Mathewshassan2023
We find considerable evidence for the convergent evolution of tandem duplicated exon substitution events in vertebrates, arthropods, and nematodes. Twelve human gene families have orthologues with tandem duplicated exon substitution events in both Drosophila melanogaster and Caenorhabditis elegans. Six of these gene families are ion transporters, suggesting that tandem exon duplication in genes that control the flow of ions into the cell has an adaptive benefit. The ancient origins, the strong indications of tissue-specific functions, and the evidence of convergent evolution suggest that these events may have played important roles in the evolution of animal tissues and organs.
A growing body of compelling evidence has emerged to validate a set of signs and symptoms that indicates the onset of disease before more typical signs and symptoms present to fulfill a diagnosis of MS. On 24 June 2021, a group of international researchers, patient advocates, and Society representatives led by Professors Helen Tremlett (University of British Columbia) and Ruth Ann Marrie (University of Manitoba) convened virtually for a workshop.
Identify key gaps in knowledge, opportunities, and research priorities regarding the prodromal stage of MS.
The group developed a new framework for MS that includes the stage of early signs and symptoms of MS-and outlined a roadmap to guide future research, with the "goal of preventing the progression to onset of typical symptoms of MS in those who present during the prodromal stage of MS".
If high-risk individuals in the early stages of MS can be identified with a high degree of certainty, there is an opportunity to intervene and minimize the risk of progressing to typical MS symptoms and a diagnosis of MS.
Standardized criteria must be developed, validated, and point of intervention found to better recognize, better diagnose, and better treat MS.
Standardized criteria must be developed, validated, and point of intervention found to better recognize, better diagnose, and better treat MS.
To involve health service users in health care and health research priority setting, different methods exist. Which method is most suitable under which circumstances is unknown. We compared a postal Delphi survey and an in-person workshop to involve health service users in priority settings for rehabilitative care and research in Germany.
One hundred and eighty-four former rehabilitants were randomly assigned to a postal Delphi survey (n = 152) or an in-person workshop (n = 32). Two hundred and seventy-sixemployees in rehabilitation were also invited to the Delphi Survey. The methodological comparison refers only to the sample of rehabilitants. Within each method, the participants agreed on the top 10 priorities for practice improvement and research in rehabilitative care. Ac-PHSCN-NH2 concentration The priorities were compared descriptively. Participants' satisfaction was measured with the Public and Patient Engagement Evaluation Tool. The usability of both methods was compared based on the effort, time and material costs requiredions are needed. Delphi surveys seem to be more suitable for easily understandable topics, larger sample sizes and when fewer financial resources are available.
The different study phases were supported by employees in rehabilitation and former rehabilitants (e.g., developing study documents, and interpreting results).
The different study phases were supported by employees in rehabilitation and former rehabilitants (e.g., developing study documents, and interpreting results).To assess the impact of cefuroxime injection of intracameral prophylaxis antibiotic on after endophthalmitis operative wound following surgery of cataract, we conducted a meta-analysis. A thorough review of the literature up to July 2022 revealed that there were 1 167 197 participants with surgery of cataract at the start of the research; 1 004 425 of these subjects received an injection of intracameral of cefuroxime, while 162 772 did not get an antibiotic as a control. Using dichotomous approaches and a random or fixed-effect model, odds ratios (OR) with 95% confidence intervals (CIs) were estimated to evaluate the impact of cefuroxime injection of intracameral prophylaxis antibiotic on after endophthalmitis operative wound following surgery of cataract. When comparing no antibiotic in participants who had surgery of cataract, the cefuroxime injection of intracameral significantly reduced the after endophthalmitis operative wound (OR, 0.14; 95% CI, 0.07-0.29, P = 0.001) with high heterogeneity (I2 = 95%). When comparing participants who received no antibiotic after surgery of cataract, the after endophthalmitis operative wound from the cefuroxime injection of intracameral was considerably lower. Although none of the 22 studies encompassed in the meta-analysis had a study with a small sample size, it is nevertheless advisable to proceed with caution when analysing the results.
Beta-blockers and selected stereoisomers of beta-blockers, like bisoprolol and S-pindolol (ACM-001), have been shown to be effective in preclinical cancer cachexia models. Here, we tested the efficacy of stereoisomers of oxprenolol in two preclinical models of cancer cachexia-the Yoshida AH-130 rat model and the Lewis lung carcinoma (LLC) mouse model.
In the Yoshida AH130 hepatoma rat cancer cachexia model and compared with placebo, 50mg/kg/d S-oxprenolol (HR 0.49, 95% CI 0.28-0.85, P=0.012) was superior to 50mg/kg/d R-oxprenolol (HR 0.83, 95% CI 0.38-1.45, P=0.51) in reducing mortality (=reaching ethical endpoints). Combination of the three doses (12.5, 25 and 50mg/kg/d) that had a significant effect on body weight loss in the S-oxprenolol groups vs the same combination of the R-oxprenolol groups lead to a significantly improved survival of S-oxprenolol vs R-oxprenolol (HR 1.61, 95% CI 1.08-2.39, P=0.0185). Interestingly, there is a clear dose dependency in S-oxprenolol-treated (5, 12.5, 25 and 50mg/kg/dnantiomer. Expression of glucose transporters Glut1 and Glut 4 was similar in all groups, as was AMPK.
