Long-term male-specific chronic pain via telomere- and p53‑mediated spinal cord cellular senescence

Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53‑mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53‑positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male‑specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male‑specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53‑specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male‑specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.     

Combined experimental and computational study of Al2O3 catalyzed transamidation of secondary amides with amines

Amides are the most extensively used substances in both synthetic organic and bioorganic chemistry. Unfortunately, the traditional synthesis of amides suffers from some important drawbacks, including low atom efficiency, high catalyst loading, separation of products from the reaction mixture and production of byproducts. Al₂O₃ is an amphoteric catalyst that activates the carbonyl carbon of the secondary amide group and helps the C–N cleavage of the reactant amide group by attacking the N–H hydrogen. By using the concepts of amphoteric properties of Al₂O₃, amides were synthesized from secondary amides and amines in the presence of triethylamine solvent. Several aliphatic and aromatic amines were used for the transamidation of N-methylbenzamide in the presence of the Al₂O₃ catalyst. Moreover, using the Gaussian09 software at the DFT level, HUMO, LUMO and the intrinsic reaction coordinates (IRCs) have also been calculated to find out the transition state of the reaction and energy. In this study, five successful compounds were synthesized by the transamidation of secondary amides with amines using a reusable Al₂O₃ catalyst. The catalyst was reused several times with no significant loss in its catalytic activity. The products were purified by recrystallization and column chromatography techniques. This catalytic method is effective for the simultaneous activation of the carbonyl group and N–H bond by using the Al₂O₃ catalyst.

Amides are the most extensively used substances in both synthetic organic and bioorganic chemistry.     

Clinical and economic outcomes of a multidisciplinary team approach in a lower extremity amputation prevention programme for diabetic foot ulcer care in an Asian population: A case‐control study

Present guidelines recommend a multidisciplinary team (MDT) approach to diabetic foot ulcer (DFU) care, but relevant data from Asia are lacking. We aim to evaluate the clinical and economic outcomes of an MDT approach in a lower extremity amputation prevention programme (LEAPP) for DFU care in an Asian population. We performed a case‐control study of 84 patients with DFU between January 2017 and October 2017 (retrospective control) vs 117 patients with DFU between December 2017 and July 2018 (prospective LEAPP cohort). Comparing the clinical outcomes between the retrospective cohort and the LEAPP cohort, there was a significant decrease in mean time from referral to index clinic visit (38.6 vs 9.5 days, P < .001), increase in outpatient podiatry follow‐up (33% vs 76%, P < .001), decrease in 1‐year minor amputation rate (14% vs 3%, P = .007), and decrease in 1‐year major amputation rate (9% vs 3%, P = .05). Simulation of cost avoidance demonstrated an annualised cost avoidance of USD $1.86m (SGD $2.5m) for patients within the LEAPP cohort. In conclusion, similar to the data from Western societies, an MDT approach in an Asian population, via a LEAPP for patients with DFU, demonstrated a significant reduction in minor and major amputation rates, with annualised cost avoidance of USD $1.86m.     

Inpatient rehabilitation outcomes in neoplastic spinal cord compression vs. traumatic spinal cord injury

