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Veterinary Dermatology Jul 2024A limited antigen diet trial and subsequent food provocation is currently the optimal method of confirming a diagnosis of food allergy in dogs and cats. However,...
A limited antigen diet trial and subsequent food provocation is currently the optimal method of confirming a diagnosis of food allergy in dogs and cats. However, performing an effective diet trial can be challenging as it requires a high level of client and pet compliance, appropriate diet selection and correct interpretation of the provocative challenge. This narrative guides the clinician through the process, highlights potential pitfalls and specifies how these can be avoided to achieve a successful outcome.
PubMed: 38956779
DOI: 10.1111/vde.13274 -
Stem Cell Research & Therapy Jul 2024The human induced pluripotent stem cells (hiPSCs) can generate all the cells composing the human body, theoretically. Therefore, hiPSCs are thought to be a candidate...
BACKGROUND
The human induced pluripotent stem cells (hiPSCs) can generate all the cells composing the human body, theoretically. Therefore, hiPSCs are thought to be a candidate source of stem cells for regenerative medicine. The major challenge of allogeneic hiPSC-derived cell products is their immunogenicity. The hypoimmunogenic cell strategy is allogenic cell therapy without using immune suppressants. Advances in gene engineering technology now permit the generation of hypoimmunogenic cells to avoid allogeneic immune rejection. In this study, we generated a hypoimmunogenic hiPSC (HyPSC) clone that had diminished expression of human leukocyte antigen (HLA) class Ia and class II and expressed immune checkpoint molecules and a safety switch.
METHODS
First, we generated HLA class Ia and class II double knockout (HLA class Ia/II DKO) hiPSCs. Then, a HyPSC clone was generated by introducing exogenous β-2-microglobulin (B2M), HLA-G, PD-L1, and PD-L2 genes, and the Rapamycin-activated Caspase 9 (RapaCasp9)-based suicide gene as a safety switch into the HLA class Ia/II DKO hiPSCs. The characteristics and immunogenicity of the HyPSCs and their derivatives were analyzed.
RESULTS
We found that the expression of HLA-G on the cell surface can be enhanced by introducing the exogenous HLA-G gene along with B2M gene into HLA class Ia/II DKO hiPSCs. The HyPSCs retained a normal karyotype and had the characteristics of pluripotent stem cells. Moreover, the HyPSCs could differentiate into cells of all three germ layer lineages including CD45 hematopoietic progenitor cells (HPCs), functional endothelial cells, and hepatocytes. The HyPSCs-derived HPCs exhibited the ability to evade innate and adaptive immunity. Further, we demonstrated that RapaCasp9 could be used as a safety switch in vitro and in vivo.
CONCLUSION
The HLA class Ia/II DKO hiPSCs armed with HLA-G, PD-L1, PD-L2, and RapaCasp9 molecules are a potential source of stem cells for allogeneic transplantation.
Topics: Humans; Induced Pluripotent Stem Cells; B7-H1 Antigen; Adaptive Immunity; Immunity, Innate; HLA-G Antigens; Programmed Cell Death 1 Ligand 2 Protein; Animals; Mice
PubMed: 38956724
DOI: 10.1186/s13287-024-03810-4 -
Reproductive Health Jul 2024Today, person-centred care is seen as a cornerstone of health policy and practice, but accommodating individual patient preferences can be challenging, for example...
BACKGROUND
Today, person-centred care is seen as a cornerstone of health policy and practice, but accommodating individual patient preferences can be challenging, for example involving caesarean section on maternal request (CSMR). The aim of this study was to explore Swedish health professionals' perspectives on CSMR and analyse them with regard to potential conflicts that may arise from person-centred care, specifically in relation to shared decision-making.
METHODS
A qualitative study using both inductive and deductive content analysis was conducted based on semi-structured interviews. It was based on a purposeful sampling of 12 health professionals: seven obstetricians, three midwives and two neonatologists working at different hospitals in southern and central Sweden. The interviews were recorded either in a telephone call or in a video conference call, and audio files were deleted after transcription.
