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Therapeutic effects ofin-vivoradiodynamic therapy (RDT) for lung cancer treatment: a combination of 15MV photons and 5-aminolevulinic acid (5-ALA)

Biomed Phys Eng Express. 2022 Oct 19. doi: 10.1088/2057-1976/ac9b5c. Online ahead of print.

ABSTRACT

OBJECTIVE: Radiodynamic therapy (RDT) uses high-energy photon beams instead of visible/near-infrared light to treat deep-seated tumors that photodynamic therapy cannot achieve due to the low penetration depth of laser beams. The purpose of this study is to investigate the therapeutic effect of RDT with 15MV photon beams combined with 5-aminolevulinic acid (5-ALA) using a mouse model.

APPROACH: A subcutaneous C57BL/6 mouse model of KP1 small-cell lung cancer cell line was used. The tumors (N=120) were randomized into four groups to observe individual and synergistic effects of 5-ALA and radiation treatment: control (untreated, N=42), radiation treatment (RT) only (N=20), 5-ALA only (N=20), and RDT (N=38). For the RT only and RDT groups, 4Gy in a single fraction was delivered to the tumors using 15MV photons. For the 5-ALA only and RDT groups, 5-ALA was injected at a dose of 100mg/kg by tail-vein 4 hours prior to RT. The tumor response was assessed by monitoring tumor growth using 1.5T MR, maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG) using [18F]FDG PET/CT, and animal survival.

MAIN RESULTS: RDT achieved a statistically significant delay in tumor growth by 52.1%, 48.1%, and 57.9% 7 days post-treatment compared to 5-ALA only, RT only, and control group (P<0.001), respectively. There were no significant differences in tumor growth between 5-ALA only and RT only groups. An additional 38.5-40.9% decrease in tumor growth was observed, showing a synergistic effect with RDT. Furthermore, RDT significantly decreased [18F]FDG uptakes in SUVmaxand TLG 7 days post-treatment by 47.4% and 66.5% (P<0.001), respectively. RDT mice survived the longest of all treatment groups.

SIGNIFICANCE: RDT with 15MV photons and 5-ALA resulted in greater tumor control compared to the control and other treatment groups. A significant synergistic effect was also observed with RDT. These preliminary results demonstrate an effective cancer treatment modality.

PMID:36263662 | DOI:10.1088/2057-1976/ac9b5c

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Association between Heart Rate Variability Indices and Depressed Mood in Patients with Panic Disorder

Clin Psychopharmacol Neurosci. 2022 Nov 30;20(4):737-746. doi: 10.9758/cpn.2022.20.4.737.

ABSTRACT

OBJECTIVE: Heart rate variability (HRV) reflects the regulation of the autonomic nervous system. Panic disorder is highly associated with autonomic dysfunction, and is often accompanied by depression. The aim of this study is to determine the association between depression and HRV indices in patients with panic disorder.

METHODS: A total of 110 outpatients diagnosed with panic disorder participated in this study. The medical records of patients with panic disorder who visited the outpatient clinic of Konkuk University Hospital between December 2018 and March 2020 were retrospectively reviewed. Measurements used in this study include the Panic Disorder Severity Scale-Self Report, Beck Depression Inventory (BDI-II), Insomnia Severity Index, and HRV. Patients were divided into depressive and non-depressive groups based on their BDI-II scores. The association between HRV indices and depressive symptoms was statistically analyzed.

RESULTS: The low frequency/high frequency (LF/HF) ratio was reduced in patients with depression (mean = -0.095, p = 0.004 in the above moderate depressive group, mean = -0.120, p = 0.020 in the severe depressive group). Significant correlations were found between depressive symptoms and standard deviation of NN interval (SDNN) (ms) (-0.19, p = 0.044), very low frequency (VLF) (ms2/Hz) (-0.22, p = 0.021), LF (-0.25, p = 0.008), HF (-0.19, p = 0.043), and LF/HF (-0.25, p = 0.009). Multiple linear regression analysis showed that BDI predicted SDNN (ms), VLF (ms2/Hz), LF, HF, and LF/HF.

CONCLUSION: We confirmed that the LF/HF ratio decreases when depression is accompanied by panic disorder. HRV indices may be useful markers for detecting depressive symptoms in patients with panic disorder.

