Exploring the molecular basis of resistance to Botrytis cinerea in chickpea genotypes through biochemical and morphological markers.

Chickpea (Cicer arietinum L.) is an important pulse crop around the globe and a valuable source of protein in the human diet. However, it is highly susceptible to various plant pathogens such as fungi, bacteria, and viruses, which can cause significant damage from the seedling phase until harvest, leading to reduced yields and affecting its production. Botrytis cinerea can cause significant damage to chickpea crops, especially under high humidity and moisture conditions. This fungus can cause grey mould disease, which can lead to wilting, stem and pod rot, and reduced yields. Chickpea plants have developed specific barriers to counteract the harmful effects of this fungus. These barriers include biochemical and structural defences. In this study, the defence responses against B. cinerea were measured by the quantification of biochemical metabolites such as antioxidant enzymes, malondialdehyde (MDA), proline, glutathione (GSH), H2O2, ascorbic acid (AA) and total phenol in the leaf samples of chickpea genotypes (one accession of wild Cicer species, viz. Cicer pinnatifidum188 identified with high level of resistance to Botrytis grey mould (BGM) and a cultivar, Cicer arietinumPBG5 susceptible to BGM grown in the greenhouse). Seedlings of both the genotypes were inoculated with (1 × 104 spore mL-1) inoculum of isolate 24, race 510 of B. cinerea and samples were collected after 1, 3, 5, and 7 days post-inoculation (dpi). The enhanced enzymatic activity was observed in the pathogen-inoculated leaf samples as compared to uninoculated (healthy control). Among inoculated genotypes, the resistant one exhibited a significant change in enzymatic activity, total phenolic content, MDA, proline, GSH, H2O2, and AA, compared to the susceptible genotype. The study also examined the isozyme pattern of antioxidant enzymes at various stages of B. cinerea inoculation. Results from scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy revealed that BGM had a more significant impact on susceptible genotypes compared to resistant ones when compared to the control (un-inoculated). In addition, SEM and FTIR spectroscopy analyses confirmed the greater severity of BGM on susceptible genotypes compared to their resistant counterparts. Our results suggest the role of antioxidant enzymes and other metabolites as defence tools and biochemical markers to understand compatible and non-compatible plant-pathogen interactions better. The present investigation will assist future plant breeding programs aimed at developing resistant varieties.

Non-dairy prebiotics: Conceptual relevance with nutrigenomics and mechanistic understanding of the effects on human health.

The increasing health awareness of consumers has made a shift towards vegan and non-dairy prebiotics counterparts. Non-dairy prebiotics when fortified with vegan products have interesting properties and widely found its applications in food industry. The chief vegan products that have prebiotics added include water-soluble plant-based extracts (fermented beverages, frozen desserts), cereals (bread, cookies), and fruits (juices & jelly, ready to eat fruits). The main prebiotic components utilized are inulin, oligofructose, polydextrose, fructooligosaccharides, and xylooligosaccharides. Prebiotics' formulations, type and food matrix affect food products, host health, and technological attributes. Prebiotics from non-dairy sources have a variety of physiological effects that help to prevent and treat chronic metabolic diseases. This review focuses on mechanistic insight on non-dairy prebiotics affecting human health, how nutrigenomics is related to prebiotics development, and role of gene-microbes' interactions. The review will provide industries and researchers with important information about prebiotics, mechanism of non-dairy prebiotics and microbe interaction as well as prebiotic based vegan products.

Morphological, ultrastructural and molecular variations in susceptible and resistant genotypes of chickpea infected with Botrytis grey mould.