Objective: To compare neurological and functional outcomes, and complications of patients with neoplastic vs traumatic spinal cord injury (SCI) after in-patient rehabilitation.Design: This study is a retrospective analysis.Setting: In-patient rehabilitation unit of a tertiary research hospital.Participants: A total of 252 patients with a SCI were included; 43 with neoplastic SCI (mean age: 60.9 ± 15.7 years, 60.5% were males) and 209 with traumatic SCI (mean age: 43.1 ± 16.8 years, 71.3% were males).Outcome measures: Comparisons were made of demographic characteristics, etiology, American Spinal Injury Association (ASIA) impairment scale, functional independence measurement (FIM) and Functional Ambulation Categories (FAC) scores, length of stay (LOS), bladder independence, medical comorbidities and complications in both groups.Results: Patients with neoplastic SCI were significantly older than those with traumatic SCI (P < 0.01). No difference was present between the groups in terms of sex and lesion level (P > 0.05). Incomplete SCI was significantly higher in the neoplastic group when compared with the traumatic group (P < 0.01). The LOS was significantly shorter in the neoplastic group than traumatic group (34.8 ± 41.03 vs. 60.02 ± 53.1, P < 0.01). There were no differences in the admission FIM scores (69.3 ± 24.7 vs. 58.7 ± 18.9, P > 0.05), discharge FIM scores (82.1 ± 25.1 vs. 74.02 ± 23.3, P > 0.05) and FIM efficiencies (0.43 ± 0.72 vs. 0.36 ± 0.51, P > 0.05) for the neoplastic and traumatic groups, respectively. However, neoplastic SCI patients demonstrated lower FIM gains compared to traumatic patients (12.9 ± 11.9 vs. 15.4 ± 15.2, P < 0.05). During rehabilitation, urinary tract infection (48.4% vs. 69.4%) and decubitus ulcer (11.6% vs. 35.9%) were significantly more common in the traumatic group than the neoplastic group (P < 0.05).Conclusion: Neoplastic SCI patients who commonly present at rehabilitation units exhibit different characteristics from traumatic SCI patients but the rehabilitation results are similar. Similar functional development can be achieved in a shorter period of time with inpatient rehabilitation in the neoplastic SCI group.     

Liver immunity,autoimmunity, and inborn errors of immunity

The liver is the front line organ of the immune system.The liver contains the largest collection of phagocytic cells in the body that detect both pathogens that enter through the gut and endogenously produced antigens.This is possible by the highly developed differentiation capacity of the liver immune system between self-antigens or non-self-antigens,such as food antigens or pathogens.As an immune active organ,the liver functions as a gatekeeping barrier from the outside world,and it can create...     

An essential review of Singapore’s response to out-of-hospital cardiac arrests: improvements over a ten-year period

Care for patients who experience out-of-hospital cardiac arrest (OHCA) has rapidly evolved in the past decade. Increased sophistication of care in the community, emergency medical services (EMS) and hospital setting is associated with improved patient-centred outcomes. Notably, Utstein survival doubled from 11.6% to 23.1% between 2011 and 2016. These achievements involved collaboration between policymakers, clinicians and researchers, and were made possible by a strategic interplay of policy, research and implementation. We review the development and current state of OHCA in Singapore using primary population-based data from the Pan-Asian Resuscitation Outcomes Study and an unstructured search of research databases. We discuss the roles of important milestones in policy, community, dispatch, EMS and hospital interventions. Finally, we relate these interventions to relevant processes and outcomes, such as the relationship between the strategic implementation of bystander cardiopulmonary resuscitation and placement of automated external defibrillator with return of spontaneous circulation, survival to discharge and survival with favourable neurological outcomes.     

Sports Nutrition and Food Knowledge among Malaysian University Athletes

Sports nutrition and food knowledge can influence athletes’ dietary intake, potentially affecting athletic performance. Limited studies have been conducted to identify sports nutrition and food knowledge among Malaysian university athletes. This study aimed to determine Malaysian university athletes’ knowledge of sports nutrition and food, and their reference sources and preferred sports nutrition education programme. Seventy athletes (52.9% females, mean weight = 61.8 kg; height = 1.66 m) aged 18.5–22.4 years responded to an online survey administered using a Google Form. A score of ≥60% was considered as adequate knowledge. The average overall knowledge score was 58.6%. The highest knowledge score was for sports nutrition, specifically food intake periodicity (84.8%), while the lowest was for general food knowledge on fat (44.6%). An analysis of specific questions revealed a lack of understanding about the recommended daily intake of fruits and vegetables (only 14.3% answered correctly), the roles of vitamins and minerals in energy production (21.4%), and good sources of unsaturated fat (37.2%). The academician was the primary reference source (81%), while magazines were the least referred to sources (36%). The university athletes preferred sports camps (33%) over the other nutrition education programme options. More initiatives are needed to improve Malaysian university athletes’ understanding and knowledge of sports nutrition and general food.