Search Results (27)

Background: Prehabilitation is increasingly being used in patients undergoing multimodality treatment for oesophagogastric cancer (OGC). Most studies to date have been small, single-centre trials. This collaborative study sought to assess the overall impact of prehabilitation on patient outcomes following OGC surgery. Methods: Data came from four prospective prehabilitation trials conducted in the UK or Ireland in patients undergoing multimodality treatment for OGC. The studies included three randomised and one non-randomised clinical trial, each comparing a prehabilitation intervention group to controls. The prehabilitation interventions included aerobic training delivered by exercise physiologists alongside dietetic input throughout the treatment pathway. The primary outcome was survival (all-cause and disease-specific mortality). Secondary outcomes were differences in complications, cardio-respiratory fitness (changes in VO_{2 peak} and anaerobic threshold (AT)), chemotherapy completion rates, hospital length of stay, changes in body mass index, tumour regression and complication rates of anastomotic leak and pneumonia. Cox and logistic regression analysis provided hazard ratios (HR) and odds ratios (OR), respectively, with 95% confidence intervals (CI), adjusted for confounders. Results: Among 165 patients included, 88 patients were in the prehabilitation group and 77 patients were in the control group. All-cause and disease-specific mortality were not improved by prehabilitation (HR 0.67 95% CI 0.21–2.12 and HR 0.82 95% CI 0.42–1.57, respectively). The prehabilitation group experienced fewer major complications (20% vs. 36%, p = 0.034; adjusted OR of 0.54; 95%CI 0.26–1.13). There was a mitigated decline in VO_2 peak following neo-adjuvant therapy (delta prehabilitation −1.07 mL/kg/min vs. control −2.74 mL/kg/min; p = 0.035) and chemotherapy completion rates were significantly higher following prehabilitation (90% vs. 73%; p = 0.016). Hospital length of stay (10 vs. 12 days, p = 0.402) and neoadjuvant chemotherapy response (Mandard 1–3 41% vs. 35%; p = 0.494) favoured prehabilitation, albeit not statistically significantly. Conclusion: Despite some limitations in terms of heterogeneity of study methodology, this study suggests a number of meaningful clinical benefits from prehabilitation before surgery for OGC patients. Current initiatives to agree on national standards for delivering prehabilitation and the results of ongoing trials will help to further refine this important intervention and expand the evidence base to support the widespread adoption and implementation of prehabilitation programs. Full article

Surgical trauma elicits a complex inflammatory stress response, contributing to postoperative morbidity and recovery variability. This response is influenced by patient-specific factors and surgical and anesthetic techniques. To isolate the impact of anesthesia on the acute phase response, we investigated plasma proteomic changes in a uniquely homogeneous cohort of healthy, living kidney donors (n = 36; propofol = 19; sevoflurane = 17) undergoing laparoscopic donor nephrectomy. Proteomic profiling of plasma samples collected preoperatively and at 2 and 24 h postoperatively revealed 633 quantifiable proteins, of which 22 showed significant perioperative expression changes. Eight proteins exhibited over two-fold increases, primarily related to the acute phase response (CRP, SAA1, SAA2, LBP), tissue repair (FGL1, A2GL), and anti-inflammatory regulation (AACT). These changes were largely independent of anesthetic type, though SAA2 and MAN1A1 showed anesthetic-specific expression. The upregulation of these proteins implicates the activation of immune pathways involved in host defense, tissue remodeling, and inflammation resolution. Our findings provide a molecular reference for the surgical stress response in healthy individuals and highlight candidate biomarkers for predicting and managing postoperative outcomes. Understanding these pathways may support the development of strategies to mitigate surgical stress and enhance recovery, particularly in vulnerable patient populations. Full article

Human studies suggest point-of-care ultrasound (POCUS) is superior to radiographs for diagnosing rib fractures, but its efficacy in veterinary medicine remains unclear. This study aimed to compare the sensitivity and specificity of POCUS and digital radiographs for detecting rib fractures in canine cadavers, using necropsy as the reference standard. Nine canine cadavers were randomly assigned to either a fracture or control group, with fractures created surgically. Blinded evaluations were performed by an expert and novice sonographer, as well as a board-certified radiologist and a novice radiograph interpreter. Sensitivity and specificity for detecting rib fractures were 83% and 99.74% for ultrasound and 82% and 99.22% for radiographs, with no significant difference between modalities. However, the time required to identify rib fractures varied significantly, with ultrasound taking considerably longer than radiograph interpretation. The expert and novice sonographers required an average of 26 and 64 min, respectively, whereas the radiologist and novice radiograph interpreter took 3 and 10 min. These findings suggest that POCUS and radiographs provide comparable accuracy in detecting rib fractures in canine cadavers. Excluding the time required to obtain radiographs, ultrasound takes longer than radiograph interpretation to identify rib fractures. While POCUS remains a valuable diagnostic tool, its practicality in a clinical setting needs further investigation. Full article