Biotic stress due to fungal infection is detrimental to the growth and development of chickpea. In our study, two chickpea genotypes viz Cicer pinnatifidum (resistant) and PBG5 (susceptible) were inoculated with (1 × 104 spore mL-1) of nectrotrophic fungus Botrytis cinerea at seedling stage. These seedlings were evaluated for morphological, ultrastructural, and molecular differences after 3, 5 and 7 days post inoculation (dpi). Visual symptoms were recorded in terms of water-soaked lesions, rotten pods and twigs with fungal colonies. Light and scanning electron microscopy (SEM) revealed the differences in number of stomata, hyphal network and extent of topographical damage in resistant (C. pinnatifidum) and susceptible (PBG5) genotypes, which were validated by stomatal index studies done by using fluorescence microscopy in the infection process of B. cinerea in leaves of both chickpea genotypes. In case of control (water inoculated) samples, there were differences in PCR analysis done using five primers for screening the genetic variations between two genotypes. The presence of a Botrytis responsive gene (LrWRKY) of size ~300 bp was observed in uninoculated resistant genotype which might have a role in resistance against Botrytis grey mould. The present investigation provides information about the variation in the infection process of B. cinerea in two genotypes which can be further exploited to develop robust and effective strategies to manage grey mould disease.

Comparative assessment on lignocellulose degrading enzymes and bioethanol production from spent mushroom substrate of Calocybe indica and Volvariella volvacea.

In the current study, we compared the production of extracellular lignocellulose degrading enzymes and bioethanol from the spent mushroom substrate (SMS) of Calocybe indica and Volvariella volvacea. From SMS at different stages of the mushroom development cycle, ligninolytic and hydrolytic enzymes were analysed. The activities of lignin-degrading enzymes, including lignin peroxidase (LiP), laccase, and manganese peroxidase (MnP) were maximal in the spawn run and primordial stages, while hydrolytic enzymes including xylanase, cellobiohydrolase (CBH), and carboxymethyl cellulase (CMCase) showed higher activity during fruiting bodies development and at the end of the mushroom growth cycle. SMS of V. volvacea showed relatively lower ligninase activity than the SMS of C. indica, but had the maximum activity of hydrolytic enzymes. The enzyme was precipitated with acetone and further purified with the DEAE cellulose column. The maximum yield of reducing sugars was obtained after hydrolysis of NaOH (0.5 M) pretreated SMS with a cocktail of partially purified enzymes (50% v/v). After enzymatic hydrolysis, the total reducing sugars were 18.68 ± 0.34 g/l (SMS of C. indica) and 20.02 ± 0.87 g/l (SMS of V. volvacea). We observed the highest fermentation efficiency and ethanol productivity (54.25%, 0.12 g/l h) obtained from SMS hydrolysate of V. volvacea after 48 h at 30 ± 2 °C, using co-culture of Saccharomyces cerevisiae MTCC 11,815 and Pachysolen tannophilus MTCC 1077.

Nutrient-Mediated Perception and Signalling in Human Metabolism: A Perspective of Nutrigenomics.

The interaction between selective nutrients and linked genes involving a specific organ reveals the genetic make-up of an individual in response to a particular nutrient. The interaction of genes with food opens opportunities for the addition of bioactive compounds for specific populations comprising identical genotypes. The slight difference in the genetic blueprints of humans is advantageous in determining the effect of nutrients and their metabolism in the body. The basic knowledge of emerging nutrigenomics and nutrigenetics can be applied to optimize health, prevention, and treatment of diseases. In addition, nutrient-mediated pathways detecting the cellular concentration of nutrients such as sugars, amino acids, lipids, and metabolites are integrated and coordinated at the organismal level via hormone signals. This review deals with the interaction of nutrients with various aspects of nutrigenetics and nutrigenomics along with pathways involved in nutrient sensing and regulation, which can provide a detailed understanding of this new leading edge in nutrition research and its potential application to dietetic practice.

Kidney transplantation in patients with multiple myeloma: narrative analysis and review of the last two decades.

There have been significant advances in the treatment of multiple myeloma in the last two decades. Approximately 25% of patients with newly diagnosed myeloma have some degree of kidney impairment. During the course of illness, nearly 50% of myeloma patients will develop kidney disease. Moreover, ∼10% of myeloma patients have advanced kidney disease requiring dialysis at presentation. Hemodialysis is associated with a significantly reduced overall survival (OS). In the setting of prolonged long-term OS due to the use of newer immunotherapeutic agents in the treatment of myeloma, patients with myeloma and advanced kidney disease may benefit from more aggressive management with kidney transplantation (KTx). Unfortunately, most data regarding outcomes of KTx in patients with myeloma come from single-center case series. With the advent of novel treatment choices, it remains unclear if outcomes of kidney transplant recipients with myeloma have improved in recent years. In this descriptive systematic review, we coalesced published patient data over the last 20 years to help inform clinicians and patients on expected hematologic and KTx outcomes in this complex population. We further discuss the future of KTx in patients with paraproteinemia.

