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Impact of Intravenous Busulfan Pharmacokinetics on Safety in Pediatric Patients who have undergone Hematopoietic Stem Cell Transplant

Published on: 3rd December, 2024

Introduction: Busulfan (Bu)-based regimens are crucial for myeloablative conditioning in pediatric allogeneic stem cell transplantation. Despite its efficacy, Intravenous Bu has a narrow therapeutic index and variable pharmacodynamics especially in children, heightening the risk of adverse events. This study explores Bu dosing and related organ toxicities in pediatric patients at a tertiary center in Saudi Arabia.Methodology: This retrospective study at King Fahad Specialist Hospital in Dammam (KFSH-D), Saudi Arabia, included pediatric patients (≤16 years) treated with intravenous Bu before bone marrow transplantation from 2010 to 2022. Pharmacokinetic dose adjustments were based on AUC targets of 900-1350 µMol-min. Descriptive measures included mean, Standard Deviation (SD), median, minimum-maximum values, counts, and percentages. Statistical analyses used Kruskal-Wallis, Chi-square, and Fisher’s exact tests. Ethical approval was obtained from KFSH-D.Results: We identified 44 pediatric patients who underwent Bu prior to HSCT. Mean age was 4.95 ± 2.49 years, with a female majority (56.8%). Primary diseases included Beta Thalassemia (34.09%), Neuroblastoma (29.55%) among others. There was no significant difference in the cohort’s demographic and clinical features of the cohort. Nonetheless, higher infections were found in the Low-AUC group (66.7%) compared to the Target-AUC (40.0%) and Higher-AUC groups (0.0%) (p = 0.015).Conclusion: This study emphasizes the need for therapeutic drug monitoring and individualized Bu dosing in pediatric HSCT to minimize toxicity and improve outcomes. Larger multicenter studies are recommended to refine dosing strategies and enhance the safety and efficacy of Bu-based regimens.
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European Clinical Laboratory, Molecular and Pathological (ECMP) criteria for prefibrotic JAK2V617F-Thrombocythemia and Polycythemia Vera versus MPL515- and CALR-Thrombocythemia and Myelofibrosis: From Dameshek to Michiels 1950-2018

Published on: 1st March, 2019

OCLC Number/Unique Identifier: 8056299472

The broad spectrum of heterozygous versus homozygous JAK2V617F mutated MPN consists ET, ET with early features of PV (prodromal PV), classical PV, masked PV, advanced PV and post-PV myelofibrosis. Combined use of bone marrow histology and increased erythrocyte counts above 5.8x1012/L can replace increased red cell mass at time of presentation as the pathognomonic clue for the correct diagnosis of hetero/homozygous or homozygous mutated PV. Erythrocyte counts are in the normal range below 5.8x1012/L in heterozygous JAK2V617F mutated ET and prodromal PV but above 5.8x1012/L in heterozygous-homozygous or homozygous mutated PV. The bone marrow cellularity and morphology in pre-fibrotic ET, prodromal PV and PV carrying the JAK2V617F mutation are overlapping showing clustered increase of large mature pleomorphic megakaryocytes (M) with no increase of cellularity (<60%) in ET. The bone marrow is hypercellular (60%-80%) due to increased erythropoiesis megakaryopoiesis (EM) in prodromal and classical PV and trilinear hypercellular (80%-100% due increased megakaryopoiesis, erythropoiesis and granulopoiesis (EMG) in advanced PV and masked PV. Bone marrow cellularity ranging from normal (<60%) in ET to increased erythropoiesis (EM) in prodromal PV to hypercellular (80-100%) in advanced PV and masked PV largely depends on increasing JAK2V617F mutation load from low to high on top of other biological MPN variables like constitutional symptoms during long-term follow-up. MPL515 mutated ET is featured by an increase of clustered small and giant megakaryocytes with hyper-lobulated staghorn-like nuclei in a normal cellular bone marrow. The third entity of pronounced JAK2/MPL wild type ET associated with primary megakaryocytic granulocytic myeloproliferation (PMGM) without PV features proved to be caused by calreticulin (CALR) mutation. CALR mutated thrombocythemia is characterized by dual proliferation of megakaryocytic and granulocytic bone marrow proliferation of dense clustered large to giant immature dysmorphic megakaryocytes with bulky (bulbous) hyperchromatic nuclei, which are not seen in MPL515-mutated Thrombocythemia and JAK2V617F-Thrombocythemia, prodromal PV and classical PV. 
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Management and Therapeutic Strategies for Spinal Muscular Atrophy

