The association between empathy and burnout in medical students: a systematic review and meta-analysis.

BACKGROUND: Burnout levels in medical students are higher than in other student groups. Empathy is an increasingly desired outcome of medical schools. Empathy is negatively associated with burnout in physicians. Our objective was to quantitatively review the available literature on associations between empathy and burnout in medical students, and to explore associations between specific empathy aspects (cognitive and affective) and burnout sub-dimensions (emotional exhaustion, depersonalization and personal accomplishment). METHODS: A comprehensive search of the literature published up until January 2024 was undertaken in the PubMed, EMBASE, CINAHL, The Cochrane Library, and PsycINFO databases. Two independent reviewers screened 498 records and quality-rated and extracted data from eligible studies. The effect size correlations (ESr) were pooled using a random-effects model and between-study variation explored with meta-regression. The review was preregistered with PROSPERO (#CRD42023467670) and reported following the PRISMA guidelines. RESULTS: Twenty-one studies including a total of 27,129 medical students published between 2010 and 2023 were included. Overall, empathy and burnout were negatively and statistically significantly associated (ESr: -0.15, 95%CI [-0.21; -0.10], p < .001). When analyzing sub-dimensions, cognitive empathy was negatively associated with emotional exhaustion (ESr: -0.10, 95%CI [-0.17; -0.03], p = .006) and depersonalization (ESr: -0.15, 95%CI [-0.24; 0.05], p = .003), and positively associated with personal accomplishment (ESr: 0.21, 95%CI [0.12; 0.30], p < .001). Affective empathy was not statistically significantly associated with emotional exhaustion, depersonalization or personal accomplishment. Supplementary Bayesian analysis indicated the strongest evidence for the positive association between cognitive empathy and personal accomplishment. Response rate and gender moderated the relationship so that higher response rates and more male respondents strengthen the negative association between empathy and burnout. CONCLUSION: Greater empathy, in particular cognitive empathy, is associated with lower burnout levels in medical students. This appears to be primarily driven by cognitive empathy's positive association with personal accomplishment. PROTOCOL REGISTRATION: #CRD42023467670.

Is adequate parenting compatible with maternal drug use? A 5-year follow-up.

INTRODUCTION: This prospective, cohort study compares child protection outcomes over the first 5 years of life in a group of children born to self-declared drug-using mothers recruited during pregnancy (cases) and a group of children matched for gestational age, chronological age, maternal neighbourhood and place of delivery whose mothers made no such declaration of problematic drug use (controls). METHODOLOGY: We monitored local child protection registers to identify cohort members who came to the attention of the local authority. RESULTS: Of the 71 original cases and 142 original controls, 55 (77%) and 96 (68%) remained in the area enrolled in local schools at 5 years of age. In total, 26 (47.3%) of the case children were subject to child protection procedures compared with 18 (18.8%) of the control children. This risk difference of 28.5% (95% CI 13.2% to 43.9%) has increased marginally since our previous report in this journal of child protection outcomes at 18 months of age (32% vs. 7%). However, the level of intervention deemed necessary to protect the child has increased significantly with six cases (compared with one control child) taken into the care of the local authority. CONCLUSIONS: Despite early maternal intentions and multiple supportive interventions, 27% of children born to women with significant substance abuse problems in our area required child protection during the pre-school years. Child protection risk assessment procedures need to weigh problematic maternal drug use heavily. Intervention studies with child welfare outcomes are needed to identify the most effective harm reduction strategies and inform public debate on how we can minimize child abuse related to substance misuse.

Methylated DNA sequences for early cancer detection, molecular classification and chemotherapy response prediction.

Molecular studies of many types of cancer have revealed that clinically evident tumours carry multiple genetic and epigenetic abnormalities, including DNA sequence alterations, chromosome copy number changes and aberrant promoter hypermethylation. Together, these aberrant changes result in the activation of oncogenes and inactivation of tumour-suppressor genes (TSG). In many cases these abnormalities can be found in premalignant lesions and even in histological normal adjacent cells. Many tumour types are difficult to detect early and are frequently resistant to available chemotherapy and radiotherapy. Therefore, the early detection, chemoprevention and the design of new therapeutic strategies based on the increased understanding of cancer molecular changes are one of the great challenges nowadays. Insertions of a methyl group at the fifth carbon of cytosines within the dinucleotide 5'- CpG-3' is the best studied epigenetic mechanism. DNA methylation acts together with others mechanisms like histone modification, chromatin remodelling and microRNAs to mould the DNA structure according to the functional state required. The aberrant methylation of the CpG islands located at the promoter region of specific genes is a common and early event involved in cancer development. Thus, hypermethylated DNA sequences from tumours are one of the most promising markers for early detection screenings as well as tumour classification and chemotherapy response in many types of cancer.

