Biochemical Outcomes Research Articles

A relationship between Single Nucleotide Polymorphism (SNP) in HSD11β1 and ADIPOQ genes and obesity related features in children and adolescents submitted on physical exercises

Obesity have overloaded the public health system and it is considered a multifactorial trait. This study aimed to verify if Single Nucleotide Polymorphisms (SNP) in ADIPOQ (rs1501299) and HSD11β1 (rs12086634) genes influence the anthropometric and biochemical outcomes (Body Mass Index (BMI), Abdominal Circumference (AC), Low Density Lipoprotein (LDL-C), High Density Lipoprotein (HDL-C), Triglycerides (TG), Total Cholesterol (TC) and Glucose (Glu)) before and after practicing physical exercises training modalities, in a sample of 126 Southern Brazilian children and adolescents. Genotyping were performed by Taqman allelic discrimination. T carriers of rs1501299 had a higher BMI reduction (b*=0.28±0.12; p=1.70.10-2) and TT genotype of rs12086634 influence on AC reduction (b*=-0.33±0.13; p=1.24.10-2), independent of sex, age and modality of physical exercise. Ultimately, we observed an association of SNP of ADIPOQ and HSD11β1 gene with anthropometric variables early in life and the importance of physical exercise on biochemical and obesity related features.

P1064 Upadacitinib is safe and effective in Ulcerative Colitis patients with prior exposure to Tofacitinib

Abstract Background Upadacitinib is a novel selective Janus Kinase (JAK) inhibitor which has recently been approved for use in ulcerative colitis. Clinical trials have rigorous criteria and excluded patients with prior exposure to JAK inhibitors. Given limited real-world effectiveness data we examined outcomes of patients treated with upadacitinib for ulcerative colitis in a real-world population, with a focus on prior tofacitinib exposure. Methods This retrospective, multi-centre study recruited patients commencing upadacitinib for moderate-to-severe ulcerative colitis from September 2022 until March 2023 from 13 Inflammatory Bowel Disease centres across Australia. Clinical, biochemical, endoscopic and intestinal ultrasound outcomes were recorded at baseline, week 8 and week 16. The primary outcome was a comparison between clinical remission using PRO2 definitions (STRIDE II guidelines) in those with prior Tofacitinib exposure compared with Tofacitinib-naïve. Secondary endpoints included clinical response, corticosteroid free clinical remission (CFCR), biochemical response and transmural remission assessed by intestinal ultrasound (IUS). Adverse events in both cohorts were also recorded. Results 152 patients were identified and included (Table 1) – 42 tofacitinib-exposed and 110 tofacitinib-naïve. Complete clinical data was available for all patients at baseline, week 8, and week 16. For the overall cohort, the rate of clinical remission was 20% (30/152) at baseline, 78% (119/152) at week 8 and 85% (129/152) at week 16. In patients with prior tofacitinib exposure, the rate of clinical remission was 23% (10/42) at baseline, 72% (30/42) at week 8 and 86% (36/42) at week 16. In tofacitinib-naïve patients, the rate of clinical remission was 19% (21/110) at baseline, 78% (86/110) at week 8 and 84% (92/110) at week 16 (Figure 1). There was no statistically significant difference in rate of clinical remission at baseline (p=0.23), week 8 (p=0.13) or week 16 (p=0.67). There was no statistically significant difference in clinical response, CFCR, biochemical response or transmural remission by IUS between the cohorts. Adverse events were seen in 40 (26%) patients over the course of 16 weeks follow-up. Most common were acne (12%), rash (4%) and nasopharyngitis (4%). No venous thromboembolism, systemic infection or cardiovascular events were observed. These events were spread evenly among both groups (p=0.37). Conclusion This is the largest real-world study to show that upadacitinib is effective and safe for patients with moderate to severe ulcerative colitis and prior tofacitinib exposure.

