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Restless legs syndrome in Parkinson’s disease: relationship with quality of life and medication

Bratisl Lek Listy. 2022;123(1):55-60. doi: 10.4149/BLL_2022_009.

ABSTRACT

OBJECTIVES: We aimed to disclose the relationship between restless leg syndrome (RLS) and antiparkinsonian treatment, and its effect on quality of life (QoL) in patients with Parkinson’s disease (PD).

BACKGROUND: Previous studies documented the prevalence of RLS among patients with PD to be higher than in the general population, but conclusions regarding the aetiology and impact were contradictory.

METHODS: We examined 101 patients with idiopathic PD. All participants completed the five-dimension/five-level-EuroQoL questionnaire (EQ-5D-5L) and the International Restless-Legs-syndrome-study-group rating Scale (IRLS).

RESULTS: The prevalence of RLS was 22.77 %. There were no statistically significant differences in levodopa or dopamine agonists (DA) doses between RLS-positive and negative participants. However, the use of levodopa as the last night-time medication was connected with a higher risk of RLS (OR=2.049, p=0.041). There was significantly lower prevalence of RLS in patients after surgical treatment for PD (p=0.024). Participants with RLS were at a greater risk for sleep disturbances (OR=3.866, p=0.023) and excessive daytime sleepiness (OR=7.202, p<0.001). Greater RLS symptoms were associated with worse QoL (higher IRLS score predicted higher EQ5D5L score, p=0.023).

CONCLUSION: RLS is prevalent among PD patients and night-time dopaminergic over-excitation with levodopa plays an important role in its pathogenesis. Since the symptoms of RLS are associated with decreased QoL, early accurate diagnosis and appropriate adjustment of dopaminergic therapy can lead to immediate relief from RLS symptoms and to QoL improvement (Tab. 4, Fig. 1, Ref. 34).

PMID:34967659 | DOI:10.4149/BLL_2022_009

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Label-Free Dynamic Imaging of Chromatin in Live Cell Nuclei by High-Speed Scattering-Based Interference Microscopy

ACS Nano. 2021 Dec 30. doi: 10.1021/acsnano.1c09748. Online ahead of print.

ABSTRACT

Chromatin is a DNA-protein complex that is densely packed in the cell nucleus. The nanoscale chromatin compaction plays critical roles in the modulation of cell nuclear processes. However, little is known about the spatiotemporal dynamics of chromatin compaction states because it remains difficult to quantitatively measure the chromatin compaction level in live cells. Here, we demonstrate a strategy, referenced as DYNAMICS imaging, for mapping chromatin organization in live cell nuclei by analyzing the dynamic scattering signal of molecular fluctuations. Highly sensitive optical interference microscopy, coherent brightfield (COBRI) microscopy, is implemented to detect the linear scattering of unlabeled chromatin at a high speed. A theoretical model is established to determine the local chromatin density from the statistical fluctuation of the measured scattering signal. DYNAMICS imaging allows us to reconstruct a speckle-free nucleus map that is highly correlated to the fluorescence chromatin image. Moreover, together with calibration based on nanoparticle colloids, we show that the DYNAMICS signal is sensitive to the chromatin compaction level at the nanoscale. We confirm the effectiveness of DYNAMICS imaging in detecting the condensation and decondensation of chromatin induced by chemical drug treatments. Importantly, the stable scattering signal supports a continuous observation of the chromatin condensation and decondensation processes for more than 1 h. Using this technique, we detect transient and nanoscopic chromatin condensation events occurring on a time scale of a few seconds. Label-free DYNAMICS imaging offers the opportunity to investigate chromatin conformational dynamics and to explore their significance in various gene activities.

PMID:34967599 | DOI:10.1021/acsnano.1c09748

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Discovery of a Series of Pyrimidine Carboxamides as Inhibitors of Vanin-1

J Med Chem. 2021 Dec 30. doi: 10.1021/acs.jmedchem.1c01849. Online ahead of print.

ABSTRACT

A diaryl ketone series was identified as vanin-1 inhibitors from a high-throughput screening campaign. While this novel scaffold provided valuable probe 2 that was used to build target confidence, concerns over the ketone moiety led to the replacement of this group. The successful replacement of this moiety was achieved with pyrimidine carboxamides derived from cyclic secondary amines that were extensively characterized using biophysical and crystallographic methods as competitive inhibitors of vanin-1. Through optimization of potency and physicochemical and ADME properties, and guided by co-crystal structures with vanin-1, 3 was identified with a suitable profile for advancement into preclinical development.

