Search

Photonic crystal fibers guide light by trapping it in a periodic array of elements in the cladding area. We fabricated photonic crystal fibers by multiple extrusions of silver halide (AgClxBr1-x) crystals which are highly transparent in the middle infrared. The core of such a fiber consisted of pure silver bromide AgBr (n=2.16 at 10.6 μm), and the cladding area consisted of concentric rings of fiber-optic elements made of pure silver chloride AgCl (n=1.98 at 10.6 μm), which lowered the refractive index of the clad. Two types of photonic crystal fibers were fabricated, one with two concentric rings and one with five concentric rings of fiber-optic elements around the core. The characterization of the fibers, such as the power distribution, the attenuation, and the numerical aperture were measured. Both fibers behaved like regular core-clad structures. Simulations on these structures showed that each of these fibers guided a small number of modes and that adding rings to the structure lowered the number of bound modes in the core. This would pave the way for the fabrication of single-mode fibers. Photonic crystal fibers offer many advantages compared to conventional fibers, and they will be extremely useful for many applications in the middle and far infrared. [ABSTRACT FROM AUTHOR]

Lymphomatoid papulosis (LyP) is a benign chronic often relapsing skin condition that belongs to the CD30‐positive cutaneous lymphoproliferative disorders. LyP typically presents as crops of lesions with a tendency to self‐resolve, and morphology can range from solitary to agminated or diffuse papules and plaques to nodules or tumours. The clinical–histological spectrum can range from borderline cases to overlap with primary cutaneous anaplastic cell lymphoma (pcALCL). Histology and immunophenotype commonly show overlap with other CD30‐positive disorders and sometimes may be identical to pcALCL, making its diagnosis more difficult. Patients with LyP have an increased risk of developing a second neoplasm such as mycosis fungoides, pcALCL and/or Hodgkin lymphoma. Clinical correlation allows its proper classification and diagnosis, which is fundamental for treatment and prognosis. This review focuses on the clinical appearance, histopathological features, diagnosis, differential diagnosis and management of LyP. [ABSTRACT FROM AUTHOR]

As part of a project to construct virus-resistant transgenic grapevines, grapevine virus A (GVA) coat protein (CP) sequences were introduced into grapevine and the model plant Nicotiana benthamiana. The engineered constructs were tested for their ability to engender resistance in N. benthamiana. A number of GVA-CP-transformed N. benthamiana lines have become resistant to GVA. Preliminary biological and molecular analyses strongly suggest that in most cases the obtained resistance is RNA-mediated. Several lines of transgenic grapevine were obtained. [ABSTRACT FROM AUTHOR]

Background: Minoritized communities in the United States have had higher COVID-19 mortality and lower vaccine uptake. The influence of previous SARS-CoV-2 infection, initial disease severity, and persistent symptoms on COVID-19 vaccine uptake in Black and Latinx communities has not been examined., Objective: To investigate whether initial COVID-19 severity, persistent symptoms, and other correlates affected vaccine uptake in a predominantly minoritized cohort hospitalized for COVID-19 during the early pandemic in New York City., Design: In this historical cohort study, we abstracted electronic health record data on demographics, comorbidities, hospital oxygen requirements, symptoms at 3 and 6 months post-admission, COVID-19 vaccinations through November 2022, and influenza vaccinations during the 2018-2019 through 2021-2022 seasons. Unadjusted and adjusted odds ratios were estimated through logistic regression analyses of correlates of COVID-19 vaccination, on-time vaccination, and boosting., Participants: Survivors among the first 1186 adult patients hospitalized for COVID-19 between March 1 and April 8, 2020 at a large quaternary care medical center in Northern Manhattan., Main Measures: Uptake of at least one COVID-19 vaccine dose, uptake of at least one booster, and on-time vaccination., Key Results: The 890 surviving individuals were predominantly Latinx (54%) and Non-Hispanic Black (15%). Most had one or more comorbidities (67%), and received at least one COVID-19 vaccine dose (78%). Among those vaccinated, 57% received at least one booster, and 31% delayed vaccination. 67% experienced persistent symptoms. Multiple logistic regression showed no association between vaccine uptake and disease severity or symptom persistence. However, older age and influenza vaccination during the COVID-19 era were associated with increased vaccination, booster uptake, and on-time vaccination., Conclusions: Pinpointing drivers of vaccine uptake and hesitancy is critical to increasing and sustaining COVID-19 vaccination as the field transitions to annual boosters. The association between influenza vaccination and increased vaccine uptake suggests that bundling vaccines for adults may be an effective delivery strategy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Delivette Castor and Magdalena Sobieszczyk report financial support was provided by Gilead Sciences, Inc. Magdalena Sobieszczyk reports a relationship with Bill & Melinda Gates Foundation that includes: funding grants. Magdalena Sobieszczyk reports a relationship with Merck & Co Inc. that includes: funding grants. Magdalena Sobieszczyk reports a relationship with Sanofi that includes: funding grants. Magdalena Sobieszczyk reports a relationship with Pfizer Inc. that