Placental abnormalities have been sporadically implicated as a source of developmental heart defects. Yet it remains unknown how often the placenta is at the root of congenital heart defects (CHDs), ...and what the cellular mechanisms are that underpin this connection. Here, we selected three mouse mutant lines, Atp11a, Smg9 and Ssr2, that presented with placental and heart defects in a recent phenotyping screen, resulting in embryonic lethality. To dissect phenotype causality, we generated embryo- and trophoblast-specific conditional knockouts for each of these lines. This was facilitated by the establishment of a new transgenic mouse, Sox2-Flp, that enables the efficient generation of trophoblast-specific conditional knockouts. We demonstrate a strictly trophoblast-driven cause of the CHD and embryonic lethality in one of the three lines (Atp11a) and a significant contribution of the placenta to the embryonic phenotypes in another line (Smg9). Importantly, our data reveal defects in the maternal blood-facing syncytiotrophoblast layer as a shared pathology in placentally induced CHD models. This study highlights the placenta as a significant source of developmental heart disorders, insights that will transform our understanding of the vast number of unexplained congenital heart defects.
To evaluate the clinical outcomes pre- and post-implementation of an evidence-informed surgical site infection prevention bundle (SSIPB) in gynecologic oncology patients within an Enhanced Recovery ...After Surgery (ERAS) care pathway.
Patients undergoing laparotomy for a gynecologic oncology surgery between January–June 2017 (pre-SSIPB) and between January 2018–December 2020 (post-SSIPB) were compared using t-tests and chi-square. Patient characteristics, surgical factors, and ERAS process measures and outcomes were abstracted from the ERAS® Interactive Audit System (EIAS). The primary outcomes were incidence of surgical site infections (SSI) during post-operative hospital admission and at 30-days post-surgery. Secondary outcomes included total postoperative infections, length of stay, and any surgical complications. Multivariate models were used to adjust for potential confounding factors.
Patient and surgical characteristics were similar in the pre- and post-implementation periods. Evaluation of implementation suggested that preoperative and intraoperative components of the intervention were most consistently used. Infectious complications within 30 days of surgery decreased from 42.1% to 24.4% after implementation of the SSIPB (p < 0.001), including reductions in wound infections (17.0% to 10.8%, p = 0.02), urinary tract infections (UTI) (12.7% to 4.5%, p < 0.001), and intra-abdominal abscesses (5.4% to 2.5%, p = 0.05). These reductions were associated with a decrease in median length of stay from 3 to 2 days (p = 0.001). In multivariate analysis, these SSI reductions remained statistically significant after adjustment for potential confounders.
Implementation of SSIPB was associated with a reduction in SSIs and infectious complications, as well as a shorter length of stay in gynecologic oncology patients.
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•A Surgical Site Infection Prevention Bundle (SSIBP) requires coordination between healthcare providers.•Evaluating the implementation of a SSIBP in gynecologic oncology patients is challenging.•SSIPB Implementation is associated with improved surgical outcomes: shorter length of stay and fewer infections.
Background:
Patenting medicine-delivery devices (inhalers and pens) is controversial when it extends market protections beyond that of the underlying therapeutic agent. We evaluated how common device ...patenting is, internationally.
Method:
Using a product sample (n = 88) and an international patent database, we assessed the issue's scope.
Results:
When comparing the 88 patent portfolios for each product in each country, Canada was found to be among the most impacted, with 90% of the portfolios containing at least one device patent and 35% of the portfolios containing device patents exclusively.
Conclusion:
Patenting of delivery devices impacts major pharmaceutical manufacturing centres worldwide. International consensus among stakeholders (regulators and payors) is needed on which device modifications represent meaningful clinical value.
In order to establish a functional role for late embryogenesis abundant (LEA) proteins in response to stress conditions in
Caenorhabditis elegans, we silenced the expression of an
LEA (
Ce-lea-1) ...gene and determined the survival of worms under stress conditions.
Ce-lea-1 transcription was induced during dehydration of
C. elegans dauer juveniles. Following partial silencing of
Ce-lea-1 transcription, we demonstrated a specific and significant reduction in worm survival during induction of desiccation, osmotic and heat stress. Together, these results establish a functional role for
Ce-lea-1 in stress survival of
C. elegans and suggest that
Ce-lea-1 may function as a component that is common to the responses to the examined stress conditions.
