Cholecystectomy clip-induced biliary stone: Case report and literature review.

ABSTRACT: Migration of cholecystectomy surgical clip into the common bile duct with subsequent stone formation is a rare phenomenon, one which may lead to complications including obstruction, pain, nausea, vomiting and fever. The mechanism of migration is largely unknown but may result from a combination of factors including necrosis, intra-abdominal pressure or poor surgical technique with migrated clip serving as a nidus for stone formation. We present a 55-year-old woman with clip-induced stone impacted at the distal common bile duct 12 years post-cholecystectomy and a review of the literature related to cholecystectomy clip stone formation. In addition, we reviewed relevant English language case reports and literature reviews by searching PubMed using search terms 'stone', 'clip', 'cholecystectomy' and 'biliary'. There was no limit to the date of publication. Our study found 68 unduplicated cases of clip-induced stones which had a wide range of onset and presenting systems. Further research is needed to identify risk factors, methods of prevention and benefits of early detection screening.

Moving past neonicotinoids and honeybees: A systematic review of existing research on other insecticides and bees.

Synthetic pesticides (e.g. herbicides, fungicides and insecticides) are used widely in agriculture to protect crops from pests, weeds and disease. However, their use also comes with a range of environmental concerns. One key concern is the effect of insecticides on non-target organisms such as bees, who provide pollination services for crops and wild plants. This systematic literature review quantifies the existing research on bees and insecticides broadly, and then focuses more specifically on non-neonicotinoid insecticides and non-honeybees. We find that articles on honeybees (Apis sp.) and insecticides account for 80% of all research, with all other bees combined making up 20%. Neonicotinoids were studied in 34% of articles across all bees and were the most widely studied insecticide class for non-honeybees overall, with almost three times as many studies than the second most studied class. Of non-neonicotinoid insecticide classes and non-honeybees, the most studied were pyrethroids and organophosphates followed by carbamates, and the most widely represented bee taxa were bumblebees (Bombus), followed by leaf-cutter bees (Megachile) and mason bees (Osmia). Research has taken place across several countries, with the highest numbers of articles from Brazil and the US, and with notable gaps from countries in Asia, Africa and Oceania. Mortality was the most studied effect type, while sub-lethal effects such as on behaviour were less studied. Few studies tested how the effect of insecticides were influenced by multiple pressures, such as climate change and co-occurring pesticides (cocktail effects). As anthropogenic pressures do not occur in isolation, we suggest that future research also addresses these knowledge gaps. Given the changing global patterns in insecticide use, and the increasing inclusion of both non-honeybees and sub-lethal effects in pesticide risk assessment, there is a need for expanding research beyond its current state to ensure a strong scientific evidence base for the development of risk assessment and associated policy.

A functional link between lariat debranching enzyme and the intron-binding complex is defective in non-photosensitive trichothiodystrophy.

The pre-mRNA life cycle requires intron processing; yet, how intron-processing defects influence splicing and gene expression is unclear. Here, we find that TTDN1/MPLKIP, which is encoded by a gene implicated in non-photosensitive trichothiodystrophy (NP-TTD), functionally links intron lariat processing to spliceosomal function. The conserved TTDN1 C-terminal region directly binds lariat debranching enzyme DBR1, whereas its N-terminal intrinsically disordered region (IDR) binds the intron-binding complex (IBC). TTDN1 loss, or a mutated IDR, causes significant intron lariat accumulation, as well as splicing and gene expression defects, mirroring phenotypes observed in NP-TTD patient cells. A Ttdn1-deficient mouse model recapitulates intron-processing defects and certain neurodevelopmental phenotypes seen in NP-TTD. Fusing DBR1 to the TTDN1 IDR is sufficient to recruit DBR1 to the IBC and circumvents the functional requirement for TTDN1. Collectively, our findings link RNA lariat processing with splicing outcomes by revealing the molecular function of TTDN1.

Epigenetic regulation of hybrid epithelial-mesenchymal cell states in cancer.

Epithelial-to-mesenchymal transition (EMT) is a process by which cells lose their epithelial characteristics and gain mesenchymal phenotypes. In cancer, EMT is thought to drive tumor invasion and metastasis. Recent efforts to understand EMT biology have uncovered that cells undergoing EMT attain a spectrum of intermediate "hybrid E/M" states, which exist along an epithelial-mesenchymal continuum. Here, we summarize recent studies characterizing the epigenetic drivers of hybrid E/M states. We focus on the histone-modification writers, erasers, and readers that assist or oppose the canonical hybrid E/M transcription factors that modulate hybrid E/M state transitions. We also examine the role of chromatin remodelers and DNA methylation in hybrid E/M states. Finally, we highlight the challenges of targeting hybrid E/M pharmacologically, and we propose future directions that might reveal the specific and targetable mechanisms by which hybrid E/M drives metastasis in patients.