P1047 Observational study of tofacitinib in Ulcerative Colitis in Sweden (ODEN) – Interim analysis of health-related quality of life and fatigue

Abstract Background Ulcerative colitis (UC) has a major impact on daily life. The Janus Kinas (JAK) inhibitor tofacitinib is effective in achieving remission in UC, but prospective real-world evidence concerning the effect on health-related quality of life (HRQoL) and fatigue are still scarce. Fatigue is a component of UC that is notoriously difficult to treat and not unambiguously related to inflammatory activity. ODEN is an ongoing Swedish multicentre prospective observational study of tofacitinib in UC. In this interim analysis, we assessed the effectiveness on HRQoL and fatigue during the first 16 weeks. Methods Patients with UC and active inflammation were enrolled 2020-2023 when starting tofacitinib as per clinical indication. To measure various aspects of impairment of daily life, the validated questionnaires Short Health Scale (SHS), EQ-5D-5L [Swedish value set], and IBD-fatigue scale (IBD-F) were used. These data and information concerning clinical, biochemical, and endoscopic outcomes were collected in an e-CRF linked to the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG). For HRQoL outcomes, per protocol analysis was applied. Paired t-test and Wilcoxon’s signed-rank test were used for mean and median differences, respectively. Results In total, 103 patients were included. Baseline data are shown in Table 1a. For patients still on tofacitinib treatment, all four dimensions of the SHS (symptoms, social function, disease related worry, and general well-being) improved significantly, Table 1b. A median decrease of one point from baseline was seen at week 8 in each of the parameters, which was maintained through week 16 with a tendency towards further improvement. EQ-5D-5L showed an impairment mainly in the aspects of pain/discomfort and ability to participate in common daily activities. Improvement in these dimensions was seen from baseline to week 16. The overall EQ-5D-5L index improved significantly from baseline (0.80) to week 8 (0.86) and week 16 (0.89), as did the EQ VAS 0-100 reflecting overall health (58, 71, and 74, respectively). A significant improvement in IBD-F part 1 and 2 was seen at week 8 and 16, Figure 1. Conclusion This study demonstrates that tofacitinib treatment covariates with positive changes in a variety of measures of patients’ quality of life, including improvements in self-assessed overall wellbeing. Finally, fatigue significantly improved during tofacitinib treatment. Thus, tofacitinib treatment shows association with meaningful improvements in multiple aspects of quality of life during the first 16 weeks of treatment.

P698 Effectiveness and Safety of Ustekinumab for Ulcerative Colitis: A Brazilian Multicentre Real-World Observational Study

Abstract Background Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicentre cohort of Brazilian patients with UC. Methods We conducted a multicentre retrospective observational cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of zero) within one year from baseline. Secondary endpoints included clinical response between weeks 12-16, endoscopic response within one year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety. Results A total of 50 patients were included (female, n=36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis (n=38, 76.0%), and 43 (86.0%) were steroid-dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n=31; vedolizumab [VDZ], n=27). The co-primary endpoints of clinical remission and endoscopic remission at 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 67.4%, and 50.0%, respectively. The UST treatment persistence rates at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and three patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-six adverse events (AEs) were reported, 15 of which were considered as serious AEs. Conclusion This is the first real-world experience study to report the effectiveness and safety of UST specifically in a Latin American population. In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.

Accelerated neurodegeneration of basal forebrain cholinergic neurons in HIV-1 gp120 transgenic mice: Critical role of the p75 neurotrophin receptor

Human Immunodeficiency Virus-1 (HIV) infection of the brain induces HIV-associated neurocognitive disorders (HAND). The set of molecular events employed by HIV to drive cognitive impairments in people living with HIV are diverse and remain not completely understood. We have shown that the HIV envelope protein gp120 promotes loss of synapses and decreases performance on cognitive tasks through the p75 neurotrophin receptor (p75NTR). This receptor is abundant on cholinergic neurons of the basal forebrain and contributes to cognitive impairment in various neurological disorders. In this study, we examined cholinergic neurons of gp120 transgenic (gp120tg) mice for signs of degeneration. We observed that the number of choline acetyltransferase-expressing cells is decreased in old (12–14-month-old) gp120tg mice when compared to age matched wild type. In the same animals, we observed an increase in the levels of pro-nerve growth factor, a ligand of p75NTR, as well as a disruption of consolidation of extinction of conditioned fear, a behavior regulated by cholinergic neurons of the basal forebrain. Both biochemical and behavioral outcomes of gp120tg mice were rescued by the deletion of the p75NTR gene, strongly supporting the role that this receptor plays in the neurotoxic effects of gp120. These data indicate that future p75NTR-directed pharmacotherapies could provide an adjunct therapy against synaptic simplification caused by HIV.

