Effect Threshold for Selenium Toxicity in Juvenile Splittail, Pogonichthys macrolepidotus A

In fish, selenium can bioaccumulate and cause adverse impacts. One of the fish species potentially at risk from selenium in the San Francisco Bay (California, USA) is the splittail (Pogonichthys macrolepidotus). Previous studies have derived a whole body NOAEL and LOAEL of 9.0 and 12.9 mg/kg-dw, respectively, for selenium in juveniles. However, the NOAEL/LOAEL approach leaves some uncertainty regarding the threshold of toxicity. Therefore, the raw data from the original experiment was re-analyzed using a logistic regression to derive EC10 values of 0.9 mg/kg-dw in feed, 7.9 mg/kg-dw in muscle, 18.6 mg/kg-dw in liver for juvenile splittail. Selenium concentrations in the dietary items of wild splittail exceed the EC10 values derived here. Thus, deformities previously reported in wild splittail may have resulted from selenium exposures via the food chain

Wake up, wake up! It's me! It's my life! patient narratives on person-centeredness in the integrated care context: a qualitative study

Person-centered care emphasizes a holistic, humanistic approach that puts patients first, at the center of medical care. Person-centeredness is also considered a core element of integrated care. Yet typologies of integrated care mainly describe how patients fit within integrated services, rather than how services fit into the patient's world. Patient-centeredness has been commonly defined through physician's behaviors aimed at delivering patient-centered care. Yet, it is unclear how 'person-centeredness' is realized in integrated care through the patient voice. We aimed to explore patient narratives of person-centeredness in the integrated care context

Feasibility and benefits of a structured prehabilitation programme prior to autologous stem cell transplantation (ASCT) in patients with myeloma; a prospective feasibility study

Evidence supports the benefits of exercise-based rehabilitation in promoting recovery in myeloma patients following autologous stem-cell transplantation (ASCT). However, ‘prehabilitation’ has never been evaluated prior to ASCT, despite evidence of effectiveness in other cancers. Utilising a mixed method approach the authors investigated the feasibility of a mixed strength and cardiovascular exercise intervention pre-ASCT. Quantitative data were collected to determine feasibility targets; rates of recruitment, adherence and adverse events, including 6 minute walking distance (6MWD) test and patient reported outcome measures (PROMs). Qualitative interviews were undertaken with a purposive sample of patients to capture their experiences of the study and the intervention. The authors recruited 23 patients who attended a mean percentage of 75% scheduled exercise sessions. However, retention rates were limited, with only 14/23 (62%) completing the programme. In these patients, the 6MWD increased from a mean of 346 to 451 m (i.e. by 105 m, 95% CI 62 to 148 m) with no serious adverse events. Whist participants found the exercise programme acceptable and reported improvement in their physical fitness and overall mental health and wellbeing prior to ASCT, the study identified challenges in hospital attendance for the prehabilitation schedule whilst receiving induction or re-induction chemotherapy. Evaluation of digitally-enhanced directed but remote prehabilitation models for this patient group is warranted. Trial registration number NCT0313592

An interdisciplinary intervention for older Taiwanese patients after surgery for hip fracture improves health-related quality of life

Abstract Background The effects of intervention programs on health-related quality of life (HRQOL) of patients with hip fracture have not been well studied. We hypothesized that older patients with hip fracture who received our interdisciplinary intervention program would have better HRQOL than those who did not. Methods A randomized experimental design was used. Older patients with hip fracture (N = 162), 60 to 98 years old, from a medical center in northern Taiwan were randomly assigned to an experimental (n = 80) or control (n = 82) group. HRQOL was measured by the SF-36 Taiwan version at 1, 3, 6, and 12 months after discharge. Results The experimental group had significantly better overall outcomes in bodily pain (β = 9.38, p = 0.002), vitality (β = 9.40, p < 0.001), mental health (β = 8.16, p = 0.004), physical function (β = 16.01, p < 0.001), and role physical (β = 22.66, p < 0.001) than the control group at any time point during the first year after discharge. Physical-related health outcomes (physical functioning, role physical, and vitality) had larger treatment effects than emotional/mental- and social functioning-related health outcomes. Conclusions This interdisciplinary intervention program may improve health outcomes of elders with hip fracture. Our results may provide a reference for health care providers in countries using similar programs with Chinese/Taiwanese immigrant populations. Trial registration NCT01052636http://deepblue.lib.umich.edu/bitstream/2027.42/78259/1/1471-2474-11-225.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78259/2/1471-2474-11-225.pdfPeer Reviewe

Retrospective Review of Positive Newborn Screening Results for Isovaleric Acidemia and Development of a Strategy to Improve the Efficacy of Newborn Screening in the UK

\ua9 2024 by the authors.Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015 and 2022 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0–9.6) and 4.0 (1.8–>70) \ub5mol/L, respectively, and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C in ‘asymptomatic’ individuals (n = 17), demonstrating a median (range) C5C of 3.0 (1.8–7.1) whilst ‘clinically affected’ patients (n = 7), showed a median (range) C5C of 13.9 (7.7–70) \ub5mol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 \ub5mol/L triggering urgent referral, and those >2.0 and <5.0 \ub5mol/L prompting second-tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder

Gonadal function in male patients after treatment for malignant lymphomas, with emphasis on chemotherapy

Gonadal function was assessed in male lymphoma survivors based on serum hormone levels (LH, FSH, testosterone, SHBG), and was related to treatment, age and observation time. Male patients ⩽50 years at diagnosis treated for Hodgkin's (HL) and/or non-Hodgkin's lymphoma (NHL) at the Norwegian Radium Hospital from 1 January 1980 to 31 December 2002 were included. Five treatment groups were defined: 1: radiotherapy only and/or low gonadotoxic chemotherapy (both HL and NHL)(‘No/low'), 2: medium gonadotoxicity chemotherapy for NHL (‘med-NHL'), 3: medium gonadotoxicity chemotherapy for HL (‘med-HL'), 4: highly gonadotoxic chemotherapy for NHL (‘high-NHL'), 5: highly gonadotoxic chemotherapy for HL (‘high-HL'). Gonadal hormone levels were categorised into three groups: 1: All gonadal hormones within normal range (normal), 2: Isolated elevated FSH, with LH, SHBG and testosterone within normal range (exocrine hypogonadism), 3: Testosterone below and/or LH above normal range (endocrine hypogonadism). One hundred and forty-four (49%) of the patients had normal gonadal hormones, 60 (20%) displayed exocrine hypogonadism and almost one-third (n=90, 30%) had endocrine hypogonadism. Compared to those treated with no/low gonadotoxic chemotherapy patients from all other treatment groups had significantly elevated risk for exocrine hypogonadism. Patients from the other treatment groups, except those in the med-NHL group, also had significantly elevated risk for endocrine hypogonadism compared with the group treated with no/low gonadotoxic chemotherapy. Men aged above 50 years at survey were about five times more likely to have endocrine hypogonadism compared with those less than 40 years. Because of the adverse health effects following long-lasting endocrine hypogonadism, gonadal hormones should be assessed regularly in male lymphoma survivors, especially after treatment with alkylating agents and high-dose chemotherapy with autologous stem cell support and in male patients who are 50 years and older

Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation

A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281–1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50 μ m. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung

Questionnaire survey of working relationships between nurses and doctors in University Teaching Hospitals in Southern Nigeria

BACKGROUND: Smooth working relationships between nurses and doctors are necessary for efficient health care delivery. However, previous studies have shown that this is often absent with negative impact on the quality of health care delivery. In 2002, we studied factors that affect nurse-doctor working relationships in University Teaching Hospitals (UTH) in Southern Nigeria in order to characterize it and identify managerial and training needs that might be used to improve it. METHOD: Questionnaire survey of doctors and nurses working in four UTH in Southern Nigeria was done in 2002. The setting and subjects were selected by random sampling procedures. Information on factors in domains of work, union activities, personnel and hospital management were studied using closed and open-ended questionnaires. RESULTS: Nurse-doctor working relationships were statistically significantly affected by poor after-work social interaction, staff shortages, activist unionism, disregard for one's profession, and hospital management and government policies. In general, nurses had better opinion of doctors' work than doctors had about nurses' work. CONCLUSION: Working relationships between doctors and nurses need to be improved through improved training and better working conditions, creation of better working environment, use of alternative methods of conflict resolution and balanced hospital management and government policies. This will improve the retention of staff, job satisfaction and efficiency of health care delivery in Nigeria

Caspase Inhibitors of the P35 Family Are More Active When Purified from Yeast than Bacteria

Many insect viruses express caspase inhibitors of the P35 superfamily, which prevent defensive host apoptosis to enable viral propagation. The prototypical P35 family member, AcP35 from Autographa californica M nucleopolyhedrovirus, has been extensively studied. Bacterially purified AcP35 has been previously shown to inhibit caspases from insect, mammalian and nematode species. This inhibition occurs via a pseudosubstrate mechanism involving caspase-mediated cleavage of a “reactive site loop” within the P35 protein, which ultimately leaves cleaved P35 covalently bound to the caspase's active site. We observed that AcP35 purifed from Saccharomyces cerevisae inhibited caspase activity more efficiently than AcP35 purified from Escherichia coli. This differential potency was more dramatic for another P35 family member, MaviP35, which inhibited human caspase 3 almost 300-fold more potently when purified from yeast than bacteria. Biophysical assays revealed that MaviP35 proteins produced in bacteria and yeast had similar primary and secondary structures. However, bacterially produced MaviP35 possessed greater thermal stability and propensity to form higher order oligomers than its counterpart purified from yeast. Caspase 3 could process yeast-purified MaviP35, but failed to detectably cleave bacterially purified MaviP35. These data suggest that bacterially produced P35 proteins adopt subtly different conformations from their yeast-expressed counterparts, which hinder caspase access to the reactive site loop to reduce the potency of caspase inhibition, and promote aggregation. These data highlight the differential caspase inhibition by recombinant P35 proteins purified from different sources, and caution that analyses of bacterially produced P35 family members (and perhaps other types of proteins) may underestimate their activity