Stepped Behavioral and Biological Screening for Oral Oncogenic HPV DNA in Middle-aged and Elderly Adults: A Feasibility Study.

Novel preventive interventions are needed to address the rising incidence of human papillomavirus (HPV)-mediated oropharyngeal cancer (HPV+ OPC). This pilot study evaluated the feasibility of a stepped, behavioral and biological screening program for oral oncogenic HPV infection, an intermediate HPV+ OPC outcome.This was a cross-sectional, feasibility study. Eligible 45-74 years old adults identified from three clinical research registries were administered a behavioral risk survey (step 1). Participant tobacco use and sexual behavior history were translated into a quantifiable risk of oral oncogenic HPV DNA, according to prior National Health and Nutrition Examination Survey analyses. Females with >2% risk and males with >7% risk were offered biological screening for oral oncogenic HPV DNA (step 2) via an oral rinse and gargle specimen.A total of 292 individuals were contacted, but only 144 (49%) were reached. Among these, 56 individuals (19%) were uninterested and 18 (13%) were ineligible. Seventy individuals began the survey and 66 completed it (step 1), among whom 46 were classified as low-risk. Among the remaining 20 participants classified as high-risk for an oral oncogenic HPV infection, 5% were current smokers and the median participant had performed oral sex on 10 unique partners. During step 2 (biological screening), 45% (9/20) completed testing, all of whom tested negative for oral oncogenic HPV DNA.In this pilot of a stepped, oral oncogenic HPV screening program, enrollment and study completion were suboptimal. These barriers to screening should be characterized and addressed before reevaluating the feasibility of this program. PREVENTION RELEVANCE: Novel preventive interventions are needed to address the rising incidence of HPV+ OPC. In this feasibility study, we characterized barriers to a two-step, behavioral and biological screening program for oral oncogenic HPV infection, an intermediate outcome for HPV+ OPC.

Low-risk human papilloma virus positive oropharyngeal cancer with one positive lymph node: Equivalent outcomes in patients treated with surgery and radiation therapy versus surgery alone.

BACKGROUND: For human papilloma virus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC), management recommendations for patients with a single metastatic lymph node <6 cm in diameter remain nebulous, leading to treatment heterogeneity in this common subgroup of patients. METHODS: We utilized the National Cancer Database to perform survival and multivariable analyses of patients with HPV+ OPSCC with one positive lymph node <6 cm and negative surgical margins. RESULTS: We found that 5-year survival is comparable between patients who receive surgery and adjuvant radiation versus surgery alone. In multivariable analyses, we found no significant difference in the hazard ratio of overall survival after adjusting for various potential confounders. CONCLUSIONS: These data suggest that patients with margin-negative HPV+ OPSCC with a single positive lymph node <6 cm have comparable survival with or without adjuvant radiation. Future studies exploring outcomes for this specific group in randomized-controlled trials will be critical for further evaluating these initial observations.

Closing the Osteoporotic-Fracture Care Gap for Frail Older Persons.

Aim To implement standardised fracture risk assessment in the frail older person. Methods Frail older patients underwent opportunistic screening for fracture risk. Roadblocks to standardised assessment were identified. An Integrated Care Team for older persons (ICT) trained in fracture risk assessment using FRAX. Clinical assessment was via a locally agreed algorithm. Data was entered onto Excel. The SQUIRE guidelines for quality improvement programmes were used to report the results. Results Of 96 patients opportunistically screened, the average age was 84 years. FRAX was completed for 19% (n=18). 89% (n=16) met the pharmacotherapy threshold. Nine were recommended pharmacotherapy. Of sixteen patients recommended for DXA, just 31% (n=5) were booked. Following implementation of a quality improvement project, 100 patients were assessed, and average age was 80 years. FRAX was completed for 62% (n=63) and 95% (n=60) required pharmacotherapy. 24% (n=14) had untreated prior fracture. All had pharmacotherapy prescribed. 59% (n=59) required DXA scanning. 70% (n=41) had DXA ordered. Conclusion ICT ownership increased FRAX assessment 3-fold and point of contact prescribing to 100%.

A rapid review investigating the potential impact of a pandemic on the mental health of young people aged 12-25 years.