Clinical, Biochemical and Neurological Outcomes in Bipolar Patients with Lithium Intoxication at A Tertiary Care Hospital Sindh

Background: Bipolar disorder (BD) affects a significant portion of the global population, with lithium being a cornerstone in its treatment. However, the therapeutic index of lithium is narrow, and its effectiveness can be overshadowed by the risk of toxicity, especially at higher serum levels. Understanding the impact of varying lithium concentrations on clinical, biochemical, and neurological outcomes is crucial in the management of BD. Objective: To assess the clinical, biochemical, and neurological changes associated with different levels of lithium toxicity in patients with bipolar disorder and to determine the safe and effective range of lithium serum levels. Methods: A prospective cross-sectional study was conducted at Jinnah Post Graduate Medical Center, Karachi, involving 100 bipolar disorder patients on lithium therapy, categorized into three groups based on their serum lithium levels: Category I (<1.2 mmol/L), Category II (1.2 – 2.5 mmol/L), and Category III (>2.5 mmol/L). Clinical assessments, laboratory investigations (including renal and thyroid function tests), and neurological evaluations were conducted. Data were analyzed using SPSS version 25, with the t-test and Chi-square test employed for quantitative and qualitative comparisons, respectively. Results: Patients with serum lithium levels above 2.5 mmol/L (Category III) demonstrated significantly higher rates of clinical toxicity, renal dysfunction, and neurological complications compared to lower lithium level groups. Renal function parameters (serum creatinine and urea) and thyroid function (TSH levels) were notably altered in Category III. The incidence of neuropsychiatric symptoms was also significantly higher in this group, with severe neurotoxic effects observed in 27% of these patients. Conclusion: The study highlights the critical importance of maintaining serum lithium levels within a therapeutic range to avoid severe adverse effects. Lithium levels above 2.5 mmol/L significantly increase the risk of renal dysfunction, thyroid abnormalities, and neurotoxicity. Regular monitoring and individualized treatment adjustments are essential for optimizing patient safety and treatment efficacy.

Clinical and biochemical outcomes after adrenalectomy for primary aldosteronism in tertiary and quaternary referral centers: data from SOPRANO study.

Hypertension cure following adrenalectomy in unilateral primary aldosteronism (PA) remains uncertain. Previous meta-analyses have shown highly variable surgical outcomes. Our study aimed to determine the unknown proportion of complete clinical and biochemical success in tertiary and quaternary referral centers. We conducted a systematic review and meta-analysis of studies reporting surgical outcomes of unilateral PA patients within the Surgical Outcome of PRimary Aldosteronism progNostic mOdels (SOPRANO) study. From 27 publications we identified 32 eligible studies, of which 22 were judged to be at low risk of bias. Eighteen were single-center studies, while fourteen were multi-center studies, with patients recruited from 132 referral centers worldwide. Adrenalectomy was performed on 5887 patients, with 4861 (83%) included in the final analysis. The pooled estimates of complete clinical and biochemical success for all studies were 39% (95% CI: 34-44%) and 99% (95% CI: 96-99%), respectively, similar to that found for studies at low risk of bias. Multivariate meta-regression analyses for all studies and low-bias risk studies revealed that BMI (P < 0.01), recruitment time period (P < 0.01), and hypertension duration (P < 0.05) inversely correlated with complete clinical success, while BMI (P < 0.05) and the number of enrolled centers (P < 0.05) inversely correlated with complete biochemical success. In summary, our findings offer robust estimates of complete clinical and biochemical success rates following adrenalectomy for unilateral PA in tertiary and quaternary referral centers and identify new potential effect modifiers that can help clinicians to inform and counsel patients about post-surgery expectations, guaranteeing effective treatment and ultimately enhancing outcomes.

