Toxicities of CAR T-cell therapy: a review of current literature.

The chimeric antigen receptor (CAR) design, first invented by Zelig Eshhar, paved the way for the use of genetically modified T-cells in targeted therapy against cancer cells. Since then, it has gone through many generations, especially with the integration of co-stimulation in the second and third-generation CARs. However, it also mounts a hyperactive immune response named as cytokine release syndrome with the release of several cytokines eventually resulting in multiple end-organ toxicities. The severity of cytokine release syndrome depends upon certain factors such as the tumor burden, choice of co-stimulation, and degree of lymphodepletion, and can manifest as pulmonary edema, vascular leak, renal dysfunction, cardiac problems, hepatic failure, and coagulopathy. Many grading criteria have been used to define these clinical manifestations but they lack harmonization. Neurotoxicity has also been significantly associated with CAR T-cell therapy but it has not been studied much in previous literature. This review aims to provide a comprehensive account of the clinical manifestations, diagnosis, management, and treatment of CAR T-cell associated neurotoxicity.

Plasma random glucose levels at hospital admission predicting worse outcomes in STEMI patients undergoing PCI: A case series.

Background: The effects of impaired plasma glucose levels on predicting clinical outcomes and in-hospital events in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) is unknown. Therefore, we evaluated random blood glucose at admission and its association with clinical outcomes in STEMI patients treated with PCI. Methods: Patients with STEMI undergoing PCI were enrolled and were divided into 4 tertiles according to random blood glucose levels. Tertile 1 had levels below 100 mg/dL, tertile 2 had 100-200 mg/dL, tertile 3 had 200-300 mg/dL, and tertile 4 had random blood glucose levels >300 mg/dL. The cumulative rates of in-hospital mortality and major adverse cardiovascular events were calculated. Results: Both the incidence of all-cause deaths and cumulative rates of major adverse cardiovascular events were significantly the lowest in patients within tertile 1. The cumulative incidence of in-hospital events was 14.3% in tertile 1, 17.6% in tertile 2, 23.5% in tertile 3, and 30.8% in tertile 4. The odds ratio of major adverse cardiovascular events was 1.286 [0.397-4.161] in tertile 2, 1.846 [0.492-6.927] in tertile 3, and 2.667 [0.693-10.254] in tertile 4. The cumulative proportion of adverse events was seen higher in tertile 4 on Kaplan-Meier log-rank (chi-square: 8.094, p = 0.044). Conclusion: Poor glycemic control or stress hyperglycemia on admission experienced the highest rates of major adverse cardiovascular events including deaths. Plasma random glucose was predictive of a worse prognosis for STEMI patients undergoing PCI in our study.

COVID-19 infection among pregnant and non-pregnant women: Comparison of biochemical markers and outcomes during COVID-19 pandemic, A retrospective cohort study.

Background: & Objectives: We conducted this single-centered retrospective study including female patients infected with COVID-19 with aim to compare laboratory findings and the outcomes between pregnant and non-pregnant women infected with COVID-19. Previous data rendered pregnant women as vulnerable population for COVID-19. Methods: We included 131 patients in our analysis out of which 60 were pregnant females and rest 71 were non-pregnant females. Results: Factors like fatigue, total leukocyte count (TLC) and neutrophils were higher in pregnant patients, while mean age, fever, hemoglobin, ferritin, D-dimer and use of mechanical ventilation was lower in pregnant patients as compared to non-pregnant females. Conclusion: Our study concluded that COVID-19 do not show significant high risk of disease severity when compared with non-pregnant females of similar age group.

Phosphorus Nutrient Management through Synchronization of Application Methods and Rates in Wheat and Maize Crops.

Management of inorganic fertilizer is very important to obtain maximum crop yield and improved nutrient use efficiency in cereal crops. Fixation of phosphatic fertilizers in alkaline soils due to calcareousness is one of the major hurdles. It induces phosphorus nutritional stress that can decrease the yield of maize and wheat. Selection of a suitable application method and proper stage of crop for phosphorus (P) fertilizer has prime importance in better uptake of P and crop production. Among different application methods, soil and foliar application are widely adopted. In wheat and maize, knee height + tasseling and stem elongation + booting are critical stages towards P deficiency. That is why field trials were conducted to evaluate the supplemental effect of foliar P on maize and wheat yields. For that, 144 mM KH2PO4 was applied as foliar at knee height + tasseling and stem elongation + boot stages in maize and wheat, respectively. Soil application of 0, 20, 40 and 60 kg P ha-1 was done through broadcast and band methods. Results showed that foliar spray of 144 mM KH2PO4 at knee height + tasseling and stem elongation + boot stages in wheat and maize significantly enhanced grains yield and phosphorus use efficiency (PUE) where P was applied as banding or broadcast at the time of sowing. A significant decreasing trend in response to increasing soil P levels validated the efficacious role and suitability of foliar P. In conclusion, the use of P as foliar at knee height + tasseling and stem elongation + boot stages is an efficacious way to manage P fertilizer.

