Normal Organ Research Articles

Apoptosis Induction, a Sharp Edge of Berberine to Exert Anti-Cancer Effects, Focus on Breast, Lung, and Liver Cancer.

Cancer is the leading cause of death and one of the greatest barriers to increased life expectancy worldwide. Currently, chemotherapy with synthetic drugs remains one of the predominant ways for cancer treatment, which may lead to drug resistance and normal organ damage. Increasing researches have suggested that apoptosis, a type of programmed cell death, is a promising way for cancer therapy. Furthermore, natural products are important sources for finding new drugs with high availability, low cost and low toxicity. As a well-known isoquinoline alkaloid, accumulating evidence has revealed that berberine (BBR) exerts potential pro-apoptotic effects on multiple cancers, including breast, lung, liver, gastric, colorectal, pancreatic, and ovarian cancers. The related potential signal pathways are AMP-activated protein kinase, mitogen-activated protein kinase, and protein kinase B pathways. In this review, we provide a timely and comprehensive summary of the detailed molecular mechanisms of BBR in treating three types of cancer (breast, lung and liver cancer) by inducing apoptosis. Furthermore, we also discuss the existing challenges and strategies to improve BBR’s bioavailability. Hopefully, this review provides valuable information for the comprehension of BBR in treating three types of cancer and highlight the pro-apoptotic effects of BBR, which would be beneficial for the further development of this natural compound as an effective clinical drug for treating cancers.

Trigger point injections and dry needling can be effective in treating long COVID syndrome-related myalgia: a case report

IntroductionMyofascial pain is a complex health condition that affects the majority of the general population. Myalgia has been recognized as a symptom of long COVID syndrome. The treatment for long COVID syndrome-related myalgia lacks research. Dry needling is a technique that involves the insertion of a needle into the tissue of, or overlaying, a pain point. Wet needling is the addition of an injection of an analgesic substance such as lidocaine while performing needling. Both dry and wet needling have are practiced as treatment modalities for myofascial pain. Limited literature exists to define long COVID syndrome-related myalgia and its relation to myofascial pain, or to examine the utility of needling techniques for this pain. We report a case of dry and wet needling as effective treatments for long COVID-related myofascial pain.Case presentationA 59-year-old, previously healthy Hispanic male with no comorbid conditions was diagnosed with COVID-19 pneumonia. The patient suffered moderate disease without hypoxia and was never hospitalized. Three months later, the patient continued to suffer from symptoms such as exertional dyspnea, “brain fog,” and myalgia. An extensive multisystem workup revealed normal cardiac, pulmonary, and end organ functions. The patient was then diagnosed with long COVID syndrome. The nature and chronicity of the patient’s myalgia meet the criteria for myofascial pain. Both wet and dry needling were used to treat the patient’s myofascial pain, with good short- and long-term therapeutic effects.ConclusionsCOVID-19 infection has been shown to exacerbate preexisting myofascial pain syndrome. Our case report indicates that long COVID syndrome-related myalgia is likely a form of new-onset myofascial pain. Additionally, both wet and dry needling can be utilized as an effective treatment modality for this pain syndrome, with short- and long-term benefits.

Normal Tissue Risk Estimation Using Biological Knowledge-Based Fuzzy Logic in Volumetric Modulated Arc Therapy of Prostate Cancer: Rectum.

