Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Soluble receptor for advanced glycation end products (sRAGE) and carotid intima-media thickness (CIMT) in type 1 diabetes Mellitus: Possible association with diabetic vascular complications

Background: Advanced glycation end products (AGEs) are a heterogeneous and complex group of biochemical compounds, resulting from nonenzymatic glycation and oxidation of protein, nucleic acids, and lipids. Aim of the study: To assess sRAGE and CIMT in patients with T1DM and their relation to glycemic control and diabetic vascular complications. Patients & methods: This study included 60 patients with mean age of 14.4 ± 3.4 years. They were subdivided into complicated and non complicated groups according to the presence of microvascular complications. Thirty age and sex matched controls were included. Patients with disease duration less than 5 years, connective tissue disease, liver dysfunction, or apparent cardiovascular disease and those on lipid lowering agents were excluded. Laboratory investigations included; HbA1c%, urinary albumin excretion (UAE), fasting lipid profile and sRAGE. Mean CIMT was measured by dopplex ultrasound. Results: Patients had higher sRAGE (1765.0 ± 451.0 pg/ml) (p < 0.001) especially the non complicated group (p = 0.18). It was directly correlated to HDL (r = 0.3, p = 0.012). Patients had increased CIMT (0.57 ± 0.14 mm) (p < 0.001) with 13.3% having carotid wall abnormalities. CIMT was directly correlated to age, weight, BMI, systolic and diastolic blood pressures, UAE, cholesterol and LDL (p < 0.05) and inversely correlated to HDL (p < 0.05). Neither CIMT nor sRAGE were correlated to glycemic control or disease duration. Conclusion: Patients with T1DM are at risk of increased CIMT with a concomitant increase in sRAGE which may be a therapeutic target for the prevention of diabetic vascular complications

Immunomodulatory Properties of Human Breast Milk: MicroRNA Contents and Potential Epigenetic Effects

Infants who are exclusively breastfed in the first six months of age receive adequate nutrients, achieving optimal immune protection and growth. In addition to the known nutritional components of human breast milk (HBM), i.e., water, carbohydrates, fats and proteins, it is also a rich source of microRNAs, which impact epigenetic mechanisms. This comprehensive work presents an up-to-date overview of the immunomodulatory constituents of HBM, highlighting its content of circulating microRNAs. The epigenetic effects of HBM are discussed, especially those regulated by miRNAs. HBM contains more than 1400 microRNAs. The majority of these microRNAs originate from the lactating gland and are based on the remodeling of cells in the gland during breastfeeding. These miRNAs can affect epigenetic patterns by several mechanisms, including DNA methylation, histone modifications and RNA regulation, which could ultimately result in alterations in gene expressions. Therefore, the unique microRNA profile of HBM, including exosomal microRNAs, is implicated in the regulation of the genes responsible for a variety of immunological and physiological functions, such as FTO, INS, IGF1, NRF2, GLUT1 and FOXP3 genes. Hence, studying the HBM miRNA composition is important for improving the nutritional approaches for pregnancy and infant&rsquo;s early life and preventing diseases that could occur in the future. Interestingly, the composition of miRNAs in HBM is affected by multiple factors, including diet, environmental and genetic factors

Synthesis, molecular docking and ADMET studies of bis-benzimidazole-based thiadiazole derivatives as potent inhibitors, in vitro α-amylase and α-glucosidase

Different research synthetic methods have been developed recently for the synthesis of bis-benzimidazole analogs to investigate various biological significances. In this present study, an attempt was made to synthesize a new series of bis-benzimidazole analogs in a fast and efficient method. A variety of spectroscopic techniques, including 13C NMR, 1H NMR, and HREI-MS, were used to establish the existence of every synthesized scaffold. Molecular docking profiles were also carried out to ascertain the binding interactions of the compounds. All derivatives (1–18) were evaluated for their biological potential to investigate the inhibitory activity of α-amylase and α-glucosidase through SAR study. Almost all derivatives were found to be engaged in a highly promising activity when compared to referenced drug acarbose (IC50 = 8.24 ± 0.08 µM), in this regard among the tested series analog 9 (IC50 = 0.10 ± 0.50 and 0.20 ± 0.50 µM respectively), showed excellent activity. Moreover, ADME predictions were also studied for potent compounds, exhibited drug like properties

New Triazinoindole Bearing Benzimidazole/Benzoxazole Hybrids Analogs as Potent Inhibitors of Urease: Synthesis, In Vitro Analysis and Molecular Docking Studies