Published on: 29th March, 2024

Spinal muscular atrophy is an autosomal recessive neuromuscular disorder characterized by progressive muscle weakness and atrophy. It is one of the most common single-gene disorders with an incidence rate of approximately 1 in 10,000 live births. The clinical manifestations are progressive hypotonia and muscle weakness due to the degeneration of alpha neurons in the anterior horn cells of the spinal cord and motor nuclei in the lower brain stem. Depending on the severity of the symptoms, SMA has five subtypes. Supportive measures can be offered for respiratory, gastrointestinal, and musculoskeletal complications. Carrier testing for all couples is recommended and this can be done by Multiplex Ligation-dependent Probe Amplification (MLPA). Prenatal diagnosis can be offered to carrier couples. Therapies must be given within the newborn period for maximum benefit and before the loss of motor neurons. It is achieved by identifying the SMA babies through Newborn screening. Several new FDA-approved drugs can reduce the progression of symptoms in SMA. However, they cannot offer a definite cure. Clinical follow-up and Neurological assessment demonstrate that SMA children can attain developmental milestones after receiving treatment, which is never normally attained in untreated cases. In utero SMA treatment with Zolgensma would enhance the survival rate and favorable neurological outcomes in the future. Base editing and Gene editing with CRISPR-Cas technologies to target the mutations and restore functional and stable SMN protein levels are the future hopes for a permanent cure of SMA.
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Knowledge, Attitude, and Practice of Healthcare Workers in Ekiti State, Nigeria on Prevention of Cervical Cancer

Published on: 3rd April, 2024

Purpose: The role of healthcare workers in cervical cancer prevention is pivotal because healthcare workers’ recommendations have been reported to be a key motivational factor for cervical cancer screening among women in Nigeria. Assessing their knowledge, attitudes, and practices on cervical cancer prevention is necessary.Patients and methods: This is a cross-sectional survey involving healthcare workers in Ekiti State, Nigeria. A questionnaire designed for the study was used to obtain data about the knowledge, attitudes, and practices of the healthcare workers. Logistic regression was used to assess the determinants of practice and a p - value of less than 0.05 was taken as statistically significant.Results: Out of 188 participants that completed the study, 165(90.7%) had good knowledge about the prevention of cervical cancer while 24(13.2%) had good practice concerning the prevention of cervical cancer. positive attitude (Odds ratio 1.24, 95% CI 1.14 - 1.35, p < 0.001) increased the odds of good practice.Conclusion: There was no association between the knowledge of cervical cancer prevention and the practice of the healthcare workers. Further research is required to explore the incongruence between knowledge and practice of cervical cancer prevention and its practice.
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“Maximum Preservation Radical Prostatectomy”: Oncological, functional and other contemporary aspects of Retzius Sparing Robotic Assisted Radical Prostatectomy

Published on: 30th April, 2020

OCLC Number/Unique Identifier: 8861737601

The surgical treatment of prostate cancer (PCa) had as its initial milestone the first prostatectomy, performed by H.H. Young at the Johns Hopkins Hospital, in 1904 [1], however, the procedure only reached a fundamental role after 1982, based on a better understanding and description of the male pelvic anatomy, by Walsh [2-6] and other [7-11]. Subsequently, minimally invasive approaches emerged: laparoscopic prostatectomy (1992) [12] and robot- assisted laparoscopic prostatectomy (RALP) (2000) [13], which modified and optimized the execution of key surgical steps of this procedure, such as bladder neck preservation, nerve-sparing dissection, and prostate apex management [14].
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Educational strategy to increase knowledge and risk perception about sexually transmitted infection in polytechnic students