Monoclonal Antibodies in Myeloma: Optimizing Targeted Therapy.

ABSTRACT: In the past several years, there have been significant advances in the therapeutic arsenal of agents used to treat multiple myeloma (MM). Despite these advances, MM remains incurable. One of the most recent therapeutic advances is the development of targeted monoclonal antibodies (MoAbs). The MoAbs have significantly improved disease response rates, and extended survival in MM patients. In this review, we highlight the current US Food and Drug Administration approved MoAbs, namely, belantamab mafodotin, daratumumab, elotuzumab, and isatuximab. The mechanisms of action and pivotal clinical trials that led to US Food and Drug Administration approval of these agents and their current therapeutic use in the management of patients with MM are discussed in detail. Lastly, we describe several novel MoAbs under clinical investigation with potential for approval in the future.

Postdischarge thromboembolic outcomes and mortality of hospitalized patients with COVID-19: the CORE-19 registry.

Thromboembolic events, including venous thromboembolism (VTE) and arterial thromboembolism (ATE), and mortality from subclinical thrombotic events occur frequently in coronavirus disease 2019 (COVID-19) inpatients. Whether the risk extends postdischarge has been controversial. Our prospective registry included consecutive patients with COVID-19 hospitalized within our multihospital system from 1 March to 31 May 2020. We captured demographics, comorbidities, laboratory parameters, medications, postdischarge thromboprophylaxis, and 90-day outcomes. Data from electronic health records, health informatics exchange, radiology database, and telephonic follow-up were merged. Primary outcome was a composite of adjudicated VTE, ATE, and all-cause mortality (ACM). Principal safety outcome was major bleeding (MB). Among 4906 patients (53.7% male), mean age was 61.7 years. Comorbidities included hypertension (38.6%), diabetes (25.1%), obesity (18.9%), and cancer history (13.1%). Postdischarge thromboprophylaxis was prescribed in 13.2%. VTE rate was 1.55%; ATE, 1.71%; ΑCM, 4.83%; and MB, 1.73%. Composite primary outcome rate was 7.13% and significantly associated with advanced age (odds ratio [OR], 3.66; 95% CI, 2.84-4.71), prior VTE (OR, 2.99; 95% CI, 2.00-4.47), intensive care unit (ICU) stay (OR, 2.22; 95% CI, 1.78-2.93), chronic kidney disease (CKD; OR, 2.10; 95% CI, 1.47-3.0), peripheral arterial disease (OR, 2.04; 95% CI, 1.10-3.80), carotid occlusive disease (OR, 2.02; 95% CI, 1.30-3.14), IMPROVE-DD VTE score ≥4 (OR, 1.51; 95% CI, 1.06-2.14), and coronary artery disease (OR, 1.50; 95% CI, 1.04-2.17). Postdischarge anticoagulation was significantly associated with reduction in primary outcome (OR, 0.54; 95% CI, 0.47-0.81). Postdischarge VTE, ATE, and ACM occurred frequently after COVID-19 hospitalization. Advanced age, cardiovascular risk factors, CKD, IMPROVE-DD VTE score ≥4, and ICU stay increased risk. Postdischarge anticoagulation reduced risk by 46%.

Outcomes of Moderate-to-Severe Acute Kidney Injury following Left Ventricular Assist Device Implantation.