includes: funding grants. Jason Zucker reports a relationship with Centers for Disease Control and Prevention that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. JZ has received a grant from the Centers for Disease Control and Prevention within the past 3 years. MES has received grants from the Gates Foundation, Merck, Sanofi, and Pfizer within the past 3 years for work outside the scope of this manuscript. Otherwise, the authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To evaluate implementation of a patient decision aid for symptomatic uterine fibroid management to improve shared decision-making at five clinical settings across the United States., Methods: We used a type 3 hybrid effectiveness-implementation stepped-wedge design and the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) planning and evaluation framework. We conducted clinician training, monthly reach tracking with feedback to site clinical leads, patient and clinician surveys, and visit audio-recordings. Implementation strategies included assessment of organizational readiness for shared decision-making, synchronous clinician training, audit and feedback of decision aid reach, and access to multiple decision aid formats. Outcomes and analyses included patient-level reach, clinician-level adoption, and associations of patient-reported decision aid exposure (as treated) and setting-level implementation (intention-to-treat) with patient-reported (collaboRATE measure) and observed (OPTION-5 measure) shared decision-making. We also designed and assessed setting-level plans for sustainability and other factors impacting sustained decision aid use., Results: The decision aid was adopted by 72 of the 74 eligible gynecologists (97%) and reached 2553 patients across five settings. CollaboRATE scores improved among patients who reported receiving the decision aid (as-treated analysis, 69% vs. 59%; OR 1.6, 95% CI 1.16-2.27). CollaboRATE scores remained consistent before and after setting-level decision aid implementation (intention-to-treat analysis, 64% vs. 63%; OR 0.86, 95% CI 0.61-1.22). Participants would prefer to receive a decision aid at multiple time points (91.9% before the visit, 90.7% during the visit, 86.5% after the visit). Shared decision-making experiences did not improve when comparing pre vs. post-implementation collaboRATE scores across included settings (intention-to-treat, 64% vs. 63%; OR 0.86, 95% CI 0.61-1.22)., Conclusion: When patients with symptomatic uterine fibroids are given decision aids, they report higher shared decision-making scores. However, the differences we observed between the as-treated and intention-to-treat results suggest that unaddressed implementation challenges continue to limit the extent to which patients receive decision aids and likely hinder their overall impact. Future efforts to implement decision aids should explore enhancing their integration into clinical workflows and standard operating procedures, supported by organizational incentives that prioritize shared decision-making., Trial Registration: ClinicalTrials.gov NCT03985449; registered 6 June 2019., (© 2024. The Author(s).)

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time., Purpose: Pharmacy transitions of care (ToC) programs have been shown to decrease 30-day hospital readmissions and improve patient outcomes, but there is limited published data on the impact of pharmacist-integrated ToC services beyond 30 days. The objective of this study was to evaluate the impact of pharmacist-integrated ToC and population health services on 30-, 60-, and 90-day all-cause readmissions in a Medicare value-based program (MV-BP) population and to compare mean times to first readmission with and without pharmacist care., Methods: A retrospective observational chart review was conducted to identify eligible hospital discharge encounters (DEs). Patients 18 years of age or older enrolled in an MV-BP were assigned to 4 study groups (a control group or one of 3 intervention arms) based on the pharmacy ToC services they received from either an inpatient ToC pharmacist or a dedicated population health pharmacist (PHP)., Results: Among 1,065 eligible DEs, 90-day follow-up was completed in 1,039 cases. The control group (n = 213) had a 90-day readmission rate of 34.74%. Intervention arm 1 (n = 201) had no significant reduction in 90-day readmissions, with a rate of 29.85% (odds ratio [OR], 0.94; 95% CI, 0.61-1.47; P = 0.80), while intervention arms 2 (n = 209), and 3 (n = 416) had significantly lower rates of readmission: 9.57% (OR, 0.26; 95% CI, 0.15-0.46; P < 0.01), and 17.07% (OR, 0.41; 95% CI, 0.27-0.61; P < 0.01), respectively., Conclusion: A combination of ToC and PHP services reduced 30-, 60-, and 90-day readmission rates in an MV-BP population. These results support the expansion of pharmacy-based ToC to minimize readmissions within 90 days for this Medicare population., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Vulvar and vaginal melanomas (VVMs) are rare and aggressive malignancies with limited prognostic models available and there is no standard reporting protocol. VVMs were selected from six tertiary Canadian hospitals from 2000-2021, resected from patients aged ≥18 years, with 6 months or longer follow-up data, and confirmation of melanocytic differentiation by at least two immunohistochemical markers. Cases were reviewed by pathologists to identify histological biomarkers. Survival outcomes were tested with Kaplan-Meier log-rank, univariate Cox, and multivariate Cox regression. There were 79 VVMs with median follow-up at 26 months. Univariate analysis revealed that tumour necrosis, tumour ulceration, positive lymph