Objective:Most radiotherapy patients with prostate cancer are treated with volumetric modulated arc therapy (VMAT). Advantages of VMAT may be limited by daily treatment uncertainties such as setup errors, internal organ motion, and deformation. The position and shape of prostate target as well as normal organ, i.e., rectum volume around the target, may change during the course of treatment. The aim of the present work is to estimate rectal toxicity estimation using a novel two-level biological knowledge-based fuzzy logic method. Both prostate and rectal internal motions as well as setup uncertainties are considered without compromising target dose distribution in the present study.Materials and Methods:The Mamdani-type fuzzy logic framework was considered in two levels. The prostate target volume changes from minimum to maximum during the course of treatment. In the first level, the fuzzy logic was applied for determining biological acceptable target margin using tumor control probability and normal tissue complication probability (NTCP) parameters based on prostate target motion limits, and then, fuzzy margin was derived. The output margin of first-level fuzzy logic was compared to currently used margins. In second-level fuzzy, rectal volume variation with weekly analysis of cone-beam computed tomography (CBCT) was considered. The biological parameter (NTCP) was calculated corresponding to rectal subvolume variation with weekly CBCT image analysis. Using irradiated volume versus organ risk relationship from treatment planning, the overlapped risk volumes were estimated. Fuzzy rules and membership function were used based on setup errors, asymmetrical nature of organ motion, and limitations of normal tissue toxicity in Mamdani-type Fuzzy Inference System.Results:For total displacement, standard errors of prostate ranging from 0 to 5 mm range were considered in the present study. In the first level, fuzzy planning target volume (PTV) margin was found to be similar or up to 0.5 mm bigger than the conventional margin, but taking the modeling uncertainty into account resulted in a good match between the calculated fuzzy PTV margin and conventional margin formulations under error 0–5 mm standard deviation (SD) range. With application of fuzzy margin obtained from first-level fuzzy, overlapped rectal volumes and corresponding NTCP values were fuzzified in second-level fuzzy using rectal volume variations. The final risk factor (RF) of rectum was qualitatively assessed and found clinically acceptable for each fractional volume of irradiated to total volume and relevant NTCP values. The reason may be at 5 mm SD displacement error range, NTCP values would be within acceptable limit without compromising the tumor dose distribution though the confounding factors such as organ motion, deformation of rectum, and in-house image matching protocols exist.Conclusion:A new approach of two-level fuzzy logic may be suitable to estimate possible organ-at-risk (OAR) toxicity biologically without compromising tumor volume that includes both prostate target and OAR rectum deformation even at displacement standard errors of prostate ranging from 0 to 5 mm range which was considered in the present study. Using proposed simple and fast method, there is an interplay between volume-risk relationship and NTCP of OARs to judge real-time normal organ risk level or alter the treatment margins, particularly concern to individual factors such as comorbidities, genetic predisposition, and other lifestyle choices even at high displacement errors >5 mm SD range.

A Low Dose Whole Lung Radiotherapy for Covid-19 Pneumonia: What have we Learned? Opinion of the International Geriatric Radiotherapy Group.

Background: Coronavirus disease 19 carry a high mortality rate among older patients and minorities such as ethnic Africans and Latinos through the induction of a cytokines storm. Many pharmacologic interventions were proposed to improve the mortality rate from normal organ damage such as pneumonia. Low dose whole lung radiotherapy has been used in the past to treat pneumonia and may improve survival through modulation of the inflammatory cytokines. However, there is a lot of controversy about the efficacy and safety of this treatment modality. Thus, a review of the clinical studies using irradiation for COVID-19 pneumonia is needed to answer those questions Methods: A literature search of PubMed and Google Scholar was conducted. Reported studies were analyzed to assess safety, efficacy, and inflammatory biomarkers response following low dose whole lung radiotherapy Results: Patients who required artificial ventilation for COVID-19 did not benefit from low dose whole lung radiotherapy, most likely due to severe lung damage. The inflammatory response may be attenuated after irradiation but it is unclear whether it is independent of the steroid effect. Conclusion: Randomized studies are required to assess the effect low dose whole lung radiotherapy for COVID-19 pneumonia and its anti-inflammatory property. Such studies are needed for emerging countries with limited resources as radiotherapy may be cost-effective to reduce hospital admission and intensive care unit monitoring.

Effects of circFOXO3 on the Proliferation and Invasion of Liver Cancer Cells by Regulating PI3K/Akt Pathway.

Objective Hepatocellular carcinoma is a malignant disease occurring in the liver and is one of the main causes of death in cancer patients. Tumor cells are the main components of tumors and have a strong proliferative capacity. They are easily transferred to other parts of the body and can produce harmful substances that destroy the normal organ structure and endanger human life and health. In this study, we investigate the effect of circFOXO3 on the proliferation and invasion of hepatocellular carcinoma cells and its possible mechanism. Methods Human hepatocellular carcinoma cells BEL-7404, Hep G2, Hep 3B2.1–7, HuH-7, Li-7, and human normal hepatocytes HHL-5 were selected, and the expression level of circFOXO3 in the cell lines was determined by qRT-PCR. The cell line with low circFOXO3 expression level (HuH-7 cells) was used for follow-up experiments. HuH-7 liver cancer cells were divided into the control group (normal cultured), circFOXO3-NC group (transfected with circFOXO3 negative control), circFOXO3 mimic group (transfected with circFOXO3 mimic), PI3K activator group (20 μmol/L PI3K activator 740Y-P), and circFOXO3 mimic + PI3K activator group (transfected with circFOXO3 mimic + treated with PI3K activator 740Y-P). The qRT-PCR method was used to determine the expression level of circFOXO3 in HuH-7 liver cancer cells in each group, WB was used to detect the expression of apoptosis, invasion, and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway related proteins in HuH-7 liver cancer cells in each group, the CCK-8 method was used to determine the viability of HuH-7 liver cancer cells in each group, flow cytometry was used to determine the apoptotic ability of HuH-7 liver cancer cells in each group, the transwell chamber experiment was used to determine the invasion ability of HuH-7 liver cancer cells in each group, and the scratch test was used to determine the migration ability of HuH-7 liver cancer cells in each group. Results circFOXO3 showed low expression in liver cancer cells; compared with the control group, the circFOXO3 expression and apoptosis rate of HuH-7 liver cancer cells in the circFOXO3 mimic group were significantly increased (P < 0.05) and the PI3K/Akt pathway-related protein expression, cell viability, invasion, and migration abilities were significantly reduced (P < 0.05); the apoptosis rate of HuH-7 liver cancer cells in the PI3K activator group was significantly reduced (P < 0.05) and the PI3K/Akt pathway related protein expression, cell viability, invasion and migration abilities were significantly increased (P < 0.05). Compared with the circFOXO3 mimic group, the apoptosis rate of HuH-7 liver cancer cells in the circFOXO3 mimic + PI3K activator group was significantly reduced (P < 0.05) and the PI3K/Akt pathway-related protein expression, cell viability, invasion and migration abilities were significantly increased (P < 0.05). Conclusion Highly expressed circFOXO3 can inhibit the proliferation and invasion of HuH-7 liver cancer cells, which may be achieved by inhibiting the PI3K/Akt pathway.

