A first report of Pseudosuccinea columella (Say, 1817), an alien intermediate host for liver fluke, in Malawi.

Starting in October 2021, quarterly malacological surveys have been undertaken in Malawi, with the sampling of 12 specified freshwater habitats throughout a calendar year. Each survey monitors the presence of aquatic intermediate snail hosts of medical and veterinary importance. In March 2023, the alien lymnaeid species Pseudosuccinea columella was encountered for the first time in the surveys, in Nsanje District. This species identity was later confirmed upon DNA analysis of mitochondrial ribosomal 16S sequences. In July 2023, P. columella was also noted at single sites within Mangochi and Chikwawa Districts, and again in Nsanje District, with an additional location observed. Of particular importance, our sampled location in Mangochi District was directly connected to Lake Malawi, which expands the species list of invasive molluscs in this lake. While P. columella is a well-known intermediate snail host for human and animal fascioliasis, screening collected snails for trematode cercariae, alongside molecular xenomonitoring, did not yield equivocal evidence of active fluke infection. However, the newly recognized presence of this alien intermediate snail host within Lake Malawi, and along the Shire River Valley, flags a new concern in altered local transmission potential for human and animal fascioliasis.

An alien intermediate snail host in Malawi - Orientogalba viridis (Quoy and Gaimard, 1832) - A new concern for schistosomiasis transmission in Africa?

The freshwater amphibious snail Orientogalba viridis commonly occurs in eastern Asia, on certain Pacific islands and more importantly has recently dispersed into Europe. Since this snail is now considered an invasive species, its distribution is of growing parasitological interest as an alien intermediate host for various trematodes, particularly liver flukes. As part of ongoing surveillance for snail-borne diseases in Malawi, a population of O. viridis was first observed in May 2023, alongside an alarming presence of a human schistosome cercaria. This snail population later underwent detailed morphological characterisation with both snail and parasite identities confirmed upon DNA barcoding. This seminal observation triggered more extensive local snail surveys, finding 3 further populations in separated rice paddies, with further field-caught snails (n = 465) screened for infection and a selection used for repeated experimental challenges with miracidia from Schistosoma haematobium and Schistosoma mattheei. Although no field-caught (and experimentally exposed) snail was seen to shed schistosome cercariae, molecular xenomonitoring for schistosomiasis provided tangible evidence of putative transmission potential. Our first report of O. viridis here in Malawi, and more broadly in Africa, flags a need for increased vigilance for this invasive species alongside local clarification(s) of its transmission potential for trematodiases of either medical and/or veterinary importance.

Surgical Management of Ebstein Anomaly: The Australia and New Zealand Experience.

BACKGROUND: Ebstein anomaly is a rare congenital anomaly of the tricuspid valve which presents challenges to cardiac surgeons due to the spectrum of the disease and the technical difficulty of valve repair. The natural history of the anomaly differs between patients presenting in the neonatal period to those presenting in adulthood. METHODS: A retrospective review of all patients >15 years of age with Ebstein anomaly, undergoing surgery on the tricuspid valve at 6 centers across Australia and New Zealand was performed. Patients from 1985 to 2019 were included in the study. RESULTS: A total of 125 patients were included in the study, 76 patients (60%) undergoing tricuspid valve repair, of which 23 patients underwent a Cone repair and 49 (40%) had a tricuspid valve replacement. The mean follow-up was 7.9 ± 7.3 years. Postoperatively, early mortality was 3 patients (2%) and 10-year survival was 91.5%. A postoperative pacemaker was required in 24 patients (19%). Reoperation was required in 21 patients (17%). There was no statistically significant difference in survival or reoperation between patients who underwent repair or replacement of the tricuspid valve; however, with a small number of patients in long-term follow-up. CONCLUSION: Older children and adult patients undergoing surgery for Ebstein anomaly in Australia and New Zealand experience good medium-term postoperative survival. Repair of the valve is achieved in a significant proportion of patients with increasing use and success with the Cone repair technique.

Caregiver experiences of hospice dementia care: a systematic review and meta-ethnography.