nodes, and metastasis at diagnosis were significantly associated with disease-specific mortality, progression, and metastasis. Multivariate analysis identified tumour necrosis as an independent prognostic factor for disease-specific mortality (HR 4.803, 95% CI 1.954-11.803, p<0.001), progression (HR 2.676, 95% CI 1.403-5.102, p=0.003), and time-to-metastasis for non-metastatic patients at diagnosis (HR 3.761, 95%CI 1.678-8.431, p=0.001). Kaplan-Meier survival analyses demonstrated that tumour necrosis was a poor prognostic factor for disease-specific, progression-free, and metastasis-free survival (p<0.001 for all comparisons). Vaginal melanomas displayed decreased survival compared to vulvar or clitoral melanomas. This study identifies tumour necrosis as an independent prognostic factor for VVMs. Vaginal melanomas specifically showed worse survival outcomes compared to vulvar or clitoral melanomas, consistent with previously reported findings in the literature, emphasising the importance of differentiating between these primary tumour epicentres for prognostication and treatment planning in the care of genital melanoma patients., (Copyright © 2024 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Introduction: Rectal bleeding commonly occurs in elderly patients using blood thinners, posing management challenges due to limited guidance on reversal agents and medication restart criteria. This study aims to review the demographics and management of elderly patients with rectal bleeding while on blood thinners., Methods: A retrospective analysis of patients aged 60 or older presenting with rectal bleeding at West Suffolk Hospital's emergency department was conducted from January 2018 to December 2020. Data were extracted from electronic records, focusing on patients using blood thinners and adhering to British Society of Gastroenterology guidelines. All patients ceased blood-thinning medications upon admission. The hospital's ethics committee approved the study, which focused on demographics, diagnosis, and management, particularly regarding re-initiation of blood-thinning medicines., Results: During the study period, 170 patients were admitted to the emergency department of West Suffolk Hospital. 93 (54.71%) patients were included in the study. The average age of the participants was 82 years, and 62.3% were male. All patients were followed up for three months. Atrial fibrillation accounted for 52% of patients, while previous strokes accounted for 20%. The most typical pathology was diverticulosis.Regarding restarting of anticoagulants, Among patients on DOAC (Direct oral anticoagulant), 39% were restarted on discharge, 23% were switched to warfarin, and another 23% were not restarted; 15% planned to restart after seven days. For those on Warfarin, 62% were restarted on discharge, 22% stopped the medication, and the rest were switched to Dual Oral Anticoagulant. Among aspirin patients, 60% were restarted at discharge, while the remaining discontinued. All patients receiving clopidogrel and dual antiplatelet therapy were started at discharge. None of the patients were readmitted during the follow-up period of 3 months., Conclusion: Restarting of blood-thinning drugs in patients with rectal bleeding is subject to individual patient variation. Necessitates more extensive trials to achieve greater standardization., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Bavikatte A et al.)

Background: Sports and physical activity are known risk factors for pelvic floor dysfunction (PFD). The aim of this study is to examine the impact of amateur running on PFD, quality of life (QoL), and sexual function., Methods: Amateur runners were contacted through social media. Their PFD, sexual function, and QoL were evaluated by self-reporting validated questionnaires (PFDI-20, PISQ-12, IIQ-7). They were divided by degree of effort into two categories, 'High effort' and 'Moderate effort'. The differences between the two groups were examined by a Mann-Whitney U Test, T-Test, and Chi-square test., Results: 180 women were included. A high incidence of PFD was found among 'High effort' runners in comparison to 'Moderate effort' runners. In addition, women who scored above the median in the PFDI-20 showed significantly greater impairment in QoL and sexual function. Interestingly, the 'High effort' group reported experiencing higher intensity orgasms compared with women in the 'Moderate effort' group. A correlation was also found between the weekly running distance and the intensity of orgasm experienced (P value = 0.004)., Conclusion: 'High effort' runners present a higher incidence of PFD in comparison to 'Moderate effort' runners. Professional pelvic floor muscle training counselling should be considered even for amateur runners. Future interventional physical therapy studies should be carried out in order to investigate preventative strategies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To assess whether advanced age is a risk factor for complications following pelvic organ prolapse (POP) repair surgeries using the Clavien-Dindo classification system., Methods: In this retrospective cohort study, 260 women who had undergone POP repair surgery at the Soroka University Medical Center (SUMC) between the years 2014-2019 were included. A univariate analysis was conducted to compare the demographical, clinical, obstetrical and operative characteristics of patients by age group (younger or older than 70 years). We performed a similar analysis to assess for the possible association between several variables and post-operative complications. Variables that were found to be associated with post-operative complications (P < 0.2) were included in a multivariate analysis along with advanced age., Results: During the 12 months follow-up period, more than half of the women had experienced at least one post-operative complication. Minor complications (grades 1-2 according to the Clavian-Dindo classification system) were the most common. One woman had died during the follow-up period, and none had experienced organ failure (grade 4). Hysterectomy, as part of POP surgery, was found to be significantly associated with post-operative complications. Additionally, grandmultiparity (> 5 births) showed a tendency towards an increased risk for post-operative complications, however this reached only borderline significance. We found no association between advanced age and post-operative complications., Conclusions: POP repair surgeries are safe for women of all ages. Major complications (grades 3-5) are rare in all age groups. Although advanced age was associated with a higher prevalence of comorbidity and a higher grade of prolapse, no significant difference in the post-operative complications was found between age groups. Concomitant hysterectomy at the time of POP repair surgery is a risk factor for post-operative complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Abuse of healthcare workers (HCWs) and lack of public trust threaten the foundation of the physician-patient relationship. This growing global problem creates an even more difficult professional environment and hinders the delivery of high-quality clinical care., Objective: The primary aim was to determine the prevalence of violence against Trinbagonian HCWs in the public sector. Secondary objectives included determining risk factors for violence and mistrust between the public and providers., Method: A cross-sectional analysis of 434 HCWs in the public sector of Trinidad and Tobago was conducted using a modified World Health Organization (WHO) data collection tool, distributed via social media and administrative emails, and snowballed for two months. Fifteen semi-structured interviews were conducted regarding trust in the healthcare system with patients selected from communities., Results: Of the 434 respondents, 45.2% experienced violence and 75.8% witnessed violence against HCWs in the past two years. Verbal abuse (41.5%) was most common. Perpetrators were patients (42.2%) and patients' relatives (35.5%). Chi-square analysis highlighted that HCWs with the highest probability of being abused were aged 25-39 (63.8%), had two to five years of work experience (24.9%), specialized in emergency and internal medicine (48.6%), and cared for psychiatric and physically disabled patients (p-value < 0.001). HCWs believed the threat of violence negatively impacted performance (64.5%), and further action was necessary for mitigation (86.4%). Patients interviewed doubted physicians' altruism and competence (80%) and honesty (53.3%), expressed mistrust in their physician (46.7%), and cited poor infrastructure/management (66.7%) and dissatisfaction with care (60.0%) as factors that contributed to violence., Conclusion: Analysis revealed that violence against Trinbagonian HCWs in the public sector deteriorated patient experience and adversely affected psychological well-being, efficiency, and job satisfaction. Results suggested mistrust of HCWs by the population. Interventions should be instituted to support at-risk HCWs and educate the public to avoid recurrence., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Dookeeram et al.)

Objective: To inquire whether obesity is a risk factor of peri- and post-operative complications following Mid-urethral sling (MUS) surgeries for SUI repair using the Clavien-Dindo classification system (CDcs)., Methods: This retrospective cohort included 304 women who undergone a MUS in a 1000 beds tertiary University medical center between the years 2012-2018. Univariate analysis was conducted to compare clinical and operative traits by BMI group and to examine associations of obesity and complications rates and severity according to the CDcs. Multivariate analysis was conducted to assess the risk for post-operative complications and adjust to potential confounders., Results: The study group included 106 (34.9%) women with BMI 30 or higher and the comparison group included 198 (65.1%) women with BMI lower than 30. In the study group we found a significantly higher prevalence of hypertension (P = 0.019), previous abdominal surgeries (P = 0.012) including cesarean section (P = 0.025), previous pelvic floor surgeries (P = 0.005) and pelvic organ prolapse (P = 0.02). In the control group we found a significantly higher rates of concomitant hysterectomy which performed during the MUS (P = 0.005). Obesity was not associated with increased rates of peri and post-operative complications (P = 0.973)., Conclusions: In our study, obesity was not associated with peri- and post-operative complications following MUS., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Recent cases of clinical failure in malaria patients in the United Kingdom (UK) treated with artemether-lumefantrine have implications for malaria chemotherapy worldwide., Methods: Parasites were isolated from an index case of confirmed Plasmodium falciparum treatment failure after standard treatment, and from comparable travel-acquired UK malaria cases. Drug susceptibility in vitro and genotypes at 6 resistance-associated loci were determined for all parasite isolates and compared with clinical outcomes for each parasite donor., Results: A traveler, who returned to the UK from Uganda in 2022 with Plasmodium falciparum malaria, twice failed treatment with full courses of artemether-lumefantrine. Parasites