Using Nanotechnology for Diagnosis and Treatment of Breast Cancer: A Review

One of the leading causes of death in women around the word is breast cancer. For the treatment of most cancers, chemotherapy is a good option. The most treatment approaches for breast cancer are radiotherapy, surgery and chemotherapy. There are some restrictions and limitations in diagnostic approaches and treatment methods. They result in the progress of new diagnosis and treatment approaches to improve the life quality of patients. Application of nanotechnology in the treatment of cancers currently has received much attention. In cancer treatments, nanotechnology plays a significant role in the drug delivery. Tumors can be targeted by nanoparticles. They have important role in controlling the drug release to accurate sites. Therefore, nanoparticles improve the drug efficiency and reduce the normal organ’s toxicity. Another ability of nanoparticles is activation of immune cells against tumors. As a result, nanoparticles can be used as a proper and efficient tool in the treatment and diagnosis of cancer. In this review we discuss about using nanotechnology and application of different nanoparticles in diagnosis and treatment of breast cancer.

89Zr Immuno-PET Imaging of Tumor PD-1 Reveals That PMA Upregulates Lymphoma PD-1 through NFκB and JNK Signaling.

Immune therapy of T-cell lymphoma requires assessment of tumor-expressed programmed cell death protein-1 (PD-1). Herein, we developed an immuno-PET technique that quantitatively images and monitors regulation of PD-1 expression on T-cell lymphomas. Methods. Anti-PD-1 IgG underwent sulfhydryl moiety-specific conjugation with maleimide-deferoxamine and 89Zr labeling. Binding assays and Western blotting were performed in EL4 murine T-cell lymphoma cells. In vivo pharmacokinetics, biodistribution, and PET were performed in mice. Results. 89Zr-PD-1 IgG binding to EL4 cells was completely blocked by cold antibodies, confirming excellent target specificity. Following intravenous injection into mice, 89Zr-PD-1 IgG showed biexponential blood clearance and relatively low normal organ uptake after five days. PET/CT and biodistribution demonstrated high EL4 tumor uptake that was suppressed by cold antibodies. In EL4 cells, phorbol 12-myristate 13-acetate (PMA) increased 89Zr-PD-1 IgG binding (305.5 ± 30.6%) and dose-dependent augmentation of PD-1 expression (15.8 ± 3.8 − fold of controls by 200 ng/ml). FACS showed strong PD-1 expression on all EL4 cells and positive but weaker expression on 41.6 ± 2.1% of the mouse spleen lymphocytes. PMA stimulation led to 2.7 ± 0.3-fold increase in the proportion of the strongest PD-1 expressing EL4 cells but failed to influence that of PD-1+ mouse lymphocytes. In mice, PMA treatment increased 89Zr-PD-1 IgG uptake in EL4 lymphomas from 6.6 ± 1.6 to 13.9 ± 3.6%ID/g (P = 0.01), and tumor uptake closely correlated with PD-1 level (r = 0.771, P < 0.001). On immunohistochemistry of tumor sections, infiltrating CD8α+ T lymphocytes constituted a small fraction of tumor cells. The entire tumor section showed strong PD-1 staining that was even stronger for PMA-treated mice. Investigation of involved signaling revealed that PMA increased EL4 cell and tumor HIF-1α accumulation and NFκB and JNK activation. Conclusion. 89Zr-PD-1 IgG offered high-contrast PET imaging of tumor PD-1 in mice. This was found to mostly represent binding to EL4 tumor cells, although infiltrating T lymphocytes may also have contributed. PD-1 expression on T-cell lymphomas was upregulated by PMA stimulation, and this was reliably monitored by 89Zr-PD-1 IgG PET. This technique may thus be useful for understanding the mechanisms of PD-1 regulation in lymphomas of living subjects.