RESULTS
In the interviews, twelve types of expressions (sub-categories) of five types of conflicts (categories) between shared decision-making and CSMR emerged. Most health professionals agreed in principle that women have the right to decide over their own body, but did not believe this included the right to choose surgery without medical indications (patient autonomy). The health professionals also expressed that they had to consider not only the woman's current preferences and health but also her future health, which could be negatively impacted by a CSMR (treatment quality and patient safety). Furthermore, the health professionals did not consider costs in the individual decision, but thought CSMR might lead to crowding-out effects (avoiding treatments that harm others). Although the health professionals emphasised that every CSMR request was addressed individually, they referred to different strategies for avoiding arbitrariness (equality and non-discrimination). Lastly, they described that CSMR entailed a multifaceted decision being individual yet collective, and the use of birth contracts in order to increase a woman's sense of security (an uncomplicated decision-making process).
CONCLUSIONS
The complex landscape for handling CSMR in Sweden, arising from a restrictive approach centred on collective and standardised solutions alongside a simultaneous shift towards person-centred care and individual decision-making, was evident in the health professionals' reasoning. Although most health professionals emphasised that the mode of delivery is ultimately a professional decision, they still strived towards shared decision-making through information and support. Given the different views on CSMR, it is of utmost importance for healthcare professionals and women to reach a consensus on how to address this issue and to discuss what patient autonomy and shared decision-making mean in this specific context.
Topics: Humans; Female; Patient-Centered Care; Sweden; Qualitative Research; Pregnancy; Decision Making, Shared; Cesarean Section; Patient Preference; Attitude of Health Personnel; Patient Participation; Adult; Decision Making
PubMed: 38956635
DOI: 10.1186/s12978-024-01831-z -
Trials Jul 2024Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and at present, India has the highest burden of acute coronary syndrome and ST-elevation...
Improving medication adherence among persons with cardiovascular disease through m-health and community health worker-led interventions in Kerala; protocol for a type II effectiveness-implementation research-(SHRADDHA-ENDIRA).
BACKGROUND
Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and at present, India has the highest burden of acute coronary syndrome and ST-elevation myocardial infarction (MI). A key reason for poor outcomes is non-adherence to medication.
METHODS
The intervention is a 2 × 2 factorial design trial applying two interventions individually and in combination with 1:1 allocation ratio: (i) ASHA-led medication adherence initiative comprising of home visits and (ii) m-health intervention using reminders and self-reporting of medication use. This design will lead to four potential experimental conditions: (i) ASHA-led intervention, (ii) m-health intervention, (iii) ASHA and m-health intervention combination, (iv) standard of care. The cluster randomized trial has been chosen as it randomizes communities instead of individuals, avoiding contamination between participants. Subcenters are a natural subset of the health system, and they will be considered as the cluster/unit. The factorial cluster randomized controlled trial (cRCT) will also incorporate a nested health economic evaluation to assess the cost-effectiveness and return on investment (ROI) of the interventions on medication adherence among patients with CVDs. The sample size has been calculated to be 393 individuals per arm with 4-5 subcenters in each arm. A process evaluation to understand the effect of the intervention in terms of acceptability, adoption (uptake), appropriateness, costs, feasibility, fidelity, penetration (integration of a practice within a specific setting), and sustainability will be done.
DISCUSSION
The effect of different types of intervention alone and in combination will be assessed using a cluster randomized design involving 18 subcenter areas. The trial will explore local knowledge and perceptions and empower people by shifting the onus onto themselves for their medication adherence. The proposal is aligned to the WHO-NCD aims of improving the availability of the affordable basic technologies and essential medicines, training the health workforce and strengthening the capacity of at the primary care level, to address the control of NCDs. The proposal also helps expand the use of digital technologies to increase health service access and efficacy for NCD treatment and may help reduce cost of treatment.