Management of disease-related malnutrition: a real-world experience with a novel concentrated high-protein energy-dense oral nutritional supplement

ABSTRACT Objective Despite the availability of a wide range of oral nutritional supplements (ONS) offerings, individuals with malnutrition are still struggling to meet their nutritional targets. A new concentrated and high-protein energy-dense ONS (≥2.1 kcal/mL;32 g protein/200 mL) with high-quality protein (60% whey protein) has emerged as a pivotal formula to reach the patient’s energy-protein requirements, enhance compliance, and maximize stimulation of muscle protein synthesis, key factors driving better nutritional, functional, and clinical outcomes. The purpose of this article is to provide our clinical experience using this new nutritionally concentrated ONS as a therapeutic strategy for patients with DRM. Methods Three clinical cases have been examined using new assessment procedures and a new form of nutritional therapy, and their impact on the nutritional and functional outcomes in patients with moderate-to-severe DRM. Results A tailored individualized nutritional interventions improved anthropometric, biochemical, and functional outcomes (Case 1,2, and 3) assessed using hand grip strength, bioimpedance and muscle ultrasound, and as well as good gastrointestinal tolerance (Case 1) and compliance to the ONS in patients with DRM (Case 1,2,3). Conclusion The use of this novel high-protein energy-dense formula with high-quality protein source (≥2.1 kcal/mL; 32 g protein/200 mL; 60% whey protein) overcome common practical challenges in the medical nutrition therapy of patients with DRM, either because these patients require a highly concentrated formulation to meet nutritional requirements due to loss of appetite, lack of interest in food, and high caloric-protein needs due to disease, and a large quantity and quality of protein to optimize muscle recovery due to sarcopenia, common in patients with moderate-severe malnutrition.

Menstrual-Cycle and Hormonal-Contraceptive Tracking in Gaelic Football: From the Lab to the Field

Purpose: The purpose of this study was to describe the implementation of menstrual-cycle (MC) and hormonal-contraceptive (HC) tracking among Gaelic Football players, including the characterization of MC status and symptomatology, and to examine the effect of MC and oral-contraceptive-pill phases on daily wellness. Methods: Fourteen highly trained players (age 24.2 [3.5] y), including non-HC (n = 6), oral contraceptive pill (n = 7), and intrauterine system (n = 1) users, prospectively tracked their MC or HC alongside daily self-reported wellness measures for 4 months. A combination of calendar-based counting, urinary ovulation prediction testing, and a midluteal serum progesterone measurement was used to assess MC status. Results: Only 2 non-HC players were eumenorrheic. Two players exhibited oligomenorrhea (cycle length, 39 [4] d), and ovulation was not detected in one of them. Luteal phase deficiency was indicated in 2 players (serum progesterone range &lt;1.0–7.5 nmol·L−1). All players except 1 reported at least 1 negative MC-related symptom or HC side effect. Linear mixed-model analyses revealed that wellness measures were not affected by oral contraceptive pill phase (P &gt; .05). Linear mixed-model analysis was not performed in non-HC users due to the small sample of eumenorrheic players (n = 2). Conclusions: Diverse reproductive profiles were observed, including HC use and subtle MC irregularities that would likely go undetected without prospective MC tracking using biochemical outcomes. This highlights the value of incorporating ovulation testing and blood sampling when establishing the MC status of athletes in applied research and practice where feasible. Applied researchers should anticipate practical challenges, including inconsistencies in ovulation testing timings and the time scale required to assess MC status among athletes.

Qigong Training Effects on Brain-Derived Neurotrophic Factor and Cognitive Functions in Sedentary Middle-Aged and Elderly Females With Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) heightens dementia and cognitive decline risk, notably impacting working memory and executive functions. This study investigates the impact of 8 weeks of qigong training on cognitive functions, blood pressure, plasma brain-derived neurotrophic factor (pBDNF), antioxidant, and biochemical outcomes in sedentary middle-aged and elderly women with T2DM. Thirty-five sedentary middle-aged and elderly women with T2DM were assigned to qigong exercise (QG = 19) or control (CG = 16) groups. Qigong exercise group performed the qigong exercise three times per week, for 8 weeks. The cognitive functions and pBDNF as primary and secondary outcomes (blood pressure parameters, antioxidant, and blood cell indices) were measured at baseline and postexercise training. While cognitive performance did not change, there was a significant interaction (Group × Time), indicating reduced pBDNF levels postintervention in the qigong exercise group (p &lt; .05). Both mean arterial blood and pulse pressure values decreased after qigong training (p &lt; .05), but no significant interaction effects (Time × Group) were seen. There was a pulse pressure reduction after qigong training (p &lt; .05), which was significantly correlated with the increase in longest digit span forward (r = −.34, p &lt; .05). Antioxidant levels decreased from PRE to POST within both groups. This study demonstrated that 8 weeks of qigong training reduced pBDNF levels in sedentary middle-aged and elderly women with T2DM, which is unrelated to cognitive function improvements but possibly indicating a favorable response to exercise. Additionally, reduced blood and pulse pressure, potentially enhancing cognitive function by favorably impacting the autonomic nervous system by qigong training.