Col6a1+/CD201+ mesenchymal cells regulate intestinal morphogenesis and homeostasis.

Intestinal mesenchymal cells encompass multiple subsets, whose origins, functions, and pathophysiological importance are still not clear. Here, we used the Col6a1Cre mouse, which targets distinct fibroblast subsets and perivascular cells that can be further distinguished by the combination of the CD201, PDGFRα and αSMA markers. Developmental studies revealed that the Col6a1Cre mouse also targets mesenchymal aggregates that are crucial for intestinal morphogenesis and patterning, suggesting an ontogenic relationship between them and homeostatic PDGFRαhi telocytes. Cell depletion experiments in adulthood showed that Col6a1+/CD201+ mesenchymal cells regulate homeostatic enteroendocrine cell differentiation and epithelial proliferation. During acute colitis, they expressed an inflammatory and extracellular matrix remodelling gene signature, but they also retained their properties and topology. Notably, both in homeostasis and tissue regeneration, they were dispensable for normal organ architecture, while CD34+ mesenchymal cells expanded, localised at the top of the crypts, and showed increased expression of villous-associated morphogenetic factors, providing thus evidence for the plasticity potential of intestinal mesenchymal cells. Our results provide a comprehensive analysis of the identities, origin, and functional significance of distinct mesenchymal populations in the intestine.

Immune cells in cardiac homeostasis and disease: emerging insights from novel technologies.

The increasing use of single-cell immune profiling and advanced microscopic imaging technologies has deepened our understanding of the cardiac immune system, confirming that the heart contains a broad repertoire of innate and adaptive immune cells. Leucocytes found in the healthy heart participate in essential functions to preserve cardiac homeostasis, not only by defending against pathogens but also by maintaining normal organ function. In pathophysiological conditions, cardiac inflammation is implicated in healing responses after ischaemic or non-ischaemic cardiac injury. The aim of this review is to provide a concise overview of novel methodological advancements to the non-expert readership and summarize novel findings on immune cell heterogeneity and functions in cardiac disease with a focus on myocardial infarction as a prototypic example. In addition, we will briefly discuss how biological sex modulate the cardiac immune response. Finally, we will highlight emerging concepts for novel therapeutic applications, such as targeting immunometabolism and nanomedicine.

ACUTE TOXICITY OF Β-KITIN EXTRACTED FROM THE SHELL OF BLUE SWIMMING CRAB (PORTUNUS PELAGICUS LINN.)

Objective: This work aimed to study the acute toxicity of β-chitin extracted from crab shells in Bal b/c mice.&#x0D; Method: The acute toxicity test was performed by following the OECD guidelines. Female mice were given single or divided doses of β-chitin (maximum 24 h) with doses of 500, 1000, 2000, 4000, and 6000 mg/kg of BW. Observations were made for 14 d, including behaviour, body weight, organ weight, and histopathology of vital organs (stomach, heart, liver, kidney, and lung).&#x0D; Results: During 14 d, no deaths and no abnormalities in behaviour, bodyweight or organ weight were observed. Qualitative histopathological observations at the highest dose showed abnormalities of the liver and kidney compared to those of the control group. Nevertheless, the abnormalities did not affect the organ function.&#x0D; Conclusion: This acute toxicity study reveals that β-chitin up to a dose of 6000 mg/kg of BW is not toxic, as proved by the normal behaviour, body weight, and vital organ weight of the animals. Further chronic toxicities study is needed to confirm its safety.