Some Physiological and Biochemical Mechanisms during Seed-to-Seedling Transition in Tomato as Influenced by Garlic Allelochemicals.

The effects of aqueous garlic extracts (AGEs), diallyl disulfide (DADS), and allicin (AAS) were investigated during seed-to-seedling transition of tomato. Independent bioassays were performed including seed priming with AGE (0, 100, and 200 µg∙mL-1), germination under the allelochemical influence of AGE, DADS, and AAS, and germination under volatile application of AGE. Noticeable differences in germination indices and seedling growth (particularly root growth and fresh weights) were observed in a dose-dependent manner. When germinated under 50 mM NaCl, seeds primed with AGE exhibited induced defense via antioxidant enzyme activities (superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)), lipid peroxidation (malondialdehyde content (MDA)), and H2O2 scavenging. Enzyme-linked immunosorbent analysis (ELISA) of the endogenous phytohormones auxin (IAA), abscisic acid (ABA), cytokinin (ZR), and gibberellic acid (GA3) in the roots and shoots of the obtained seedlings and the relative expression levels of auxin-responsive protein (IAA2), like-auxin (LAX5), mitogen-activated protein kinase (MAPK7 and MPK2), respiratory burst oxidase homolog (RBOH1), CHI3 and SODCC1 suggested allelopathic functions in stimulating growth responses. Our findings suggest that garlic allelochemicals act as plant biostimulants to enhance auxin biosynthesis and transportation, resulting in root growth promotion. Additionally, the relative expressions of defense-related genes, antioxidant enzymes activities and phytohormonal regulations indicate activation of the defense responses in tomato seedlings resulting in better growth and development. These results, thus, provide a basis to understand the biological functions of garlic allelochemicals from the induced resistance perspective in plants.

Root order-based traits of Manchurian walnut & larch and their plasticity under interspecific competition.

Manchurian walnut and larch are key timber species of northeast China but information on (fine) root traits of both species is scarce. Plasticity of root traits in mixed plantations has been studied rarely although this could give important insights into mechanisms of root competition. This study examined root traits by branching order in 30-yr-old monocultures and their plasticity in mixed plantations. In monocultures, Manchurian walnut and larch differed in key fine root traits. Larch roots hold more absorptive root orders, larger diameter and lower specific root length/area. Walnut root orders featured greater cortex:stele ratios, N-concentrations and respiration rates. Under interspecific competition, the proportion of walnut root tips increased, the biomass/length of larch root orders 1-3 decreased. Larch possessed a greater morphological and anatomical plasticity of terminal root orders than walnut. Mycorrhizal colonization rates of walnut were reduced. Both species differed fundamentally in their fine root properties. Absorptive fine root orders reacted plastic under interspecific competition while traits of higher root orders remained unchanged. In mixture, larch roots possessed a greater plasticity in traits related to resource uptake (efficiency) than walnut roots whose reaction norm is suggested to be predominantly based on interference competition via juglone exudation.

Investigation of Staphylococcus aureus, prevailing in the environment of Khyber Teaching Hospital, Peshawar, Pakistan.

The hospital environment plays an important role in the spread of microorganisms, including multi drug resistant (MDR) strains. Patients can acquire Methicillin-Resistant Staphylococcus aureus (MRSA) which can reside in the clinical setup that are not cleaned and can spread through air droplets, bed clothing, and healthcare workers. The purpose of this study was to investigate the prevalence of S. aureus in the Khyber Teaching Hospital (KTH). A total of 200 samples were collected from the floor, walls, air and inanimate objects in different wards of the KTH, during May 2012 to September 2012. These samples were screened for the recovery of S. aureus. Recovered organisms were subjected to susceptibility testing and investigated for the detection of various toxin and antibiotic resistance genes by Polymerase Chain Reaction (PCR). A total of 64 samples yielded S. aureus, out of which 37 (57.81%) were proved as MRSA. No isolate was found resistant to Vancomycin, however 81.25% of the isolates were found susceptible to Linezolid and Amikacin. The susceptibility to Fusidic acid, Chloramphenicol, Rifampicin, Doxycycline and Meropenem was observed as 79.69%, 76.56%, 75.00, 73.44% and 68.75% respectively. The frequency of sea, seb and sec genes were 56.25%, 43.75% and 12.5% in the recovered isolates. Erm C was more prevalent (28.12 %) than the ermA and ermB. The prevalence of pvl in MRSA was 21.62 % which is less than 33.33% in the MSSA isolates. S. aureus and especially MRSA are frequently prevalent in the KTH. Therefore, every immune-compromised patient is prone to infections caused by S. aureus. This will lead to high morbidity/mortality rate, prolong hospital stay and add extra cost to the health system.