from the patient exhibited significantly reduced susceptibility to artemisinin (ring-stage survival, 17.3% [95% confidence interval {CI}, 13.6%-21.1%]; P < .0001) and lumefantrine (effective concentration preventing 50% of growth = 259.4 nM [95% CI, 130.6-388.2 nM]; P = .001). Parasite genotyping identified an allele of pfk13 encoding both the A675V variant in the Pfk13 propeller domain and a novel L145V nonpropeller variant. In vitro susceptibility testing of 6 other P. falciparum lines of Ugandan origin identified reduced susceptibility to artemisinin and lumefantrine in 1 additional line, also from a 2022 treatment failure case. These parasites did not harbor a pfk13 propeller domain variant but rather the novel nonpropeller variant T349I. Variant alleles of pfubp1, pfap2mu, and pfcoronin were also identified among the 7 parasite lines., Conclusions: We confirm, in a documented case of artemether-lumefantrine treatment failure imported from Uganda, the presence of pfk13 mutations encoding L145V and A675V. Parasites with reduced susceptibility to both artemisinin and lumefantrine may be emerging in Uganda., Competing Interests: Potential conflicts of interest. B. C. Y. reports a clinical lecturer starter grant paid via institution from Academy of Medical Sciences and funding to institution from the Oxford University National Institute for Health and Care Research Biomedical Research Centre grant. P. L. C. reports grants or contracts from the World Health Organization for the Molecular External Quality Assessment Scheme. J. M. reports grant to institution 203919/Z/16/Z from Wellcome Trust Clinical PhD and grant to institution from UCL Global Challenges, and participation as chair of a data and safety monitoring board for Triage Test for All Oral DR-TB Regimen (TRiAD Study). L. E. N. reports royalties or licenses paid to author from Peter’s Atlas of Tropical Medicine and Parasitology (Elsevier, author). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Purpose: The aim of this study was to utilize an intersectional framework to examine academic faculty's lived experiences during COVID-19. Specifically, we set out to: (1) describe the multiple intersectional identities ( e.g. , gender, race/ethnicity, rank, caregiver status, disability status) represented by the faculty, (2) examine potential disparities in well-being, workload, and productivity linked to these intersectional factors, and (3) identify qualitative themes endorsed by faculty as they relate to lived experiences during COVID-19. Methods: This was a cross-sectional mixed-methods research study. The Center for Women in Medicine and Science (CWIMS) at the University of Minnesota developed and implemented a survey between February-June of 2021 in response to national reports of disparities in the impacts of COVID-19 on faculty with lived experiences from multiple intersections. Results: There were 291 full-time faculty who participated in the study. Quantitative findings indicated that faculty with multiple intersectional identities ( e.g. , woman+assistant professor+caregiver+underrepresented in medicine) reported greater depression symptoms, work/family conflict, and stress in contrast to faculty with fewer intersectional identities. Furthermore, faculty with more intersectional identities reported higher clinical workloads and service responsibilities and lower productivity with regard to research article submissions, publications, and grant submissions in contrast to faculty with fewer intersectional identities. Qualitative findings supported quantitative findings and broadened understanding of potential underlying reasons. Conclusions: Findings confirm anecdotal evidence that faculty with lived experiences from multiple intersections may be disproportionately experiencing negative outcomes from the pandemic. These findings can inform decisions about how to address these disparities moving into the next several years with regard to promotion and tenure, burnout and well-being, and faculty retention in academic medical settings. Given these findings, it is also important to intentionally plan responses for future public health crises to prevent continued disparities for faculty with multiple intersectional identities.

Repeated cocaine exposure produces an enhanced locomotor response (sensitization) paralleled by biological adaptations in the brain. Previous studies demonstrated region-specific responsivity of adenosine monophosphate-activated protein kinase (AMPK) to repeated cocaine exposure. AMPK maintains cellular energy homeostasis at the organismal and cellular levels. Here, our objective was to quantify changes in phosphorylated (active) and total AMPK in the cytosol and synaptosome of the medial prefrontal cortex, nucleus accumbens, and dorsal striatum following acute or sensitizing cocaine injections. Brain region and cellular compartment selective changes in AMPK and pAMPK were found with some differences associated with acute withdrawal versus ongoing cocaine treatment. Our additional goal was to determine the behavioral and molecular effects of pretreatment with the indirect AMPK activator metformin. Metformin potentiated the locomotor activating effects of acute cocaine but blocked the development of sensitization. Sex differences largely obscured any protein-level treatment group effects, although pAMPK in the NAc shell cytosol was surprisingly reduced by metformin in rats receiving repeated cocaine. The rationale for these studies was to inform our understanding of AMPK activation dynamics in subcellular compartments and provide additional support for repurposing metformin for treating cocaine use disorder.