Abstract P226: Design and rationale of a first in human (FIH) phase 1/1b study evaluating KIN-2787, a potent and highly selective pan-RAF inhibitor, in adult patients with BRAF mutation positive solid tumors

Abstract Background BRAFV600 mutations (BRAF Class I mutations) encode a highly active monomeric oncogenic kinase that can be targeted by approved RAF kinase inhibitors in patients (pts) with melanoma (MEL), NSCLC, colorectal &amp; anaplastic thyroid cancers. In other discrete patient populations, molecularly distinct BRAF alterations drive dimer-dependent oncogenic signaling including BRAF Class II and III alterations. Class II alterations include single nucleotide variants (SNVs), indels and gene fusions that induce BRAF homodimer formation leading to oncogenic kinase activation. Class III mutations, typically SNVs, are low activity kinase mutations that promote RAF dimerization and oncogenic MAPK pathway signaling that is RAS-dependent. Approved BRAF inhibitors have limited clinical activity in diverse solid tumors driven by BRAF Class II or III alterations, highlighting the urgency to develop effective targeted therapies for these patients. KIN-2787 is a potent, highly selective pan-RAF type II kinase inhibitor designed to target both monomeric &amp; dimeric forms of the mutant BRAF kinase and minimize paradoxical activation, a liability often observed with other RAF inhibitors that can adversely impact tolerability &amp; require addition of a MEK inhibitor to suppress pathway activation. KIN-2787 has favorable pharmaceutical properties, achieves substantial systemic exposures in pre-clinical toxicology studies &amp; induces regressions in human cancer xenograft models driven by BRAF Class I, II or III mutations. Methods This is a FIH, multicenter, non-randomized, open-label, Ph1 study (NCT04913285) of KIN-2787 in adult patients with BRAF mutant advanced &amp; metastatic solid tumors (AMST). KIN-2787 will be given orally bid continuously in 28-day cycles until drug intolerance or disease progression. Planned sample size is approx. 115 pts in two parts: Part A is a dose-escalation to MTD open to pts with AMST driven by BRAF Class I, II or III genomic alterations. Part B will evaluate a selected dose of KIN-2787 in 3 cohorts of pts with MEL, NSCLC, or other AMST, each driven by BRAF Class II or III alterations. Standard Ph1 enrollment criteria are required (ECOG PS ≤ 2, normal organ function, prior receipt of standard treatment or medical judgment that such is not appropriate). Patients may have measurable or evaluable disease per RECIST v1.1. Key exclusion criteria include known active brain metastases from non-brain tumors, prior receipt of BRAF-, MEK-, or MAPK-directed inhibitor therapy (unless for FDA approved indications), HBV &amp; HCV seropositivity. Primary endpoints are safety/tolerability (Part A), and preliminary antitumor activity: objective response rate (ORR), disease control rate (DCR), duration of response (DOR), &amp; duration of stable disease (Part B). Secondary objectives include pharmacokinetic (PK) and pharmacodynamic (PD) assessments including tissue and blood-based measures of MAPK signaling inhibition. This study recently opened for Part A recruitment in the United States (NCT04913285). Citation Format: Meredith McKean, Shumei Kato, Alexander Spira, Yan Xing, Hao Xie, Elizabeth Buchbinder, Ken Kobayashi, Richard Williams. Design and rationale of a first in human (FIH) phase 1/1b study evaluating KIN-2787, a potent and highly selective pan-RAF inhibitor, in adult patients with BRAF mutation positive solid tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P226.

Abstract P099: Radionuclide imaging of low-density-lipoprotein receptor (LDLR)-overexpressing glioblastoma: A preclinical study of Gallium-68 RMX-VH

