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PrACTiC: A Predictive Algorithm for Chemoradiotherapy-Induced Cytopenia in Glioblastoma Patients
Full text linkBackground. Chemotherapy-induced cytopenia is the most frequent side effect of chemoradiotherapy in glioblastoma patients
which may lead to reduced delivery of treatment. *is study aims to develop a predictive model that is able to forecast the
cytopenia induced by temozolomide (TMZ) during concomitant chemoradiotherapy. Methods. Medical records of 128 patients
with newly diagnosed glioblastoma were evaluated to extract the baseline complete blood test before and during the six weeks of
chemoradiotherapy to create a dataset for the development of ML models. Using the constructed dataset, different ML algorithms
were trained and tested. Results. Our proposed algorithm achieved accuracies of 85.6%, 88.7%, and 89.3% in predicting
thrombocytopenia, lymphopenia, and neutropenia, respectively. Conclusions. *e algorithm designed and developed in this study,
called PrACTiC, showed promising results in the accurate prediction of thrombocytopenia, neutropenia, and lymphopenia
induced by TMZ in glioblastoma patients. PrACTiC can provide valuable insight for physicians and help them to make the
necessary treatment modifications and prevent the toxicitie
The COVID‑19‑diabetes mellitus molecular tetrahedron
Full text linkAccumulating molecular evidence suggests that insulin resistance, rather than SARS-CoV-2- provoked beta-cell impair-
ment, plays a major role in the observed rapid metabolic deterioration in diabetes, or new-onset hyperglycemia, during the
COVID-19 clinical course. In order to clarify the underlying complexity of COVID-19 and diabetes mellitus interactions, we
propose the imaginary diabetes-COVID-19 molecular tetrahedron with four lateral faces consisting of SARS-CoV-2 entry
via ACE2 (lateral face 1), the viral hijacking and replication (lateral face 2), acute inflammatory responses (lateral face 3),
and the resulting insulin resistance (lateral face 4). The entrance of SARS-CoV-2 using ACE2 receptor triggers an array of
multiple molecular signaling beyond that of the angiotensin II/ACE2-Ang-(1–7) axis, such as down-regulation of PGC-1 α/
irisin, increased SREBP-1c activity, upregulation of CD36 and Sirt1 inhibition leading to insulin resistance. In another arm
of the molecular cascade, the SARS-CoV-2 hijacking and replication induces a series of molecular events in the host cell
metabolic machinery, including upregulation of SREBP-2, decrement in Sirt1 expression, dysregulation in PPAR-ɣ, and
LPI resulting in insulin resistance. The COVID-19-diabetes molecular tetrahedron may suggest novel targets for therapeutic
interventions to overcome insulin resistance that underlies the pathophysiology of worsening metabolic control in patients
with diabetes mellitus or the new-onset of hyperglycemia in COVID-19.
Keywords Covid-19 · Diabetes mellitus · Insulin resistance · Inflammation · ACE2 receptor · SARS-CoV-
Maternal aromatase inhibition via letrozole altered RFamide-related peptide-3 and gonadotropin-releasing hormone expression in pubertal female rats
Full text linkObjective(s): Despite prevalence of polycystic ovary syndrome (PCOS) among childbearing women and development of many animal models for this syndrome, information on its etiology is still scarce. The intrauterine hyperandrogenic environment may underlie changes at the level of hypothalamus, pituitary, ovary organization in female offspring, and PCOS later in life. Letrozole has been shown to mimic reproductive and metabolic characteristics of PCOS in adult rodent models. Therefore, this research aimed to assess the condition in a prenatal letrozole-treated rat model.
Materials and Methods: Twenty-eight female rats dams receiving letrozole at certain doses during late pregnancy were used in the trial. Pregnant Sprague-Dawley rats (n=21) received letrozole treatment on gestation days 16–18 at doses of 1.25, 1.0, 0.75, 0.5, and 0.25 mg/kg body weight (BW).
Results: Prenatal letrozole treatment delayed parturition time and reduced the litter size in pregnant dams (P<0.0001). Late puberty onset, irregular ovarian cyclicity, increased anogenital distance (AGD), body weight gain, serum testosterone concentration, and reduced estradiol levels (P<0.0001) were observed in the female offspring of dams receiving 1.25 and 1 mg/kg BW letrozole. Furthermore, letrozole at 1.25 and 1 mg/kg BW showed increased RFRP and decreased GnRH mRNA expression (P<0.0001). Letrozole treatment at doses of 1 mg/kg BW and lower was not fetotoxic.
Conclusion: It was concluded that 1 mg/kg BW letrozole may be suggested for prenatal PCOS induction.