PMID:36263648 | DOI:10.9758/cpn.2022.20.4.737

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Intestinal histomorphological and molecular alterations in patients with Parkinson’s disease

Eur J Neurol. 2022 Oct 20. doi: 10.1111/ene.15607. Online ahead of print.

ABSTRACT

BACKGROUND: Changes in gut microbiota composition, enteric inflammation, impairments of the intestinal epithelial barrier (IEB) and enteric neuro-immune system have been reported in Parkinson’s disease (PD) patients and could contribute to the onset of both neurological and gastrointestinal symptoms. However, their mutual interplay has rarely been investigated. This study evaluated, in an integrated manner, changes in faecal microbiota composition, morpho-functional alterations of the colonic mucosal barrier and changes of inflammatory markers in blood and stools of PD patients.

METHODS: 19 PD patients and 19 asymptomatic subjects were enrolled. Blood lipopolysaccharide binding protein (LBP, marker of altered intestinal permeability) and Interleukin-1β (IL-1β), as well as stool IL-1β and tumour necrosis factor (TNF) levels, were evaluated. Gut microbiota analysis was performed. Epithelial mucins, collagen fibres, Claudin-1 and S-100 positive glial cells as markers of an impairment of the intestinal barrier and mucosal remodelling were evaluated on colonic mucosal specimens collected during colonoscopy.

RESULTS: Faecal microbiota analysis revealed a significant difference in the α-diversity in PD patients compared to controls, while no differences were found in the beta diversity. Compared to controls, PD patients showed a significant increase in plasma LBP, as well as faecal TNF and IL-1β levels. The histological analysis showed a decrease in epithelial neutral mucins and claudin-1 expression, and an increased expression of acidic mucins, collagen fibres and S-100 positive glial cells.

CONCLUSIONS: PD patients are characterized by intestinal inflammation and increased IEB permeability, as well as colonic mucosal barrier remodeling, associated with changes in gut microbiota composition.

PMID:36263629 | DOI:10.1111/ene.15607

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Increased Serum Brain-derived Neurotrophic Factor, Nerve Growth Factor, Glial-derived Neurotrophic Factor and Galanin Levels in Children with Attention Deficit Hyperactivity Disorder, and the Effect of 10 Weeks Methylphenidate Treatment

Clin Psychopharmacol Neurosci. 2022 Nov 30;20(4):635-648. doi: 10.9758/cpn.2022.20.4.635.

ABSTRACT

OBJECTIVE: This study aimed to investigate the levels of serum brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF) and galanin in children with attention deficit hyperactivity disorder (ADHD).

METHODS: The study included 58 cases with ADHD and 60 healthy controls. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL) together with Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) criteria were used for diagnostic evaluation. Sociodemographic data form and Conners’ Parent/Teacher Rating Scale-Revised:Long Form were applied to all cases. The serum levels of BDNF, NGF, GDNF, and galanin were evaluated in all subjects. Afterwards, methylphenidate was started in the ADHD group. ADHD cases were reevaluated in terms of the serum levels of BDNF, NGF, GDNF, galanin at the 10th week of treatment.

RESULTS: Before the treatment, the levels of BDNF, NGF, GDNF, galanin were significantly higher in the ADHD group compared to the control group. The levels of BDNF, NGF, GDNF, galanin were found to be significantly lower after treatment in ADHD group compared to pre-treatment. No correlation was between scale scores and the serum levels of BDNF, NGF, GDNF, galanin.

CONCLUSION: The levels of neurotrophic factors and galanin were thought to be parameters worth evaluating in ADHD. Further studies on the subject with longer-term treatments and larger sample groups are required.

PMID:36263639 | DOI:10.9758/cpn.2022.20.4.635

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Transmission roles of symptomatic and asymptomatic COVID-19 cases: a modelling study

Epidemiol Infect. 2022 Sep 27;150:e171. doi: 10.1017/S0950268822001467.