Abstract Introduction: One of the factors that limit the efficacy of the drugs, especially in primary brain tumors, is the permeability of the blood-brain barrier (BBB). The low-density lipoprotein receptor (LDL-R) expressed at the BBB mediates the transport of endogenous ligands through the BBB. We developed a new radiolabeled peptide targeting both the human and murine LDLR and able i) to cross the BBB and ii) to target tumors such as glioblastoma that express high levels of the LDLR. The objective of this study was to determine the LDLR targeting properties, the pharmacokinetics of 68Ga radiolabeled RMX-VH in a glioblastoma model that expresses the human LDLR (hLDLR). Methods: The nonclinical studies of 68Ga-RMX-VH were completed in U87MG, A172, U373 glioblastoma cancer cell lines and xenografts mice models. The studies determined in vivo time-dependent accumulation of this agent, in vitro dose-depended cellular uptake, and cellular competition studies. We compared the tumor-specific accumulation of 68Ga-RMX-VH and normal organ distribution in female and male athymic nude mice. Radiotracer, RMX-VH (10-30ug) was labeled with isotope-Ga68 (10-25mCi, ITM GmBH). U87MG and A172- derived xenografts were generated in athymic nude mice (10 weeks) and PET/CT images were acquired using G4 PET/Xray camera (Sofie Biosciences) at 1h, 2h, 3h, and 4h post-injection. The followed up biodistribution studies were done at 30 min, 1h, 2h, and 3 hrs. post-injection. The organs and tumor were collected, weighed, and the tissue radioactivity was measured with Wizard2 Gamma Counter (Perkin-Elmer, Waltham, MA). The percentage of injected dose per gram of tissue (%ID/g) was calculated and decay-corrected. Results: Our studies confirmed the in vitro and in vivo selectivity and specificity of 68Ga-RMX-VH toward LDLR-positive tumors. 68Ga-RMX-VH is a small peptide (MW: 1432.7 g/mol) and renal excretion was expected as a route of agent elimination. The tumor-specific uptake of radiotracer in U87MG xenografts was 1.8%ID/g at 1h and remained unchanged at 3h post-injection. The kidney retention of the agent reached 12.2%ID/g and decreased to 10.2%ID/g. The accumulation of radiotracer in the liver, ovaries, and intestine correlated well with the known normal expression of LDLR. The tumor-to-muscle ratio was 5.97 at 1h; increased to 26.1 and 22.39 at 2h and 3h. The elimination t1/2 of radiotracer was only 18.6 min, with a clearance CL of 502 ml/min. Adsorption from the site of administration is rapid as the Cmax was 5 min. The tumor-specific uptake and normal organ distribution of 68Ga-RMX-VH were lower in male mice than in females. This correlated with differences in lipid and lipoproteins metabolism in males and females. Conclusions: RMX-VH showed favorable hLDLR targeting properties in vitro and in vivo in glioblastoma mice models. Our results suggest that hLDLR may serve as a target for imaging for glioblastoma. The first-in-human exploratory IND study of Ga68-RMX-VH will be initiated in Q2 of 2021. Citation Format: Izabela Tworowska, Leo Garcia Flores II, Xuewei Qu, Cédric Malicet, Nilesh Wagh, David Ranganathan, Jonathan Nowak, Pascaline Lecorche, Jamal Temsamani, Ebrahim S. Delpassand. Radionuclide imaging of low-density-lipoprotein receptor (LDLR)-overexpressing glioblastoma: A preclinical study of Gallium-68 RMX-VH [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P099.

Parental Readiness in Caring for Low Birth Weight: Pediatric Nursing Intervention

Background: low birth weight babies (LBW) weighing less than 2500 are babies at high risk because in general, they are smaller than normal birth weight babies and immature organ function. LBW requires special care to anticipate life-threatening emergency conditions. The care process for meeting the special needs of LBW requires the involvement of parents during the hospital and after discharge from the hospital. Nurses as educators have an important role in preparing parents to care for LBW after returning from the hospital. Purpose: This study aims to determine the effect of child nursing interventions through the education of LBW infant care with parents' readiness to care for LBW. Methods: This research is a quantitative study, using a quasi-experimental design with a pre-post-test with control. The population of this study was parents who had LBW babies in Kendal District Hospital with the sampling technique using accidental sampling, the total sample was 40 parents with LBW babies. The sample was classified into two groups, namely, 20 respondents as the intervention group and 20 respondents as the control group. Results: The results of this study indicate that there was a significant differences in parent readiness scores in caring for LBW between those who were given and not given education with a P value of 0.000, used an independent sample t-test and there was an effect of education on the readiness of parents in caring for LBW used the Chi-square test with a p value of 0.002. Conclusion: Providing education to parents with LBW is one of the implementations of pediatric nursing to prepare parents to care for LBW.

Brachytherapy Approach Using 177Lu Conjugated Gold Nanostars and Evaluation of Biodistribution, Tumor Retention, Dosimetry and Therapeutic Efficacy in Head and Neck Tumor Model.

Brachytherapy can provide sufficient doses to head and neck squamous cell carcinoma (HNSCC) with minimal damage to nearby normal tissues. In this study, the β−-emitter 177Lu was conjugated to DTPA-polyethylene glycol (PEG) decorated gold nanostars (177Lu-DTPA-pAuNS) used in surface-enhanced Raman scattering and photothermal therapy (PTT). The accumulation and therapeutic efficacy of 177Lu-DTPA-pAuNS were compared with those of 177Lu-DTPA on an orthotopic HNSCC tumor model. The SPECT/CT imaging and biodistribution studies showed that 177Lu-DTPA-pAuNS can be accumulated in the tumor up to 15 days, but 177Lu-DTPA could not be detected at 24 h after injection. The tumor viability and growth were suppressed by injected 177Lu-DTPA-pAuNS but not nonconjugated 177Lu-DTPA, as evaluated by bioluminescent imaging. The radiation-absorbed dose of the normal organ was the highest in the liver (0.33 mSv/MBq) estimated in a 73 kg adult, but that of tumorsphere (0.5 g) was 3.55 mGy/MBq, while intravenous injection of 177Lu-DTPA-pAuNS resulted in 1.97 mSv/MBq and 0.13 mGy/MBq for liver and tumorsphere, respectively. We also observed further enhancement of tumor-suppressive effects by a combination of 177Lu-DTPA-pAuNS and PTT compared to 177Lu-DTPA-pAuNS alone. In conclusion, 177Lu-DTPA-pAuNS may be considered as a potential radiopharmaceutical agent for HNSCC brachytherapy.

