Based on adverse effects of biosimilar(s), for oncological treatment modalities (radiation/chemotherapy), posted in FAERS and VigiBase, an effort has been made to derive a temporal correlation between CLS and hemodynamic (Fluid dynamic/mechanics properties) dysregulation lead exacerbated mortality rate in NCT01663701. Idiopathic (unknown etiology) systemic capillary leak syndrome (SCLS) or Capillary leak syndrome (CLS), also known as vascular leak syndrome (VLS), with clinical features such as leakage of the plasma (reversible plasma extravasation with fluid resuscitation), vascular collapse accompanied by a classic triad of hypoalbuminemia, hemoconcentration, and hypotension in the absence of secondary causes of shock with edema. Fluid management is an effective clinical management strategy for an improved prognosis (verbatim in part and modified from J Clin Med. 2018; seven (11); J Clin Med. 2019; 8(2)). The clinical presentation of CLS with a corollary of Virchow’s triad ( https://www.ncbi.nlm.nih.gov/books/NBK539697/) and the critical events for a laminar to turbulence transition ( ELTT) is systematically correlated. Virchow’s triad I ‐ Endothelial damage:ELTT 1. Region of instability of small wavy disturbances called Tollmien‐Schlichting wave ELTT 2. Periodicity accompanied by the appearance of vortices ELTT 3. Peak‐Valley development in vortices, ELTT 4. Vorticity concentration and shear layer development with inflectional profile appearance and disappearance in Tollmien‐Schlichting wave pattern, Virchow’s triad II ‐ Venous stasis: ELTT 5. Breakdown: evolution of a staggered vortex pattern twice the wavelength of Tollmien‐Schlichting waves ( a high frequency fluctuations of hairpin eddies ‐ eddy currents, disrupts the laminar flow of blood, bringing platelets in close contact with the vascular wallVirchow’s triad III ‐ Hypercoagulability: ELTT 6. Cascading of vortices and turbulent‐spot development, (spots of thrombus lead to increased turbulence thus reduction in blood flow. Infarction and ischemia Thrombi often result in reduced blood flow to tissue (ischemia) or complete obstruction (absolute irreversible stasis NFP=0 mmHG, ?) of blood flow leading to cell death(infarction) with concurrent impairment of global net filtration pressure (NFP) in mark transition of laminar to turbulent flow pattern. Taken together, herewith it is suggested that a better understanding of the components of multifactorial mode of turbulence modelling in particular on time scale, blood viscosity, velocity profile, NFP gradient, and structural integrity of blood vessels (endothelial damage) of the capillary bed in the context of thromboembolic events [DDx: ischemic stroke(CVA), disseminated intravascular coagulation (DIC), deep vein thrombosis (DVT), pulmonary embolism and CLS], would enable better stratification of clinical risk factors, precision in clinical decision making amalgamating differential diagnosis for an accurate prognosis in early resuscitation protocol on sepsis such as NCT01663701. Support or Funding Information...
The agrarian community of the Texas Department of State Health Services Region 8 (TXHSR8) is subjected to exposure to a variety of risk factors causing susceptibility to infectious disease such as a. Socioeconomic disparities in access to the reasonable antibiotics and preventive medicine, b. Low wind flow induced spread of antibiotic resistance genes across the region, c. Wastewater storage from the fracking sites across the HSR8, d. Waterborne infectious diseases from Rio Grande River basin, e. Multinational without appropriate health check, delivering babies in the regional healthcare facilities, f. annual migrant worker flow across the region to northern prairies and repatriation: 4,241 migrants / 2017–18 fiscal year, g. Floating population across the U.S – Mexico border crossing: Weekly border crossings average 72,900, adding 150,000 people to the Eagle Pass‐Piedras Negras population, h. Live stocks shipment across the border from Mexico to the United States, i. Produce / Processed food shipment across the U.S – Mexico border crossing: ex: approximately 119, 000 – 145,000 trucks, estimated 5.8 million pounds of produce per annum, j. vector‐borne disease, and k. Multinational workforce crossing across the U.S‐Mexico. As per the McDonald–Kreitman test, using a two‐way contingency table, where Ds = the number of synonymous substitutions per gene, Dn = the number of non‐synonymous substitutions per gene, Ps = the number of synonymous polymorphisms per gene, Pn = the number of non‐synonymous polymorphisms per gene, applying the