Methylated DNA sequences for early cancer detection, molecular classification and chemotherapy response prediction

Molecular studies of many types of cancer have revealed that clinically evident tumours carry multiple genetic and epigenetic abnormalities, including DNA sequence alterations, chromosome copy number changes and aberrant promoter hypermethylation. Together, these aberrant changes result in the activation of oncogenes and inactivation of tumour-suppressor genes (TSG). In many cases these abnormalities can be found in premalignant lesions and even in histological normal adjacent cells. Many tumour types are difficult to detect early and are frequently resistant to available chemotherapy and radiotherapy. Therefore, the early detection, chemoprevention and the design of new therapeutic strategies based on the increased understanding of cancer molecular changes are one of the great challenges nowadays. Insertions of a methyl group at the fifth carbon of cytosines within the dinucleotide 5'- CpG-3' is the best studied epigenetic mechanism. DNA methylation acts together with others mechanisms like histone modification, chromatin remodelling and microRNAs to mould the DNA structure according to the functional state required. The aberrant methylation of the CpG islands located at the promoter region of specific genes is a common and early event involved in cancer development. Thus, hypermethylated DNA sequences from tumours are one of the most promising markers for early detection screenings as well as tumour classification and chemotherapy response in many types of cancer (AU)

The effectiveness of psychological treatments for treatment-resistant depression: a systematic review.

OBJECTIVE: A systematic review of all studies (controlled and uncontrolled) to evaluate psychological interventions with treatment-resistant depression. METHOD: A systematic search to identify studies evaluating a psychological intervention with adults with a diagnosis of major depressive disorder who had not responded to at least one course of antidepressant medication. RESULTS: Twelve studies met inclusion criteria, of which four were controlled and eight uncontrolled. Treatment effect sizes were computable for four studies and ranged from 1.23 to 3.10 with a number of better quality studies demonstrating some improvements in patients following a psychological intervention. CONCLUSION: Psychological treatments for depression are commonly delivered and often recommended following the failure of medication. The paucity of evidence for their effectiveness in these situations is a significant problem. There is a need for studies with a strong controlled design investigating the effectiveness of psychological treatments for patients with treatment-resistant depression.

How great is the risk of abuse in infants born to drug-using mothers?

UNLABELLED: This prospective, cohort study reports early child protection and surveillance process markers for children born to self-proclaimed drug-using mothers. BACKGROUND: A strong association is reported between maternal drug use and child abuse in North American studies. There are no systematic data describing this association for the UK population. Given the heterogeneous nature of drug cultures and associated behaviour it is difficult to generalize from US data to the UK population. METHODS: The study group consisted of all women referred to a hospital-based antenatal clinic for pregnant drug users. Infants of non-drug users were matched for social class and gestational age. At 18 months the Bristol and surrounding area child protection registers and child health surveillance records were searched. Infants were coded as to whether they were the subject of an enquiry, case conference, registration, registration with subsequent deregistration, or taken into care. RESULTS: There were 68 infants of drug users and 127 infants of non-drug users. Most (81%) of drug users were heroin and/or methadone users; half were using/had used intravenously. Child health surveillance uptake for both groups is lower than that reported for the Avon population as a whole during the study period, consistent with the relatively deprived populations represented. There is no statistically significant difference between the drug users and non-drug users. The overall risk of child protection proceedings was higher in children of drug users than in children of non-drug users. However, closer inspection of the data shows most of the excess risk is explained by the small group taken into care and the much larger group for whom the concerns were relatively shortlived as shown by their subsequent deregistration during the study period. CONCLUSIONS: Maternal drug use does not necessarily lead to unacceptable standards of parenting. More UK-based research is needed to inform the risk assessment process for child protection.

Maillard reaction kinetics in model preservation systems in the vicinity of the glass transition: experiment and theory.