ABSTRACT

Coronavirus disease 2019 (COVID-19) asymptomatic cases are hard to identify, impeding transmissibility estimation. The value of COVID-19 transmissibility is worth further elucidation for key assumptions in further modelling studies. Through a population-based surveillance network, we collected data on 1342 confirmed cases with a 90-days follow-up for all asymptomatic cases. An age-stratified compartmental model containing contact information was built to estimate the transmissibility of symptomatic and asymptomatic COVID-19 cases. The difference in transmissibility of a symptomatic and asymptomatic case depended on age and was most distinct for the middle-age groups. The asymptomatic cases had a 66.7% lower transmissibility rate than symptomatic cases, and 74.1% (95% CI 65.9-80.7) of all asymptomatic cases were missed in detection. The average proportion of asymptomatic cases was 28.2% (95% CI 23.0-34.6). Simulation demonstrated that the burden of asymptomatic transmission increased as the epidemic continued and could potentially dominate total transmission. The transmissibility of asymptomatic COVID-19 cases is high and asymptomatic COVID-19 cases play a significant role in outbreaks.

PMID:36263615 | DOI:10.1017/S0950268822001467

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Placental proteome in late‑onset of fetal growth restriction

Mol Med Rep. 2022 Dec;26(6):356. doi: 10.3892/mmr.2022.12872. Epub 2022 Oct 20.

ABSTRACT

Fetal growth restriction (FGR) occurs when the fetus does not reach its genetically programmed intrauterine potential for growth and affects ~5‑10% of pregnancies. This condition is one of the leading causes of perinatal mortality and morbidity associated with obstetric and neonatal complications. Placental dysfunction in FGR causes an impairment in the transfer of nutrients and oxygen from the mother to the developing fetus. Maternal adaptations to placental insufficiency may also play a role in the pathophysiology of FGR. The present study aimed to compare the proteome of the placentas of 18 women with the physiological course of pregnancy and eutrophic fetus [estimated fetal weight (EFW) >10th percentile; control group] and 18 women with late FGR (EFW <10th percentile) diagnosed after 32 weeks of pregnancy, according to the Delphi consensus (study group). The U. Mann‑Whitney test was used to compare two independent groups. The R. Spearman correlation coefficient significance test was used to assess the existence of a relationship between the analyzed measurable parameters. P<0.05 was considered to indicate a statistically significant difference. The tests showed the presence of 356 different proteins which were responsible for the regulation of gene transcription control, inhibiting the activity of proteolytic enzymes, regulation of trophoblast proliferation and angiogenesis and inflammatory response. In the FGR placental proteome, other detected proteins were mostly involved in response to oxidative stress, cellular oxidation and detoxication, apoptosis, hemostatic and catabolic processes, energy transduction protein interactions, cell proliferation, differentiation and intracellular signaling. The present study used chromatographic mass‑spectrometry to compare the placental proteome profiles in pregnancies complicated by late‑onset FGR and normal pregnancy. Comparative analysis of proteomes from normal and FGR placentas showed significant differences. Further research is needed to clarify maternal and fetal adaptations to FGR.

PMID:36263610 | DOI:10.3892/mmr.2022.12872

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Clinical and Ultrasonic Risk Factors for High Volume Central Lymph Node Metastasis in cN0 Papillary Thyroid microcarcinoma: A Meta-Analysis

Clin Endocrinol (Oxf). 2022 Oct 20. doi: 10.1111/cen.14834. Online ahead of print.

ABSTRACT

BACKGROUND: Papillary thyroid microcarcinoma (PTMC) comprises more than 50% of all newly detected cases of papillary thyroid carcinoma (PTC). High volume lymph node metastasis (involving >5 lymph nodes) (hv-LNM) is associated with PTMC recurrence. In half of the clinically node-negative (cN0) PTMC patients, central lymph node metastasis (CLNM) is pathologically present. However, clinical risk factors for high volume CLNM (hv-CLNM) in cN0 PTMC have not been defined well. Therefore, we aimed to obtain evidence for hv-CLNM risk factors in cN0 PTMC.

METHODS: Data on patients who visited our hospital between January 2020 and December 2021 were collected; preoperative diagnosis of cN0 and a postoperative pathological confirmation of PTMC were obtained. After filtering by inclusion versus exclusion criteria, the obtained data (N=2268) were included in the meta-analysis. Relevant studies published as of April 10, 2022 were identified from Web of Science, PubMed, WANFANG, and CNKI databases. These eligible studies were included in the meta-analysis and the association between clinicopathological factors and hv-CLNM in cN0 PTMC was assessed. SPSS and MetaXL were used for statistical analyses.