OBJECTIVES: In March 2020, the World Health Organization (WHO) officially declared the spread of coronavirus disease 2019 (COVID-19) as a pandemic. Adolescence and early adulthood are peak times for the onset of mental health difficulties. Exposure to a pandemic during this vulnerable developmental period places young people at significant risk of negative psychological experiences. The objective of this research was to summarise existing evidence on the potential impact of a pandemic on the mental health of 12-25 year olds. METHODS: A rapid review of the published peer-reviewed literature, published between 1985 and 2020, using PsycINFO (Proquest) and Medline (Proquest) was conducted. Narrative synthesis was used across studies to identify key themes and concepts. RESULTS: This review found 3,359 papers, which was reduced to 12 papers for data extraction. Results regarding the prevalence of psychological difficulties in youth were mixed, with some studies finding this group experience heightened distress during an infectious disease outbreak, and others finding no age differences or higher distress among adults. Gender, coping, self-reported physical health and adoption of precautionary measures appear to play a role in moderating the psychological impact of an infectious disease outbreak. Most studies were conducted after the peak of an epidemic/pandemic or in the recovery period. CONCLUSIONS: More longitudinal research with young people, particularly adolescents in the general population, before and during the early stages of an infectious disease outbreak is needed to obtain a clear understanding of how best to support young people during these events.

Management referral triaging process pilot study: a 'telephone first' approach.

BACKGROUND: In this Occupational Health Department (OHD), a 'telephone first' approach was introduced to triage management referrals with potential to convert to Telephone Independent Medical Assessment (TIMA). Telephone consultation has been widely used in the UK's NHS in the occupational health setting. AIMS: To evaluate TIMA effectiveness and efficiency of OHD resources; comparing the outcome of a triage call compared to previous default allocation of next available appointment, percentage of telephone triage calls converted to TIMA and appointment waiting times. To assess use of OHD resources arising from TIMA. To evaluate service user satisfaction following TIMA. To examine service user characteristics. METHODS: As management referrals were received, service users were given a telephone contact. Data were collected and anonymized regarding service users, who also consented to receive feedback questionnaire. Cross-sectional analysis of this management referral cohort was carried out. RESULTS: Two hundred and sixty-one management referrals were received in the specified period. Eighty per cent had a TIMA carried out (n = 208); 64% of management referrals with TIMA had a report issued (n = 166). Response rate to feedback questionnaire was 38% (n = 70); 94% of survey participants found TIMA acceptable going forward for management referrals (n = 66). CONCLUSIONS: Introduction of a 'telephone first' approach resulted in improved efficiency of this OHD, allowing maximum workforce planning, and positive service user feedback.

Allelic variants between mouse substrains BALB/cJ and BALB/cByJ influence mononuclear cardiomyocyte composition and cardiomyocyte nuclear ploidy.

Most mouse cardiomyocytes (CMs) become multinucleated shortly after birth via endoreplication and interrupted mitosis, which persists through adulthood. The very closely related inbred mouse strains BALB/cJ and BALB/cByJ differ substantially (6.6% vs. 14.3%) in adult mononuclear CM level. This difference is the likely outcome of a single X-linked polymorphic gene that functions in a CM-nonautonomous manner, and for which the BALB/cByJ allele is recessive to that of BALB/cJ. From whole exome sequence we identified two new X-linked protein coding variants that arose de novo in BALB/cByJ, in the genes Gdi1 (R276C) and Irs4 (L683F), but show that neither affects mononuclear CM level individually. No BALB/cJ-specific X-linked protein coding variants were found, implicating instead a variant that influences gene expression rather than encoded protein function. A substantially higher percentage of mononuclear CMs in BALB/cByJ are tetraploid (66.7% vs. 37.6% in BALB/cJ), such that the overall level of mononuclear diploid CMs between the two strains is similar. The difference in nuclear ploidy is the likely result of an autosomal polymorphism, for which the BALB/cByJ allele is recessive to that of BALB/cJ. The X-linked and autosomal genes independently influence mitosis such that their phenotypic consequences can be combined or segregated by appropriate breeding, implying distinct functions in karyokinesis and cytokinesis.

Measuring the performance of the Mental Health Continuum-Short Form (MHC-SF) in a primary care youth mental health service.