Etomidate alleviates ovarian ischemia-reperfusion injury in rats.

This study investigates the protective effects of etomidate against oxidative damage in an experimental model of ovarian ischemia-reperfusion injury. A total of 24 female rats were randomized into three groups. Group 1 served as the control. Group 2 underwent an ovarian torsion/detorsion procedure. Group 3 underwent similar procedures as Group 2; additionally, 4 mg/kg of etomidate was administered intraperitoneally 30 minutes before ovarian detorsion. Blood samples were analyzed for lipid peroxidation, pro-inflammatory cytokine levels, and antioxidant enzyme activity RESULTS: Biochemical analysis of blood samples revealed reductions in pro-inflammatory cytokines, including interleukin-1 Beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), in Group 3 compared to Group 2 (p=0.005, p=0.016, and p<0.001, respectively). Additionally, a decrease in malondialdehyde (MDA) levels was observed in Group 3 compared to Group 2 (p<0.001). In contrast, activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), were significantly increased in Group 3 compared to Group 2 (p=0.031 and p=0.001, respectively). Furthermore, Group 3 demonstrated notable reductions in histopathological scores for follicular degeneration, vascular occlusion, bleeding, and inflammation compared to Group 2 (p<0.001, p<0.001, p<0.001, and p=0.001, respectively). Etomidate alleviates ischemia-reperfusion injury in a rat ovarian torsion-detorsion model by improving both histopathological and biochemical outcomes.

The Effect on 2nd Trimester Biochemical Markers and Pregnancy Outcomes of Patients with Isolated Choroid Plexus Cyst Diagnosed in the Prenatal Period

Amaç: Prenatal ultrasonografide saptanan izole Koroid Pleksus Kistlerinde ikinci trimester yapılan biokimyasal belirteçlerine ve gebelik sonuçları üzerine etkisini araştırmak amaçlanmıştır. &#x0D; Materyal Metod: Çalışma retrospektif olarak dizayn edilmiş olup 2017-2022 yılları arasında Etlik Zübeyde Hanım Kadın Hastalıkları ve Eğitim Araştırma Hastanesinde yapılmıştır. Gebeliğinde izole koroid pleksus kisti saptanan 32 gebe ve tarama ve ultrasonografisi normal olan 31 gebe kontrol grubu olarak dahil edilmiştir. &#x0D; Bulgular: Çalışmaya toplam 63 gebe dahil edilmiştir. 32 gebede izole koroid pleksus kisti (KPK) vardı ve 31 gebe normaldi. Gruplar arasında Estriol (E3) MoM KPK olan grupta diğer gruba göre düşüktü ve istatiksel olarak anlamlıydı ama yinede kabul edilen sınır değerler arasındaydı diğer biokimyasal parametreler açısından anlamlı istatiksel fark bulunmadı. Doğum sonuçları arasında fark bulunamadı. Hiçbir yenidoğanda anomali saptanmadı. &#x0D; Sonuç: 2. Trimestar biokimyasal belirteçleri normal olan ve izole KPK sı olan fetuslarda anomali riski çok düşüktür

Inulin-type fructans with different degrees of polymerization improve insulin resistance, metabolic parameters, and hormonal status in overweight and obese women with polycystic ovary syndrome: A randomized double-blind, placebo-controlled clinical trial.

