Application of Laser-Induced Acoustic Desorption for Molecular Rotational Resonance Spectroscopy.

Molecular Rotational Resonance (MRR) spectroscopy is a uniquely precise tool for the determination of molecular structures of volatile compounds in mixtures, as the characteristic rotational transition frequencies of a molecule are extremely sensitive to its 3D structure through the moments of inertia in a three-dimensional coordinate system. This enables identification of the compounds based on just a few parameters that can be calculated, as opposed to, for example, mass spectrometric data, which often require expert analysis of 10-20 different signals and the use of many standards/model compounds. This paper introduces a new sampling technique for MRR, laser-induced acoustic desorption (LIAD), to allow the vaporization of nonvolatile and thermally labile analytes without the need for excessive heating or derivatization. In this proof-of-concept study, LIAD was successfully coupled to an MRR instrument to conduct measurements on seven compounds with differing polarities, molecular weights, and melting and boiling points. Identification of three isomers in a mixture was also successfully performed using LIAD/MRR. Based on these results, LIAD/MRR is demonstrated to provide a powerful approach for the identification of nonvolatile and/or thermally labile analytes with molecular weights up to 600 Da in simple mixtures, which does not require the use of reference compounds. In the future, applications to more complex mixtures, such as those relevant to pharmaceutical research, and quantitative aspects of LIAD/MRR will be reported.

Genome-wide analysis reveals allelic variation and chromosome copy number variation in paromomycin-resistant Leishmania donovani.

In the absence of adequate diagnosis and treatment, leishmaniasis remains a major public health concern on a global scale. Drug resistance remains a key obstacle in controlling and eliminating visceral leishmaniasis. The therapeutic gap due to lack of target-specific medicine and vaccine can be minimized by obtaining parasite's genomic information. This study compared whole-genome sequence of paromomycin-resistant parasite (K133PMM) developed through in vitro adaptation and selection with sensitive Leishmania clinical isolate (K133WT). We found a large number of upstream and intergenic gene variations in K133PMM. There were 259 single nucleotide polymorphisms (SNPs), 187 insertion-deletion (InDels), and 546 copy number variations (CNVs) identified. Most of the genomic variations were found in the gene's upstream and non-coding regions. Ploidy estimation revealed chromosome 5 in tetrasomy and 6, 9, and 12 in trisomy, uniquely in K133PMM. These contain the genes for protein degradation, parasite motility, autophagy, cell cycle maintenance, and drug efflux membrane transporters. Furthermore, we also observed reduction in ploidy of chromosomes 15, 20, and 23, in the resistant parasite containing mostly the genes for hypothetical proteins and membrane transporters. We chronicled correlated genomic conversion and aneuploidy in parasites and hypothesize that this led to rapid evolutionary changes in response to drug induced pressure, which causes them to become resistant.

Wheat transcriptome profiling reveals abscisic and gibberellic acid treatments regulate early-stage phytohormone defense signaling, cell wall fortification, and metabolic switches following Fusarium graminearum-challenge.

BACKGROUND: Treatment of wheat with the phytohormones abscisic acid (ABA) and gibberellic acid (GA) has been shown to affect Fusarium head blight (FHB) disease severity. However, the molecular mechanisms underlying the elicited phenotypes remain unclear. Toward addressing this gap in our knowledge, global transcriptomic profiling was applied to the FHB-susceptible wheat cultivar 'Fielder' to map the regulatory responses effected upon treatment with ABA, an ABA receptor antagonist (AS6), or GA in the presence or absence of Fusarium graminearum (Fg) challenge. RESULTS: Spike treatments resulted in a total of 30,876 differentially expressed genes (DEGs) identified in 'Fielder' (26,004) and the Fg (4872) pathogen. Topology overlap and correlation analyses defined 9689 wheat DEGs as Fg-related across the treatments. Further enrichment analyses demonstrated that these included expression changes within 'Fielder' defense responses, cell structural metabolism, molecular transport, and membrane/lipid metabolism. Dysregulation of ABA and GA crosstalk arising from repression of 'Fielder' FUS3 was noted. As well, expression of a putative Fg ABA-biosynthetic cytochrome P450 was detected. The co-applied condition of Fg + ABA elicited further up-regulation of phytohormone biosynthesis, as well as SA and ET signaling pathways and cell wall/polyphenolic metabolism. In contrast, co-applied Fg + GA mainly suppressed phytohormone biosynthesis and signaling, while modulating primary and secondary metabolism and flowering. Unexpectedly, co-applied Fg + AS6 did not affect ABA biosynthesis or signaling, but rather elicited antagonistic responses tied to stress, phytohormone transport, and FHB disease-related genes. CONCLUSIONS: Observed exacerbation (misregulation) of classical defense mechanisms and cell wall fortifications upon ABA treatment are consistent with its ability to promote FHB severity and its proposed role as a fungal effector. In contrast, GA was found to modulate primary and secondary metabolism, suggesting a general metabolic shift underlying its reduction in FHB severity. While AS6 did not antagonize traditional ABA pathways, its impact on host defense and Fg responses imply potential for future investigation. Overall, by comparing these findings to those previously reported for four additional plant genotypes, an additive model of the wheat-Fg interaction is proposed in the context of phytohormone responses.