RESULTS: The meta-analysis included 10 previous studies (11734 patients) and 2268 patients enrolled in our hospital for a total of 14002 subjects. The results of which suggested that younger age (<40, OR = 3.28, 95% CI = 2.75-3.92, p<0. 001 or <45 OR = 2.93, 95%CI = 2.31-3.72, p<0. 001), male sex (OR = 2.81, 95% CI = 2.25-3.52, p<0.001), tumor size>5mm (OR = 1.85, 95%CI = 1.39-2.47, p<0.001), multifocality (OR = 1.88, 95%CI = 1.56-2.26, p<0.001), extrathyroidal extension (OR = 2.58, 95%CI = 2.02-3.30, p<0. 001), capsule invasion (OR = 2.02, 95%CI = 1.46-2.78, p<0.001), microcalcification (OR = 3.25, 95%CI = 2.42-4.36, p<0.001), and rich blood flow (OR = 1.65, 95%CI = 1.21-2.25, p = 0.002) were the significant factors related to an elevated hv-CLNM risk in cN0 PTMC patients. Hashimoto thyroiditis (OR = 0.76, 95%CI = 0.55-1.07, p = 0.114), irregular margin (VS regular margin, OR = 0.96, 95%CI = 0.68-1.33, p = 0.787), and hypoechoic (VS Non-hypoechoic, OR = 1.27, 95%CI = 0.84-1.92, p = 0.261) showed no significant association with hv-CLNM.

CONCLUSION: Younger age, tumor size>5mm, males, extrathyroidal extension, multifocality, microcalcification, capsular invasion, and rich blood flow were the significant clinicopathological risk factors for hv-CLNM risk in cN0 PTMC patients. These predictors may compensate for the sensitivity of imaging diagnosis in the preoperative period, thus helping in the effective identification of PTMCs with an invasive phenotype. This article is protected by copyright. All rights reserved.

PMID:36263602 | DOI:10.1111/cen.14834

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New insights into smoking and urinary tract infections during pregnancy using pregnancy-pair design: A population-based register study

Acta Obstet Gynecol Scand. 2022 Oct 20. doi: 10.1111/aogs.14473. Online ahead of print.

ABSTRACT

INTRODUCTION: Pregnancy itself predisposes to urinary tract infections (UTI). There appears to be a higher prevalence of infections and genitourinary diseases among pregnant smokers than among non-smokers. The present study is a retrospective observational register study aiming to investigate whether maternal smoking is associated with the prevalence of UTIs during pregnancy by utilizing a pregnancy-pair analysis.

MATERIAL AND METHODS: Information about pregnancies and maternal smoking was obtained from the Finnish Medical Birth Register. The study sample consisted of all singleton pregnancies (n = 723 433) of women giving birth between January 2006 and December 2018 in Finland. Information on maternal smoking was collected in three categories: (1) non-smoking; (2) quit smoking during the first trimester; and (3) continued smoking throughout the pregnancy. Information about maternal UTI diagnoses during pregnancy was received from the Hospital Discharge Register and the Medical Birth Register. UTIs were categorized as lower and upper UTIs according to the International Statistical Classification of Diseases and Related Health Problems (ICD)-10 diagnosis codes. Risks were calculated as odds ratios (OR) by logistic regression with 95% confidence intervals (CI) further adjusted for maternal characteristics (aOR). Finally, pregnancy-pair analyses were performed: mothers who had changed smoking status (no smoking/any smoking) between consecutive pregnancies (n = 27 246 pregnancy-pairs) were analyzed as one cluster and compared with non-smokers.

RESULTS: Smokers had UTIs more often compared with the non-smokers. The association was even stronger among those who continued to smoke (aOR 1.60, 95% CI 1.51-1.70) than among those who smoked only during the first trimester (aOR 1.27, 95% CI 1.18-1.37) compared with non-smokers. In pregnancy-pair analysis, smoking was associated with upper UTIs during pregnancy (OR 1.49, 95% CI 1.05-2.12) compared with non-smokers, but after the adjustments this association was attenuated (aOR 1.27, 95% CI 0.88-1.82). No association in lower UTIs was observed in the pregnancy-pair design.