BACKGROUND: Although acute kidney injury (AKI) is a common complication following cardiac surgery, less is known about the occurrence and consequences of moderate/severe AKI following left ventricular assist device (LVAD) implantation. METHODS: All patients who had an LVAD implanted at our center from 2008 to 2016 were reviewed to determine the incidence of, and risk factors for, moderate/severe (stage 2/3) AKI and to compare postoperative complications and mortality rates between those with and those without moderate/severe AKI. RESULTS: Of 246 patients, 68 (28%) developed moderate/severe AKI. A multivariable logistic regression comprising body mass index and prior sternotomy had fair predictive ability (area under the curve = 0.71). A 1-unit increase in body mass index increased the risk of moderate/severe AKI by 7% (odds ratio = 1.07; 95% confidence interval: 1.03-1.11); a prior sternotomy increased the risk more than 3-fold (odds ratio = 3.4; 95% confidence interval: 1.84-6.43). The group of patients with moderate/severe AKI had higher rates of respiratory failure and death than the group of patients with mild/no AKI. Patients with moderate/severe AKI were at 3.2 (95% confidence interval: 1.2-8.2) times the risk of 30-day mortality compared to those without. Even after adjusting for age and Interagency Registry for Mechanically Assisted Circulatory Support profile, those with moderate/severe AKI had 1.75 (95% confidence interval: 1.03-3.0) times the risk of 1-year mortality compared to those without. DISCUSSION: Risk-stratifying patients prior to LVAD placement in regard to AKI development may be a step toward improving surgical outcomes.

A Direct Aspiration First Pass Technique for Mechanical Thrombectomy in the Setting of a Suspected Cerebral Aneurysm.

There is little guidance in the literature on which thrombectomy technique is preferred in patients with acute ischemic stroke and concomitant aneurysms. Here, we present the case of a 58-year-old female with an acute ischemic stroke requiring emergent thrombectomy that was complicated by the presence of multiple, nonruptured intracranial aneurysms. Imaging confirmed an occlusion of the right middle cerebral artery and multiple nonruptured intracranial aneurysms. The patient was administered intravenous recombinant tissue plasminogen activator and the thrombus was aspirated via a direct aspiration first pass technique (ADAPT). Her symptoms improved significantly postoperatively with a consequent National Institutes of Health Stroke Scale (NIHSS) score of 0. The purpose of this case report is to give an overview and compare various techniques that can help guide the physician for safe, early revascularization while reducing recanalization time in patients having an ischemic stroke who also harbor intracranial aneurysms.

Ameliorative effect of ursolic acid on renal fibrosis in adenine-induced chronic kidney disease in rats.

Ursolic acid (UA), an ursane-type pentacyclic triterpenoid commonly found in apple peels and holy basil has been shown to possess many beneficial effects. Renal fibrosis is a complication of kidney injury and associated with increased risk of morbidity and mortality. In our previous investigation, a lupane-type pentacyclic triterpenoid, betulinic acid (BA) was found to have protective effect on chronic kidney disease (CKD) and renal fibrosis. This prompted us to explore the therapeutic value of UA, a chemically related compound to BA in CKD. CKD was induced by feeding adenine with the feed at a concentration of 0.75% for 28 days. UA at the dose rate of 30 mg/kg in 0.5% carboxy methyl cellulose (CMC) was administered by oral route, simultaneously with adenine feeding for 28 days. Adenine feeding increased the kidney weight to body weight index, decreased the kidney function due to injury as indicated by increased markers like serum urea, uric acid, creatinine, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) and initiated the fibrotic response in kidney by increasing the profibrotic proteins viz. transforming growth factor-beta (TGF-ß), connective tissue growth factor (CTGF), fibronectin and collagen. However, treatment with UA reversed the damage induced by adenine as shown by reduced kidney injury and fibrosis markers which was further clearly evident in histological picture indicating the suitability of UA for use in CKD.

Preoperative Embolization in Tandem with Surgical Resection for Cerebral Arteriovenous Malformations.

A number of treatment options are available for cerebral arteriovenous malformations (AVMs) including surgical resection, stereotactic radiosurgery, and endovascular embolization. Endovascular embolization may be used pre-operatively to reduce the size of large AVMs and thus reduce surgical complications. Here we present two patients who successfully underwent preoperative embolization of their AVMs and subsequent surgery. Preoperative embolization is a viable option for AVMs to reduce complications and improve patient outcomes.