ABO blood group discrepancies among blood donors in Regional Blood Transfusion Centre GTB Hospital, Delhi, India.

BACKGROUND: Regional Blood Transfusion Centre (RBTC), GTB Hospital, Delhi is providing safe and quality blood to one third of Delhi population. A discrepancy exists when reactions in forward grouping do not match with reverse grouping or if the previous and current results do not match. AIM: To analyze ABO blood group discrepancies in an algorithmic manner, and to access the incidence and causes of ABO discrepancies among blood donors. MATERIAL AND METHODS: Retrospective data of blood donors with blood group discrepancies was recorded in Regional Blood Transfusion Centre (East) Delhi, during a period of 3years from January 2010 to May 2013. DiaMed-ID Card Micro Typing System using Gel Cards (Cressier sur Morat, Switzerland) were used for determination of the ABO/Rh blood groups combined with reverse grouping. A detailed serological workup of these cases was studied for recognition and resolution of the blood group discrepancy. RESULTS: Total number of donors during the study period were 104,010 (30,120; 31,117; 32,173 and 10,600 respectively). Blood group discrepancies were found in 51 cases (0.04%). There were 30 (58.8%) cases with low avidity anti-B Antibodies, 10 (19.6%) cases with weaker expression or subgroups of A, 2 (3.9%) cases with weaker expression or subgroups of B, 5(9.8%) cases with unexpected alloantibodies (Anti-N and Anti-M, Anti-Lea) and one(1.9%) case of Bombay blood group. In 3 cases, discrepancy could not be resolved and were referred to reference laboratory for confirmation by molecular analysis. The most frequent cause of discrepancy in forward grouping was found to be weak A or B antigen expressions and in reverse grouping decreased anti-B titers was most common. CONCLUSION: All discrepancies reported on ABO cell and serum grouping must be investigated further, so that correct blood group is reported, minimizing the chances of transfusion reaction. A note of caution should be mentioned on the blood group card to prevent ABO incompatibility in case of transfusion.

Prevalence of irregular red blood cell antibodies among healthy blood donors in Delhi population.

OBJECTIVES: To evaluate the prevalence of the anti-red blood cell antibodies among healthy blood donors. MATERIAL AND METHODS: Antibody screening of all voluntary blood donor serum was performed as routine immunohematological procedure. Positive sera were further investigated to identify the specificity of irregular erythrocyte antibody by commercially available red cell panel (ID-Dia Panel, Diamed-ID Microtyping System). RESULT: A total of 47,450 donors were screened for the presence of irregular erythrocyte antibodies. A total of forty-six donors showed presence of alloantibodies in their serum (46/47,450%, 0.09%), yielding a prevalence of 0.09%. Most frequent alloantibodies identified were of MNS blood group system. The results showed statistically a higher prevalence of RBC alloantibodies in females than in males. CONCLUSION: Screening for presence of alloantibodies in donor blood is important to provide compatible blood products and to avoid transfusion reactions.

The spectrum of microvascular patterns in adult diffuse glioma and their correlation with tumor grade.