OBJECTIVES: Hospices are regarded as gold standard providers of end-of-life care. The term hospice, however, is broadly used, and can describe a type of care offered in a variety of health care services (e.g. nursing homes). It thus becomes complex for families to decide between services. We aimed to review the evidence around the experience of family carers of people with dementia accessing in-patient hospice settings for end-of-life care. METHOD: We registered the review protocol on PROSPERO. We used PerSPE(C)TiF to systematically organise our search strategy. The evidence was reviewed across six databases: PubMed, EMBASE, PsycINFO, ASSIA, ISI Web, and CINAHL. We used meta-ethnography as per the eMERGe guidance for data interpretation. RESULTS: Four studies were included. Two third-order constructs were generated through meta-ethnography: expectations of care and barriers to quality of care. We found that carers had expectations of care, and these could change over time. If discussion was not held with hospice staff early on, the carers could experience reduced care quality due to unmatched expectations. Unmatched expectations acted as barriers to care and these were found in terms of carers not feeling adequately supported, and/or having the person discharged from hospice, which would entail increased care responsibility for carers. CONCLUSION: In view of an increase in new dementia cases over time and with hospice services being under pressure, integrating palliative care services within community-based models of care is key to reducing the risk of having inadequate and under resourced services for people with dementia.

Experiences of hospice dementia care: A qualitative study of bereaved carers and hospice clinicians.

BACKGROUND: Nearly 50 million people worldwide have dementia and the increasing numbers requiring end-of-life and palliative care, has led to national efforts to define standards of care for this patient group. Little research, however, has been done to date about the experience of hospice care for people with dementia accessing these services. This study explores the views of hospice dementia care for bereaved carers of people with dementia and hospice clinicians. METHODS: We used purposive sampling for participant recruitment. Semi-structured qualitative interviews were conducted with bereaved carers and hospice clinical staff. Interviews were audio recorded and the transcriptions were analysed through thematic analysis. A total of 12 participants were interviewed from one service in the Northwest region in the UK. All were female and white British. RESULTS: Participants described their experience of hospice dementia care in three main themes: Pre-access to service, roles and responsibility within hospice care, ease and difficulty of last period of end-of-life care. CONCLUSION: Rapid response teams delivering hospice home care could represent a better option to inpatient care and may be preferred by patients. This type of service, however, may require joined-up care with other community services, and this type of care needs to be considered and planned. Future studies should evaluate this type of community care.

Using natural language processing to characterize and predict homeopathic product-associated adverse events in consumer reviews: comparison to reports to FDA Adverse Event Reporting System (FAERS).

OBJECTIVE: Apply natural language processing (NLP) to Amazon consumer reviews to identify adverse events (AEs) associated with unapproved over the counter (OTC) homeopathic drugs and compare findings with reports to the US Food and Drug Administration Adverse Event Reporting System (FAERS). MATERIALS AND METHODS: Data were extracted from publicly available Amazon reviews and analyzed using JMP 16 Pro Text Explorer. Topic modeling identified themes. Sentiment analysis (SA) explored consumer perceptions. A machine learning model optimized prediction of AEs in reviews. Reports for the same time interval and product class were obtained from the FAERS public dashboard and analyzed. RESULTS: Homeopathic cough/cold products were the largest category common to both data sources (Amazon = 616, FAERS = 445) and were analyzed further. Oral symptoms and unpleasant taste were described in both datasets. Amazon reviews describing an AE had lower Amazon ratings (X2 = 224.28, P < .0001). The optimal model for predicting AEs was Neural Boosted 5-fold combining topic modeling and Amazon ratings as predictors (mean AUC = 0.927). DISCUSSION: Topic modeling and SA of Amazon reviews provided information about consumers' perceptions and opinions of homeopathic OTC cough and cold products. Amazon ratings appear to be a good indicator of the presence or absence of AEs, and identified events were similar to FAERS. CONCLUSION: Amazon reviews may complement traditional data sources to identify AEs associated with unapproved OTC homeopathic products. This study is the first to use NLP in this context and lays the groundwork for future larger scale efforts.

Varicella zoster virus reactivation reported with isatuximab use.

Isatuximab is a CD38-directed antibody indicated for the treatment of relapsed or refractory multiple myeloma. The Division of Pharmacovigilance at the U.S. Food and Drug Administration (FDA) reviewed case reports from postmarketing sources, including the FDA Adverse Event Reporting System (FAERS), PubMed, and Embase, to investigate a potential association between isatuximab and the risk of varicella zoster virus (VZV) reactivation. We identified 20 reports of which 15 met our case definition and causality criteria. All 15 patients (80% male, median age = 60 years) received isatuximab for a hematologic neoplasm; eight (53%) for previously untreated multiple myeloma. All cases described additional risk factors for VZV reactivation, including concomitant proteasome inhibitor and/or immunomodulatory drug (n = 10, 67%) use. Based on this postmarket analysis, the U.S. Prescribing Information for isatuximab was updated to include this new safety information, including recommendations for antiviral prophylaxis.