CONCLUSIONS: Maternal smoking was associated with a higher prevalence of UTIs during pregnancy in the standard comparison. The observed association was fully attenuated in the pregnancy-pair analysis, in which smoking was dichotomized. This study suggests that the association between maternal smoking during pregnancy and adverse maternal health effects might be more complex than previously thought.

PMID:36263583 | DOI:10.1111/aogs.14473

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Assessment of palpitation complaints in patients with benign paroxysmal positional vertigo

Eur Rev Med Pharmacol Sci. 2022 Oct;26(19):6979-6984. doi: 10.26355/eurrev_202210_29880.

ABSTRACT

OBJECTIVE: The detection of cardiac arrhythmias during vertigo attacks along with the resolution of vertigo by treating the arrhythmias is defined as cardiac vertigo. The cause of palpitations that develop following attacks of non-cardiac vertigo is unknown. We aimed to investigate the effect of benign paroxysmal positional vertigo (BPPV) on the cardiac conduction system and evaluate patients’ palpitation complaints using 24-hour ambulatory ECG (Holter) monitoring.

PATIENTS AND METHODS: Sixty-five patients with BPPV and forty-eight healthy controls were included in the study. ECG was performed on all participants, and ECG parameters were measured. Holter monitoring was performed, and the recordings were analyzed. Evaluation of the time-domain heart rate variability (HRV) results was done.

RESULTS: The average age of the vertigo group was 49.1 ± 7.8 years. In terms of demographic or laboratory data, there was no statistically significant difference between the groups (p>0.05). The study group’s ECG parameters, including Pd, TpTe, and TpTec, were longer, and the TpTe/QT and TpTe/QTc ratios were higher (p<0.05). Holter monitoring detected abnormal rhythms in 41 (63%) of the study group patients and three (6.2%) of the control group patients. The SDNN, LF, and LF/HF values, which are known as HRV markers, were significantly different in the vertigo group compared to the control group (p<0.001).

CONCLUSIONS: This study revealed that the risk of arrhythmias increased following attacks of BPPV in patients without a known history of cardiac vertigo.

PMID:36263578 | DOI:10.26355/eurrev_202210_29880

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Evaluation of the effect of CPAP treatment on voice in obstructive sleep apnea with objective and subjective voice analyzes

Eur Rev Med Pharmacol Sci. 2022 Oct;26(19):6972-6978. doi: 10.26355/eurrev_202210_29879.

ABSTRACT

OBJECTIVE: Obstructive sleep apnea (OSA) is a multifactorial disease that is the most common among sleep-related respiratory disorders. In our study, we aimed to compare the objective and subjective voice analysis results of the patients with CPAP treatment indication after polysomnography performed in the sleep disorders center before the start of CPAP treatment, the 1st month, and the 3rd month after the treatment.

PATIENTS AND METHODS: Patients were asked to say the vowels /ɑ:/ for 5 seconds, respectively for voice recording. MPT and S/Z ratios were also recorded. Using the Praat voice analysis program Jitter%, Shimmer%, HNR, f0 values were obtained. VHI-10 questionnaire was applied. The voice analysis results of the patients before and after the treatment were compared.

RESULTS: 26 patients were included in the study. Since 8 of these patients did not come to the 3rd month evaluation, the study was completed with the data of 18 patients. In our study, at the end of the 3rd month, no difference was found in terms of the fundamental frequency, Shimmer%, HNR, and S/Z values. There was a statistically significant decrease in Jitter% at the 1st month after treatment and 3rd month after treatment compared to pre-treatment (p=0.05, p=0.018). There was a statistically significant decrease in MPT at the 1st month after treatment and 3rd month after treatment compared to pre-treatment (p<0.001, p<0.001). There was a statistically significant decrease in VHI-10 at the 1st month and 3rd month after treatment compared to pre-treatment. Furthermore, there was statistically significant difference between 3rd month after treatment compared to 1st month after treatment. (p=0.043, p=0.030, p=0.029).

CONCLUSIONS: Our study showed that CPAP treatment had both objective and subjective positive effects on voice recovery in the OSA patient group.

PMID:36263577 | DOI:10.26355/eurrev_202210_29879