BACKGROUND: Primary brain tumors constitute the leading cause of cancer-related mortality. Among them, adult diffuse gliomas are the most common type, affecting the cerebral hemispheres and displaying a diffuse infiltrative pattern of growth in the surrounding neuropil that accounts for about 80% of all primary intracranial tumors. The hallmark feature of gliomas is blood vessel proliferation, which plays an important role in tumor growth, tumor biological behavior, and disease outcome. High-grade gliomas exhibit increased vascularity, the worst prognosis, and lower survival rates. Several angiogenic receptors and factors are upregulated in glioblastomas and stimulate angiogenesis signaling pathways by means of activating oncogenes and/or down-regulating tumor-suppressor genes. Existing literature has emphasized that different microvascular patterns (MVPs) are displayed in different subtypes of adult diffuse gliomas. METHODS: We examined the distribution and biological characteristics of different MVPs in 50 patients with adult diffuse gliomas. Haematoxylin and eosin staining results, along with periodic acid-Schiff and CD34 dual-stained sections, were examined to assess the vascular patterns and correlate with different grades of diffuse glioma. RESULTS: The present observational study on adult diffuse glioma evaluated tumor grade and MVPs. Microvascular sprouting was the most common pattern, while a bizarre pattern (type 2) was associated with the presence of a high-grade glioma. Vascular mimicry was observed in 6% of cases, all of which were grade 4 gliomas. CONCLUSIONS: This study supplements the role of neo-angiogenesis and aberrant vasculature patterns in the grading and progression of adult diffuse gliomas, which can be future targets for planning treatment strategies.

Cytological Perspective in a Case of Doege-Potter Syndrome With Hypoinsulinemic Hypoglycemia.

Solitary fibrous tumor (SFT) of the lung is a rare mesenchymal neoplasm of uncertain histogenesis, unknown molecular features, and unpredictable clinical behavior, characterized by NAB2-STAT6 fusion. Hypoglycemia accompanying SFT (Doege-Potter syndrome) is an uncommon presentation. We present the cytomorphological features on biopsy imprint smears of a histopathologically confirmed case of SFT of the lung with an uncommon presentation. A 76-year-old non-smoker, non-alcoholic, and non-diabetic man presented with complaints of intermittent episodes of confusion with syncopal attacks (>10 episodes) for six months. The patient had no respiratory complaints and no history of weight loss. Laboratory investigations revealed fasting blood sugar of 38 mg/dl with low serum insulin and C-peptide levels. Physical examination revealed reduced air entry on the left side of the chest. Chest X-ray showed left-sided homogenous opacity. High-resolution computed tomography (HRCT) of the chest showed a large left-sided lung mass. A biopsy was performed. Biopsy imprint smears were cellular and showed tumor cells arranged in clusters and fragments with traversing capillaries displaying monomorphic pump to oval nuclei, fine granular evenly dispersed chromatin, regular nuclear membrane, inconspicuous nucleoli, and a moderate amount of wispy cytoplasm. Foci of intercellular hyaline stromal material were noted. A cytodiagnosis of low-grade mesenchymal neoplasm was made. Histopathology revealed a cellular tumor comprising tightly packed round to fusiform cells arranged around blood vessels with intervening thick collagen, positive for CD99, vimentin, BCL2, CD34, and STAT6 and negative for EMA, CK AE1/AE3, S100, TLE1, and SMA. Familiarity with cytomorphology plays a pivotal role in clinching an early diagnosis of this rare neoplasm of the lung, particularly in the setting of presentation with hypoglycemia.

Understanding Perioperative Acute Myocardial Ischemia Following Coronary Artery Bypass Grafting.

Surgical revascularization and coronary artery bypass grafting are often pursued as treatment for obstructive coronary artery disease. Despite trends of increased referrals for complex percutaneous coronary intervention, surgical revascularization often remains the standard of care for patients with multivessel or complex coronary artery disease. Myocardial ischemia during the perioperative and postoperative periods during coronary artery bypass grafting remains a challenge. Nuanced consideration is necessary to decide on interventions that include conservative management and percutaneous or repeat surgical revascularization.

Impact of COVID-19 outbreak on healthcare workers in a Tertiary Healthcare Center in India: a cross sectional study.