Potential drug-drug interactions in medical intensive care unit of a tertiary care hospital in Pakistan.

Background Patients admitted to intensive care unit (ICU) present with severe and life-threatening illnesses. Most of them suffer from various comorbidities. They usually receive complex pharmacotherapy with large number of medicines which increase the risk of drug-drug interactions (DDIs). Objective The present report aimed to investigate prevalence and levels of potential DDIs (pDDIs) in medical ICU. Methods Medications profiles of 416 patients were checked for pDDIs using Micromedex Drug-Reax(®). Prevalence, levels of severity and levels of documentation were reported. Results Of total 416 patients, 310 were exposed to pDDIs (overall prevalence = 74.5 %). Likewise, a prevalence rate of 13.9 % was recorded for contraindicated pDDIs, 52.2 % for major pDDI and 58.4 % for moderate pDDI. This study reported 740 interacting drug pairs that were presented in total 1686 pDDIs. Of 1686 pDDIs, 4.3 % were of contraindicated severity, 33.8 % of major severity and 49.6 % of moderate severity, whereas 45.5 % were of fair scientific evidence and 41.4 % of good scientific evidence. Conclusion In this study, pDDIs were found highly prevalent in ICU patients at a rate of 74.5 %. Most of the pDDIs had moderate severity; however, substantial number of interactions (38.1 %) had major and contraindicated severity.

New cholinesterase inhibitory constituents from Lonicera quinquelocularis.

A phytochemical investigation on the ethyl acetate soluble fraction of Lonicera quinquelocularis (whole plant) led to the first time isolation of one new phthalate; bis(7-acetoxy-2-ethyl-5-methylheptyl) phthalate (3) and two new benzoates; neopentyl-4-ethoxy-3, 5-bis (3-methyl-2-butenyl benzoate (4) and neopentyl-4-hydroxy-3, 5-bis (3-methyl-2-butenyl benzoate (5) along with two known compounds bis (2-ethylhexyl phthalate (1) and dioctyl phthalate (2). Their structures were established on the basis of spectroscopic analysis and by comparison with available data in the literature. All the compounds (1-5) were tested for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities in dose dependent manner. The IC50 (50% inhibitory effect) values of compounds 3 and 5 against AChE were 1.65 and 3.43 µM while the values obtained against BChE were 5.98 and 9.84 µM respectively. Compounds 2 and 4 showed weak inhibition profile.

Antibacterial, Antifungal, Cytotoxic, Phytotoxic, Insecticidal, and Enzyme Inhibitory Activities of Geranium wallichianum.

The present study describes the phytochemical investigations of the crude extracts of rhizomes and leaves of Geranium wallichianum. The crude extracts were fractionated to obtain n-hexane, ethyl acetate, and n-butanol fractions, which were subjected to different biological activities and enzyme inhibition assays to explore the therapeutic potential of this medicinally important herb. The results indicated that the crude extracts and different fractions of rhizomes and leaves showed varied degree of antimicrobial activities and enzyme inhibitions in different assays. Overall, the rhizome extract and its different fractions showed comparatively better activities in various assays. Furthermore, the purified constituents from the repeated chromatographic separations were also subjected to enzyme inhibition studies against three different enzymes. The results of these studies showed that lipoxygenase enzyme was significantly inhibited as compared to urease. In case of chemical constituents, the sterols (2-4) showed no inhibition, while ursolic acid (1) and benzoic ester (6) showed significant inhibition of urease enzymes.

Isolation of medical students: communication barrier and its effect on career.

BACKGROUND: Communication barriers affect student-student interaction and student-patient interaction. This study is aimed at exploring the social, cultural and academic spheres where medical students feel getting isolated. METHOD: Questionnaire based cross-sectional survey was undertaken at Ayub Medical College, Abbottabad in the month of July, 2013. Cluster sampling technique was employed. RESULTS: Linguistic problems in the college greatly affected medical students. Female medical student are comparatively more affected. These problems were less common in 1st year and most common in 3rd year where clinical classes are started. There are distinct gender based problems in communicating among male and female student with as many as 37.2% reported feeling difficulty in communicating with students of opposite gender. However this difficulty in communication gradually faded on proceeding from 1st year towards final year. About frank interaction with opposite gender, 65.9% students felt that society had negative impact upon it. While communicating with patients of opposite gender, almost a quarter of students (27.3%) reported facing difficulties, 56.9% students reported to have abject apathy towards the colleagues of opposite gender. CONCLUSION: Linguistic issues, gender discrimination, negative impact of society and lack of concern for fellow colleagues is affecting student-student interaction and student-patient interaction. There is need to create student friendly environment.