Peripheral Inflammatory Biomarkers of Methamphetamine Withdrawal Patients Based on the Neuro-Inflammation Hypothesis: The Possible Improvement Effect of Exercise

Methamphetamine (MA) induced addiction and neuroinflammation has been implicated. Based on the neuroinflammation hypothesis, this study aims to investigate how exercise influences the craving of patients in MA withdrawal, and explore the mechanism of peripheral inflammation. A total of 90 patients in MA withdrawal were recruited. No difference was noted in the number of years of drug use and the frequency of drug use among patients, and the withdrawal time was within 2 months. The subjects were grouped based on the degree of craving induced by the cues: non-craving control group (NCC group), craving control group (CC group), and craving exercise group (CE group). The CE group was subjected to aerobic combined resistance training. Then, the ELISA method was used to detect plasma IL-6, TNF-α, and IL-1β concentrations; Visual Analog Scale (VAS) measurement of cue-induced cravings under Virtual Reality (VR) exposure (VR-VAS) and the Desires for Drug Questionnaire (DDQ) were used to assess cravings. Consequently, plasma IL-6, TNF-α, IL-1β, levels, and the VR-VAS and DDQ scores of MA withdrawal patients were significantly reduced after exercise. This study confirmed that 8 weeks of incremental load aerobic combined with resistance training reduces peripheral inflammation and significantly reduces the level of craving for MA.

Single Cell Scale Neuronal and Glial Gene Expression and Putative Cell Phenotypes and Networks in the Nucleus Tractus Solitarius in an Alcohol Withdrawal Time Series

Alcohol withdrawal syndrome (AWS) is characterized by neuronal hyperexcitability, autonomic dysregulation, and severe negative emotion. The nucleus tractus solitarius (NTS) likely plays a prominent role in the neurological processes underlying these symptoms as it is the main viscerosensory nucleus in the brain. The NTS receives visceral interoceptive inputs, influences autonomic outputs, and has strong connections to the limbic system and hypothalamic-pituitary-adrenal axis to maintain homeostasis. Our prior analysis of single neuronal gene expression data from the NTS shows that neurons exist in heterogeneous transcriptional states that form distinct functional subphenotypes. Our working model conjectures that the allostasis secondary to alcohol dependence causes peripheral and central biological network decompensation in acute abstinence resulting in neurovisceral feedback to the NTS that substantially contributes to the observed AWS. We collected single noradrenergic and glucagon-like peptide-1 (GLP-1) neurons and microglia from rat NTS and measured a subset of their transcriptome as pooled samples in an alcohol withdrawal time series. Inflammatory subphenotypes predominate at certain time points, and GLP-1 subphenotypes demonstrated hyperexcitability post-withdrawal. We hypothesize such inflammatory and anxiogenic signaling contributes to alcohol dependence via negative reinforcement. Targets to mitigate such dysregulation and treat dependence can be identified from this dataset.

Patient characteristics and procedural outcomes of moderate sedation for endoscopic procedures in patients with obesity: A retrospective, propensity score-matched study

Background Endoscopic procedures are performed commonly with moderate sedation. Obesity can pose a challenge in its safe administration. This study was aimed at assessing outcomes of endoscopy procedures performed with moderate sedation in obese patients. Patients and methods This was a retrospective study of patients undergoing esophagogastroduodenoscopy (EGD) and/or colonoscopy with moderate sedation from July 17, 2017 to December 31, 2019. Demographics, comorbidities, outpatient medications and procedure-related outcomes (procedure time, recovery time, cardiopulmonary adverse events, 7-day post-procedure hospitalization, cecal intubation time, withdrawal time, tolerance of moderate sedation and sedation medications administered) were compared for patient with and without obesity after propensity score matching. Standard statistical methods were used for analysis. Results A total of 7601 procedures were performed with moderate sedation for 5746 patients. Propensity score matching identified 1360 and 1740 pairs of EGDs and colonoscopies with moderate sedation for patients with and without obesity. Recovery time was found to be shorter for obese patients undergoing EGD (OR: 0.989, 95 % CI: 0.981–.998; P = 0.01). Obese patients did not differ from non-obese patients in any other procedure-related outcomes for EGDs or colonoscopies. Conclusions Outcomes for endoscopy procedures performed with moderate sedation were noted to be similar between obese and non-obese patients. These findings suggest that moderate sedation can be used safely for endoscopic procedures in patients with obesity.