TRIAL REGISTRATION
The trial has been registered with the Clinical Trial Registry of India (CTRI), reference number CTRI/2023/10/059095.
Topics: Humans; Medication Adherence; India; Community Health Workers; Cardiovascular Diseases; Randomized Controlled Trials as Topic; Cost-Benefit Analysis; Reminder Systems; Telemedicine; House Calls; Implementation Science; Treatment Outcome; Cardiovascular Agents; Multicenter Studies as Topic
PubMed: 38956612
DOI: 10.1186/s13063-024-08244-0 -
Journal of Eating Disorders Jul 2024Patients with avoidant/restrictive food intake disorder (ARFID) commonly present with loss of weight or faltering growth in the setting of poor nutrition. However,...
BACKGROUND
Patients with avoidant/restrictive food intake disorder (ARFID) commonly present with loss of weight or faltering growth in the setting of poor nutrition. However, patients with ARFID can present with micronutrient deficiencies without weight loss. In patients with ARFID, clinicians should be vigilant for micronutrient deficiencies and their presentations.
CASE PRESENTATION
We report a unique case of ARFID in a twelve-year-old girl, who developed micronutrient deficiencies and presented with acute visual loss with a preceding history of impaired night vision. Ophthalmic examination revealed xerophthalmia and bilateral optic neuropathy. Investigations showed severe Vitamin A and folate deficiencies which accounted for her clinical findings. In addition, she was also found to have low Vitamin B12, copper, and Vitamin D levels. She had a history of selective eating from a young age with a diet consisting largely of carbohydrates, with no regular intake of meat, dairy, fruit and vegetables. This was not driven by weight or body image concerns. The patient's symptoms improved significantly with appropriate vitamin replacement and continued multidisciplinary care.
CONCLUSIONS
This report describes a patient with ARFID presenting with visual complaints. In this case, the selective eating behaviours resulted in xeropthalmia and optic neuropathy. Micronutrient deficiencies are uncommon in developed countries. When these deficiencies are suspected, eating disorders, such as ARFID, should be considered. Similarly, clinicians caring for patients with restrictive eating disorders including ARFID should be familiar with the clinical presentations of various micronutrient deficiencies and consider evaluation and treatment for micronutrient deficiencies when clinically indicated.
PubMed: 38956602
DOI: 10.1186/s40337-024-01042-8 -
International Breastfeeding Journal Jul 2024Limited research has explored the associations of gestational age (GA) and breastfeeding practices with growth and nutrition in term infants.
BACKGROUND
Limited research has explored the associations of gestational age (GA) and breastfeeding practices with growth and nutrition in term infants.
METHODS
This multicenter cross-sectional study recruited 7299 singleton term infants from well-child visits in Shandong, China, between March 2021 and November 2022. Data on GA, gender, ethnicity, birth weight, parental heights, gestational diabetes and hypertension, age at visit, breastfeeding practices (point-in-time data at visit for infants < 6 months and retrospective data at 6 months for infants ≥ 6 months), complementary foods introduction, infant length and weight, were collected. 7270 infants were included in the analysis after excluding outliers with Z-scores of length (LAZ), weight or weight for length (WLZ) <-4 or > 4. Linear regression models adjused for covariates explored the impact of GA and breastfeeding practices on LAZ and WLZ, while logistic regression models evaluated their effect on the likelihood of moderate and severe stunting (MSS, LAZ<-2), moderate and severe acute malnutrition (MSAM, WLZ<-2) and overweight/obesity (WLZ > 2). Sensitivity analysis was conducted on normal birth weight infants (2.5-4.0 kg).
RESULTS
Infants born early-term and exclusively breastfed accounted for 31.1% and 66.4% of the sample, respectively. Early-term birth related to higher WLZ (< 6 months: β = 0.23, 95% confidence interval (CI): 0.16, 0.29; ≥6 months: β = 0.12, 95% CI: 0.04, 0.20) and an increased risk of overweight/obesity throughout infancy (< 6 months: OR: 1.41, 95% CI 1.08, 1.84; ≥6 months: OR: 1.35, 95% CI 1.03, 1.79). Before 6 months, early-term birth correlated with lower LAZ (β=-0.16, 95% CI: -0.21, -0.11) and an increased risk of MSS (OR: 1.01, 95%CI 1.00, 1.02); Compared to exclusive breastfeeding, exclusive formula-feeding and mixed feeding linked to lower WLZ (β=-0.15, 95%CI -0.30, 0.00 and β=-0.12, 95%CI -0.19, -0.05, respectively) and increased risks of MSAM (OR: 5.57, 95%CI 1.95, 15.88 and OR: 3.19, 95%CI 1.64, 6.19, respectively). Sensitivity analyses confirmed these findings.
CONCLUSIONS
The findings emphasize the health risks of early-term birth and the protective effect of exclusive breastfeeding in singleton term infants, underscoring the avoidance of nonmedically indicated delivery before 39 weeks and promoting exclusive breastfeeding before 6 months.
Topics: Humans; Breast Feeding; Cross-Sectional Studies; Female; Male; Infant, Newborn; Infant; China; Gestational Age; Infant Nutritional Physiological Phenomena; Term Birth; Retrospective Studies; Adult; Nutritional Status
PubMed: 38956574
DOI: 10.1186/s13006-024-00653-w -
BMC Medical Imaging Jul 2024The detection and management of intracranial aneurysms (IAs) are vital to prevent life-threatening complications like subarachnoid hemorrhage (SAH). Artificial...
BACKGROUND
The detection and management of intracranial aneurysms (IAs) are vital to prevent life-threatening complications like subarachnoid hemorrhage (SAH). Artificial Intelligence (AI) can analyze medical images, like CTA or MRA, spotting nuances possibly overlooked by humans. Early detection facilitates timely interventions and improved outcomes. Moreover, AI algorithms offer quantitative data on aneurysm attributes, aiding in long-term monitoring and assessing rupture risks.
METHODS
We screened four databases (PubMed, Web of Science, IEEE and Scopus) for studies using artificial intelligence algorithms to identify IA. Based on algorithmic methodologies, we categorized them into classification, segmentation, detection and combined, and then their merits and shortcomings are compared. Subsequently, we elucidate potential challenges that contemporary algorithms might encounter within real-world clinical diagnostic contexts. Then we outline prospective research trajectories and underscore key concerns in this evolving field.
RESULTS
Forty-seven studies of IA recognition based on AI were included based on search and screening criteria. The retrospective results represent that current studies can identify IA in different modal images and predict their risk of rupture and blockage. In clinical diagnosis, AI can effectively improve the diagnostic accuracy of IA and reduce missed detection and false positives.
CONCLUSIONS
The AI algorithm can detect unobtrusive IA more accurately in communicating arteries and cavernous sinus arteries to avoid further expansion. In addition, analyzing aneurysm rupture and blockage before and after surgery can help doctors plan treatment and reduce the uncertainties in the treatment process.
Topics: Intracranial Aneurysm; Humans; Artificial Intelligence; Algorithms; Magnetic Resonance Angiography
PubMed: 38956538
DOI: 10.1186/s12880-024-01347-9 -
European Journal of Human Genetics :... Jul 2024The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate pharmacogenetics implementation in clinical practice by developing evidence-based guidelines to...