selection pressure imparted by aforesaid factors affecting agrarian community of TXHSR8, we predict that Dn/Ds > Pn/Ps less variation within the population but significant difference between rest of the community implying a divergence and a positive selection also referred to as directional selection. Applying the preceding contributing factors to determine the beneficial effect of the mutation that Ka/Ks ratio would be significantly above one indication that selects few mutations would be helpful for the survival of the agrarian community. Taken together, it is suggested that factors above play a significant role in ‘Genetic Drift” (flow of genes across the population) through mutation. Subsequently, the agrarian community is better adapted in responding to the changes impinging upon the gene pool that would be the best fit for the survival. As per “Cladistics” agrarian community –TXHSR8 represent a “paraphyletic clade” with “shared derived character” unique to this particular clade. Evolutionary factors such as “Maximum parsimony” assumes that the agrarian community –TXHSR8 that requires the fewest evolutionary events would have maximum likelihood alteration in antibiotic resistance genes (ARG). Evolutionary factors such as “Maximum parsimony” assumes that the agrarian community –TXHSR8 that requires the fewest evolutionary events would have maximum likelihood alteration in ARG.Support or Funding InformationSupported by the Professional Development Funds by SWTJC to Subburaj KannanThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The mechanism(s) of biosimilar induced adverse clinical events in inflammatory disorders and its impact on the evolution of ARCP inherent on the incidence of morbidity and the mortality rate remains to be substantiated. A biosimilar to Neulasta (Pegfilgrastim) administered for myelosuppressive chemotherapy has been reported to have a clinically significant incidence of febrile neutropenia. Similar modalities with other biosimilars have also been presented (Int J Hematol.2010 Dec;92(5):765–8; Case Rep Nephrol Urol. 2012 Jul–Dec; 2(2): 165–171); The contraindication for the original formulation is reported to be acute respiratory distress syndrome (ARDS), Glomerulonephritis (GN), Leukocytosis, and Capillary Leak Syndrome (CLS). As per the differential diagnosis for the febrile neutropenia could be of acute respiratory distress syndrome (ARDS) with or without pulmonary edema. Under such clinical presentation tissue hypoxia (Stagnant anoxia (Hypoxicischemic injury), Anoxic anoxia?) with or without “Sweet Syndrome” with an unknown etiology waning the ventilation‐perfusion coupling in patients undergoing chemo/radiation therapy for clinical oncology modalities (J. Clin. Med. 2019, 8(2), 143). CLS has been ascribed with reversible plasma extravasation and loss of net filtration pressure gradient (NFP) in the microcirculation which is analogous to sepsis, septic shock, septicemia impelled hypotension possibly (hypovolemic shock?) with the end result of multiple organ failure (Kidney International, 2017: 92:1, 37). It is hypothesized that such clinical presentation of ensuing hypoxia (plausibly systemic anoxia?) causing VA/Q (VA = alveolar ventilation; Q= blood flow) is below normal which is about 2% of cardiac output (CO) referred to as “shunted blood” (deoxygenated). The total amount of “shunted blood” in the capillary bed – microcirculation per minute is “Physiological shunt” with dysregulated net filtration pressure (NFP) potentially a state of critical closing pressure (CCP) ebb the capillary exchange. Under such physiological sate declining perfusion pressure / perfusion index (PI) and tissue pO2 causing progressive hypoxia and/or anoxia. It is suggested that hypoxia serve as a trigger for generating an adverse pressure gradient impacting the expression pattern of antibiotic resistance gene(s) repertoire (ARCP). Altered ARGR expression profile is known to cause selection pressure on ARCP. In particular, ensuing anaerobic milieu in vivo, engender selection pressure on anaerobic AR pathogens including Gram negative rods, Gram‐positive cocci, Gram‐positive spore‐ and non‐spore‐forming bacilli and Gram‐negative cocci resulting in an aberrant expression pattern of ARGR. Taken together, such the clinical presentation would likely to lead to patients treated with biosimilar(s) become unresponsive to antibiotic therapy leading to an emergence of ARCP impairing the ability for clinical stratification and a defined point of clinical intervention preempting an instant CCP subsequent emergence Antibiotic Resistance Pandemic...
