identify clinical, laboratory, neuroimaging, pathologic or management-related associations with 2 year outcome in patients with primary CNS vasculitis. We conducted a cohort study at a single tertiary care referral centre of prospectively (2018-2019) and retrospectively (2010-2018) identified individuals with primary CNS vasculitis (diagnosis was proven by either brain biopsy or cerebral digital subtraction angiography). Clinical, imaging and histopathologic findings, treatment, and functional outcomes were recorded. Univariate and stepwise multiple logistic regression were applied. P-value<0.05 was considered statistically significant. The main outcome measures were documentation of clinical improvement or worsening (defined by mRS scores) and identification of independent predictors of good functional outcome (mRS 0-2) at 2 years. We enrolled eighty-two biopsy and/or angiographically proven PCNSV cases. The median age at presentation was 34 years with a male predilection and a median diagnostic delay of 23 months. Most patients presented with seizures (70.7%). All patients had haemorrhages on MRI. Histologically lymphocytic subtype was the commonest. Corticosteroids with cyclophosphamide was the commonest medication used. The median mRS at follow-up of 2 years was 2 (0-3), and 65.2% of patients achieved a good functional outcome. Myelitis and longer duration of illness before diagnosis were associated with poorer outcomes. The presence of hemorrhages on SWI sequence of MRI might be a sensitive imaging marker. Treatment with steroids and another immunosuppressant probably reduced relapse rates in our cohort. We have described the third largest PCNSV cohort and multi-centre randomised controlled trials are required to study the relative efficacy of various immunosuppressants.Study registration: CTRI/2018/03/012721.

Late-onset cobalamin C disease: rare but treatable.

Cobalamin C disease is the most common inborn error of cobalamin metabolism, resulting from mutations in methylmalonic aciduria and homocystinuria type C protein (MMACHC) gene. There is associated elevation of homocysteine and methylmalonic acid and decreased synthesis of methionine. It is a multisystem disorder characterised by cognitive impairment, psychiatric manifestations, haematological manifestations and thromboembolic phenomena. Its variable clinical presentation and wide age distribution at presentation necessitates a high index of diagnostic suspicion. The diagnosis is suggested by amino acid chromatography and confirmed by sequencing analysis of the MMACHC gene Parenteral hydroxycobalamin and betaine can bring significant clinical and biochemical improvement and is the recommended long-term therapy.

Target-based anticancer indole derivatives and insight into structure‒activity relationship: A mechanistic review update (2018-2021).

Cancer, which is the uncontrolled growth of cells, is the second leading cause of death after heart disease. Targeting drugs, especially to specific genes and proteins involved in growth and survival of cancer cells, is the prime need of research world-wide. Indole moiety, which is a combination of aromatic-heterocyclic compounds, is a constructive scaffold for the development of novel leads. Owing to its bioavailability, high unique chemical properties and significant pharmacological behaviours, indole is considered as the most inquisitive scaffold for anticancer drug research. This is illustrated by the fact that the U.S. Food and Drug Administration (FDA) has recently approved several indole-based anticancer agents such as panobinostat, alectinib, sunitinib, osimertinib, anlotinib and nintedanib for clinical use. Furthermore, hundreds of studies on the synthesis and activity of the indole ring have been published in the last three years. Taking into account the facts stated above, we have presented the most recent advances in medicinal chemistry of indole derivatives, encompassing hot articles published between 2018 and 2021 in anticancer drug research. The recent advances made towards the synthesis of promising indole-based anticancer compounds that may act via various targets such as topoisomerase, tubulin, apoptosis, aromatase, kinases, etc., have been discussed. This review also summarizes some of the recent efficient green chemical synthesis for indole rings using various catalysts for the period during 2018-2021. The review also covers the synthesis, structure‒activity relationship, and mechanism by which these leads have demonstrated improved and promising anticancer activity. Indole molecules under clinical and preclinical stages are classified into groups based on their cancer targets and presented in tabular form, along with their mechanism of action. The goal of this review article is to point the way for medicinal chemists to design and develop effective indole-based anticancer agents.

SimELIT: A Novel GUI-Based Comprehensive Ion Trajectory Simulation Software for Mass Spectrometry.

Ion trajectory simulation in mass spectrometry systems from injection to detection is technically challenging but very important for better understanding the ion dynamics in instrument development. Here, we present SimELIT (Simulator of Eulerian and Lagrangian Ion Trajectories), a novel ion trajectory simulation platform. SimELIT is built upon a suite of multiphysics solvers compiled into OpenFOAM (an open-source numerical solver library particularly used for computational mechanics), with a simple web-based graphical user interface (GUI) allowing users to define the details of OpenFOAM cases and run simulations. SimELIT is a modular program and can provide extensions of physics (e.g., gas flows, electrodynamic fields) and thus enable ion trajectory simulations from the ion source to detector. The current version (SimELIT) provides two numerical solvers for ion trajectory simulations─(1) a Lagrangian particle tracker in vacuum and (2) a Eulerian ion density solver in background gas in the presence of electric fields. Here, we describe the architecture of SimELIT, including its use of Docker and the React Framework, and demonstrate the computation of ion trajectories of multiple m/z values in a static/linear voltage drop in vacuum (across a 1 m long flight tube). Further, the drift motion of ions under 1 Torr pressure conditions in a static background (N2) gas through a 20 V/cm static electric field is shown. The results produced from SimELIT were compared with SIMION and theoretical estimates. In addition, we report the computation of ion trajectories in electrodynamic fields within a planar FAIMS device operating at atmospheric pressure.