89Zr-pembrolizumab imaging as a non-invasive approach to assess clinical response to PD-1 blockade in cancer

Programmed cell death protein 1 (PD-1) antibody treatment is standard of care for melanoma and non-small-cell lung cancer (NSCLC). Accurately predicting which patients will benefit is currently not possible. Tumor uptake and biodistribution of the PD-1 antibody might play a role. Therefore, we carried out a positron emission tomography (PET) imaging study with zirconium-89 (89Zr)-labeled pembrolizumab before PD-1 antibody treatment. Patients with advanced or metastatic melanoma or NSCLC received 37 MBq (1 mCi) 89Zr-pembrolizumab (∼2.5 mg antibody) intravenously plus 2.5 or 7.5 mg unlabeled pembrolizumab. After that, up to three PET scans were carried out on days 2, 4, and 7. Next, PD-1 antibody treatment was initiated. 89Zr-pembrolizumab tumor uptake was calculated as maximum standardized uptake value (SUVmax) and expressed as geometric mean. Normal organ uptake was calculated as SUVmean and expressed as a mean. Tumor response was assessed according to (i)RECIST v1.1. Eighteen patients, 11 with melanoma and 7 with NSCLC, were included. The optimal dose was 5 mg pembrolizumab, and the optimal time point for PET scanning was day 7. The tumor SUVmax did not differ between melanoma and NSCLC (4.9 and 6.5, P= 0.49). Tumor 89Zr-pembrolizumab uptake correlated with tumor response (Ptrend= 0.014) and progression-free (P= 0.0025) and overall survival (P= 0.026). 89Zr-pembrolizumab uptake at 5 mg was highest in the spleen with a mean SUVmean of 5.8 (standard deviation ±1.8). There was also 89Zr-pembrolizumab uptake in Waldeyer's ring, in normal lymph nodes, and at sites of inflammation. 89Zr-pembrolizumab uptake in tumor lesions correlated with treatment response and patient survival. 89Zr-pembrolizumab also showed uptake in lymphoid tissues and at sites of inflammation.

Preventive effects of yogurt fortified with purple roselle extract against cardiotoxicity in rats exposed with 2,3,7,8-tetrachlorodibenzo-p-dioxin

Dioxin is one of the environmental persistent organic pollutants that harm animal and human health. Prolonged exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can disrupt normal organ function including heart. Yogurt is known to have antioxidant properties, and fortification natural plant-based antioxidant purple roselle (Hibiscus sabdariffa L) extract into yogurt can improve the antioxidant potential. The purpose of this study was to determine the preventive effect of yogurt fortified with purple roselle on dioxin exposure rats (Rattus norvegicus) based on the levels of Malondialdehyde (MDA) and histopathological of the heart. This experimental study using a completely randomized design (CRD). A total of 30 male Wistar rats were divided into 5 groups (NC, PC, T1, T2, T3), a dose of 200 ng/kg BW TCDD and 1 mL of roselle yogurt 0.5%, 1.0%, and 1.5% were given orally for 12 days. MDA levels were analyzed using the Thiobarbituric Acid (TBA) assay and histopathology of the heart using the Haematoxylin Eosin (HE) staining method. Statistical analysis using one-way Analysis of Variance (ANOVA). Histopathology changes were analyzed descriptively. The results showed that TCDD exposure induced oxidative stress in heart tissue and yogurt roselle has the potential to prevent an increase of MDA levels significantly (p&lt;0.05). Furthermore, TCDD can cause histopathological alterations such as necrosis and hemorrhage, and yogurt roselle was proven to prevent cardiotoxicity due to TCDD exposure.

Helminthic invasion in malaria patients

In the light of modern teachings, parasitic worms are considered not only as causative agents of helminthic diseases, very diverse in etiology and clinical course, but to a large extent also as the primary source of very frequent infectious diseases, as inoculators of microbial flora, as a factor that acts with its poisonous properties on the body, disrupting normal organ function and predisposing it to other diseases and to severe disease. With the development of most infectious diseases, the first role belongs to worms, and the second to bacteria; the course and death of the disease should be considered as the result of the combined destructive work of both. One should not be hypnotized by germs only (Cadeak).