S-oxprenolol is superior to R-oxprenolol in cancer cachexia animal models and shows promise for a human application in cancer cachexia.
S-oxprenolol is superior to R-oxprenolol in cancer cachexia animal models and shows promise for a human application in cancer cachexia.
Understanding the morphology of the distal femur is essential for improving bone-implant match in total knee arthroplasty (TKA) and understanding the mechanisms behind knee kinematics. However, little is known about the asymmetry of the posterior condyles. Thus, this study aimed to thoroughly investigate asymmetries in sizes and shapes between the medial and lateral posterior condyles before and after femoral resections during TKA in osteoarthritic (OA) knees.
Three-dimensional femoral models of 74 OA knees were constructed using computed tomography images. The morphologic measurements of the posterior condyle pre- and post-simulated osteotomy for TKA included the radii of the posterior condyles fitted to a circle on the sagittal and axial planes of the femoral coordinate system, the inclination angle of the articular surface and resected surface, and the width and height of the resected surface. Differences in the data were assessed using Student's t-test, and correlations were evaluated using the PearsoA. These findings provides valuable morphological information and may help improve the implant designs for TKA.
This study found asymmetrical inclination of the resected surface and coronal radii between the medial and lateral posterior condyles, which may relate to the posterolateral overhang of the lateral condyle after TKA and the progression of the knee OA. These findings provides valuable morphological information and may help improve the implant designs for TKA.
This multicenter phase 1b/2 trial aimed to explore the maximum tolerated dose (MTD), activity, and safety of anlotinib plus chemotherapy in patients with T790M-negative epidermal growth factor receptor (EGFR)-mutant advanced nonsquamous non-small cell lung cancer (NSCLC) after resistance to first- or second-generation EGFR tyrosine kinase inhibitors (TKIs).
In the phase 1b stage, patients received anlotinib (8/10/12 mg, days 1-14) combined with cisplatin (75 mg/m
, day 1) or carboplatin (AUC=5, day 1) plus pemetrexed (500 mg/m
, day 1) for a 3-week cycle based on a 3 + 3 dose-escalation design. In the phase 2 single-arm stage, anlotinib was administered at MTD combined with platinum plus pemetrexed for fourcycles, followed by anlotinib maintenance therapy. The primary endpoint of the phase 2 stage was progression-free survival (PFS).
The study was prematurely terminated due to slow accrual after 19 patients had been enrolled between January 18, 2019, and March 21, 2021. The MTD of anlotinib was 12 mg. The median PFS was 5.75 (95% confidence interval, 4.37-7.52) months. The objective response rate was 47.4% (95% confidence interval, 24.5%-71.1%). In the 12 mg group, seven (58.3%) patients experienced grade 3-4 treatment-related adverse events, and the most common ones were hypertension (6 [50.0%]), decreased platelet count (2 [16.7%]), and hypertriglyceridemia (1 [8.3%]). No treatment-related deaths occurred.
Anlotinib plus platinum and pemetrexed showed promising antitumor activity with manageable toxicity in patients with T790M-negative EGFR-mutant advanced nonsquamous NSCLC after progression on first- or second-generation EGFR TKIs.
Anlotinib plus platinum and pemetrexed showed promising antitumor activity with manageable toxicity in patients with T790M-negative EGFR-mutant advanced nonsquamous NSCLC after progression on first- or second-generation EGFR TKIs.Co-infected hosts, individuals that carry more than one infectious agent at any one time, have been suggested to facilitate pathogen transmission, including the emergence of supershedding events. However, how the host immune response mediates the interactions between co-infecting pathogens and how these affect the dynamics of shedding remains largely unclear. We used laboratory experiments and a modeling approach to examine temporal changes in the shedding of the respiratory bacterium Bordetella bronchiseptica in rabbits with one or two gastrointestinal helminth species. Experimental data showed that rabbits co-infected with one or both helminths shed significantly more B. bronchiseptica, by direct contact with an agar petri dish, than rabbits with bacteria alone. Co-infected hosts generated supershedding events of higher intensity and more frequently than hosts with no helminths. To explain this variation in shedding an infection-immune model was developed and fitted to rabbits of each group. Simulations suggested that differences in the magnitude and duration of shedding could be explained by the effect of the two helminths on the relative contribution of neutrophils and specific IgA and IgG to B. bronchiseptica neutralization in the respiratory tract. However, the interactions between infection and immune response at the scale of analysis that we used could not capture the rapid variation in the intensity of shedding of every rabbit. We suggest that fast and local changes at the level of respiratory tissue probably played a more important role. This study indicates that co-infected hosts are important source of variation in shedding, and provides a quantitative explanation into the role of helminths to the dynamics of respiratory bacterial infections.