Polycystic ovary syndrome (PCOS) is associated with reproductive disorders and adverse cardiometabolic risk factors that can negatively impact the general health of women. Inulin-type fructans (ITFs) are proposed to beneficially affect risk factors associated with metabolic disorders. Whether ITFs can help with the management of PCOS by modifying insulin resistance (IR) and androgen levels has not yet been explored. The aim of this study was to investigate the effects of ITFs with different degrees of polymerization on insulin resistance, blood lipids, anthropometric measures, and hormonal status in overweight and obese women with PCOS. In a randomized double-blind placebo-controlled trial, seventy-five women with PCOS aged 18-40 years old were randomly assigned to receive 10 g/day of high-performance inulin (HPI) or oligofructose-enriched inulin (OEI) or maltodextrin for 12 weeks. Biochemical and clinical outcomes were measured at baseline and after the intervention. Participants in the HPI and OEI groups experienced improvements in waist circumference, total testosterone, free androgen index, sex hormone-binding globulin, and triglycerides compared to the placebo group. Also, the number of women with irregular menses or oligomenorrhoea decreased significantly in both ITF groups. Participants in the HPI group reported lower body mass, fasting insulin, and HOMA-IR, as well as a higher quantitative insulin sensitivity check index. ITF supplementation, especially with long-chain ITFs, when given for 12 weeks may improve metabolic outcomes, androgen status and clinical manifestations in women with PCOS.

Riboflavin: a scoping review for Nordic Nutrition Recommendations 2023.

Only a few studies have explored relationships between riboflavin intake and function and a few studies have examined the effects of supplements on various clinical or biochemical outcomes. None of these studies, however, make a useful contribution to understanding requirements in healthy populations. Thus, there is no strong evidence to change the recommendations. The requirement for riboflavin is estimated based on the relationship between intake and biochemical indices of riboflavin status, including urinary excretion and enzyme activities.

The effect of mindfulness meditation on dental anxiety during implant surgery: a randomized controlled clinical trial

Dental implant surgery is almost always associated with patient anxiety. Anxiety during dental surgical procedures triggers an increase in sympathetic activity. Mindfulness meditation (MM) is often associated with high levels of relaxation in the form of increased parasympathetic tone and decreased sympathetic activity. However, the effect of MM on dental anxiety is not clear. The current study aimed to show the effects of a MM as a sedative technique during dental implant surgery by examining the State-Trait Anxiety Inventory (STAI-S), bispectral index (BIS), cortisol levels (CL), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and saturation (SpO2) parameters. HR, SBP, DBP, SpO2, BIS score and CLs were compared at the baseline, immediately before-, during-, and immediately after surgery between the test and control groups. We found that the MM resulted in significant decrease in BIS together with positive effects on hemodynamic parameters (decrease of HR, SBP, DBP and increase of SpO2), psychological findings (improvement on STAI-S scores) and biochemical outcomes (decreased CL). In conclusion, the results demonstrate that MM appeared to be a reliable strategy for managing stress during dental implant operation with benefits in psychological, physiological and biochemical outcomes.

Increased Delta and Theta Power Density in Sickle Cell Disease Individuals with Chronic Pain Secondary to Hip Osteonecrosis: A Resting-State Eeg Study.

Identify the presence of a dysfunctional electroencephalographic (EEG) pattern in individuals with sickle cell disease (SCD) and hip osteonecrosis, and assess its potential associations with depression, anxiety, pain severity, and serum levels of brain-derived neurotrophic factor (BDNF). In this cross-sectional investigation, 24 SCD patients with hip osteonecrosis and chronic pain were matched by age and sex with 19 healthy controls. Resting-state EEG data were recorded using 32 electrodes for both groups. Power spectral density (PSD) and peak alpha frequency (PAF) were computed for each electrode across Delta, Theta, Alpha, and Beta frequency bands. Current Source Density (CSD) measures were performed utilizing the built-in Statistical nonparametric Mapping Method of the LORETA-KEY software. Our findings demonstrated that SCD individuals exhibited higher PSD in delta and theta frequency bands when compared to healthy controls. Moreover, SCD individuals displayed increased CSD in delta and theta frequencies, coupled with decreased CSD in the alpha frequency within brain regions linked to pain processing, motor function, emotion, and attention. In comparison to the control group, depression symptoms, and pain intensity during hip abduction were positively correlated with PSD and CSD in the delta frequency within the parietal region. Depression symptoms also exhibited a positive association with PSD and CSD in the theta frequency within the same region, while serum BDNF levels showed a negative correlation with CSD in the alpha frequency within the left insula. This study indicates that individuals with SCD experiencing hip osteonecrosis and chronic pain manifest a dysfunctional EEG pattern characterized by the persistence of low-frequency PSD during a resting state. This dysfunctional EEG pattern may be linked to clinical and biochemical outcomes, including depression symptoms, pain severity during movement, and serum BDNF levels.

