Objective: Biological processes are the sum of metabolic reactions that result in intermediate and end metabolite products. These processes are the reflection of genetic regulation and are profoundly impacted by environmental influence and changes, including those associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to assess the untargeted plasma metabolomic profile of children and adolescents with ADHD and to compare them with healthy controls and to study associations of dysregulated metabolic parameters with the clinical and socio-demographic parameters of ADHD. Methods: This study involved 42 registered cases of ADHD among children aged 6 to 16 years, diagnosed based on DSM-5 criteria. Each case was matched by age and gender with 24 healthy controls. The severity of ADHD was evaluated using the ADHD Rating Scale, while behavioral issues were assessed through the Child Behavior Checklist. The gas chromatography-mass spectrometry technique was employed to examine changes in plasma metabolite content. Results: We identified a total of 45 metabolites in the ADHD subtypes, which exhibited altered levels compared to the control group. The content of these metabolites and associated metabolic pathways showed significant differences between ADHD subjects and controls. Furthermore, we analyzed biomarkers derived from the compounds with the greatest fold changes in accumulation levels. Conclusion The identification and analysis of these metabolites and metabolic pathways represent a promising new approach for tracking disease progression in ADHD. The findings of this study indicate that metabolite-based biomarkers may hold considerable potential for effective disease management.

INTRODUCTION: The National Institute of Health and Care Excellence (NICE) has defined the terms, 'acute coronavirus disease 2019' (COVID-19), 'ongoing symptomatic COVID-19' and 'post-COVID-19 syndrome', with the latter two described as having persistent symptoms after the onset of COVID-19 symptoms for 4-12 weeks and >12 weeks, respectively. Persistent symptoms can either be due to the after-effects of COVID-19 or new-onset diseases after acute COVID-19. All symptoms observed beyond 4 weeks after the onset of COVID-19 need not be present at the time of onset. Previous studies on persistent post-COVID-19 symptoms have not mentioned new-onset diseases after acute COVID-19, and only a select few studies have discussed such new-onset symptoms. METHODS: Ninety-five patients who attended the post-COVID-19 clinic completed the requisite follow-up till 16 weeks after COVID-19 symptom onset. Data was recorded on a predesigned proforma. Necessary investigations were conducted to rule out any other cause of persistent symptoms. RESULTS: Fatigue (62.1%), breathlessness (50.5%) and cough (27.4%) were the most common symptoms present beyond 4 weeks after the onset of COVID-19 symptoms. Forty-nine (51.57%) patients developed post-COVID-19 syndrome - their severity of symptoms (odds ratio [OR] 17.77) and longer duration of hospital stay (OR 1.095) during acute disease were significantly associated with the development of post-COVID-19 syndrome. During follow-up, 25 patients developed new-onset symptoms, such as diabetes mellitus, hypertension and idiopathic tachycardia. CONCLUSION Patients can have persistent symptoms, new-onset symptoms and new-onset diseases after recovery from acute COVID-19.
Humans ; COVID-19/diagnosis* ; Female ; Male ; Prospective Studies ; Middle Aged ; Adult ; Fatigue/etiology* ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Aged ; Cough/etiology* ; Dyspnea/etiology*

Purpose: Aging leads to immune dysfunction, including altered T-cell phenotypes such as the ­CD5 low state. This study investigated how the exon switch regulates CD5 expression in aging in an interleukin-10 (IL-10)-dominated environment and the involvement of CCAAT/enhancer-binding protein beta (CEBP-β) in this process. Methods: The expression of messenger RNA (mRNA) was analyzed for E1A and E1B in T cells from young and older adults. The effect of IL-10 treatment on the exon switch was assessed by measuring the E1A and E1B mRNA expression in young T cells. MatInspector analysis identified CEBP-β binding sites upstream of E1A and E1B start sites.The effect of IL-10 on CEBP-β isoforms expression was assessed using western blot, and that on CEBP-β binding onto the E1A and E1B upstream was assessed using chromatin immunoprecipitation assays. The short hairpin RNA (shRNA) silencing of CEBP-β was performed to confirm its role in E1A/E1B expression. Results: Older individuals showed increased E1B and decreased E1A mRNA expression. IL-10 treatment of young T cells persuaded a similar shift. IL-10 changed CEBP-β binding, reducing its association with the E1B upstream region while increasing its binding to E1A. IL-10 also upregulated the liver-enriched inhibitory protein of CEBP-β. shRNA silencing of CEBP-β reduced E1B expression. Conclusion IL-10-driven exon switching alters CD5 expression in aged T cells, increasing E1B and decreasing E1A through CEBP-β regulation. These findings reveal a novel mechanism underlying fundamental immune aging and suggest potential targets for immune modulation. These insights may have clinical implications in chronic inflammatory diseases, autoimmune disorders, and cancer therapies.