Rates of reactant consumption for the Maillard reaction between lysine and glucose were measured for a noncrystallizing trehalose-sucrose-water matrix in the glass transition region. At temperatures above the glass transition temperature (T(g)), the consumption rates showed Arrhenius temperature dependence with activation energies of 135 and 140 kJ mol(-1) for lysine and glucose, respectively. Finite reaction rates were observed for glassy samples that were faster than that of one of the nonglassy samples. A comparison of experimental results with predicted diffusion-controlled reaction rate constants indicated that the reaction was reaction-controlled at temperatures above T(g) and approached the diffusion-influenced regime in the glassy state. The needs for further research on reactant diffusivity, the theory of the orientation dependence of reactivity, and a detailed understanding of the reaction mechanism and kinetics were identified.

Molecular detection of prostate cancer in urine by GSTP1 hypermethylation.

Novel approaches for the early detection and management of prostate cancer are urgently needed. Clonal genetic alterations have been used as targets for the detection of neoplastic cells in bodily fluids from many cancer types. A similar strategy for molecular diagnosis of prostate cancer requires a common and/or early genetic alteration as a specific target for neoplastic prostate cells. Hypermethylation of regulatory sequences at the glutathione S-transferase pi (GSTP1) gene locus is found in the majority (>90%) of primary prostate carcinomas, but not in normal prostatic tissue or other normal tissues. We hypothesized that urine from prostate cancer patients might contain shed neoplastic cells or debris amenable to DNA analysis. Matched specimens of primary tumor, peripheral blood lymphocytes (normal control), and simple voided urine were collected from 28 patients with prostate cancer of a clinical stage amenable to cure. Genomic DNA was isolated from the samples, and the methylation status of GSTP1 was examined in a blinded manner using methylation-specific PCR. Decoding of the results revealed that 22 of 28 (79%) prostate tumors were positive for GSTP1 methylation. In 6 of 22 (27%) cases, the corresponding urine-sediment DNA was positive for GSTP1 methylation, indicating the presence of neoplastic DNA in the urine. Furthermore, there was no case where urine-sediment DNA harbored methylation when the corresponding tumor was negative. Although we only detected GSTP1 methylation in under one-third of voided urine samples, we have demonstrated that molecular diagnosis of prostate neoplasia in urine is feasible. Larger studies focusing on carcinoma size, location in the prostate, and urine collection techniques, as well as more sensitive technology, may lead to the useful application of GSTP1 hypermethylation in prostate cancer diagnosis and management.

Characterisation of Wnt gene expression during the differentiation of murine embryonic stem cells in vitro: role of Wnt3 in enhancing haematopoietic differentiation.

The first haematopoietic stem cells in mammalian and non-mammalian vertebrates are derived from mesoderm, therefore genes that are important in mesoderm patterning and formation might also play an essential role in haematopoietic stem cell commitment and differentiation. Several members of the Wnt gene family are expressed in very specific patterns in embryonic mesoderm and have previously been shown to act as haematopoietic growth factors. In order to investigate in detail the role that such secreted proteins play in the biology of early haematopoietic commitment we have used in vitro differentiation of murine embryonal stem (ES) as a model system. Using reverse-transcriptase polymerase chain reaction analysis we identified several candidate Wnt genes whose expression pattern was consistent with a role in generation, maintenance and/or differentiation of early haematopoietic progenitor cells including three genes previously shown to have a role in haematopoiesis (Wnt5a, Wnt2b and Wnt10b). The most interesting candidate was Wnt3, because of its strong and regulated expression during in vitro differentiation of murine ES cells as well as its early embryonic expression in mesoderm. Overexpression of Wnt3 was sufficient to cause a consistent increase in the number of embryoid bodies committing to haematopoiesis further strengthening the evidence that this protein can enhance haematopoietic commitment during in vitro differentiation of ES cells. In addition, overexpression of Wnt3 caused a marked upregulation of Brachyury expression, thus providing some evidence that Brachyury may be one of the target genes for the Wnt3 signalling pathway.

Papillary urothelial hyperplasia is a clonal precursor to papillary transitional cell bladder cancer.