Evaluation of the clinical parameters and volumetric analysis of gingival crevicular fluid for chlohexidine vying silver nanoparticle mouthwash the avant garde for chronic periodontitis

BACKGROUND: Oral cavity ecosystem represents a dynamic pattern. Scaling and root planing (SRP) is the gold standard approach for treatment of chronic periodontitis but used alone it may not be effective in removing periodontal pathogens from sites where access is poor. Although chlorhexidine is the most effective mouthwash against oral microorganisms, the side effects of long- term use suggest the need for an alternative. Hence, this study has been undertaken to know effectiveness of silver nanoparticle mouthwash with chlorhexidine mouthwash which is effective on common microorganisms of oral cavity. OBJECTIVE: To evaluate and compare the clinical and biochemical outcome of chlorhexidine (CHX) and silver nanoparticle as an adjunct to scaling and root planing (SRP) in patients with chronic periodontitis. METHODS: Ninety- two patients with generalized moderate to severe chronic periodontitis from the Dept. of Periodontology who fulfilled the inclusion and exclusion criteria were recruited for the study. In the experimental clinical trial, the clinical parameters likewise; Plaque index (PI), Gingival index (GI), probing depth (PD), clinical attachment loss (CAL) were assessed. The volumetric analysis of gingival crevicular fluid (GCF) levels were assessed at baseline and follow up visits. The IBM SPSS Statistics for Windows software, v. 20.0 (IBM Corp., Armonk, USA), was used. The data was numerically coded and entered into the program. Both the descriptive statistics and the inferential statistics were analyzed to compare the responses between the groups. RESULTS: The statistical analysis was carried out by descriptive as well as inferential statistics and both groups demonstrated significant intragroup reduction in PI, GI, PPD, CAL, GCF from baseline to 3 months follow-up. There were statistically significant intragroup differences between both the groups for all of the parameters. CONCLUSION: Silver nanoparticle mouthwash can be an alternative adjunct for non-surgical periodontal therapy in patients with chronic periodontitis. Results of this study indicated that both the mouth rinse demonstrated an equal range of effectiveness. These conclusions were supported by the clinical parameters and biochemical outcomes.

Postoperative ACTH-stimulated aldosterone predicts biochemical outcome in primary aldosteronism.

Primary aldosteronism (PA) is the most common surgically curable cause of hypertension. Unilateral aldosterone-producing adenoma can be treated with adrenalectomy. Clinical and biochemical outcomes are assessed 6-12 months after adrenalectomy according to PASO consensus criteria. Earlier prediction of biochemical remission would be desirable as it could reduce cumbersome follow-up visits. We hypothesized that postoperative ACTH stimulated plasma aldosterone concentrations (PAC) measured shortly after adrenalectomy can predict PASO outcomes. Retrospective cohort study. We analyzed 100 patients of the German Conn's registry who underwent ADX and postoperative ACTH stimulation tests within the first week after adrenalectomy. 6-12 months after adrenelectomy we assessed clinical and biochemical outcomes according to PASO criteria. Serum cortisol and PAC were measured by immunoassay at baseline and 30 min after the intravenous ACTH infusion. We used receiver operating characteristics (ROC) curve analysis and matched the parameters to PASO outcomes. 81% of patients had complete, 13% partial and 6% absent biochemical remission. Complete clinical remission was observed in 28%. For a cut-off of 58.5pg/ml, stimulated PAC could predict partial/absent biochemical remission with a high sensitivity (95%) and reasonable specificity (74%). Stimulated PAC's area under the curve (AUC) (0.89; CI 0.82-0.96) was significantly higher than other investigated parameters. Low postoperative ACTH stimulated PAC was predictive of biochemical remission. If confirmed, this approach could reduce follow-up visits to assess biochemical outcome.