Twenty-four analogs based on triazinoindole bearing benzimidazole/benzoxazole moieties (1&ndash;25) were synthesized. Utilizing a variety of spectroscopic methods, including 1H-, 13C-NMR, and HREI-MS, the newly afforded compounds (1&ndash;25) were analyzed. The synthesized analogs were tested against urease enzyme (in vitro) as compared to the standard thiourea drug. All triazinoindole-based benzimidazole/benzoxazole analogs (1&ndash;25) exhibited moderate to excellent inhibition profiles, having IC50 values of 0.20 &plusmn; 0.01 to 36.20 &plusmn; 0.70 &mu;M when evaluated under the positive control of thiourea as a standard drug. To better understand the structure&ndash;activity relationship, the synthesized compounds were split into two groups, &ldquo;A&rdquo; and &ldquo;B.&rdquo; Among category &ldquo;A&rdquo; analogs, analogs 8 (bearing tri-hydroxy substitutions at the 2,4,6-position of aryl ring C) and 5 (bearing di-hydroxy substitutions at the 3,4-position of aryl ring C) emerged as the most potent inhibitors of urease enzyme and displayed many times more potency than a standard thiourea drug. Besides that, analog 22 (which holds di-hydroxy substitutions at the 2,3-position of the aryl ring) and analog 23 (bearing ortho-fluoro substitution) showed ten-fold-enhanced inhibitory potential compared to standard thiourea among category &ldquo;B&rdquo; analogs. Molecular docking studies on the active analogs of each category were performed; the results obtained revealed that the presence of hydroxy and fluoro-substitutions on different positions of aryl ring C play a pivotal role in binding interactions with the active site of the targeted urease enzyme

Settler-Colonialism, Memoricide and Indigenous Toponymic Memory: The Appropriation of Palestinian Place Names by the Israeli State

Cartography, place-naming and state-sponsored explorations were central to the modern European conquest of the earth, empire building and settler-colonisation projects. Scholars often assume that place names provide clues to the historical and cultural heritage of places and regions. This article uses social memory theory to analyse the cultural politics of place-naming in Israel. Drawing on Maurice Halbwachs’ study of the construction of social memory by the Latin Crusaders and Christian medieval pilgrims, the article shows Zionists’ toponymic strategies in Palestine, their superimposition of Biblical and Talmudic toponyms was designed to erase the indigenous Palestinian and Arabo-Islamic heritage of the land. In the pre-Nakba period Zionist toponymic schemes utilised nineteenth century Western explorations of Biblical ‘names’ and ‘places’ and appropriated Palestinian toponyms. Following the ethnic cleansing of Palestine in 1948, the Israeli state, now in control of 78 percent of the land, accelerated its toponymic project and pursued methods whose main features were memoricide and erasure. Continuing into the post-1967 occupation, these colonial methods threaten the destruction of the diverse historical cultural heritage of the land

Cortisol Levels and Risk for Psychosis: Initial Findings from the North American Prodrome Longitudinal Study

BACKGROUND: Studies of biomarkers of hypothalamic-pituitary-adrenal (HPA) activity indicate that psychotic disorders are associated with elevated cortisol. This study examined cortisol levels in healthy controls and individuals who meet clinical high risk (CHR) criteria for psychosis. It was hypothesized that cortisol levels would be; a) elevated in the CHR group relative to controls, b) positively correlated with symptom severity, and c) most elevated in CHR patients who transition to psychotic level severity. METHODS: Baseline assessments were conducted at eight centers in the North American Prodrome Longitudinal Study (NAPLS). The present CHR sample included 256 individuals meeting Structured Interview for Prodromal Syndromes (SIPS) criteria, and 141 controls, all of whom underwent baseline assessment and measurement of salivary cortisol. RESULTS: Consistent with previous reports, there was an effect of age on cortisol, with increases through the adolescent/early adult years. Analysis of covariance (ANCOVA) showed a main effect of diagnostic group, with the CHR group showing higher cortisol. There were modest, positive correlations of cortisol with baseline symptom severity, and ANCOVA revealed higher baseline cortisol in those who transitioned to psychotic level symptoms when compared to healthy controls and CHR subjects who remitted. CONCLUSIONS: The present findings add to accumulating evidence of heightened cortisol secretion in CHR individuals. The findings also indicate nonspecific associations between cortisol levels and symptom severity, as well as symptom progression. The role of HPA activity in prediction of conversion to psychosis, and its relation with other biomarkers of risk, should receive attention in future research