Observation of the effect of gravity on the motion of antimatter.

Einstein's general theory of relativity from 19151 remains the most successful description of gravitation. From the 1919 solar eclipse2 to the observation of gravitational waves3, the theory has passed many crucial experimental tests. However, the evolving concepts of dark matter and dark energy illustrate that there is much to be learned about the gravitating content of the universe. Singularities in the general theory of relativity and the lack of a quantum theory of gravity suggest that our picture is incomplete. It is thus prudent to explore gravity in exotic physical systems. Antimatter was unknown to Einstein in 1915. Dirac's theory4 appeared in 1928; the positron was observed5 in 1932. There has since been much speculation about gravity and antimatter. The theoretical consensus is that any laboratory mass must be attracted6 by the Earth, although some authors have considered the cosmological consequences if antimatter should be repelled by matter7-10. In the general theory of relativity, the weak equivalence principle (WEP) requires that all masses react identically to gravity, independent of their internal structure. Here we show that antihydrogen atoms, released from magnetic confinement in the ALPHA-g apparatus, behave in a way consistent with gravitational attraction to the Earth. Repulsive 'antigravity' is ruled out in this case. This experiment paves the way for precision studies of the magnitude of the gravitational acceleration between anti-atoms and the Earth to test the WEP.

Substance Use, Sexual Agreements, and Sexual Risk Behaviors Among Adolescent Sexual Minority Males (Aged 13-17) in the United States.

PURPOSE: Despite the fact that adolescence represents a distinct developmental period wherein dating and sexual relationships are emergent, much of what is known about substance use, sexual agreements, and sexual risk behaviors among adolescent sexual minority males (ASMM) is extrapolated from research on adults. This study tested associations between substance use and sexual risk behaviors among ASMM and examined whether relationship status and sexual agreements moderated these associations. METHODS: Cross-sectional online survey data were collected from 2,892 HIV negative ASMM aged 13-17 years between November 2017 and March 2020. All were sexually active with male partners and not on pre-exposure prophylaxis. A multigroup hurdle model predicted the occurrence and frequency of condomless anal sex (CAS) with casual partners. RESULTS: Non-monogamous ASMM were more likely to use illicit drugs and more likely to have CAS with casual partners compared with single ASMM and those in monogamous relationships. Among ASMM who had CAS at least once, those in relationships (both monogamous and nonmonogamous) had CAS more frequently than single ASMM. Binge drinking (odds ratio (OR) = 1.47, p < .001), cannabis (OR = 1.30, p < .001), and illicit drug use (including prescription drug misuse) (OR = 1.77, p < .001) were associated with the occurrence of CAS with casual partners but only binge drinking (rate ratio (RR) = 1.23, p = .027) and illicit drugs (RR = 1.75, p < .001) were associated with its frequency. DISCUSSION: While results aligned with adult studies in many respects, unlike adult sexual minority males, these findings suggest partnered ASMM-particularly those in nonmonogamous relationships-were at highest risk of substance use and associated sexual HIV transmission risk.

Patterns of ethanol intake in male rats with partial dopamine transporter deficiency.

Mesolimbic dopamine signaling plays a major role in alcohol and substance use disorders as well as comorbidities such as anxiety and depression. Growing evidence suggests that alcohol drinking is modulated by the function of the dopamine transporter (DAT), which tightly regulates extracellular dopamine concentrations. Adult male rats on a Wistar Han background (DAT+/+) and rats with a partial DAT deletion (DAT+/-) were used in this study. First, using fast-scan cyclic voltammetry in brain slices containing the nucleus accumbens core from ethanol-naïve subjects, we measured greater evoked dopamine concentrations and slower dopamine reuptake in DAT+/- rats, consistent with increased dopamine signaling. Next, we measured ethanol drinking using the intermittent access two-bottle choice paradigm (20% v/v ethanol vs. water) across 5 weeks. DAT+/- rats voluntarily consumed less ethanol during its initial availability (the first 30 min), especially after longer periods of deprivation. In addition, DAT+/- males consumed less ethanol that was adulterated with the bitter tastant quinine. These findings suggest that partial DAT blockade and concomitant increase in brain dopamine levels has potential to reduce drinking and ameliorate alcohol use disorder (AUD).

Hyperimmune egg yolk antibodies developed against Clostridium perfringens antigens protect against necrotic enteritis.