The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate pharmacogenetics implementation in clinical practice by developing evidence-based guidelines to optimize pharmacotherapy based on pharmacogenetic test results. The current guideline describes the gene-drug interaction between CYP2D6 and venlafaxine, mirtazapine and duloxetine. In addition, the interaction between CYP2C19 and mirtazapine and moclobemide is presented. The DPWG identified a gene-drug interaction that requires therapy adjustment for CYP2D6 and venlafaxine. However, as the side effects do not appear to be related to plasma concentrations, it is not possible to offer a substantiated advice for dose reduction. Therefore, the DPWG recommends avoiding venlafaxine for CYP2D6 poor and intermediate metabolisers. Instead, an alternative antidepressant, which is not, or to a lesser extent, metabolized by CYP2D6 is recommended. When it is not possible to avoid venlafaxine and side effects occur, it is recommended to reduce the dose and monitor the effect and side effects or plasma concentrations. No action is required for ultra-rapid metabolisers as kinetic effects are minimal and no clinical effect has been demonstrated. In addition, a gene-drug interaction was identified for CYP2D6 and mirtazapine and CYP2C19 and moclobemide, but no therapy adjustment is required as no effect regarding effectiveness or side effects has been demonstrated for these gene-drug interactions. Finally, no gene-drug interaction and need for therapy adjustment between CYP2C19 and mirtazapine and CYP2D6 and duloxetine were identified. The DPWG classifies CYP2D6 genotyping as being "potentially beneficial" for venlafaxine, indicating that genotyping prior to treatment can be considered on an individual patient basis.
PubMed: 38956296
DOI: 10.1038/s41431-024-01648-1 -
Scientific Reports Jul 2024As the node positioning of underwater wireless sensor networks is easily affected by tidal motion, ocean current motion and multipath effect, the node positioning...
As the node positioning of underwater wireless sensor networks is easily affected by tidal motion, ocean current motion and multipath effect, the node positioning accuracy is low. In order to better improve the positioning accuracy of moving nodes of underwater wireless sensor networks, a method of locating mobile nodes of underwater wireless sensor based on tidal motion model is proposed. Firstly, the Time Difference of Arrival (TDOA) localization optimized by niche genetic algorithm is used to initialize each node. The integration of niche technology can effectively find multiple excellent solutions in the solution space, thus providing more abundant solution choices. This algorithm has excellent performance in multi-modal optimization problems, and can avoid the algorithm falling into local optimal solutions, so as to obtain more comprehensive optimization results. The simulation results show that the proposed algorithm has better positioning accuracy than the traditional Chan algorithm and Taylor algorithm. Then, each node is updated in real time by the optimized tidal movement model formula predicted by Kalman filter algorithm. The prediction algorithm is used to compare the real-time predicted update position of the node with the actual position. The positioning distance error of the prediction algorithm is also enough to meet the practical application requirements.
PubMed: 38956263
DOI: 10.1038/s41598-024-65201-2 -
Scientific Reports Jul 2024The design and radiosynthesis of [F]NT376, a high potency inhibitor of class-IIa histone deacetylases (HDAC) is reported. We utilized a three-step radiochemical approach...
The design and radiosynthesis of [F]NT376, a high potency inhibitor of class-IIa histone deacetylases (HDAC) is reported. We utilized a three-step radiochemical approach that led to the radiosynthesis of [F]NT376 in a good radiochemical yield, (17.0 ± 3%, decay corrected), high radiochemical purity (> 97%) and relatively high molar activity of 185.0 GBq/µmol (> 5.0 Ci/µmol). The repositioning of the F-radiolabel into a phenyl ring (F-Fluoro-aryl) of the class-IIa HDAC inhibitor avoided the shortcomings of the direct radiolabeling of the 5-trifluoromethyl-1,2,4-oxadiazole moiety that was reported by us previously and was associated with low molar activity (0.74-1.51 GBq/µmol, 20-41 mCi/µmol). This radiochemical approach could find a wider application for radiolabeling similar molecules with good radiochemical yield and high molar activity.
Topics: Histone Deacetylase Inhibitors; Fluorine Radioisotopes; Radiopharmaceuticals; Drug Design; Humans; Radiochemistry; Oxadiazoles
PubMed: 38956204
DOI: 10.1038/s41598-024-65668-z