Published on: 19th March, 2020

OCLC Number/Unique Identifier: 8577723979

Introduction: The incidence of STI-HIV/AIDS is on the rise, making adolescents a vulnerable group at risk. Objective: To increase the knowledge and perception of risk about STI-HIV/AIDS, through Educational Intervention in students of the Polytechnic Institute ¨Hermanos Gómez¨ of the Municipality San José de las Lajas, Mayabeque Province. Method: Quasi-experimental study, intervention at the ¨Hermanos Gómez Polytechnic Institute, of the Municipality of San José de la Lajas, through affective, participatory, animation and reflection techniques, the universe being made up of 17 students aged 16-17 years of specialty in Industrial Chemistry, during the period from December 2014 to November 2015. The variables used were: knowledge about STI-HIV/AIDS and perception of risk towards said diseases. Results: after the intervention, an increase in the level of knowledge of the main STIs in the study was evident: Syphilis, Condylomas, HIV/AIDS, Gonorrhea, Trichomonas, Candida Albicans and Herpes simplex, which were adequately identified by 60%; 71% recognized the routes of sexual transmission, 60% the typical clinical manifestations, an increase in the levels of knowledge about the use of condoms to prevent STIs, and in the same way the perception of risk in an 83% after the intervention. Conclusion: After the intervention, there was an increase in knowledge of STIs, transmission routes, clinical manifestations, condom use, and risk perception.
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Anti COVID-19 immunity developed as assessed in a community-based oncological center

Published on: 7th October, 2020

OCLC Number/Unique Identifier: 8861739910

Introduction: Serology (antibody) tests for the SARS-CoV-2 have been proposed as an instrument to inform health authorities about immunization during the COVID-19 pandemic. As there is a significant part of the population that may have some degree of immunity, it is of great interest to communicate the immunization results obtained in the first 500 healthcare workers (HCW), patients and relatives tested in a community-based Oncological Center. Materials and methods: Between April 9th, 2020 and May 8th, 2020, a group of healthcare workers (HCW), their families, and general public who had had the COVID-19 or had been in close contact with confirmed cases of COVID-19 were screened for IgG SARS-CoV-2 antibodies. The tests were carried out in a rigorous manner, strictly following the guidelines approved by the Spanish Ministry of Health (Ministerio de Sanidad). Results: The major objective of this study was to determine the proportion of asymptomatic infected individuals and those who had already secreted IgG against SARS-CoV-2 in our cancer treatment center or in the community of Barcelona. Patients were tested with PCR, Rapid diagnostic test (RDT) or enzyme-linked immunoabsorbent assay (ELISA). A total of 521 participants were tested, 206 with RDT and 315 with ELISA, 59 (11,32%) resulted positive to SARS-CoV-2. Conclusion: RDT and ELISA proved to be effective and sensible enough to determine the extent of SARS-CoV-2 immunization in a community-based oncological center. The degree of immunization reached is nowadays far away from what can be considered desirable for a herd immunization.
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Zn2+ Ions-Immune Virucidal activities for children and adults with preventions against 2019-nCoV and COVID-19 infection

Published on: 28th July, 2020

OCLC Number/Unique Identifier: 8873197329

Zinc induced pediatric preventing respiratory 2019-nCoV is required that supplementation with zinc gluconate 20 mg in Zn deficient children resulted in a nearly twofold reduction of acute lower respiratory infections as well as the time to recovery. Zinc supplementation in children is associated with a reduction in the incidence and prevalence of pneumonia. Preventing 2019-nCoV pneumonia is required that zinc supplementation alone (10 to 20 mg) for more than 3 months significantly reduces in the rate of pneumonia. zinc pediatric intake may be required to be effective range 10~20 mg/d for 2019-CoV prevention, 10~30 mg/d for reduction of COVID-19 bronchitis, and 20~30 mg/d for recovery from COVID-19 pneumonia, in which Zn2+ could bind with viral surface proteins by Zn2+ions-centered tetrahedrally coordination pattern. On the other hand, for aults, the zinc-homeostatic immune concentration may provide a protective role against the COVID-19 pandemic, likely by improving the host’s resistance against viral infection. 50 mg of zinc per day might provide an additional shield against the COVID-19 pandemic, possibly by increasing the host resistance to viral infection to minimize the burden of the disease. In order to prevent that an outbreak of respiratory sickness caused by a novel coronavirus (COVID-19) has become a serious public threat and disrupted many lives,assessing the efficacy of FDA-approved Zn-ejector drugs such as disulfiram combined with interferon to treat COVID-19 infected patients has been proposed. The key strategies for preventing lung damages include avoiding direct lung infection, altering host-virus interactions, promoting immune responses, diluting virus concentrations in lung tissues by promoting viral migration to the rest of the body, maintaining waste removal balance, protecting heart function and renal function, avoiding other infections, reducing allergic reactions and anti-inflammatory. The interactions had been found on the binding specificity by Zn2+ ions-centered tetrahedral geometric coordination of the inhibitors against 3C and 3C-like proteases. In addition, transient zinc chelation TPEN and EPDTC have been noted as preventing virus replication. Zinc-induced ROS production in COVID-19 respiratory ailment and pneumonia occurs both in children and adults. In children. ROS production in zinc (Ⅱ)-immune pediatric patient with COVID-19 bronchitis and pneumonia cannot be elucidated yet. In adults, zinc induced ROS generation in pulmonary COVID-19 infected cells is that alterations of ROS-producing and scavenging pathways that are caused by respiratory viral infections are implicated in inflammation, lung epithelial disruption, and tissue damage, and, in some cases, even pulmonary fibrosis. The involvement of oxidative stress in cell deaths caused during RNA virus infection and ROS production is correlated with host cell death.
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Analysis and Control of a Glucose-insulin Dynamic Model

Published on: 29th January, 2026

The dynamics of the glucose-insulin regulatory system are highly nonlinear and must be understood to be controlled effectively. Bifurcation analysis and multiobjective nonlinear model predictive control (MNLMPC) are performed on a glucose-insulin dynamic model. MATCONT was used for the bifurcation analysis, and for the MNLMPC calculations, the optimization language PYOMO is used in conjunction with the solvers IPOPT and BARON. The bifurcation analysis revealed a Hopf bifurcation point and a limit point. A Hopf bifurcation point is a tipping point where a system that was behaving steadily suddenly starts to oscillate or cycle on its own, like a machine that begins to vibrate instead of staying still. A limit point is a tipping point at which pushing a system a little further suddenly causes it to jump to a completely different state, rather than changing smoothly. MNLMC converged on the Utopia solution. The Hopf bifurcation point, which leads to an unwanted limit cycle, is eliminated by an activation factor. A limit cycle is a repeating pattern of behavior that a system naturally settles into over time, like a steady heartbeat or a clock that keeps ticking. The limit point (which causes multiple steady-state solutions from a singular point enables the Multiobjective nonlinear model predictive control calculations to converge to the Utopia point (the best possible solution) in the model. A Utopia solution in multi-objective nonlinear model predictive control is an ideal operating point at which all goals are simultaneously perfectly optimized.
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Regeneration of deep intrabony periodontal defects with enamel matrix derivative: A case report

Published on: 19th March, 2021

OCLC Number/Unique Identifier: 9029521328

A clinical case of treatment of two severe intrabony defects on the aesthetic zone is reported and followed for one year. The biomaterial of choice was enamel matrix derivative (Emdogain®; Straumann™) alone with a preservation papilla flap and a minimally invasive surgical technique. After surgical treatment, the patient was kept in a supportive periodontal therapy programme with 6-month interval between appointments. In the one year after surgery appointment, clinical and radiographic changes were observed, showing periodontal health and stability. 
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