Necrotic enteritis (NE) is a widespread infectious disease caused by Clostridium perfringens that inflicts major economic losses on the global poultry industry. Due to regulations on antibiotic use in poultry production, there is an urgent need for alternative strategies to mitigate the negative effects of NE. This paper presents a passive immunization technology that utilizes hyperimmune egg yolk immunoglobulin Y (IgY) specific to the major immunodominant antigens of C. perfringens. Egg yolk IgYs were generated by immunizing hens with 4 different recombinant C. perfringens antigens, and their protective effects against NE were evaluated in commercial broilers. Six different spray-dried egg powders were produced using recombinant C. perfringens antigens: α-toxin, NE B-like toxin (NetB; EB), elongation factor-Tu (ET), pyruvate:ferredoxin oxidoreductase, a mixture of 4 antigens (EM-1), and a nonimmunized control (EC). The challenged groups were either provided with different egg powders at a 1% level or no egg powders (EN). The NE challenge model based on Eimeria maxima and C. perfringens dual infection was used. In Experiments 1 and 2, the EB and ET groups exhibited increased body weight gain (BWG; P < 0.01), decreased NE lesion scores (P < 0.001), and reduced serum NetB levels (P < 0.01) compared to the EN and EC groups. IgY against NetB significantly reduced Leghorn male hepatocellular cytotoxicity in an in vitro test (P < 0.01). In Experiment 3, the protective effect of the IgYs mixture (EM-2) against C. perfringens antigens (NetB and EFTu) and Eimeria antigens (elongation factor-1-alpha: EF1α and Eimeria profilin: 3-1E) was tested. The EM-2 group showed similar body weight, BWG, and feed intake from d 7 to 22 compared to the NC group (P < 0.05). On d 20, the EM-2 group showed comparable intestinal permeability, NE lesion scores, and jejunal NetB and collagen adhesion protein levels to the NC group (P < 0.05). In conclusion, dietary mixture containing antibodies to NetB and EFTu provides protection against experimental NE in chickens through passive immunization.

The relevance of false positive acid phosphatase reactions indicative of the presence of seminal fluid from oral and vaginal samples.

The Body Fluid Forum of the Association of Forensic Science Providers recognised concerns raised by forensic practitioners regarding the lack of data to inform on the incidence of significant AP (Acid Phosphatase) reactions from vaginal and oral samples, i.e. those which might be misinterpreted as indicating the presence of semen. This is particularly relevant in the light of appeal court rulings regarding the need for data to support evaluations. This paper presents collaborative data on the nature and incidence of AP reactions from vaginal and oral swabs provided by donors. The results demonstrate that caution is required with mid to strong purple AP reactions from direct testing of oral swabs and with mid purple reactions from vaginal swabs. The use of a Bayesian approach to assist with the provision of opinions regarding the presence of seminal fluid is highlighted.

Opioid and stimulant attributed treatment admissions and fatal overdoses: Using national surveillance data to examine the intersection of race, sex, and polysubstance use, 1992-2020.

BACKGROUND: We use national surveillance data to evaluate race/ethnicity by sex/gender differences and trends in substance use treatment admissions and overdose deaths involving opioid and stimulant use. METHODS: We used data (1992-2019) from the Treatment Episode Dataset-Admissions to identify treatment admissions and the Center for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (1999-2020) to identify overdose deaths. We assessed treatment admissions and related drug overdose deaths per 100,000 adults by sex and race/ethnicity for opioid and stimulant groups: cocaine, opioid, methamphetamines, cocaine and opioid use, cocaine and methamphetamines, and opioid and methamphetamines. RESULTS: We found significant variations in treatment admissions and deaths by race/ethnicity and sex/gender. Cocaine-related treatment admissions and deaths were most prevalent among Non-Hispanic Black individuals over the study years, yet lower rates were evident among individuals from other racial/ethnic groups. Notably, Non-Hispanic Black men experienced larger increases in cocaine-only admissions than men of other racial/ethnic groups between 1992 and 2019. Men had higher opioid and stimulant treatment admissions and overdose deaths than women. We observed skyrocketing methamphetamine deaths among American Indian/Native Alaskan men and women from 1992 to 2019. DISCUSSION: Steep increases in overdose deaths fueled by methamphetamines among Non-Hispanic Native Americans and cocaine among Non-Hispanic Black individuals suggest a need for more effective interventions to curb stimulant use. Variations by race/ethnicity and sex/gender also suggest interventions should be developed through an intersectionality lens.

Seed type and origin-dependent seedling emergence patterns in Danthonia californica, a species commonly used in grassland restoration.