This paper describes a patient with an inoperable gastrointestinal stromal tumour with moderate volume malignant ascites. A large-volume paracentesis caused haemodynamic instability and a myocardial infarction. An indwelling right-sided peritoneal catheter was inserted following further ascites build-up. The patient experienced spontaneous acute rupture of tumour and subsequent loculated ascites. An additional second catheter was inserted to the left side of the abdomen following reaccumulation of ascites following liquefaction of cyst contents and successful one-off drainage on the left side of abdomen. This is the first case report of a patient with two indwelling catheters: we describe learning points pertaining to those as well as the rupture of gastrointestinal stromal tumours. Haemodynamic instability after paracentesis in malignant-related ascites has also not been described., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: 'Perturbation-based balance training' (PBBT) is a training method that was developed to improve balance reactive responses to unexpected balance loss. This training method is more effective in reducing fall rates than traditional balance training methods. Many PBBTs are performed during standing or treadmill walking which targeted specifically step reactive responses, we however, aimed to develop and build a mechatronic system that can provide unexpected perturbation during elliptical walking the Elliptical Perturbation System (the EPES system), with the aim of improving specifically the trunk and upper limbs balance reactive control., Methods: This paper describes the development, and building of the EPES system, using a stationary Elliptical Exercise device, which allows training of trunk and upper limbs balance reactive responses in older adults., Results: The EPES system provides 3-dimensional small, controlled, and unpredictable sudden perturbations during stationary elliptical walking. We developed software that can identify a trainee's trunk and arms reactive balance responses using a stereo camera. After identifying an effective trunk and arms reactive balance response, the software controls the EPES system motors to return the system to its horizontal baseline position after the perturbation. The system thus provides closed-loop feedback for a person's counterbalancing trunk and arm responses, helping to implement implicit motor learning for the trainee. The pilot results show that the EPES software can successfully identify balance reactive responses among participants who are exposed to a sudden unexpected perturbation during elliptical walking on the EPES system., Conclusions: EPES trigger reactive balance responses involving counter-rotation action of body segments and simultaneously evoke arms, and trunk reactive response, thus reactive training effects should be expected., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Drugs of abuse induce cell type-specific adaptations in D1- and D2-medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore) that can bias signalling towards D1-MSNs and enhance relapse vulnerability. Whether Δ 9 -tetrahydrocannabinol (THC) use initiates similar neuroadaptations is unknown. D1- and D2-Cre transgenic rats were transfected with Cre-dependent reporters and trained to self-administer THC + cannabidiol (THC + CBD). After extinction training spine morphology, glutamate transmission, CB1R function and cFOS expression were quantified. We found that extinction from THC + CBD induced a loss of large spine heads in D1- but not D2-MSNs and commensurate reductions in glutamate synaptic transmission. Also, presynaptic CB1R function was impaired selectively at glutamatergic synapses on D1-MSNs, which augmented the capacity to potentiate glutamate transmission. Using cFOS expression as an activity marker, we found no change after extinction but increased cFOS expression in D1-MSNs after cue-induced drug seeking. Contrasting D1-MSNs, CB1R function and glutamate synaptic transmission on D2-MSN synapses were unaffected by THC + CBD use. However, cFOS expression was decreased in D2-MSNs of THC + CBD-extinguished rats and was restored after drug seeking. Thus, CB1R adaptations in D1-MSNs partially predicted neuronal activity changes, posing pathway specific modulation of eCB signalling in D1-MSNs as a potential treatment avenue for cannabis use disorder (CUD)., (© 2023 Society for the Study of Addiction.)

Background: Early evidence suggested that the impact of the COVID-19 pandemic was less severe in Africa compared to other parts of the world. However, more recent studies indicate higher SARS-CoV-2 infection and COVID-19 mortality rates on the continent than previously documented. Research is needed to better understand SARS-CoV-2 infection and immunity in Africa., Methods: In early 2021, we studied the immune responses in healthcare workers (HCWs) at Lagos University Teaching Hospital ( n  = 134) and Oxford-AstraZeneca COVID-19 vaccine recipients from the general population ( n  = 116) across five local government areas (LGAs) in Lagos State, Nigeria. Western blots were used to simultaneously detect SARS-CoV-2 spike and nucleocapsid (N) antibodies ( n  = 250), and stimulation of peripheral blood mononuclear cells with N followed by an IFN-γ ELISA was used to examine T cell responses ( n  = 114)., Results: Antibody data demonstrated high SARS-CoV-2 seroprevalence of 72·4% (97/134) in HCWs and 60·3% (70/116) in the general population. Antibodies directed to only SARS-CoV-2 N, suggesting pre-existing coronavirus immunity, were seen in 9·7% (13/134) of HCWs and 15·5% (18/116) of the general population. T cell responses against SARS-CoV-2 N ( n  = 114) were robust in detecting exposure to the virus, demonstrating 87·5% sensitivity and 92·9% specificity in a subset of control samples tested. T cell responses against SARS-CoV-2 N were also observed in 83.3% of individuals with N-only antibodies, further suggesting that prior non-SARS-CoV-2 coronavirus infection may provide cellular immunity to SARS-CoV-2., Conclusions: These results have important implications for understanding the paradoxically high SARS-CoV-2 infection with low mortality rate in Africa and supports the need to better understand the implications of SARS-CoV-2 cellular immunity., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BBH is a co-founder of Mir Biosciences, Inc., a company that develops T cell-based diagnostics/vaccines for infections, cancer, and autoimmunity. No other competing financial interests., (© 2023 The Author(s).)

The major cause for skin cancer is the excessive and unprotected exposure to ultraviolet radiation (UVR), which can be prevented by engaging in sun protection behaviours. As longitudinal studies on both adolescents' and adults' performances of sun protection behaviours are limited, the current study aimed to investigate changes in sun protection in these population segments in Western Australia, a region with high annual UVR. During six summer seasons (2015/16 to 2020/21), cross-sectional surveys were conducted among 1806 adolescents (14 to 17 years old) and 1808 adults (18-45 years old), investigating the frequency of five sun protection behaviours (wearing clothing, applying sunscreen, wearing a hat, wearing sunglasses, and seeking shade) and sun avoidance (staying indoors). Over the six-year period, staying indoors increased in both groups. Among adolescents, a decrease in wearing clothing and sunglasses and an increase in seeking shade was demonstrated, and hat and sunscreen use remained relatively stable. Among adults, an increase in sunscreen use was shown, whereas all other sun-related behaviours remained consistent over the six-year period. The results from this study can provide directions for health communications focusing on improving sun protection behaviours among both adolescent and adult populations.

Objective: Pathological involvement of cervical conization margins is a risk factor for recurrence, although management of these patients is controversial. We aimed to define risk factors for positive margins and compare recurrence following additional surgical intervention compared to conservative management., Methods: A retrospective study of all conizations at our center between 2010 and 2019. Univariate analysis identified characteristics associated with positive margins. Women were stratified by mode of management comparing three groups (surveillance, repeat conization or hysterectomy) then two groups (surveillance vs. additional surgery). Kaplan Meyer survival curves compared cumulative recurrence stratified by mode of management. Pathological results of subsequent surgical procedures were examined for residual disease., Results: Of 448 conizations performed, 131 (29.2%) had positive margins which were associated with menopause, high-grade cytology and endocervical gland involvement. Women who underwent surveillance (n = 45) were more likely to be nulliparous, with low-grade histology and less endocervical gland involvement. Women who underwent hysterectomy (n = 61) were more likely to be postmenopausal and parous. Recurrence did not differ significantly in the three-group (p = 0.073) or two-group model (6.4% vs. 7.1% p = 0.869). Kaplan Meyer survival curves depicting cumulative recurrence did not differ significantly in either model (log rank test p = 0.642 for the three-group model, and p = 0.868 for the two-group model). Residual disease was found in 51.6% of hysterectomy specimens and 52.6% of repeat conizations., Conclusion: Surveillance is non-inferior to additional surgery in cases with positive conization margins and constitutes a valid option specifically for younger women at risk of future obstetric complications and those susceptible post-hysterectomy complications., Competing Interests: Declaration of competing interest The authors declare no potential conflict of interest., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Vocalization is a widespread social behavior in vertebrates that can affect fitness in the wild. Although many vocal behaviors are highly conserved, heritable features of specific vocalization types can vary both within and between species, raising the questions of why and how some vocal behaviors evolve. Here, using new computational tools to automatically detect and cluster vocalizations into distinct acoustic categories, we compare pup isolation calls across neonatal development in eight taxa of deer mice (genus Peromyscus) and compare them with laboratory mice (C57BL6/J strain) and free-living, wild house mice (Mus musculus domesticus). Whereas both Peromyscus and Mus pups produce ultrasonic vocalizations (USVs), Peromyscus pups also produce a second call type with acoustic features, temporal rhythms, and developmental trajectories that are distinct from those of USVs. In deer mice, these lower frequency "cries" are predominantly emitted in postnatal days one through nine, whereas USVs are primarily made after day 9. Using playback assays, we show that cries result in a more rapid approach by Peromyscus mothers than USVs, suggesting a role for cries in eliciting parental care early in neonatal development. Using a genetic cross between two sister species of deer mice exhibiting large, innate differences in the acoustic structure of cries and USVs, we find that variation in vocalization rate, duration, and pitch displays different degrees of genetic dominance and that cry and USV features can be uncoupled in second-generation hybrids. Taken together, this work shows that vocal behavior can evolve quickly between closely related rodent species in which vocalization types, likely serving distinct functions in communication, are controlled by distinct genetic loci., Competing Interests: Declaration of interests H.E.H. is a member of the Advisory Board for Current Biology., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Clinical studies and structural analyses of salivary stones strongly suggest a linkage between higher saliva calcium (Ca 2+ ) and salivary stone formation, sialolithiasis; however, the process and the mechanism leading to Ca 2+ overload during sialolithiasis is not well understood. Here, we show that TRPC3 null (-/-) mice presented with a reduction in Ca 2+ entry and current in ductal cells with higher saliva [Ca 2+ ] suggesting diminished transepithelial Ca 2+ flux across the salivary ductal cells, leaving more Ca 2+ in ductal fluid. Significantly, we found that TRPC3 was expressed in mice and human salivary ductal cells, while intraductal stones were detected in both mice (TRPC3 -/- ) and patient (sialolithiasis) salivary glands. To identify the mechanism, we found that TRPC3 was crucial in preventing the expression of calcification genes (BMP2/6, Runx2) in ductal cells which may be due to higher extracellular Ca 2+ in SMG tissues. Similarly, inflammatory (IL6, NLRP3), fibrotic (FN1, TGFβ1) and apoptotic (Bax1/Bcl2) markers were also elevated, suggesting that the loss of TRPC3 induces genetic changes that leads to salivary gland cell death and induction of inflammatory response. Overall, ablation of TRPC3 -/- leads to higher saliva [Ca 2+ ], along with elevated detrimental gene expressions, altogether contributing to salivary gland stone formation., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

A woman in her mid-50s was referred to a plastic surgeon with an 8-year history of undiagnosed, localised severe, reproducible pain of the right thigh. Treatment with oral and topical analgesics, corticosteroids, acupuncture and physiotherapy did not provide symptom relief. She was referred to multiple specialists over the preceding 8 years including chronic pain physicians, physiatry, orthopaedic surgery and plastic surgery. Investigations including sonographic and MRI eventually revealed a non-specific soft tissue abnormality in the area of tenderness, which was excised en bloc. Histopathology revealed an extradigital glomus tumour. The patient's symptoms immediately and permanently resolved postexcision.Physicians seeing patients suffering from undiagnosed focal, reproducible pain should consider extradigital glomus tumours in their differential diagnosis. Workup for extradigital glomus tumour includes focused sonographic or MRI over the area of pain. Additionally, local injection of an anaesthetic agent can be used to assist with diagnosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Older adults face racism, sexism, and ageism. As the U.S. population ages, it is important to understand how the current population views older adults., Methods: Participants recruited through Amazon's Mechanical Turk provided perceptions of older Black and White models' photographs. Using mixed-effect models, we assessed interactions between race and gender of participants and models., Results: Among Participants of Color and White participants ( n  = 712, 70% non-Hispanic White, 70% women, mean 37.81 years), Black models were perceived as more attractive, less threatening, and sadder than White models, but differences were greater for White participants (race-by-race interaction: attractive p  = 0.003, threatening p  = 0.009, sad p  = 0.016). Each gender perceived their respective gender as more attractive (gender-by-gender interaction p  < 0.0001). Male and female participants perceived male models as happier than female models, but differences were greater for male participants ( p  = 0.026). Irrespective of participant age group, women were perceived as more threatening ( p  = 0.012). Other perceptions were not significant., Discussion: Participants had few biases toward older Black and White models, while gender biases favored men., Competing Interests: Authors declare no conflict of interest., (© Forest Melton et al., 2022; Published by Mary Ann Liebert, Inc.)

Background: The mobile integrated health-community paramedicine (MIH-CP) program affiliated with the University of Maryland Medical Center focuses on improving patient transitions from hospital to home by addressing both medical and social determinants of health. Until recently, only self-contained health systems could integrate inpatient and outpatient medication data. Without some means to track patients in transition, there is a significant risk of medication-related problems and errors., Objective: To evaluate the impact of the MIH-CP program on medication adherence among patients with congestive heart failure (CHF) and/or chronic obstructive pulmonary disease (COPD)., Methods: This is a pilot observational study designed to compare adherence to drug regimens prescribed at hospital discharge (measured by the proportion of days covered [PDC]) between patients enrolled in the MIH-CP program and a propensity-matched control group. Propensity scores were calculated using 11 demographic, diagnostic, third-party payer, and patient care-associated variables. Discharge medication details were obtained from electronic medical records. PDC for each of the medications were calculated from pharmacy claims data., Results: Eighty-three patients were included in the study; forty-three patients were placed in the intervention group and 40 were propensity-matched controls. After adjusting for age, sex, and third-party payer, findings indicated that medication adherence was higher among patients enrolled in the MIH-CP program compared with control during the first 30 days post-discharge, specifically among patients diagnosed with CHF (8% difference in PDC, 95% confidence interval [CI], -0.12-0.28%) and COPD (14% difference, 95% CI, -0.15-0.43%), although neither result achieved statistical significance. The differences in medication adherence between patients who were enrolled and those who were not enrolled in the MIH-CP program diminished after 30 days post-discharge., Conclusion: This pilot study demonstrated a trend toward improved medication adherence among patients enrolled in the MIH-CP program. Future research involving a larger patient cohort will be required to confirm these preliminary findings., Competing Interests: None declared., (© 2022 The Authors.)