Numerous speculations have continually emerged, trying to explore the association between COVID-19 infection and a varied range of demographic and clinical factors. Frontline healthcare workers have been the primary group exposed to this infection, and there have been limited global research that examine this cohort. However, while there are a few large studies conducted on Indian healthcare professionals to investigate their potential risk and predisposing factors to COVID-19 infection, to our knowledge there are no studies evaluating the development of long COVID in this population. This cross-sectional study systematically utilized the demographic and clinical data of 3329 healthcare workers (HCW) from a tertiary hospital in India to gain significant insights into the associations between disease prevalence, severity of SARS-Cov-2 infection and long COVID. Most of the study population was found to be vaccinated (2,615, 78.5%), while 654 (19.65%) HCWs were found to be SARS-CoV-2 positive at least once. Of the infected HCWs, 75.1% (491) did not require hospitalization, whereas the rest were hospitalized for an average duration of 9 days. A total of 206 (6.19%) individuals were found to be suffering from long COVID. Persistent weakness/tiredness was the most experienced long-COVID symptom, while females (1.79, 1.25-2.57), individuals who consumed alcohol (1.85, 1.3-2.64) or had blood group B (1.9, 1.33-2.7) were at a significantly higher risk for developing long COVID.

Selective Quantification of Chemotropic Responses of Fusarium graminearum.

Chemotropism refers to the directional growth of a living organism toward a chemical stimulus. Molecular mechanisms underlying chemotropism of fungal pathogens have recently been enabled by advancements in biological chemotropic assays, with a particular focus on the roles of G-protein-coupled receptors and their plant-derived ligands in chemotropism. Here we describe in detail an assay that enables quantification of chemotropic responses of Fusarium graminearum, with variations recently reported for Fusarium oxysporum and Trichoderma atroviride.

Unusual Manifestation of Mercuric Chloride Poisoning as Intratubular Nephrocalcinosis - A Rare Case Report.

Mercuric chloride salts are highly toxic compounds that have been linked to suicidal or accidental poisoning. Because of their high solubility, mercuric chloride salts can cause acute tubular injury, corrosive effects in the gastrointestinal system, hematemesis and hematochezia, circulatory collapse, and death. Here, we report an unusual case of mercuric chloride poisoning in a 17-year-old girl who manifested with acute tubular necrosis in association with intratubular nephrocalcinosis and emphasize the role of hemodialysis in the patient's successful recovery.

Current challenges in treatment and management of spontaneous coronary artery dissection.

Though an infrequent cause of acute coronary syndrome, spontaneous coronary artery dissection is an increasingly recognized cardiovascular condition predominantly seen in middle-aged females. Its pathophysiology is defined by separation of coronary arterial wall layers which cause acute coronary syndrome-like presentations with relatively high recurrence rates. Overall, there is a lack of reported literature and understanding of the short- and long-term management for spontaneous coronary artery dissection. Therapeutic approaches include, but are not limited to, percutaneous coronary intervention, surgical revascularization, antithrombotic therapy, and beta-blocker therapy. There is a significant absence of randomized control trials to help guide both interventional and medical management for spontaneous coronary artery dissection. This review is aimed to review the current literature regarding risk factors and considerations for the short- and long-term management of spontaneous coronary artery dissection.

Spontaneous coronary artery dissection is a condition commonly found in middle-aged females with symptoms that mimic a traditional 'heart-attack.' The condition differs where it is without actual arterial blood clot formation within the coronary arteries. In general, spontaneous coronary artery dissection involves the tearing of certain layers within coronary artery walls causing the expansion of layers with bleeding in between, consequently causing arterial blockage. In general, there is a lack of consensus on therapeutic strategy for this condition given a limited amount of data. This review article expands on the current data regarding the management of spontaneous coronary artery dissection including interventional versus medical management. Despite being rare, this acute disease process can have significant implications; however, it has been found that a more conservative approach with close monitoring is generally recommended.

Aortopathy: Effects of Lipid-Lowering Therapy.

Aortopathies can be congenital or acquired. Aortic atherosclerosis, abdominal aortic aneurysm, and degenerative aortic stenosis are some of the major manifestations of acquired aortopathy. Dyslipidemia, an imbalance of plasma lipid levels, is strongly associated with common aortopathies. A relationship between abdominal aortic aneurysm, degenerative aortic stenosis, and dyslipidemia has been identified in the literature but finding effective preventive strategies has been challenging. Nevertheless, lipid-lowering therapy remains a mainstay of both treatment and prevention. In patients with aortic atheroma, statins were found to be protective through the review of this study. There is currently no place for statins in the treatment or prevention of disease progression in patients with calcific aortic stenosis. Their low cost, widespread availability, and strong safety profile tip the risk-to-benefit ratio toward statins for abdominal aortic aneurysms but more research is needed. A review of proprotein convertase subtilisin/kexin type 9 inhibitors may yield similar benefits for all aortopathy patients; however, those results are not yet available.

Commotio Cordis: A Comprehensive Review.