Comparison of Disease Profiles and Three-Month Outcomes of Patients with Neurological Disorders with and without COVID-19: An Ambispective Cohort Study.

Objective: Neurological emergencies saw a paradigm shift in approach during the coronavirus disease-2019 (COVID-19) pandemic with the challenge to manage patients with and without COVID-19. We aimed to compare the various neurological disorders and 3 months outcome in patients with and without SARS-CoV-2 infection. Methods: In an ambispective cohort study design, we enrolled patients with and without SARS CoV-2 infection coming to a medical emergency with neurological disorders between April 2020 and September 2020. Demographic, clinical, biochemical, and treatment details of these patients were collected and compared. Their outcomes, both in-hospital and at 3 months were assessed by the modified Rankin Scale (mRS). Results: Two thirty-five patients (235) were enrolled from emergency services with neurological disorders. Of them, 81 (34.5%) were COVID-19 positive. The mean (SD) age was 49.5 (17.3) years, and the majority of the patients were male (63.0%). The commonest neurological diagnosis was acute ischemic stroke (AIS) (43.0%). The in-hospital mortality was higher in the patients who were COVID-19 positive (COVID-19 positive: 29 (35.8%) versus COVID-19 negative: 12 (7.8%), P value: <0.001). The 3 months telephonic follow-up could be completed in 73.2% of the patients (142/194). Four (12.1%) deaths occurred on follow-up in the COVID-19 positive versus fifteen (13.8%) in the COVID-19 negative patients (P value: 1.00). The 3-month mRS was worse in the COVID-19 positive group (P value <0.001). However, this was driven by higher in-hospital morbidity and mortality in COVID-19 positive patients. Conclusion: Patients with neurological disorders presenting with COVID-19 infection had worse outcomes, including in-hospital and 3 months disability.

Impact of the COVID-19 Pandemic on the Frequency, Clinical Spectrum and Outcomes of Pediatric Guillain-Barré Syndrome in India: A Multicentric Ambispective Cohort Study.

Objective: To study impact of COVID-19 pandemic on frequency, clinical/electrophysiological profile and treatment outcomes in pediatric Guillain-Barré syndrome (GBS). Background: GBS is the most frequent cause of pediatric acute flaccid paralysis. The effect of the COVID-19 pandemic on pediatric GBS is unclear in the literature. Methods: We conducted an ambispective, multicentric, cohort study involving 12 of 27 centres in GBS Consortium, during two periods: pre-COVID-19 (March-August 2019) and during COVID-19 (March-August 2020). Children ≤12 years who satisfied National Institute of Neurological Diseases and Stroke criteria for GBS/variants were enrolled. Details pertaining to clinical/laboratory parameters, treatment and outcomes (modified Rankin Scale (mRS) at discharge, GBS Disability score at discharge and 3 months) were analysed. Results: We enrolled 33 children in 2019 and 10 in 2020. Children in 2020 were older (median 10.4 [interquartile range 6.75-11.25] years versus 5 (2.5-8.4) years; P = 0.022) and had more sensory symptoms (50% versus 18.2%; P = 0.043). The 2020 group had relatively favourable mRS at discharge (median 1 (1-3.5) versus 3 (2-4); P = 0.042) and GBS disability score at 3 months (median 0 (0-0.75) versus 2 (0-3); P = 0.009) compared to 2019. Multivariate analysis revealed bowel involvement (P = 0.000) and ventilatory support (P = 0.001) as independent predictors of disability. No child in 2020 had preceding/concurrent SARS-CoV2 infection. Conclusions: The COVID-19 pandemic led to a marked decline in pediatric GBS presenting to hospitals. Antecedent illnesses, clinical and electrophysiological profile of GBS remained largely unchanged from the pre-pandemic era.

Patients with Neurological Illnesses and Their Experience During the Lockdown: A Teleinterview-based Study.

Background: Governments have imposed lockdowns in the wake of the COVID-19 pandemic. Hospitals have restricted outpatient clinics and elective services meant for non-COVID illnesses. This has led to patients facing unprecedented challenges and uncertainties. This study was carried out to assess patients' concerns and apprehensions about the effect of the lockdown on their treatments. Materials and Methods: An ambispective, observational cross-sectional single centre study was conducted. Patients were contacted telephonically and requested to answer a structured questionnaire. Their responses were documented and summarized as frequency and proportions. Results: A total of 727 patients were interviewed. Epilepsy (32%) was the most common neurological illness in our cohort followed by stroke (18%). About half the patients and/or their caregivers reported health-related concerns during the lockdown. The primary concern was how to connect with their treating neurologist if need arose. Forty-seven patients (6.4%) had drug default. Among patients on immunomodulatory treatments, only eight patients had drug default. High compliance rates were also observed in the stroke and epilepsy cohorts. Of the 71 patients who required emergency care during the lockdown, 24 could reach our hospital emergency. Fourteen patients either had a delay or could not seek emergency care. Two-thirds of our patients found the telemedicine experience satisfactory. Conclusion: The ongoing pandemic will continue to pose challenges to both physicians and patients. Patients in follow-up may need to be contacted regularly and counselled regarding the importance of maintaining drug compliance. Telemedicine can be used to strengthen the healthcare delivery to patients with non-COVID illnesses.