Danthonia californica Bolander (Poaceae)is a native perennial bunchgrass commonly used in the restoration of prairie ecosystems in the western United States. Plants of this species simultaneously produce both chasmogamous (potentially outcrossed) and cleistogamous (obligately self-fertilized) seeds. Restoration practitioners almost exclusively use chasmogamous seeds for outplanting, which are predicted to perform better in novel environments due to their greater genetic diversity. Meanwhile, cleistogamous seeds may exhibit greater local adaptation to the conditions in which the maternal plant exists. We performed a common garden experiment at two sites in the Willamette Valley, Oregon, to assess the influence of seed type and source population (eight populations from a latitudinal gradient) on seedling emergence and found no evidence of local adaptation for either seed type. Cleistogamous seeds outperformed chasmogamous seeds, regardless of whether seeds were sourced directly from the common gardens (local seeds) or other populations (nonlocal seeds). Furthermore, average seed weight had a strong positive effect on seedling emergence, despite the fact that chasmogamous seeds had significantly greater mass than cleistogamous seeds. At one common garden, we observed that seeds of both types sourced from north of our planting site performed significantly better than local or southern-sourced seeds. We also found a significant seed type and distance-dependent interaction, with cleistogamous seedling emergence peaking approximately 125 km from the garden. These results suggest that cleistogamous seeds should be considered for greater use in D. californica restoration.

Posterior stabilised total knee arthroplasty is associated with improved post-operative knee specific function, health related quality of life and greater satisfaction when compared to cruciate retaining protheses.

PURPOSE: To assess whether there were differences in knee specific function, health related quality of life (HRQoL), and satisfaction between patients with a cruciate retaining (CR) or a posterior stabilised (PS) total knee arthroplasty (TKA) at 1 and 2 years postoperatively. METHODS: A retrospective review of TKA (CR and PS) patients from a prospectively collected arthroplasty database. Patient demographics, body mass index and ASA grade, Oxford knee score (OKS) and EuroQol 5-dimension (EQ-5D) 3-level, which was used to assess HRQoL, were collected preoperatively and 1 year and 2 years postoperatively. Regression was used to adjust for confounding factors. RESULTS: The sample included 3122 TKA, of which 1009 (32.3%) were CR and 2112 (67.7%) were PS. The PS group were more likely to be female (odd ratio (OR) 1.26, p = 0.003) and undergo resurfacing of the patella (OR 6.63, p < 0.001). There was a significantly greater improvement in the 1 year OKS in the PS group (mean difference (MD) 0.9, p = 0.016). The PS TKA was independently associated with a greater 1 year (MD 1.1, 95% CI 0.4 to 1.9, p = 0.001) and 2 years (MD 0.8, p = 0.037) post-operative improvements in OKS. PS TKA was also independently associated with a greater 1 year (MD 0.021, p = 0.024) and 2 years (MD 0.022, p = 0.025) post-operative and change in EQ-5D utility compared to the CR group. The PS group was more likely to be satisfied with their outcome at 1 year (OR 1.75, p < 0.001) and at 2 years (OR 1.38, p = 0.001) when adjusting for confounders. CONCLUSION: PS TKA was associated with a better knee specific function and HRQoL when compared to CR, but the clinical significance of this is not clear. However, the PS group was more likely to be satisfied with their outcome compared to the CR group.

First Evidence of Axial Shape Asymmetry and Configuration Coexistence in

The excited states of N=44 ^{74}Zn were investigated via γ-ray spectroscopy following ^{74}Cu ß decay. By exploiting γ-γ angular correlation analysis, the 2_{2}^{+}, 3_{1}^{+}, 0_{2}^{+}, and 2_{3}^{+} states in ^{74}Zn were firmly established. The γ-ray branching and E2/M1 mixing ratios for transitions deexciting the 2_{2}^{+}, 3_{1}^{+}, and 2_{3}^{+} states were measured, allowing for the extraction of relative B(E2) values. In particular, the 2_{3}^{+}→0_{2}^{+} and 2_{3}^{+}→4_{1}^{+} transitions were observed for the first time. The results show excellent agreement with new microscopic large-scale shell-model calculations, and are discussed in terms of underlying shapes, as well as the role of neutron excitations across the N=40 gap. Enhanced axial shape asymmetry (triaxiality) is suggested to characterize ^{74}Zn in its ground state. Furthermore, an excited K=0 band with a significantly larger softness in its shape is identified. A shore of the N=40 "island of inversion" appears to manifest above Z=26, previously thought as its northern limit in the chart of the nuclides.

Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study.

Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual's cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies.