Nevin Manimala

Clin Exp Dent Res. 2022 Oct 20. doi: 10.1002/cre2.668. Online ahead of print.

ABSTRACT

OBJECTIVE: Periodontitis is one of the most important periodontal diseases that can be affected by many factors. Although the mechanism of periodontitis development is not yet fully understood, previous studies suggest that apoptosis may be one of the pathological factors that can affect the process of the disease by destroying old and damaged cells. Low expression of P53 protein is one of the reasons for delaying cell death that allows damaged cells to survive longer and gives more time for the chance of mutations and pathogenesis. Because of the important role of P53 in gingival cells of patients with chronic periodontitis, the objective of our study is to evaluate the P53 protein expression in gingival tissues of patients with chronic periodontitis by immunohistochemistry methods.

MATERIALS AND METHODS: In this cross-sectional study, 35 patients with severe to moderate chronic periodontitis (loss of attachment ≥3 mm, probing depth ≥5 mm) with no treatment and 25 people who were healthy for periodontal problems were examined. Gingival biopsies from marginal and attached gingiva were obtained, prepared, and mounted on slides. Then, the expression of P53 on each slide was evaluated by optic microscopy after using P53 antibodies and staining with hematoxylin-eosin (immunohistochemistry method). Data were analyzed using independent t-test, Mann-Whitney U-test, and Spearman correlation test using SPSS Statistics version 18.0.

RESULTS: The mean ages of participants in the case and control groups were 37.58 and 32.09, respectively. Our results showed that the expression of P53 was not significant in periodontitis compared to the control group (p > .05). Also, gender could not affect the expression of P53 in both groups (p > .05), and there was no significant relationship between age and P53 gene incidence.

CONCLUSION: Chronic periodontitis has no significant effect on P53 expression, so changes in apoptosis due to P53 expression in periodontitis are not significant.

PMID:36263737 | DOI:10.1002/cre2.668

Curr Med Res Opin. 2022 Oct 20:1-19. doi: 10.1080/03007995.2022.2135836. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess treatment patterns and initial and maintenance dosing of biologics over 3 years in pediatric patients with ulcerative colitis (UC) or Crohn’s disease (CD), utilizing data from the ImproveCareNow registry.

METHODS: Pediatric patients diagnosed with UC or CD and aged 2-17 years were included in the study. Descriptive statistics were employed to summarize baseline demographics. The proportion of patients on medication for UC or CD were analyzed at the baseline visit, 1-year, and 3-year time points (Cohort 1). Biologic maintenance dosage was calculated only for patients who had data for dose and weight at all time points (Cohort 2).

RESULTS: In Cohort 1 (UC =1784; CD =4720), baseline treatment in UC included corticosteroid, 5-ASA, and 6-MP/AZA; at 1-year and 3-year time points, treatment with 5-ASA and corticosteroid decreased, whereas 6-MP/AZA and anti-TNFs increased. In CD, baseline treatment included corticosteroid, anti-TNF, 6-MP/AZA, and methotrexate; use of corticosteroids decreased, whereas the use of methotrexate and anti-TNFs increased over 3 years. In Cohort 2 (UC =350; CD =1,537), at first maintenance dose, UC patients on infliximab received a mean dose of 10.5mg/kg/8wk, adalimumab (weight <40kg and ≥40kg) 1.3mg/kg/2wk and 0.8mg/kg/2wk, and vedolizumab 6.9mg/kg/8wks. At the first maintenance dose, CD patients on infliximab received a mean dose of 8.1mg/kg/8wk, adalimumab (weight <40kg) 1.1mg/kg/2wk, adalimumab (weight ≥40kg) 0.8mg/kg/2wk, and vedolizumab 10.5mg/kg/8wks.

CONCLUSION: The use of corticosteroids was common at the initial visit in patients. Anti-TNFs remain the most used class of biologics, however, reported doses in our study were substantially higher than the standard dosing guidelines.

PMID:36263735 | DOI:10.1080/03007995.2022.2135836

HIV Med. 2022 Oct 20. doi: 10.1111/hiv.13426. Online ahead of print.

ABSTRACT

BACKGROUND: The ongoing COVID-19 pandemic has been impeding HIV diagnosis and treatment worldwide. Data on the impact of COVID-19 on late diagnosis (LD) in Germany are lacking. Here we present novel data of a single-centre German HIV cohort assessing LD during COVID-19.

METHODS: This is a non-interventional, single-centre retrospective cohort assessing the rate of LD comparing HIV diagnoses pre-COVID-19 with those during the COVID-19 pandemic. New diagnoses between 1 January 2019 and 1 February 2020 were classified as pre-COVID-19, and diagnoses between 1 February 2020 and 1 October 2021 were classified as during COVID-19.

RESULTS: Between 1 January 2019 and 1 October 2021, 75 patients presented with newly diagnosed HIV infection, 34 pre-COVID-19 and 41 during COVID-19. LD increased to 83% (n = 34/41) during COVID-19 versus 59% (n = 20/34) pre-COVID-19, and CDC stage C3 rose to 44% (n = 18) versus 27%. Hospitalization rate increased to 49% (n = 20) during COVID-19 versus 29% pre-COVID-19, and 12% (n = 5) presented with HIV-associated neurological disease, whereas none were observed in the pre-COVID-19 group. The incidence of LD (p = 0.020), CD4 count < 350 cells/μL (p = 0.037) and < 200 cells/μL (p = 0.022) were statistically significantly associated with the ongoing COVID-pandemic. An association with HIV transmission risk was borderline significant (p = 0.055).

CONCLUSIONS: Despite comparable annual rates of new HIV diagnoses, LD has been increasing during the COVID-19 pandemic, resulting in more opportunistic infections and higher hospitalization rates, possibly reflecting pandemic-related shortages in HIV testing and care facilities. Maintaining HIV testing opportunities and access to treatment during a pandemic is crucial so as not to impede WHO elimination goals and so as to prevent an increase in AIDS-related morbidity and mortality.

PMID:36263724 | DOI:10.1111/hiv.13426

Hosp Pediatr. 2022 Oct 20:e2021006450. doi: 10.1542/hpeds.2021-006450. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Molecular diagnostics provide a rapid and sensitive diagnosis of gastroenteritis compared with a stool culture. In this study, we seek to describe the changes in medical management and outcomes of children with Salmonella gastroenteritis as our hospital system adopted molecular diagnostics.

METHODS: This study is a retrospective chart review of children <18 years of age diagnosed with nontyphoidal Salmonella gastroenteritis between 2008 and 2018 at a large pediatric health care system in the southeastern United States. Those with immunocompromising conditions and hemoglobinopathies were excluded. Patients diagnosed via molecular testing were compared with those diagnosed solely by stool culture for aspects of management including admission rates, blood culture obtainment, and antibiotic administration.

RESULTS: Of 965 eligible patients with Salmonella gastroenteritis, 264 (27%) had a stool molecular test and 701 (73%) only had a stool culture performed. Groups were similar in age and presentation. Those diagnosed by molecular methods had higher hospitalization rates (69% vs 50%, P <.001), more blood cultures obtained (54% vs 44%, P <.01), and received more antibiotics (49% vs 34%, P <.001) despite statistically similar rates of bacteremia (11% vs 19%, P = .05).

CONCLUSIONS: The rapid diagnosis of Salmonella gastroenteritis by molecular methods was associated with increased hospital admission rates, blood culture obtainment, and antibiotic use. This suggests possible overmedicalization of uncomplicated Salmonella gastroenteritis, and clinicians should remain cognizant of the possibility of providing low-value care for uncomplicated disease.

PMID:36263712 | DOI:10.1542/hpeds.2021-006450

Food Funct. 2022 Oct 20. doi: 10.1039/d2fo01280d. Online ahead of print.

ABSTRACT

This study assessed the effects of propolis supplementation on glucose homeostasis, lipid profile, liver function, anthropometric indices and meta-inflammation in patients with non-alcoholic fatty liver disease (NAFLD). In this double-blind placebo-controlled randomized clinical trial, 44 patients with NAFLD confirmed by ultrasonography findings were randomly allocated into either the “propolis” (n = 23) or “placebo” (n = 21) group along with a calorie-restricted diet (-500 kcal d^-1) for 8 weeks. Fasting serum levels of metabolic factors, liver enzymes, and inflammatory factors, as well as anthropometric indices, dietary intake and appetite status were assessed pre-and post-intervention. The liver fibrosis score, homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were also calculated. The weight, body mass index (BMI), waist and hip circumferences, and waist to height ratio significantly decreased in both groups (p < 0.001), while the waist to hip ratio (p = 0.006) and serum level of total cholesterol (p = 0.038) decreased only in the propolis arm. However, no significant changes in anthropometric measurements and lipid profile were found between the groups at the end of the intervention. Fasting blood sugar (p = 0.037), the serum insulin level (p = 0.040), HOMA-IR (p = 007), desire to eat sweet foods (p = 0.005) and the NAFLD fibrosis score (p = 0.013) decreased significantly in the propolis group compared to the placebo group, post-intervention after adjusting for baseline values and potential confounders. However, QUICKI showed a significant increase (p = 0.015) in the propolis arm compared to the placebo at the study endpoint. Although there were significant reductions in the serum levels of inflammatory factors including tumor necrosis factor-α (TNF-α), toll-like receptor-4 (TLR-4) and monocyte chemoattractant protein-1 (MCP-1), as well as liver enzymes and severity of fatty liver, between-group differences were not statistically significant after adjusting for the potential confounding factors. The estimated number needed to treat (NNT) due to 8-week propolis supplementation (510 mg per day) for at least 1-point improvement in NAFLD severity was found to be approximately 3. In conclusion, propolis supplementation along with a calorie-restricted diet for 8 weeks could significantly improve the glucose homeostasis, hepatic fibrosis score and liver function in patients with NAFLD. Further clinical trials are encouraged to study the effects of propolis supplementation in patients with long-term NAFLD.

PMID:36263703 | DOI:10.1039/d2fo01280d

J Clin Endocrinol Metab. 2022 Oct 20:dgac614. doi: 10.1210/clinem/dgac614. Online ahead of print.

ABSTRACT

INTRODUCTION: Systemic lupus erythematosus (SLE) and hypothyroidism often coexist in observational studies; however, the causal relationship between them remains controversial.

METHODS: Complementary genetic approaches, including genetic correlation, Mendelian randomization (MR) and colocalization analysis, were conducted to assess the potential causal association between SLE and primary hypothyroidism using summary statistics from large-scale genome-wide association studies (GWASs). The association between SLE and thyroid-stimulating hormone (TSH) was further analyzed to help interpret the findings. In addition, findings were verified using a validation dataset, as well as through different MR methods with different model assumptions.

RESULTS: The linkage disequilibrium score regression revealed a shared genetic structure between SLE and primary hypothyroidism, with the significant genetic correlation estimated to be 0.2488 (p = 6.00 × 10-4). MR analysis with the inverse variance weighted (IVW) method demonstrated a bidirectional causal relationship between SLE and primary hypothyroidism. The odds ratio (OR) of SLE on primary hypothyroidism was 1.037 (95% CI, 1.013-1.061; p = 2.00 × 10-3) and that of primary hypothyroidism on SLE was 1.359 (95% CI, 1.217-1.520; p < 0.001). The OR of SLE on TSH was 1.007 (95% CI, 1.001-1.013; p = 0.032) .However, TSH was not causally associated with SLE (p = 0.152). Similar results were found using different MR methods. In addition, colocalization analysis suggested that shared causal variants existed between SLE and primary hypothyroidism. The results of the validation analysis indicated a bidirectional causal relationship between SLE and primary hypothyroidism, as well as shared loci.

CONCLUSION: In summary, a bidirectional causal relationship between SLE and primary hypothyroidism was observed with complementary genetic approaches.

PMID:36263677 | DOI:10.1210/clinem/dgac614

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 (SUV_max) 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 SUV_maxand 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

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

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

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