PMID:34967602 | DOI:10.1021/acs.jmedchem.1c01849

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Association between c-Myc Expression with Clinicopathological Features in T And NK Cell Lymphomas

Asian Pac J Cancer Prev. 2021 Dec 1;22(12):4011-4016. doi: 10.31557/APJCP.2021.22.12.4011.

ABSTRACT

BACKGROUND: c-Myc has become significantly involved in aggressive B-cell non Hodgkin lymphoma (NHL), but little is known about its importance in T and NK cell NHL (TNKcNHLs) in association with prognostic factors. The study is to investigate the significance of c-Myc expression with clinicopathological features of TNKcNHLs patients.

METHODOLOGY: A cross-sectional study of 32 archived tissue blocks of TNKcNHLs were immunohistochemically stained with c-Myc. The results were microscopically evaluated and statistically analysed to examine the association between the clinicopathological data with the c-Myc expression.

RESULTS: c-Myc protein expressions were detected in 25/32 (78.1%) cases. The median age was 38-years. Malay ethnicity (92.0%) with 21 males and 11 females. c-Myc expressions were seen in T lymphoblastic lymphoma (20%), ALK-positive ALCL (16%) ,PTCL,NOS (16%), extra nodal NK/T-cell lymphoma, nasal type (12%), extra-nodal involvement (78.1%), elevated serum LDH (83.3%) and high ECOG performance status (82.4%). However, no statistical significant of c-Myc in association with the clinicopathological parameters (p > 0.05).

CONCLUSION: There was no statistically significant association of clinicopathological parameters and histological subtypes of TNKcNHLs contributed by small samples tested. However, the attribution of c-Myc in this disease should be further explored.

PMID:34967583 | DOI:10.31557/APJCP.2021.22.12.4011

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Black Turmeric and Aloe Vera in the Management of Oral Submucous Fibrosis: A Prospective Clinical Study

Asian Pac J Cancer Prev. 2021 Dec 1;22(12):3941-3947. doi: 10.31557/APJCP.2021.22.12.3941.

ABSTRACT

AIM: To determine the therapeutic efficacy of Kali haldi in the management of Oral submucous Fibrosis (OSMF) v/s steroid therapy.

MATERIALS AND METHODS: A clinical prospective study was conducted on 42 patients of oral submucous fibrosis were equally divided into 2 groups. Group A patients were treated with a mixture of powdered Kali Haldi and aloe vera gel in equal ratio 3 times a day for 3 months. Group B patients were treated with intralesional injection of hydrocortisone and hyaluronidase for 6 weeks with oral antioxidant supplements for 3 months. Burning sensation, cheek flexibility, mouth opening, and tongue protrusion were evaluated before, during, and after treatment at an interval of 15 days, 1 month, 2, month and 3 months.

RESULTS: Statistically significant results were obtained at the end of 3 months duration for both the groups (P < 0.001). The Symptomatic correction was more evident in the case of Group A patients than Group B. Response of the ayurvedic regimen was potentially better as compared to the regular steroid therapy.

CONCLUSION: The study concludes that Combination therapy works wonders in the case of OSMF in stages I, II, III and can be a good option, comparatively safe and with negligible side effects, but potent and equally effective management of oral submucous fibrosis. Henceforth, it will be better to do such kinds of studies on a vast scale including larger samples and longer duration to check the efficacy and durability of this ancient ayurvedic regimen.

PMID:34967575 | DOI:10.31557/APJCP.2021.22.12.3941

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Intronic Variant of MUTYH Gene Exhibits A Strong Association with Early Onset of Breast Cancer Susceptibility in Indonesian Women Population

Asian Pac J Cancer Prev. 2021 Dec 1;22(12):3985-3991. doi: 10.31557/APJCP.2021.22.12.3985.

ABSTRACT

OBJECTIVE: Several studies have recently indicated a huge shifting pattern toward early age onset cases in breast cancer (BC) patients. However, the studies exerted relatively limited to the Caucasian population. This preliminary study is aimed to investigate the genetic risk factors for young BC patients specifically in Indonesia population.