Repeat Cardiac Transplant Indicated by Severe Cardiac Allograft Vasculopathy in a Patient With Danon Disease.

Danon disease is a rare, X-linked dominant, lysosomal storage disorder, presenting with cardiomyopathy mostly in adolescent men. Male patients face a high mortality rate and rarely live to the age of 25 years unless they receive a heart transplant. Because they generally undergo heart transplantation at a young age, many patients ultimately face both short- and long-term complications. We present a 32-year-old man diagnosed with Danon disease; a nonsense mutation in the LAMP-2 gene. Progressive heart failure symptoms resulted in initial heart transplant at age 27 years. He subsequently developed severe cardiac allograft vasculopathy that led to graft failure requiring a redo orthotopic heart transplant. This is one of only two reported Danon disease cases described to date surviving repeat orthotopic heart transplants. We present this case to highlight the importance of heart transplantation in the management of Danon disease, to emphasize the risk of cardiac allograft vasculopathy post-transplant, and to discuss management strategies.

Percutaneous Vertebral Artery Access for Embolization of Cerebrovascular Disease: Illustrative Case and Operative Technique.

Intracranial arteriovenous malformations can be further complicated by the development of aneurysms, which themselves carry the risk of rupture and hemorrhage. New endovascular techniques allow for more treatment options for these lesions in the setting of arteriovenous malformations. Here we present the case of a patient who developed an aneurysm in the setting of an arteriovenous malformation and subsequently underwent successful endovascular treatment via percutaneous access of the vertebral artery along with reviewing the literature on further treatment options and developments.

Mycotic Pseudoaneurysm Associated with Skull Base Osteomyelitis Treated with Endovascular Embolization.

Pseudoaneurysms occur due to malformations in arterial wall uniformity, leading to blood collection between the outer arterial layers and resultant outpouching of the vessel. Unlike true aneurysms, pseudoaneurysms do not involve all layers of the blood vessel. Mycotic pseudoaneurysms can occur after associated vessel adventitia infection, leading to transmural dissection. Here we present a case of a 78-year-old man with a history of chronic otitis externa and osteomyelitis who presented with increasing right ear pain with bloody discharge and associated headache. Catheter angiography demonstrated a large pseudoaneurysm in the right middle meningeal artery (MMA) at the base of the skull. Based on the clinical findings and the patient's history, the patient was ultimately diagnosed with mycotic pseudoaneurysms of the MMA. The patient was subsequently treated with antibiotics as well as endovascular embolization and recovered without any complications.

Intracranial Ischemic Infarct Due to Blunt Force Trauma in a High School Football Player.

Ischemic stroke is an uncommon cause of death among teenagers and young adults; however, the etiologies differ when compared to ischemic strokes in older individuals. Large-vessel atherosclerosis and small-vessel disease causing ischemic stroke are rare for the teenage population, while cervicocerebral arterial dissections account for up to 20% of ischemic strokes. Here, we present the case of a 16-year-old male who developed internal carotid artery dissection (ICAD) after a head injury and subsequently developed ischemic stroke and seizures.

To Stent or Not to Stent: A Tale of Two Occlusions.

Stenting and balloon angioplasty, along with mechanical thrombectomy, have gained notability as adjunctive treatment options to intravenous tissue plasminogen activator (IV-tPA) for tandem internal carotid artery (ICA) and middle cerebral artery (MCA) occlusions (TIM occlusions). Acute ischemic strokes (AISs) secondary to TIM occlusions are associated with poor patient outcomes primarily due to low recanalization rates following intravenous thrombolysis, consequently prompting the need for more invasive recanalization efforts. Often, the treatment algorithm is based on the success of the initial angioplasty, suspected volume of completed infarction, and whether or not thrombolytics are utilized. Here, we present two patients with AIS due to TIM occlusions where two different treatment modalities were implemented for recanalization efforts. Patient 1 did not receive IV-tPA and was successfully managed with balloon angioplasty and subsequent carotid stenting followed by direct oral anticoagulant (DOAC) administration. Patient 2 received IV-tPA and balloon angioplasty without carotid stenting followed by intracranial mechanical thrombectomy. Complete recanalization was attained in both cases. Administration of IV-tPA can make subsequent carotid stenting a potentially higher-risk treatment option for patients with TIM due to potential hemorrhagic complications in the setting of requisite antiplatelet agents. Each case of AIS resulting from a TIM must be considered unique, and the use of IV thrombolytics, balloon angioplasty, carotid stenting, and mechanical thrombectomy alone or in combination must be tailored to the individual clinical parameters.