Papilloma and papillary hyperplasia (PH) have been proposed to be the putative precursor lesions of papillary transitional-cell carcinoma of the urinary bladder. We examined 15 PH lesions and 4 papillomas for loss of heterozygosity (LOH) at 17 microsatellite markers on 9 chromosomal arms. Eight of 15 (53%) PHs were clonal, demonstrating LOH of at least 1 microsatellite marker. In contrast, none of the papillomas showed any genetic changes among the markers tested. In PH, chromosomal arm 9q was the most frequently lost (4/15), followed by 9p and 18q (n = 2) and, less frequently, 8p, 10q, 11p and 17p (n = 1). Furthermore, 2 hyperplastic lesions demonstrated LOH at 9q only, confirming the notion that allelic loss on chromosomal arm 9q is among the earliest events in bladder-cancer progression. In 1 patient, identical LOH patterns were observed between PH and a recurrent transitional-cell carcinoma. Our molecular data demonstrate that at least a proportion of PHs represent pre-cancerous lesions of the bladder that subsequently progress to papillary bladder cancer. Moreover, chromosomal arm 9q may harbor a tumor-suppressor gene(s) inactivated in the earliest stages of human bladder tumorigenesis.

mTert expression correlates with telomerase activity during the differentiation of murine embryonic stem cells.

Telomerase, the enzyme which maintains the ends of linear chromosomes in eukaryotic cells, is found at low levels in somatic stem cells but while this is incapable of preventing the progressive erosion of telomeres occurring as a consequence of cell division, such cells show greater proliferative capacity than normal somatic cells hence examination of telomerase activity in such stem cells is of interest. Our aim in this work was to examine the relationship between expression of the reverse transcriptase component (mTert) of murine telomerase. We report here the insertion of a reporter cassette comprising a segment of the promoter sequence of murine Tert gene coupled to the coding sequence of green fluorescent protein (GFP) into murine embryonic stem (ES) cells and show that this is sufficient for mimicking the expression of mTert. We show that the expression of mTert is very closely linked to telomerase activity and that both are substantially reduced upon differentiation of ES cells into more committed lineages giving us a potential reporter system for the selection and isolation of ES cells possessing different levels of telomerase activity.

Carnitine supplementation of parenterally fed neonates.

BACKGROUND: Carnitine, a quaternary amino acid, plays an important role in the oxidation of long chain fatty acids. Both breast milk and infant formulas contain carnitine. However, it is not routinely provided in parenteral nutrition solutions. Non supplemented parenterally fed infants have very low tissue carnitine levels. The clinical significance of this is uncertain. Carnitine deficiency may be an etiological factor in the limited ability of premature babies to utilize parenteral lipid. In vitro studies have suggested that fatty acid oxidation is impaired when the tissue carnitine levels fall below 10% of normal. Therefore relative carnitine deficiency may impair fatty acid oxidation, thus reducing the available energy and impairing growth. OBJECTIVES: The primary aim of this review is to determine whether carnitine supplementation of parenterally fed neonates will improve weight gain. The secondary aims are to determine the effect on lipid tolerance and ketogenesis. SEARCH STRATEGY: Computerised searches were carried out by both reviewers. Searches were made of Medline, Embase, The National Research Register (UK), the Cochrane Controlled Trials Register and expert informants. The MeSH headings used were carnitine and parenteral nutrition. SELECTION CRITERIA: Only randomised trials were considered. Trials were included if they involved carnitine supplementation alone, parenterally fed newborn infants, and measured at least one outcome of interest (weight gain, plasma fatty acids, plasma triglycerides, quantity of lipid tolerated, respiratory quotient or beta hydroxybutyrate levels). DATA COLLECTION AND ANALYSIS: The two reviewers searched the literature separately and reached a consensus for inclusion of trials. Data were extracted and evaluated by the two reviewers independently of each other. Authors were contacted if possible to clarify or provide missing data. MAIN RESULTS: Fourteen studies were identified, six met the selection criteria. The results of the review are limited by the fact that the studies were generally short term and studied different outcomes. One study examined short term and long term weight gain, three reported only short term weight gain, three reported biochemical results in response to a short lipid challenge, and two reported results obtained during normal parenteral nutrition. Among infants supplemented with carnitine, there was no evidence of effect on weight gain, lipid utilization or ketogenesis. REVIEWER'S CONCLUSIONS: We found no evidence to support the routine supplementation of parenterally fed neonates with carnitine.

Observations on the crystallization of oligogalacturonates.

Oligogalacturonates were produced by the limited enzymic hydrolysis of polygalacturonic acid and purified by ion-exchange chromatography. The fractions obtained were of limited polydispersity, determined by analytical ion-exchange chromatography. Oligomers with an average degree of polymerization of 10-15 were readily crystallized from aqueous salt solutions at neutral pH as single crystals. Crystal morphology of the salts examined, Na+, K+ and Ca2+ were characteristic of the salt. The wide-angle X-ray diffraction patterns obtained for the sodium salt were consistent with published fibre diffraction data of this salt form.