Keywords
Gonadotropin-releasing hormone Hypothalamus Letrozole Polycystic ovary syndrome Prenatal Rat RFamide-related peptide-
Comparison of 18F-NaF Imaging, 99mTc-MDP Scintigraphy, and 18F-FDG for Detecting Bone Metastases
Full text linkBone is a common metastasis site in several malignancies, most importantly prostate and breast cancers. Given the significance of the early and accurate diagnosis of bone metastases for preliminary staging, treatment planning and monitoring, restaging, and survival prediction in patients with malignancy, it is critical to compare and contrast the strengths and weaknesses of imaging modalities. Although technetium-99m-labeled diphosphonates [99mTc-MDP] scintigraphy has been used for assessing skeletal involvement, there is a renewed interest in fluorine-18-labeled sodium fluoride [18F-NaF] bone imaging with positron emission tomography or positron emission tomography/computed tomography, since this approach provides essential advantages in bone metastases evaluation. This review study aimed to discuss the basic and technical aspects of 18F-NaF imaging and its mechanism of action, and compare this modality with the 99mTc-MDP bone scan and 18F-fluorodeoxyglucose using current evidence from the pertinent literature and case examples of the center in the study
Effects of four herbs as a dietary on properties of egg and immune response against Newcastle and avian influenza vaccine in Japanese laying quail
No full textThis study shows the effectiveness of diet containing Trachyspermum copticum (TC), Majorana hortensis Minch (MH), Stachys lavandulifolia Vahl (SL), and Zingiber officinale (ZO) on the growth performance, biochemical factors, and qualitative agents of eggs of Japanese quail (Coturnix japonica) and their immune responses against Newcastle and Avian Influenza vaccine. For this prepose, 675 quails were divided into 9 groups with three replicates and fed with different treatment diets (basic diet with no supplements (control treatment diet) and diets supplemented with one of two levels (0.5 and 2%) of each plant powders). Data showed that the use of TC 2% increased the Haugh unit significantly (P < 0.05) compared with the control (P < 0.05). At the end of the experiment, shell weight (g) and shell thickness were also remarkably enhanced in treated groups compared with the control group. Moreover, the findings of this study showed the thiobarbituric acid and yolk cholesterol level reduced remarkably (P < 0.05) in the MH and SL groups without significant adverse effect on albumen protein (%) and total protein (%) level. In this study, TC-2%, ZO-2%, and SL-2% all increased the antibody titers against avian influenza. The use of a diet containing MH-2% increased Newcastle disease in Japanese quail in comparison to both controls and different levels of other medicinal herb powders. Based on these results, using these four herbal plant powders in Japanese quail, diets could positively affect their egg qualitative and biochemical factors
Investigating an iron-doped fullerene cage for adsorption of niacin (vitamin B3): DFT analyses of bimolecular complex formations
No full textBy the importance of developing further applications of nanostructures in biologically related systems, a representative model of iron (Fe)-doped fullerene cage (Cage) was investigated in this work for adsorbing the niacin (Nic) vitamin B3 component. Density functional theory (DFT) calculations were performed and the results indicated three possible configurations of Cage-Nic bimolecular complexes. In this regards, the interaction details and strengths were analyzed by means of the features of quantum theory of atoms in molecules (QTAIM) and binding energies. The results approved a reasonable strength of formations of Cage-Nic bimolecular complexes besides showing the localization of frontier molecular orbitals at the Cage side for conducting a targeted delivery process. Moreover, the illustrated diagrams of density of states (DOS) indicated various values of energy gaps; 6.103, 5.779, and 6.319 eV, for the complexes showing the benefits of employed Cage for sensor function of the adsorbed Nic component
Silymarin Administration Attenuates Cirrhotic-induced Cardiac Abnormality in the Rats: A Possible Role of β1-adrenergic Receptors and L-type Voltage-Dependent Calcium Channels
Full text linkBackground: Cirrhotic cardiomyopathy is a well-recognized cardiac dysfunction in cirrhotic patients. Studies have confirmed the protective effects of silymarin in different types of cardiac injury. This study aimed to examine the effectiveness and molecular mechanism of silymarin against myocardial dysfunction and hypertrophy in a rat model of cirrhosis.
Methods: The experiment was performed at Alborz University of Medical Sciences (Karaj, Iran) during 2020-2021. Thirty-two male Wistar rats were randomly divided into four groups of Sham-operated (control group for surgical procedures), Bile Duct Ligated (BDL), and two Silymarin extract (SE)-treated groups of 300 and 600 mg/Kg/day. After 28 days, serum levels of AST, ALT, GGT, and ALP, liver histopathological status, as well as cardiac mechanical function, were assessed. Cardiac β1-adrenergic receptors (β1-AR), L-type voltage-dependent calcium channels (L-VDCC), and GATA4 mRNA expression were also determined using real-time RT-PCR. Data analysis was performed using the one-way ANOVA followed by Duncan’s multiple range test. Histological data has been analyzed with Kruskal-Wallis nonparametric test. The analysis was performed at P≤0.05.