Invasive Testing for Preoperative Localization of Parathyroid Tumors.

The identification of parathyroid tumor(s) in patients with persistent/recurrent primary hyperparathyroidism (PHPT) is critical for a successful reoperative surgery. If noninvasive studies (ultrasound, computed tomography, magnetic resonance imaging, sestamibi) fail to conclusively localize the tumor, invasive procedures (arteriography and selective venous sampling) are performed. To describe our experience with invasive studies for parathyroid tumor localization and provide follow-up data on selective arterial hypocalcemic stimulation with central venous sampling, a technique developed at our center. We identified patients who underwent preoperative invasive testing for localization of parathyroid tumor from 1991 to 2020. The result of each invasive localization study [arteriogram, hypocalcemic stimulation and selective venous sampling (SVS)] was categorized as true-positive, false-positive, and false-negative based on histology and biochemical outcome. Ninety-four patients with 96 tumor occurrences underwent invasive testing for parathyroid tumor localization. Arteriogram, hypocalcemic stimulation, and SVS accurately localized the tumor in 47 of 94 (50%), 56 of 93 (60%), and 51 of 62 (82%) tumors, respectively. Hypocalcemic stimulation was more likely to correctly localize the tumor when arteriogram showed a blush [37 of 50 (74%) vs 19 of 43 (44%), P = .01]. When both arteriogram and hypocalcemic stimulation yielded concordant positive findings, SVS did not change management in the 18 cases in which all 3 were performed. Twelve patients remained with persistent PHPT; all had recurrent disease with multiple affected glands. Hypocalcemic stimulation is a useful adjunct in patients with PHPT who require invasive localization and can obviate the need for SVS. Clinical Trial number: NCT04969926.

DNA methylation clustered by predicted chromatin state reveals distinct association patterns with neuropathologic and biochemical measures in the AD brain

AbstractBackgroundAlzheimer’s disease (AD) is neuropathologically characterized by amyloid‐β (Aβ) plaques and tau neurofibrillary tangles often quantified by Thal phase and Braak stage, respectively. Aβ also frequently deposits in the cerebrovasculature with severity categorized by a cerebral amyloid angiopathy (CAA) score. These and related measures often show high variability within AD suggesting distinct underlying mechanisms, the identification of which may reveal important biological insights into AD pathophysiology. We hypothesize that, within the AD brain, neuropathology and levels of core AD‐related proteins are influenced by variations in DNA methylation (DNAm). To test this, we performed epigenome‐wide association studies (EWAS) using DNAm clusters from the temporal cortex (TCX) and cerebellum (CER) with AD‐related neuropathologic measures (Braak, Thal, and CAA) and brain biochemical levels of five proteins (apoE, Aβ40, Aβ42, tau, and p‐tau).MethodsDNAm from neuropathologically‐confirmed AD cases available through the Mayo Clinic brain bank was measured by reduced representation bisulfite sequencing (RRBS) from 471 brain samples, 200 of which had both TCX and CER measures. Neuropathology was scored by an experienced neuropathologist. TCX levels of five AD‐related proteins from three tissue fractions (buffer‐, detergent‐, and in‐soluble) were measured by ELISA (Liu 2020). CpG methylation (CpGm) was binned by a 15‐state chromatin model (Kundaje 2015) and averaged. Averaged CpGm clusters were tested for their association with each endophenotype through multi‐variable linear regression. The influence of CpGm clusters on expression levels of nearby genes was also investigated through multi‐variable regression.ResultsOur innovative binning method demonstrated expected and biologically relevant CpGm patterns. We identified multiple epigenome‐wide significant CpGm clusters unique to each AD‐related endophenotype and brain region. Comparisons between the TCX and CER further revealed brain region‐specific enrichment of distinct CpGm clusters. Significant CpGm clusters were further characterized by their influence on gene expression.ConclusionsAlthough all neuropathologic and biochemical endophenotypes tested are core to AD pathophysiology, our results suggest each has a distinct epigenetic architecture underlying their variability in the AD brain. By discovering brain region‐specific DNAm changes that contribute to each neuropathologic or biochemical outcome, we can identify core components of complex mechanisms that individually and jointly contribute to AD.