Papillomaviruses (PVs) frequently infect humans as well as non-human species. While most PV infections are asymptomatic, PVs can also cause hyperplastic papillomas (warts) as well as pre-neoplastic and neoplastic lesions. In this review, the life cycle of PVs is discussed, along with the mechanisms by which PVs cause hyperplastic and neoplastic diseases. The humoral and cell-mediated immune responses to PVs are reviewed, giving context to the later discussion on the use of vaccines to reduce canine and feline PV-associated disease. Both dogs and cats are infected by numerous different PV types classified into multiple different PV genera. The taxonomic classification of PVs is reviewed, along with the significance of this classification. The PV-associated diseases of dogs and cats are then described. These descriptions include the clinical presentation of the disease, the causative PV types, the histological features that allow diagnosis, and, where appropriate, possible treatment options. The review is comprehensive and contains the latest information about PVs and the diseases they cause in dogs and cats. Full article

Recent progress has seen multiple Ta₂O₅ polymorphs generated by different synthesis techniques. However, discrepancies arise when these polymorphs are produced in widely varying thermodynamic conditions and characterized using different techniques. This work aimed to characterize and compare Ta₂O₅ particles formed at high and low temperatures using nanosecond pulsed laser ablation (PLA) and continuous wave (CW) laser heating of a local area of tantalum in either air or an ¹⁸O₂ atmosphere. Scanning electron microscopy (SEM) and Raman spectroscopy of the micrometer-sized particles generated by PLA were consistent with either a localized amorphous Ta₂O₅ phase or a similar, but not identical, crystalline β-Ta₂O₅ phase. The Raman spectrum of the material formed at the point of CW laser impingement was in good agreement with the previously established ceramic “H-Ta₂O₅” phase. TEM and electron diffraction analysis of these particles indicated the phase structure matched an oxygen-vacated superstructure of monoclinic H-Ta₂O₅. Further from the point of laser impingement, CW heating produced particles with a Raman spectrum that matched β-Ta₂O₅. We confirmed that the high-temperature ceramic phase characterized in previous work by Raman spectroscopy was the same monoclinic phase characterized in different work by TEM and could be produced by direct laser heating of metal in air. Full article

Background: Despite a range of available treatments, it is still sometimes challenging to treat patients with severe post-partum hemorrhage (sPPH). Objective: This study evaluated the efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 (NCT04723979), OS-2, OS-3, and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligations, arterial embolization, or hysterectomy) and safety (incidence of thromboembolic events (TE) and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa-exposed women only. Results: A total of 446 women exposed to rFVIIa and 1717 non-exposed controls were included. In the RCT, fewer rFVIIa-exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio: 0.11; 95% confidence interval: 0.03–0.35). In OS-1, more rFVIIa-exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio: 2.46; 95% confidence interval: 1.06–5.99). In OS-2, 17% (3/18) of rFVIIa-exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio: 0.33; 95% confidence interval: 0.03–1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa-exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa on the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment. Full article

Background: It is critical to understand the wide-ranging clinical and non-clinical effects of genome sequencing (GS) for parents in the NICU context. We assessed parents’ experiences with GS as a first-line diagnostic tool for infants with suspected genetic conditions in the NICU. Methods: Parents of newborns (N = 62) suspected of having a genetic condition were recruited across five hospitals in the southeast United States as part of the SouthSeq study. Semi-structured interviews (N = 78) were conducted after parents received their child’s sequencing result (positive, negative, or variants of unknown significance). Thematic analysis was performed on all interviews. Results: Key themes included that (1) GS in infancy is important for reproductive decision making, preparing for the child’s future care, ending the diagnostic odyssey, and sharing results with care providers; (2) the timing of disclosure was acceptable for most parents, although many reported the NICU environment was overwhelming; and (3) parents deny that receiving GS results during infancy exacerbated parent–infant bonding, and reported variable impact on their feelings of guilt. Conclusion: Parents reported that GS during the neonatal period was useful because it provided a “backbone” for their child’s care. Parents did not consistently endorse negative impacts like interference with parent–infant bonding. Full article