Optimal Timing of Simethicone Supplement for Bowel Preparation: A Prospective Randomized Controlled Trial

Background and Aims. Simethicone (SIM), as an antifoaming agent, has been shown to improve bowel preparation during colonoscopy. However, the optimal timing of SIM addition remained undetermined. We aimed to investigate the optimal timing of SIM addition to polyethylene glycol (PEG) to improve bowel preparation. Methods. Eligible patients were randomly assigned to two groups: the SIM evening group (SIM addition to PEG in the evening of the day prior to colonoscopy) and the SIM morning group (SIM addition to PEG in the morning of colonoscopy). The primary outcome was Bubble Scale (BS). The secondary outcomes were Boston Bowel Preparation Scale (BBPS) and adenoma detection rate (ADR). Results. A total of 419 patients were enrolled in this study. The baseline characteristics of the patients were similar in both groups. No significant differences were observed in terms of BS (8.76 ± 0.90 vs. 8.65 ± 1.16, P = 0.81), ADR (34.1% vs. 30.8%, P = 0.47), Boston Bowel Preparation Scale (BBPS) (8.59 ± 0.94 vs. 8.45 ± 1.00, P = 0.15), and withdrawal time (8.22 ± 2.04 vs. 8.01 ± 2.51, P = 0.094) between the two groups. Moreover, safety and compliance were similar in both groups. However, the SIM evening group was associated with shorter cecal intubation time (3.80 ± 1.81 vs. 4.42 ± 2.03, P < 0.001), higher BS (2.95 ± 0.26 vs. 2.88 ± 0.38, P = 0.04) in the right colon, and diminutive ADR (62.5% vs. 38.6%, P = 0.022) in the right colon, when compared to the SIM evening group. Conclusions. The SIM addition to PEG in the evening of the day prior to colonoscopy can shorten cecal intubation time and improve BS scores and diminutive ADR of the right colon compared with the SIM addition to PEG in the morning of colonoscopy in bowel preparation.

Single-Tear Proteomics: A Feasible Approach to Precision Medicine

Lacrimal fluid is an attractive source of noninvasive biomarkers, the main limitation being the small sample amounts typically collected. Advanced analytical methods to allow for proteomics profiling from a few microliters are needed to develop innovative biomarkers, with attractive perspectives of applications to precision medicine. This work describes an effective, analytical pipeline for single-tear analysis by ultrahigh-resolution, shotgun proteomics from 23 healthy human volunteers, leading to high-confidence identification of a total of 890 proteins. Highly reproducible quantification was achieved by either peak intensity, peak area, or spectral counting. Hierarchical clustering revealed a stratification of females vs. males that did not emerge from previous studies on pooled samples. Two subjects were monitored weekly over 3 weeks. The samples clustered by withdrawal time of day (morning vs. afternoon) but not by follow-up week, with elevated levels of components of the immune system in the morning samples. This study demonstrates feasibility of single-tear quantitative proteomics, envisaging contributions of this unconventional body fluid to individualized approaches in biomedicine.

Standardization of Dose and Delivery of Oxytetracycline against Streptococcus agalactiae Infection in Genetically Improved Farmed Tilapia (GIFT)

Background: Tilapia (Oreochromis niloticus) is one of the most important aquaculture species in India. Streptococcus agalactiae is a highly debilitating pathogen of farmed tilapia. In this study, oxytetracycline (OTC) dose and delivery were standardized against S. agalactiae infection in genetically improved farmed tilapia (GIFT) and pharmacokinetics after oral administration was evaluated. Methods: LD50 value of S. agalactiae was found to be 6.2×106 CFU/fish. Two methods of drug delivery were investigated at three different doses of 50, 70 and 90 mg/kg against the S. agalactiae infection. Pharmacokinetics of OTC was studied after per os administration of 100 mg/kg body weight per day and analysing the residues in kidney, liver and muscle at different time intervals. Result: Per os delivery of OTC 90 mg/kg controlled S. agalactiae infection and the withdrawal time of OTC to fall below MRL of 0.05 µg/g at 30°C was 21 days in kidney and liver and 14 days in muscle. The study indicated that the S. agalactiae infection in tilapia could be controlled by OTC and fish can be marketed after providing a withdrawal period of 14 days.