Commotio cordis is a rare, however, potentially fatal, cardiovascular phenomenon arising from direct chest wall trauma, causing sudden cardiac arrest and potentially death. It is primarily seen in young athletes who participate in contact and organized sports. Though debated, the cause of commotio cordis is believed to involve specific timing of chest impact during ventricular electrical activity leading to severe arrhythmic events. Due to sudden onset, the first step in management is immediate and effective basic life support with automated external defibrillation, followed by advanced cardiac life support. Future considerations should include secondary prevention measures such as protective padding in contact sports. It is paramount that clinicians are vigilant in recognizing potential cases of commotio cordis in the field and provide immediate care. This review consolidates the current understanding of commotio cordis, emphasizing the importance of awareness and early intervention. Future research is warranted, including retrospective and observational studies to identify high-risk patterns or trends associated with the condition.

Review and Key Takeaways of the 2021 Percutaneous Coronary Intervention Guidelines.

The 2021 Percutaneous Coronary Intervention guidelines completed by American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions provide a set of guidelines regarding revascularization strategies. With emphasis on equity of care, multidisciplinary heart team use, revascularization for acute coronary syndrome, and stable ischemic heart disease, the guidelines create a thorough framework with recommendations regarding therapeutic strategies. In this comprehensive review, our aim is to summarize the 2021 revascularization guidelines and analyze key points regarding each recommendation.

Bland Urine Sediment in a Child with Acute Kidney Injury.

Tubulointerstitial nephritis (TIN) or acute interstitial nephritis (AIN) is a renal lesion characterized by inflammatory infiltrate limited to the renal interstitium and tubules. Three-fourths of the cases are drug induced, other causes being systemic and autoimmune diseases, and infections. Various drugs have been implicated, the most common being antibiotics such as ß-lactams. Cephalosporins causing AIN have been reported uncommonly, particularly in children. Although renal biopsy confirms the diagnosis, urinalysis provides pertinent diagnostic clues against the backdrop of the clinico-laboratory profile. The presence of white blood cells, white cell casts, and red blood cells in urine sediment have been described in literature. However, a relatively normal urinalysis may be present in some cases and may pose a diagnostic challenge. We present a case of ceftriaxone-induced AIN in a child with bland urine sediment at initial presentation. To the best of our knowledge, this is the first report of ceftriaxone-induced AIN in the pediatric age group.

Dual antiplatelet therapy with concomitant anticoagulation: current perspectives on triple therapy.

Anticoagulation and antiplatelet therapy are individually mainstays of treatment for multiple cardiovascular conditions. Antiplatelet therapy, most commonly with dual agents, is vital in the setting of coronary artery disease with acute coronary syndrome requiring percutaneous coronary intervention to prevent in-stent complications. A multitude of cardiovascular conditions with increased thromboembolic risk also require anticoagulation, including atrial fibrillation, venous or arterial thrombosis, and prosthetic heart valves to name a few. There is often an overlap in comorbidities as our patient population ages and becomes more complex, frequently necessitating a combination of both anticoagulation and antiplatelet agents, known as "triple therapy". To reduce or treat thromboembolic disease states as well as reduce platelet aggregation for coronary stent protection, many patients are placed at an increased bleeding risk without compelling evidence of reduction in major adverse cardiac events. With this comprehensive review of the existing literature, we aim to analyse different strategies and durations of triple therapy medication regimens.

Role of Medicinal Plants in the Management of Inflammatory Disorders: An Overview.

Owing to the enhanced toxicity as well as consequences of allopathic medication, the research on herbal therapies is developing progressively. As a result, medicinal herbs are beginning to play a substantial role in the advancement of the dominant therapeutic medications. Since ancient times, the use of herbs has performed a vital part in human well-being as well in the invention of cutting-edge pharmaceuticals. Inflammation and related illnesses are a major health concern for the entire human population. Pain-inducing drugs including opiates, non-steroidal anti-inflammatory drugs, glucocorticoids, and corticosteroids have severe side effects and these therapies suffer from the recurrence of symptoms too after discontinuing the treatment. As a result, the diagnosis along with the advancement of medications with anti-inflammatory properties is the priority to conquer the drawbacks of the existing therapies. The present review article provides insight into the literature comprising promising phytochemicals from various medicinal plants tested through different model systems and employed for alleviating inflammation in several inflammatory disorders as well as clinical status of the herbal products.