The human management of honey bees (Apis mellifera) has resulted in the widespread introduction of subspecies outside of their native ranges. One well known example of this is Apis mellifera mellifera, native to Northern Europe, which has now been significantly introgressed by the introduction of C lineage honey bees. Introgression has consequences for species in terms of future adaptive potential and long-term viability. However, estimating introgression in colony-living haplodiploid species is challenging. Previous studies have estimated introgression using individual workers, individual drones, multiple drones, and pooled workers. Here, we compare introgression estimates via three genetic approaches: SNP array, individual RAD-seq, and pooled colony RAD-seq. We also compare two statistical approaches: a maximum likelihood cluster program (ADMIXTURE) and an incomplete lineage sorting model (ABBA BABA). Overall, individual approaches resulted in lower introgression estimates than pooled colonies when using ADMIXTURE. However, the pooled colony ABBA BABA approach resulted in generally lower introgression estimates than all three ADMIXTURE estimates. These results highlight that sometimes one individual is not enough to assess colony-level introgression, and future studies that do use colony pools should not be solely dependent on clustering programs for introgression estimates. Full article

Health care workers in the U.S. are experiencing alarming rates of burnout. Furthermore, the COVID-19 pandemic has worsened this issue. Psychosocial peer-support programs that address general distress and are tailored to health care systems are needed. A Care for Caregivers (CFC) Program was developed at an American metropolitan university hospital and outpatient health care system. The CFC program trains “Peer Caregivers” and managers and has four components: the identification of colleagues in need of support; psychological first aid; linkage to resources; and the promotion of hope among colleagues experiencing demoralization. Qualitative interviews (n = 18) were conducted with Peer Caregivers and Managers participating in the initial piloting of the program. Results suggest that the CFC program shifts the organizational culture, teaches staff skills for recognizing and supporting others in distress, and supports those staff who are already providing these services informally. Findings suggest that staff distress resulted primarily from external factors and secondarily from internal organizational stressors. External stressors were exacerbated by the COVID-19 pandemic. Although the program has promise for addressing staff burnout, other organizational efforts are needed to simultaneously promote staff wellness. Ultimately, psychosocial peer support programs for health care workers are feasible and potentially impactful, but also require other systemic changes within a health care system to improve and sustain staff well-being. Full article

The conceptualisation and visualisation of physical activity through 3D-printed objects offers a unique means by which to elicit positive behaviour change. This study aimed to explore whether 3D-printed models of physical activity obtain autotopographical meaning in youths and the influence of such models on their sense of personal and social identity. Following participation in a seven-week faded intervention, whereby habitual physical activity was measured and used to create individual 3D models, the views of 61 participants (36 boys; 10.9 ± 3.0 years) were explored via semi-structured focus groups. Within the over-arching theme of ‘3D-Printed Models’, key emergent sub-themes were structured around ‘Autotopography’, ‘Reflection’, ‘In-group norms’, and ‘Significant others’. Investing meaning in the material representations facilitated social activation and self-reflection on their own behaviour, both of which are key elements of identity formation. The influential role of significant others (familial and peers) within initial model interpretation and their potential long-term efficacy as a behaviour change approach was highlighted. 3D-printed models present a novel concept and intervention approach and may represent a useful component within behaviour change engagement strategies in children and adolescents. Full article

The clinical use of genomic analysis has expanded rapidly resulting in an increased availability and utility of genomic information in clinical care. We have developed an infrastructure utilizing informatics tools and clinical processes to facilitate the use of whole genome sequencing data for population health management across the healthcare system. Our resulting framework scaled well to multiple clinical domains in both pediatric and adult care, although there were domain specific challenges that arose. Our infrastructure was complementary to existing clinical processes and well-received by care providers and patients. Informatics solutions were critical to the successful deployment and scaling of this program. Implementation of genomics at the scale of population health utilizes complicated technologies and processes that for many health systems are not supported by current information systems or in existing clinical workflows. To scale such a system requires a substantial clinical framework backed by informatics tools to facilitate the flow and management of data. Our work represents an early model that has been successful in scaling to 29 different genes with associated genetic conditions in four clinical domains. Work is ongoing to optimize informatics tools; and to identify best practices for translation to smaller healthcare systems. Full article