The Importance of Catheter Angiography in Computed Tomography Angiography-Negative Subarachnoid Hemorrhage.

Computed tomography angiography (CTA) has become an effective tool in the evaluation of patients with subarachnoid hemorrhage (SAH), but it still has limitations. Up to 15% of non-traumatic SAH cases are negative on CTA. The benefits of catheter angiography in the evaluation of certain cases of CTA-negative SAH have been previously demonstrated. Here, we present the case of a 48-year-old female who presented with headache and right-sided hemiparesis, who later became apneic and required intubation. A computed tomography (CT) scan of the head demonstrated a diffuse SAH. A CTA of the head and neck showed no vascular abnormality. Catheter angiography diagnosed a conical-shaped aneurysm at the left A1-A2 junction of the anterior communicating artery complex measuring 3.5 mm by 1 mm. The aneurysm was successfully treated with a craniotomy and microvascular clipping using a 4.7 mm curved Yasargil miniclip (Aesculap, Tuttlingen, Germany). This case illustrates the importance and benefit of catheter angiography in CTA-negative cases of SAH.

Delayed Endovascular Stenting for Severe Vertebral Artery Stenosis with Precarious Thrombosis.

A significant but less recognized cause of ischemic stroke and transient ischemic attack (TIA) is atherosclerosis of the vertebrobasilar system, which accounts for 20% of ischemic strokes. Pathology of the vertebrobasilar system can present significant challenges in determining the course of treatment. Due to the complexity of the vertebrobasilar system, there is slight disagreement about how to approach patients with atherosclerotic pathology of the posterior circulation. Two such approaches are either stenting of the vertebral or basilar artery or aggressive medical management. Here, we present the case of a 63-year-old male who presented with lightheadedness, diaphoresis, two episodes of loss of consciousness, and the abrupt onset of unilateral right-sided paresis. A computed tomography angiogram (CTA) of the head and neck demonstrated complex posterior circulation vertebrobasilar vascular stenosis and occlusions. There was an unstable clot located at the junction of the vertebral and basilar arteries requiring a carefully nuanced approach. The patient was started on dual antiplatelet therapy and heparin in an effort to resolve the clot. Repeat CTA after five days revealed resolution of the unstable clot; however, the distal intradural right vertebral artery remained occluded and the left vertebral artery remained stenosed. The patient was then treated with a balloon-mounted coronary stent to eliminate the stenosis, which ultimately restored normal posterior fossa flow dynamics. This case serves as a testament to the variability and complexity of vertebrobasilar arteriopathies as well as the benefit of experienced neurointerventionalists in the successful management of these cases.

Large Transcalvarial Meningioma: Surgical Resection Aided by Preoperative Embolization.

Meningiomas are the most common type of primary brain tumors, accounting for about 30% of all brain tumors. Meningiomas originate from the meninges and can be associated with any part of the skull. Classification of meningiomas is based upon the World Health Organization (WHO) classification system and prognosis of meningiomas can be determined via histologic grading. Surgery is the gold standard treatment option for all types of meningiomas. Due to the high vascularity of some meningiomas, surgical resection can lead to certain complications including intraoperative blood loss and hemorrhage. Strategies for complication avoidance include preoperative embolization of the meningioma vascular supply. Preoperative embolization has been shown to assist in surgical resection of selected tumors and decrease intraoperative blood loss. We present a case of successful preoperative embolization for a large, complex, transcalvarial meningioma along with a literature review on this topic.