Melody-based treatments for patients with aphasia rely on the notion of preserved musical abilities in the RH, following left hemisphere damage. However, despite evidence for their effectiveness, the ...role of the RH is still an open question. We measured changes in resting-state functional connectivity following melody-based intervention, to identify lateralization of treatment-related changes. A patient with aphasia due to left frontal and temporal hemorrhages following traumatic brain injuries (TBI) more than three years earlier received 48 sessions of melody-based intervention. Behavioral measures improved and were maintained at the 8-week posttreatment follow-up. Resting-state fMRI data collected before and after treatment showed an increase in connectivity between motor speech control areas (bilateral supplementary motor areas and insulae) and RH language areas (inferior frontal gyrus pars triangularis and pars opercularis). This change, which was specific for the RH, was greater than changes in a baseline interval measured before treatment. No changes in RH connectivity were found in a matched control TBI patient scanned at the same intervals. These results are compatible with a compensatory role for RH language areas following melody-based intervention. They further suggest that this therapy intervenes at the level of the interface between language areas and speech motor control areas necessary for language production.
To determine the characteristic features and outcome of pulmonary carcinoid tumors in Israel.
Retrospective analysis of the clinicopathologic data and outcome of patients from four major hospitals in ...Israel in the last 20 years.
There were 142 cases of pulmonary carcinoid tumors: typical (n = 128) and atypical (n = 14). We calculated an annual incidence of about 2.3 to 2.8 cases per 1 million population. The ratio of female to male patients was 1.6:1. The prevalence of smoking was similar to the general population in patients with typical carcinoids and twice as high in the atypical group. Bronchial obstruction was the cause of most of the presenting symptoms and signs and included obstructive pneumonitis, pleuritic pain, atelectasis, and dyspnea (41%). Carcinoid syndrome was extremely rare and occurred in only one patient with metastatic disease. Most of the tumors (68%) arose in the major bronchi. Diagnosis was made using fiberoptic bronchoscopy in 52% of patients without evidence of endobronchial hemorrhage. Nodal involvement and distant metastases occurred in 57% and 21%, respectively, in the atypical group, and 10% and 3%, respectively, in the typical group. The treatment of choice was surgical: lobectomy (56%) or pneumonectomy (16%). The respective 5-year survival rates for patients with typical and atypical tumors were 89% and 75% (not significant), and the 10-year survival rates were 82% and 56% (p < 0.05). A review of large series from the literature is presented.
Pulmonary carcinoid is an uncommon tumor in the Israeli population. With early diagnosis and aggressive surgical therapy, long-term prognosis is excellent.
The developmentally arrested life stage of the entomopathogenic nematode Steinernema feltiae is exposed to threats of survival, including desiccation. We adopted a comprehensive approach to the study ...of the molecular mechanisms of desiccation stress tolerance in S. feltiae IS-6. We identified, expressed sequence tags (ESTs) that are differentially expressed during desiccation stress in S. feltiae IS-6 infective juveniles using DNA subtractive hybridization. These ESTs included genes that are known to be stress related, genes that are homologous to hypothetical Caenorhabditis elegans proteins, and novel genes that may be involved in traits specific to S. feltiae. Expression pattern characterization revealed that all analyzed ESTs were induced during 8 and 24 hr of dehydration of S. feltiae IS-6. Our results unveiled some of the components of the genetic networks that are activated in S. feltiae IS-6 during dehydration and suggested a differing pattern of temporal regulation during nematode dehydration.
Nematodes are among the most successful organisms in withstanding stress conditions associated with water loss, and viable individuals have been recovered from dry desert soils. Little is known about ...the biochemical and molecular events underpinning nematodes’ physiological responses to dehydration. Post-genomics research in
Caenorhabditis elegans may offer an opportunity to understand the stress response better. This review focuses on recent progress in understanding the molecular mechanisms of water-loss associated stress response in the model nematode
C. elegans and in parasitic nematodes and discusses the scope for applying the knowledge and tools derived from a model organism for the study of wild, environmentally-adapted, parasitic nematodes, in the light of the emergence of genomics research of non-model organisms.
The ability to withstand desiccation by entering anhydrobiosis is important for the survival of many nematode species. We are interested in the metabolic changes that occur during dehydration in the ...semiarid strain IS-6 of the insect parasitic nematode Steinernema feltiae. These changes may enable IS6 to be more tolerant to desiccation than temperate strains. We identified genes of IS-6 that exhibit changes in transcript levels during dehydration. These included glycogen synthase (Sf-gsy-1), which is the rate-limiting enzyme in the synthesis of glycogen, which is likely to play a role in desiccation survival. We established the changes in the steady state level of Sf-gsy-1 transcripts upon dehydration and determined the biochemical changes in the level of its product, glycogen, during the dehydration and rehydration of nematodes. Our results suggest a shift from glycogen to trehalose synthesis during dehydration, which is regulated at least in part by suppression of glycogen synthase transcription.
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