Background: This study aimed to evaluate and compare the efficacy of oral premedication with ibuprofen on the anesthetic efficacy of inferior alveolar nerve block (IANB) using 2% lignocaine and 1:100000 epinephrine in tobacco-chewing (TC) and non-tobacco-chewing (NTC) patients with symptomatic irreversible pulpitis (SIP) during nonsurgical endodontic intervention (NEI). Methods: This multicenter, prospective, double-blind, two-arm parallel-group randomized controlled trial involving 160 patients was conducted for a period of 9 months. The patients were classified into the study (TC patients) and control (NTC patients) groups, which were subdivided into two subgroups 1 hour before the procedure based on oral premedication with tab ibuprofen 600 mg. Nicotine dependence was assessed using the Modified Fagerstrom Tolerance Nicotine Scale. Patients were administered an IANB injection of 2% lignocaine containing epinephrine 1:100000 after premedication. Pulpal anesthesia before NEI was confirmed using electric pulp testing and cold spraying. Patients rated their pain on the 10-point visual analog scale (VAS) during NEI thrice at the dentin, pulp, and instrumentation levels. No pain at each level indicated the success of anesthesia. Results: The success and failure rates did not differ between the premedication and non-premedication subgroups in the TC or NTC groups (P > 0.05). However, the success rate was higher in the premedication subgroup of the NTC group (52.5%) than in the TC group (45%). Most patients with premedication experienced failure at the instrumentation level, whereas patients in the non-premedication group experienced pain at the dentin level. Failure rates of IANB did not differ significantly at different levels between the groups (P > 0.05). The mean VAS scores differed significantly at the dentin level in both groups, with lower values in the premedication group (P < 0.05). Conclusions The efficacy of ibuprofen premedication with IANB during NEI did not differ significantly between the TC and NTC patients with SIP. The effect of premedication was more significant in the NTC group than in the TC group. A causal relationship between nicotine consumption and the success of premedication could not be established, and further studies are required to validate the results of the present study.

Background/Aims: Inflammatory bowel disease (IBD) is increasingly being recognized in elderly patients. Data on clinical spectrum of elderly-onset IBD patients is lacking from India. Methods: A cross-sectional retrospective analysis of a prospectively maintained database of patients diagnosed with IBD was conducted at 2 centers in India. The clinical spectrum of elderly-onset IBD including demographic profile (age and sex), clinical presentation, disease characteristics (disease behavior and severity, extent of disease), and treatment were recorded and compared with adult-onset IBD. Results: During the study period, 3,922 (3,172 ulcerative colitis [UC] and 750 Crohn’s disease [CD]) patients with IBD were recorded in the database. A total of 186 patients (4.74%; 116 males [62.36%]) had elderly-onset IBD (69.35% UC and 30.64% CD). Diarrhea, blood in stools, nocturnal frequency and pain abdomen were the commonest presentations for UC, whereas pain abdomen, weight loss and diarrhea were the most frequent symptoms in CD. For both elderly onset UC and CD, majority of the patients had moderately severe disease. Left-sided colitis was the commonest disease location in UC. Isolated ileal disease and inflammatory behavior were the most common disease location and behavior, respectively in CD. 5-Aminosalicylates were the commonest prescribed drug for both elderly onset UC and CD. Thiopurines and biologics were used infrequently. Prevalence of colorectal cancer was higher in elderly onset IBD. Conclusions Elderly onset IBD is not uncommon in India. Both the elderly onset UC and CD were milder, with no significant differences in disease characteristics (disease extent, location and behavior) when compared to adult-onset IBD. Colorectal cancer was more common in elderly onset IBD.

Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential.

Background and Objectives: Single-sided deafness (SSD) leads to non-participation of the diseased ear in generating adequate auditory input, which results in poor speech discrimination in noisy surroundings. The present study objectively compared the audiological benefits rendered by contralateral routing of signal (CROS) hearing aid and bone conduction device (BCD) in patients with SSD >70 dB HL using the modified hearing in noise test (HINT). Materials and Methods: Patients with SSD >70 dB HL in poor and clinically normal hearing in the better ear were enrolled. Patients aged <18 or >70 years, with a history of neurological insult or ear infection in the last 3 months, mental retardation, psychiatric or developmental disorders, and diabetes were excluded. Modified HINT was performed with the affected ear unaided, aided with CROS hearing aid, and with BCD, generating three groups. Noise signal was presented at a fixed intensity of 65 dB at the neutral position in the center and speech signal was presented to either ear sequentially. The test was repeated with the speech signal fixed at the neutral position and the noise signal presented to either ear. Results: BCD led to a better signal-to-noise ratio (SNR) than CROS hearing aid in all situations except when noise was centralized and speech was presented to the affected ear. Conclusions A benefit was observed when auditory rehabilitation was used for the affected ear as demonstrated by better SNR scores. The results showed that BCD performed better than CROS hearing aid.