OBJECTIVES: Mental health is regarded as more than the absence of mental health difficulties, with clinical and research focus moving towards measurement of well-being. The Mental Health Continuum-Short Form (MHC-SF) was developed to assess overall and emotional, social and psychological well-being. Little is known about the use of the MHC-SF with young people engaging with mental health services. The current pilot study sought to examine the performance of the MHC-SF in an Irish primary care youth mental health service for 12-25 year olds. METHODS: A sample of 229 young people (female n=143; male n=85, unknown n=1) aged 12-24 years (M=15.87, SD=2.51) who completed the MHC-SF prior to commencing their first intervention session in Jigsaw participated in this study. The psychometric properties of the MHC-SF were investigated using confirmatory factor analysis (CFA) and Cronbach's alpha for internal consistency. RESULTS: CFA supported the three-factor structure of the MHC-SF for emotional, social, and psychological well-being, and very good internal consistency was observed. CONCLUSION: Findings provide evidence for the psychometric properties of the MHC-SF in a primary care youth mental health setting, and suggest that the MHC-SF's three-factor structure is valid for use in this context. Limitations and recommendations for future research are discussed.

Role of the intertidal predatory shore crab Carcinus maenas in transmission dynamics of ostreid herpesvirus-1 microvariant.

Ostreid herpesvirus-1 microVar (OsHV-1 µVar) has been responsible for significant mortalities globally in the Pacific oyster Crassostrea gigas. While the impact of this virus on the Pacific oyster has been significant, this pathogen may have wider ecosystem consequences. It has not been definitively determined how the virus is sustaining itself in the marine environment and whether other species are susceptible. The shore crab Carcinus maenas is a mobile predator and scavenger of C. gigas, commonly found at Pacific oyster culture sites. The aim of this study was to investigate the role of the crab in viral maintenance and transmission to the Pacific oyster. A field trial took place over 1 summer at different shore heights at 2 Irish Pacific oyster culture sites that are endemic for OsHV-1 µVar. Infection of OsHV-1 µVar in tissues of C. maenas at both shore heights of both sites was detected by polymerase chain reaction (PCR), quantitative PCR (qPCR), in situ hybridization and direct Sanger sequencing. In addition, a laboratory trial demonstrated that transmission of the virus could occur to naïve C. gigas within 4 d, from C. maenas previously exposed to the virus in the wild. These findings provide some insight into the possibility that the virus can be transmitted through marine food webs. The results also suggest viral plasticity in the hosts required by the virus and potential impacts on a range of crustacean species with wider ecosystem impacts if transmission to other species occurs.

Evidence of degradation of hair corticosterone in museum specimens.

Researchers increasingly rely on non-invasive physiological indices, such as glucocorticoid (GC) levels, to interpret how vertebrates respond to changes in their environment. Recently, hair GCs have been of particular interest, because they are presumed stable over long periods of storage, which may facilitate the study of large-scale spatial and temporal patterns of stress in mammals. In the current study, we evaluated the stability of hair corticosterone levels in museum specimens, and the potential effects of different museum curation treatments. Using deer mouse (Peromyscus maniculatus) specimens collected from Vancouver Island (11 sites, 82 individuals) over 76 years, we found that specimens collected earlier in the 20th century had lower hair corticosterone than more recently collected specimens. These results suggest that hair hormone levels may not be stable over decades of storage time. We then subjected hair samples collected from white-footed mouse (Peromyscus leucopus, n = 36) to 3 different museum curation treatments, and found that borax lowered hair corticosterone levels relative to control samples, but air drying samples, or treating them with turpentine had no effect. Our results present a source of concern for the use of museum specimens for hair hormone analysis, and for studying long term trends in glucocorticoid levels.

[Study of the relations between the pain of childbirth and postpartum, and depressive and traumatic symptoms]. / Étude des relations entre la douleur de l'accouchement et du post-partum, et les symptômes dépressifs et traumatiques.

OBJECTIVES: This study aims to determine the incidence of pain in childbirth and postpartum on depressive and post-traumatic symptomatology 6weeks after delivery. METHODS: One hundred and nine women who gave birth in maternity hospitals of type 2$participated in the study. Two to four days after delivery they have completed five self-administered questionnaires to assess pain of childbirth (QDSA), dramatization of pain (PCS-CF), satisfaction of childbirth (CEQ), peri-traumatic distress (IDP) and depressive symptoms (EPDS) and visual analogue scales to measure immediate postnatal pain. Six weeks after birth they have again completed questionnaires to measure pain (QDSA and visual analogue scales) and depressive symptoms (EPDS) and a scale measuring posttraumatic symptomatology (IES-R). RESULTS: The pain of childbirth and immediate postpartum was associated with depressive (r=0.27 and r=0.31 respectively) and traumatic symptomatology (r=0.30 and r=0.34 respectively) in postpartum. Regression analysis, however, revealed that only the depressive symptomatology and the affective dimension of postpartum pain at six weeks post-partum was related to post-traumatic stress. CONCLUSION: The results of this study highlight the importance to support the pain of childbirth but also the pain occurring in the postpartum period.