Based on the observations from the livestock show in the Maverick County, Texas, (MCJLS) (January 2006 to January 2017), and data analysis from the Texas Department of State Health Services, Health and Human Services (TDSHS‐HHS): Pertussis Emerging and Acute Infectious Disease Infectious Disease Control Unit (IDCU) and CDC, a prototype for “Transmission Model” conferring the herd protection (Herd Immunity) in combination with WASH interventions is presented here. Pertussis, a respiratory illness commonly known as whooping cough, is a contagious disease caused by Bordetella pertussis. The respiratory infection is spread via aerosol (in bacteria‐contaminated air droplets) from an infected person's cough or sneeze. Transmission often occurs from older family members to infants or children. Five doses of the DTaP vaccine, is recommended while protection gained from pertussis vaccines decline over time referred as “waning immunity.” To counter the decrease in immunity, a TDaP vaccine, a booster vaccine for tetanus and diphtheria with limited protection for pertussis. Here we present a hypothesis that immunity acquired through “community living inclusive of herd of livestock” (Herd) by the agrarian community mitigate the waning immunity there by confer the protection from the pertussis despite the observed antibiotic resistance observed across the nation and also emerging trend across the globe. Annually the MCJLS in Eagle Pass, Texas with over 300 youth exhibitors, presenting steers, goats, lambs, Hogs, and also chickens. Our observations and information gathered during the past ten years of the stock show could be best summarized as the proximity and duration of the exposure to the livestock animals and community (model) living represent the “WASH” interventions suggested in the transmission model for “Herd Immunity” (Am J Trop Med Hyg. 2016; 95(5):1201). Based on the Texas ‐ Pertussis Incidence Rates Maps by Year, Maverick County has relatively lowest pertussis incidence. Hypothetically, the scheduled DTap/TDap vaccinations conferred immunity weakens over the period of time would make the HSR8 susceptible for the pertussis which is contrary to the incidence report of TDSHS‐HHS‐IDCU. Furthermore, community living in HSR8 exemplifies the community model conferring cross protection among the agrarian community members, in addition to the protection from the scheduled pertussis immunization in combination with WASH interventions serve as a prototype for “Transmission Model” for “Herd Immunity”Support or Funding InformationSupported by the Professional Development Funds by SWTJC to Subburaj KannanThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Here we present the impact of migratory pattern on the AR. Our model for this investigation is MC‐TDSHSR8. This location for this study based on the following factors:Rate of border crossing by the residents of Mexico ‐ United States. Factors such as, the proportion of migrant individuals to the total number (before and after migration) of individuals in the population referred as migration ratio (M); the difference between the allelic (gene) frequencies (af) of the migrant individuals and that of the resident population into which migration has occurred are contributing factors altering the af. Migration ratio (m) in MC‐TDSHSR8 for 2016 is estimated as follows: m=M / (N+M) where M is the number of migrant individuals, and N is the number of individuals in population before migration. Maverick County population estimates, as of July 1, 2017, 58,216 while Foreign born persons, represent 33.1% and a variable number for migrants per annum. Thus, the Migration ratio (m): M=9,975; N=58,216; Solving for m= 9975 / 58,216+9975 = 0.146. If the frequency of allele a in the population before migration is Q0 (58,261); migrant individuals = Qm (9975) ; migration ratio = m(0.146); frequency after the migration = Q1, weighted average of the two frequencies Q0 and Qm (58216+9975)/2=34095.5; then Q1= Q0(1−m) +mQm . Thus, the amount of change in the value of q. represented by Q, due to migration in one generation will be: Dq = m (Qm − Q0) ; solving for Dq = 0.146 (9975–58216)= −7043. If the migration from a given population was recurrent, the rate of migration was the same in each generation (the migration ratio, m, had the same value), and migration occurred for n generation, would be:Dq =Qn − Qm=(1−m)n(Qo−Qm) or (1−m)n=(Qn − Qm) / (Q0 − Qm), where Qn is the value of Q after n generations of constant recurrent migration from the same population, n is the number of generations for which migration has taken place. However, the data on migrant workers were variable due to multitude of contributing factors dependent on the socioeconomic cultural family criteria. Given the incertitude of data on migrant workers, determining the Dq for gene frequency after given number of generation would be considered as erroneous. However, the trend on the impact of the migration ratio (m) as an evolutionary force or evolutionary factors in the alteration of ARG frequencies were solved as per Wright‐Fisher Model (WFM)– Migration represented as r+1: z(r+1)| z(r) ~Bin(2N, (1−m) x(r) +mxc. Addressing the multitude of evolutionary pressure on af of ARG, as a function of g:[0,1]→ [0,1], implying the alteration of sampling probability of binomial distribution presented in Equation: z(r+1)| z(r) ~Bin(2N, x(r)) yielding z(r+1)| z(r) ~Bin(2N, g(x(r)) implies that evolutionary pressures such as genetic drift, mutation and migration are linear in x, referred as General Linear Evolutionary Pressure Model.Support or Funding InformationSupported by Professional Development Funds to Subburaj KannanThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.