Chagas disease (CD) is caused by the parasite Trypanosoma cruzi and affects 6–7 million people worldwide. The diagnosis is still challenging, due to extensive parasite diversity encompassing seven genotypes (TcI-VI and Tcbat) with diverse ecoepidemiological, biological, and pathological traits. Chemotherapeutic intervention is usually effective but associated with severe adverse events. The development of safer, more effective therapies is hampered by the lack of biomarker(s) (BMKs) for the early assessment of therapeutic outcomes. The mammal-dwelling trypomastigote parasite stage expresses glycosylphosphatidylinositol-anchored mucins (tGPI-MUC), whose O-glycans are mostly branched with terminal, nonreducing α-galactopyranosyl (α-Gal) glycotopes. These are absent in humans, and thus highly immunogenic and inducers of specific CD anti-α-Gal antibodies. In search for α-Gal-based BMKs, here we describe the synthesis of neoglycoprotein NGP11b, comprised of a carrier protein decorated with the branched trisaccharide Galα(1,2)[Galα(1,6)]Galβ. By chemiluminescent immunoassay using sera/plasma from chronic CD (CCD) patients from Venezuela and Mexico and healthy controls, NGP11b exhibited sensitivity and specificity similar to that of tGPI-MUC from genotype TcI, predominant in those countries. Preliminary evaluation of CCD patients subjected to chemotherapy showed a significant reduction in anti-α-Gal antibody reactivity to NGP11b. Our data indicated that NGP11b is a potential BMK for diagnosis and treatment assessment in CCD patients. Full article

Preoperative undernutrition is a prognostic indicator for postoperative mortality and morbidity. Evidence suggests that treating undernutrition can improve surgical outcomes. This study explored the provision of nutritional screening, assessment and support on surgical cancer wards in low- and middle-income countries (LMICs). This was a qualitative study and participants took part in one focus group or one individual interview. Data were analysed thematically. There were 34 participants from Ghana, India, the Philippines and Zambia: 24 healthcare professionals (HCPs) and 10 patients. Results showed that knowledge levels and enthusiasm were high in HCPs. Barriers to adequate nutritional support were a lack of provision of ward and kitchen equipment, food and sustainable nutritional supplements. There was variation across countries towards nutritional screening and assessment which seemed to be driven by resources. Many hospitals where resources were scarce focused on the care of individual patients in favour of an integrated systems approach to identify and manage undernutrition. In conclusion, there is scope to improve the efficiency of nutritional management of surgical cancer patients in LMICs through the integration of nutrition assessment and support into routine hospital policies and procedures, moving from case management undertaken by interested personnel to a system-based approach including the whole multidisciplinary team. Full article

Two new pyrrolylquinoline-substituted heteroaromatic-containing compounds bearing a central boron bridge have been prepared by a short, high-yielding sequence consisting of Suzuki-coupling of 8-bromoquinoline and N-Boc 2-pyrroleboronic acid, thermolytic tert-butyloxycarbonyl deprotection, and subsequent boron chelation (either using boron trifluoride or triphenylborane). Both derivatives display longer wavelength absorption maxima (λ^abs_max) than a previously reported indolopyridine-BPh₂ analogue, in agreement with the smaller HOMO-LUMO energy gap predicted by DFT quantum chemical calculations. Both of the pyrrolylquinoline-boron chelates display weak emission (quantum yields 0.3–0.9%) and the BPh₂ complex displays a very broad, long-wavelength emission (λ^em_max = 715 nm, MeCN), which may be due to dimer emission and results in a large pseudo-Stokes’ shift (7753 cm⁻¹) for this compound. Full article

Clostridioides (also known as Clostridium) difficile is a Gram-positive anaerobic, spore producing bacterial pathogen that causes severe gastrointestinal infection in humans. The current chemotherapeutic options are inadequate, expensive, and limited, and thus inexpensive drug treatments for C. difficile infection (CDI) with improved efficacy and specificity are urgently needed. To improve the solubility of our cationic amphiphilic 1,1′-binaphthylpeptidomimetics developed earlier that showed promise in an in vivo murine CDI model we have synthesized related compounds with an N-arytriazole or N-naphthyltriazole moiety instead of the 1,1′-biphenyl or 1,1′-binaphthyl moiety. This modification was made to increase the polarity and thus water solubility of the overall peptidomimetics, while maintaining the aromatic character. The dicationic N-naphthyltriazole derivative 40 was identified as a C. difficile-selective antibacterial with MIC values of 8 µg/mL against C. difficile strains ATCC 700057 and 132 (both ribotype 027). This compound displayed increased water solubility and reduced hemolytic activity (32 µg/mL) in an in vitro hemolysis assay and reduced cytotoxicity (CC₅₀ 32 µg/mL against HEK293 cells) relative to lead compound 2. Compound 40 exhibited mild efficacy (with 80% survival observed after 24 h compared to the DMSO control of 40%) in an in vivo murine model of C. difficile infection by reducing the severity and slowing the onset of disease. Full article