METHODS: DNA samples were extracted from 79 BC patients aged younger than 40 years old and 90 healthy samples. These DNA samples were sequenced using Illumina NextSeq 500 platform and preprocessed to extract the single-nucleotide polymorphisms (SNPs) data. Firstly, multiple univariate logistic regressions were performed to test the association between each SNP and BC incidence in young patients. Furthermore, to analyze the polygenic effects derived from multiple SNPs, we employed a multivariate logistics regression.

RESULTS: There were only 15 SNPs passed our 95% call rate threshold thus subsequently were used in the association test. One of these variants, rs3219493, emerged to be significantly associated with early-onset BC (p-value = 0.025, OR = 3.750, 95% CI = 1.178-11.938). This result is consistent with the multivariate logistic regression model, where the pertinent variant was found statistically significant (p-value = 0.008, OR = 8.398, 95% CI = 1.720-40.920). This variant was identified as an intronic variant within MUTYH gene which has been reported in several published studies to exhibit an association with the incidence of breast cancer in China, Italy and Sephardi Jews population. However, there is no evident this gene impacting the risk of developing early onset of BC in Indonesia population.

CONCLUSION: Despite our limitation in terms of sample size analyzed in this preliminary study, our finding on significant association of intronic MUTHY with the early onset of BC in Indonesia led to a broadened insight of population-based unique aspect to being taken into an in-depth account for and advancement of chemotherapy.

PMID:34967580 | DOI:10.31557/APJCP.2021.22.12.3985

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Trends in Breast Cancer Incidence in Iraq During the Period 2000-2019

Asian Pac J Cancer Prev. 2021 Dec 1;22(12):3889-3896. doi: 10.31557/APJCP.2021.22.12.3889.

ABSTRACT

BACKGROUND: Breast cancer is the most common cancer among women around the world.

OBJECTIVE: This study aims to explore the time trends in the incidence of breast cancer in Iraq in twenty years period (2000 to 2019) to assist health officials and decision-makers in planning and organizing programs to controlling breast cancer growth and enhance women’s health.

METHODS: Breast cancer data from 2000 to 2019 were obtained from the Iraqi Cancer Registry’s yearly book series (Ministry of Health). The United Nations Population Division provides annual population estimates by 5-year age groups and gender. Joinpoint regression analysis was used to calculate and assess age-specific and age-standardized incidence rates.

RESULTS: A total of 72,022 breast cancer cases were identified among women in Iraq between 2000 and 2019. The average age-standardized incidence rate (ASIRs) was 37.883/100,000. Breast cancer ASIR Iraq exhibited a significantly rising trend during the study period, with an average annual percentage change (AAPC) of +3.192%. Furthermore, a significant increase in breast cancer incidence for the age group 40-49 (AAPC = +2.162%), 50-59 (AAPC=+3.210%), 60-69 (AAPC=+5.551%), and age 70 and over (AAPC=+7.943%) were observed. When compared to other countries in the world, Iraq had a moderate rate of breast cancer ASIR.

CONCLUSIONS: In summary, our finding revealed an increase in the incidence rates of breast cancer among Iraqi women from 2000 to 2019. Further research is needed to explore risk factors including levels of overweight, dietary changes, physical inactivity, obesity, smoking, high marriage age, and low birth rates to prevent and control breast cancer.

PMID:34967568 | DOI:10.31557/APJCP.2021.22.12.3889

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Polo-Like Kinase 1(PLK1) Immunohistochemical Expression in Triple Negative Breast Carcinoma: A Probable Therapeutic Target

Asian Pac J Cancer Prev. 2021 Dec 1;22(12):3921-3925. doi: 10.31557/APJCP.2021.22.12.3921.

ABSTRACT

BACKGROUND: Breast cancer is the most commonly diagnosed female cancer and is a major cause of cancer-related deaths in women. Triple-negative breast cancer (TNBC) is defined as ER, PR and HER2 negative, which are characterized by rapid progression with low survival rates with limited therapeutic choices. Polo-like kinase 1 protein acts as a cell division regulator which is highly expressed in many tumors making it a potentially valuable target for antiproliferative therapies. In this study we tried to evaluate the value of this marker as a possible therapeutic target in TNBC.

METHODS: This research studied the immunohistochemical expression of PLK1 done on 49 paraffin blocks of TNBC female patients and then correlated with the different clinicopathological parameters.

RESULTS: Our results showed high PLK1 expression in 91.9% of cases. Most of the high grade tumors showed high PLK1 high score (76.9%). All cases showing lymph node metastasis showed high PLK1 expression, implying a statistically significant correlation between PLK1 expression and tumor grade as well as N stage.

CONCLUSION: PLK1, although a negative prognostic factor, but is a promising therapeutic target for treating TNBC patients.

PMID:34967572 | DOI:10.31557/APJCP.2021.22.12.3921

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Spiritual Care Needs of Terminal Ill Cancer Patients

Asian Pac J Cancer Prev. 2021 Dec 1;22(12):3773-3779. doi: 10.31557/APJCP.2021.22.12.3773.

ABSTRACT

OBJECTIVE: Terminal ill cancer patients experience spiritual distress and need spiritual care. They are in need of palliative care in the long term to alleviate suffering. The aim of the study was to investigate spiritual needs of terminal ill cancer patients.

METHODS: This study is a cross-sectional study. The participants were Thai terminal ill cancer patients from seven hospitals in northern, northeast, central, and southern regions of Thailand. Three-hundred-and-twenty-two participants were purposively selected. The instrument used in this study was a spiritual needs scale, consisting of 41 items with 4-point rating scale. Statistical analysis was F-test for one-way analysis of variance.

RESULTS: The majority of terminal ill cancer patients aged fifty-one years old. Most of them were females with end stage cancer status that did not respond to treatment. The overall spiritual needs of terminal ill cancer patients were at the moderate level (M = 18.21, SD = 2.56). The highest mean was found in the ‘prepare for death’ dimension, followed by the ‘have meaning, values, and life purposes’ and the ‘have opportunity to pursue most important things in life’ dimensions respectively and had different spiritual needs among status (F(3,318) = 3.66, p < 0.05), number of family members (F(8,313) = 5.07, p < 0.05), living with family (F(2,319) = 3.91, p < 0.05), and spiritual anchor (F(2,319) = 4.13, p < 0.05).

CONCLUSION: The study results provide insight into spiritual needs of terminal ill cancer patients which assists in improving the provision of holistic care to let the patients be happy at end-of-life phase.

PMID:34967555 | DOI:10.31557/APJCP.2021.22.12.3773

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Impact of Weight Loss on Patients with Locally Advanced Esophageal and Esophagogastric Junction Cancers Treated with Chemoradiotherapy

Asian Pac J Cancer Prev. 2021 Dec 1;22(12):3847-3855. doi: 10.31557/APJCP.2021.22.12.3847.

ABSTRACT

INTRODUCTION: Malnutrition and weight loss are commonly observed in patient with esophageal and esophagogastric junction (EGJ) cancers. Chemoradiotherapy (CRT) is a mainstay of treatment for locally advanced esophageal and EGJ cancers. Impact of weight loss on patients with treated with CRT was not well studied.

METHODS: Patients with locally advanced esophageal and EGJ cancer who received CRT were identified in our institutional database and allocated into low (LWL) and high (HWL) weight loss groups. HWL was defined as weight loss >5% of baseline during CRT.

RESULTS: A total of 167 patients were underwent definitive (n=89) or preoperative (n=78) CRT, respectively. HWL was observed in 46% and 55% of patients treated with definitive and preoperative CRT, respectively. Cisplatin/5FU regimen used during CRT was a significant predictive factor for weight loss in multivariate analysis (OR 2.07, 95% CI 1.09-3.94; p=0.026). In the definitive CRT group, patients in the HWL group experienced significantly worse overall survival than those in the LWL group (1.2 years vs 1.95 years; p=0.003). Multivariate analysis revealed that baseline albumin (>3.0 g/dL) was significantly associated with longer OS of definitive CRT patients (HR 2.15, 95% CI 1.1-4.19; p=0.024). Tolerability and toxicities during CRT were not statistically different between groups.

CONCLUSION: Significant weight loss during CRT was frequently observed in patients with locally advanced esophageal and EGJ cancers. Baseline hypoalbuminemia was an independent prognostic factor for OS in patients treated with definitive CRT. Nutritional support before and during treatment should be considered to potentially improve patients’ outcomes.<br />.

PMID:34967563 | DOI:10.31557/APJCP.2021.22.12.3847