Anti Ulceration Efficacy of Boiled Aqueous Leaf Extract of Morinda lucida on Ethanol Induced Gastric Ulceration Rats

Stomach ulceration study was carried on 25 groups (5 rats each of the groups), groups (E, E1, E2, , E3 and EC, placed on 24 hours fasting before the single dose of intra peritoneal dose administration of 5ml/kg body weight of 99% ethanol and after one hour, received daily extract of dilution doses of ((500, 1000, 1500) mg /kg) body weight and 100 mg /kg body weight cimentidine (standard drug) respectively for 7 days. Groups (EA1, EA2, , EA3 and EAC, ) were treated with the same extract doses and drug concentration for 7 days before the dose ethanol administration. Group Eand 0 served as a positive control and a negative control respectively. On day 9, target organs; stomach and intestines were harvested under anaesthetize weighed, gross macroscopically and histomorphological studied. Result of the study showed plant inhibition on ethanol induced gastric ulceration; the standard drug (cemetidine) and the mapped extract doses of ((500, 1000, 1500) mg /kg) body weight respectively showed normal organ architecture. Ulcer index study activities 70% indicating evidence of curative and preventive index range 35 to 43% showed some inhibition as seen on the gastric mucosa of the treated group. It was observed that the treatment and anti- ulceration effect of boiled aqueous leaf extract metabolites showed reduction on the histomorphological changes in the gastric mucosa and provided inhibition effectiveness of ethanol induced injury.

Quantification and Dosimetric Impact of Normal Organ Motion During Adaptive Radiation Therapy Plan Verification Using a 1.5 Tesla Magnetic Resonance Equipped Linear Accelerator (MR LINAC)

<h3>Purpose/Objective(s)</h3> Patients receiving adaptive radiation therapy (RT) undergo contour and plan modification prior to treatment delivery. This process takes time to complete, ranging from 15 to 60 minutes or longer. We hypothesize that during the time required to create an adapted RT plan, normal organ movement will result in unanticipated doses delivered to local organs at risk. This study quantifies the dosimetric impact of abdominal organ motion during the time required to create an adaptive RT plan. <h3>Materials/Methods</h3> Patients receiving 5-fraction treatments with MR guided adaptive RT using a 1.5 Tesla MR LINAC were prospectively enrolled in an ongoing imaging study (NCT03500081). Two sets of MRIs were acquired: the first (pre-beam MRI) used to contour organs at the start of treatment, and the second (verification MRI) used to verify organ position immediately before beam-on. Both MRIs were collected in commercially available software. Each normal organ within 1cm of radiation targets was contoured on the verification MRI. The differences in organ position between the two MRIs represents the normal organ movement during the time required for plan adaptation. Max dose (Dmax), volumetric 0.5 cubic centimeter (cc) dose (D0.5cc), volumetric 3000cGy (V30), and volumetric 2000cGy (V20) were calculated. Mixed model tests analyzing differences between the MRI sets were performed using a data management and decision management software. <h3>Results</h3> Thirty adapt-to-shape patients were included. Recontoured normal organs included colon, duodenum, small bowel, and stomach, for a total of 120 new individually created contour volumes. The table below summarizes the mean differences of Dmax in the normal organs between the MRI sets for various organs at risk. Note that only small bowel demonstrated a statistically significant difference in Dmax doses. The D0.5cc, and V30 were also statistically significant for small bowel. <h3>Conclusion</h3> Statistically significant differences in small bowel doses are demonstrated when doses are calculated using the verification MRI. This is likely due to the small bowel's increased mobility compared to other organs analyzed. There is an absence of statistically significant differences in all other abdominal organ doses between these scans. These results reflect that highly mobile structures, such as small bowel, benefit from acquisition of a verification MRI following daily adaptive plan generation. Future research should focus on methods to shorten the adaption duration and/or account for these unanticipated doses, as they represent a significant limitation of adaptive MR guidance.

Study on Brain Tumor Classification Through MRI Images Using a Deep Convolutional Neural Network

Brain tumor (Glioma) is one of the deadliest diseases that attack humans, now even men or women aged 20-30 are suffering from this disease. To cure tumor in a person, doctors use MRI machine, because the results of MRI images are proven to provide better image results than CT-Scan images, but sometimes it is difficult to distinguish between the MRI images having tumors with that images not having tumor from MRI image results. It is because of resulting contrast is like any other normal organ. However, using features of image processing techniques like scaling, contrast enhancement and thresh-holding based in Deep Neural Networks the scheme can classify the results more appropriately and with high accuracy. In this paper, this study reveals the nitty-gritty of Brain tumor (Gliomas) and Deep Learning techniques for better inception in the field of computer-vision.