Results: BDL was associated with a significant elevation in serum AST, ALT, GGT, and ALP, development of necrosis and fibrosis of the liver texture, increased Heart Weight and Heart Weight to Body Weight ratio, enhanced cardiac mechanical function as well as a significant up-regulation of ventricular β1-AR and L-VDCC. Administration of SE600, but not SE300, significantly reduced the serum levels of the enzymes and alleviated signs of liver necrosis and fibrosis. Cirrhotic-induced cardiac dysfunction was also restored by SE600, but not by the lower dose. In addition, cardiac expression of the β1-AR and L-VDCC was down-regulated toward normal values by either higher or lower doses of the SE.
Conclusion: Silymarin treatment in higher dose attenuated cirrhosis-associated cardiac remodeling and reduced cardiac mechanical dysfunctions
Perceptions of Caregiving by Family Caregivers of Older Adults with Dementia in Iran: A Qualitative Study
No full textThe concept of caring appraisal, which includes positive and negative aspects of care, has been considered as one of the key concepts in caregivers’ studies and is affected by the knowledge, attitudes, values, beliefs, and social norms in their society. In this respect, the perception of family caregivers’ can be studied from a cultural perspective. The aim of the present study was to explore the self-appraisal concept of caring based on the experience of family caregivers of older adults with dementia in Iran. In this qualitative study, data were collected through in-depth, semi-structured interviews. Twelve participants (family caregivers of elderly with dementia) were interviewed between January and September 2016. The transcribed texts were analyzed using inductive qualitative content analysis recommended by Graneheim and Lundman (2004). Six main categories were extrapolated: “Perceived burden,” “Satisfaction with care,” “Personal growth,” “Caregiving gains,” “Philosophy of care” and “Loss and threat.” According to the findings, the family caregivers’ appraisal of their care not only included negative aspects, but also covered a number of positive aspects, which in them the cultural and social factors prevailing in Iranian society played a significant role
A Randomized Trial of Sitagliptin and Spironolactone With Combination Therapy in Hospitalized Adults With COVID-19
Full text linkCOVID-19 may cause respiratory distress syndrome and death. Treatment of COVID-19 to prevent complications remains a priority.
Objective
Our investigation sought to determine whether combination of spironolactone and sitagliptin could reduce mortality for inpatients with SARS-CoV-2 infection.
Methods
This single-blind, 4-arm, prospective randomized clinical trial was conducted at Shiraz and Bushehr University of Medical Sciences hospitals between December 2020 and April 2021. We randomized hospitalized adult patients with COVID-19 pneumonia into 4 groups: control, combination therapy, sitagliptin add-on, or spironolactone add-on. The primary outcome was the clinical improvement of the patients in the hospital as measured on an 8-point numerical scale. The secondary outcomes included intubation, ICU admission, end organ damages, CT findings, and paraclinical information.
Results
A total of 263 admitted patients were randomly assigned to control group (87 patients), combination group (60 patients), sitagliptin group (66 patients), and spironolactone group (50 patients). There were no significant differences in baseline characteristics, except for higher age in control group. The intervention groups, especially combination therapy, had better clinical outcomes (clinical score on fifth day of admission: 3.11 ± 2.45 for controls, 1.33 ± 0.50 for combination, 1.68 ± 1.02 for sitagliptin, and 1.64 ± 0.81 for spironolactone; P = 0.004). However, the mortality rate was lower in patients who received spironolactone (21.84% control, 13.33% combination, 13.64% sitagliptin, 10.00% spironolactone; P = 0.275). Our intervention reduced lung infiltration but not the area of involvement in lungs.
Conclusion
Sitagliptin and spironolactone can potentially improve clinical outcomes of hospitalized COVID-19 patients
Monitoring and eco-toxicity effect of paraben-based pollutants in sediments/seawater, north of the Persian Gulf
No full textThe current work is documented as the first record of the characteristics, removal efficiency, partitioning behavior, fate, and eco-toxicological effects of paraben congeners in a municipal wastewater treatment plant (WWTP, stabilization ponds) and hospital WWTPs (septic tank and activated sludge), as well as seawater-sediments collected from runoff estuarine stations (RES) and coastal stations (CS) of the north of the Persian Gulf. The median values of Σparabens at the raw wastewater and effluent of the studied WWTPs were 1884 ng/L and 468 ng/L, respectively. The activated sludge system had a greater removal efficiency (56.10%) in removing ∑parabens than the septic tank (45.05%) and stabilization pond (35.54%). The discharge rates of methyl paraben (MeP) was computed to be 2.23, 21.18, and 9.12 g/d/1000 people for stabilization ponds, septic tank, and activated sludge, respectively. Median concentrations of Σparabens in seawater (103.42 ng/L) and sediments (322.05 ng/g dw) from RES stations were significantly larger than from CS stations (61.2 and 262.0 ng/g dw in seawater and sediments, respectively) (P < 0.05). The median of field-based koc for Σparabens was 130.81 cm3/g in RES stations and 189.51 cm3/g in CS stations. It was observed that the concentration of parabens could have negative impacts on some living aquatic populations (invertebrates and bacteria), but the risk was not significant for fishes and algae