Primary left ventricular leiomyosarcoma: a case report.

Cardiac leiomyosarcomas are a rare subset of the already infrequent, primary malignant cardiac neoplasia spectrum. The most common site for a primary leiomyosarcoma of the ventricle is on the right with fewer than five globally reported cases in the left ventricle. Most present with non-specific symptoms but attention is usually sought after the appearance of compressive symptoms or arrhythmias. We present a case of a left ventricular leiomyosarcoma in a 50-year old female patient that had a delayed diagnosis and its subsequent surgical resection and oncological management with docetaxel and gemcitabine. This case highlights the need for a high index of suspicion for cardiac masses especially if there are competing chronic diseases with similar symptomatology. Given the rare presentation of left ventricular leiomyosarcomas, case reports may provide valuable information that is otherwise unavailable.

SMRT-AgRenSeq-d in potato (Solanum tuberosum) as a method to identify candidates for the nematode resistance Gpa5.

Potato is the third most important food crop in the world. Diverse pathogens threaten sustainable crop production but can be controlled, in many cases, through the deployment of disease resistance genes belonging to the family of nucleotide-binding, leucine-rich-repeat (NLR) genes. To identify effective disease resistance genes in established varieties, we have successfully established SMRT-AgRenSeq in tetraploid potatoes and have further enhanced the methodology by including dRenSeq in an approach that we term SMR-AgRenSeq-d. The inclusion of dRenSeq enables the filtering of candidates after the association analysis by establishing a presence/absence matrix across resistant and susceptible varieties that is translated into an F1 score. Using a SMRT-RenSeq-based sequence representation of the NLRome from the cultivar Innovator, SMRT-AgRenSeq-d analyses reliably identified the late blight resistance benchmark genes Rpi-R1, Rpi-R2-like, Rpi-R3a, and Rpi-R3b in a panel of 117 varieties with variable phenotype penetrations. All benchmark genes were identified with an F1 score of 1, which indicates absolute linkage in the panel. This method also identified nine strong candidates for Gpa5 that controls the potato cyst nematode (PCN) species Globodera pallida (pathotypes Pa2/3). Assuming that NLRs are involved in controlling many types of resistances, SMRT-AgRenSeq-d can readily be applied to diverse crops and pathogen systems.

Cognitive impairment, anxiety and depression: a map of Cochrane evidence relevant to rehabilitation for people with post COVID-19 condition.

INTRODUCTION: Currently, no evidence exists on specific treatments for post COVID-19 condition (PCC). However, rehabilitation interventions that are effective for similar symptoms in other health conditions could be applied to people with PCC. With this overview of systematic reviews with mapping, we aimed to describe the Cochrane evidence on rehabilitation interventions proposed for cognitive impairment, anxiety and depression in different health conditions that can be relevant for PCC. EVIDENCE ACQUISITION: We searched the last five years' Cochrane Systematic Review (CSRs) using the terms "cognitive impairment," "depressive disorder," "anxiety disorder," their synonyms and variants, and "rehabilitation" in the Cochrane Library. We extracted and summarized the available evidence using a map. We grouped the included CSRs for health conditions and interventions, indicating the effect and the quality of evidence. EVIDENCE SYNTHESIS: We found 3596 CSRs published between 2016 and 2021, and we included 17 on cognitive impairment and 37 on anxiety and depression. For cognitive impairment, we found 7 CSRs on participants with stroke, 3 with cancer, 2 with Parkinson's disease, and one each for five other health conditions. Each intervention improved a different domain, and included exercises, cognitive and attention-specific training, and computerized cognition-based training (from very low to high-quality evidence). For anxiety and depression, we found 10 CSRs including participants with cancer, 8 with stroke, 3 with chronic obstructive pulmonary disease, and 2 or 1 each in 11 other health conditions. Exercise training, physical activity and yoga resulted effective in several pathologies (very low- to moderate-quality evidence). In specific diseases, we found effective acupuncture, animal-assisted therapy, aromatherapy, educational programs, home-based multidimensional survivorship programs, manual acupressure massage, memory rehabilitation, non-invasive brain stimulation, pulmonary rehabilitation, and telerehabilitation (very low- to moderate-quality evidence). CONCLUSIONS: These results are the first step of indirect evidence able to generate helpful hypotheses for clinical practice and future research. They served as the basis for the three recommendations on treatments for these PCC symptoms published in the current WHO Guidelines for clinical practice.

Premature Infants Have Normal Maturation of the T Cell Receptor Repertoire at Term.

Premature infants are known to have immature immune systems compared to term infants; however, the impacts of ex utero immune development are not well characterized. Our previous retrospective clinical review showed prolonged T cell lymphopenia in a subset of extremely premature infants, suggesting that they may have lasting abnormalities in their T cell compartments. We used T cell receptor (TCR) repertoire sequencing to analyze the composition of the T cell compartment in premature and term infants in our NICU. We collected twenty-eight samples from individual subjects and analyzed the number of clonotypes, repertoire diversity, CDR3 length, and V gene usage between groups based on gestational age at birth and postmenstrual age at the time of sample collection. Further, we examined the TCR repertoire in infants with severe bronchopulmonary dysplasia (BPD) and those with abnormal T cell receptor excision circle (TREC) assays. Former extremely premature infants who were corrected to term postmenstrual age had TCR repertoire diversity that was more similar to term born infants than extremely premature infants, supporting normal maturation of the repertoire. Infants with severe BPD did not appear to have increased abnormalities in repertoire diversity. Decreased TCR repertoire diversity was associated with repeatedly abnormal TREC screening, although the diversity was within the normal range for subjects without low TRECs. This study suggests that extremely premature infants demonstrate normal maturation of the T cell repertoire ex utero. Further work is needed to better characterize postnatal T cell development and function in this population.

Preliminary evaluation of dynamic glucose enhanced MRI of the human placenta during glucose tolerance test.

BACKGROUND: To investigate dynamic glucose enhanced (DGE) chemical exchange saturation transfer (CEST) MRI as a means to non-invasively image glucose transport in the human placenta. METHODS: Continuous wave (CW) CEST MRI was performed at 3.0 Tesla. The glucose contrast enhancement (GCE) was calculated based on the magnetization transfer asymmetry (MTRasym), and the DGE was calculated with the positive side of Z-spectra in reference to the first time point. The glucose CEST (GlucoCEST) was optimized using a glucose solution phantom. Glucose solution perfused ex vivo placenta tissue was used to demonstrate GlucoCEST MRI effect. The vascular density of ex vivo placental tissue was evaluated with yellow dye after MRI scans. Finally, we preliminarily demonstrated GlucoCEST MRI in five pregnant subjects who received a glucose tolerance test. For human studies, the dynamic R2* change was captured with T2*-weighted echo planar imaging (EPI). RESULTS: The GCE effect peaks at a saturation B1 field of about 2 µT, and the GlucoCEST effect increases linearly with the glucose concentration between 4-20 mM. In ex vivo tissue, the GlucoCEST MRI was sensitive to the glucose perfusate and the placenta vascular density. Although the in vivo GCE baseline was sensitive to field inhomogeneity and motion artifacts, the temporal evolution of the GlucoCEST effect showed a consistent and positive response after oral glucose tolerance drink. CONCLUSIONS: Despite the challenges of placental motion and field inhomogeneity, our study demonstrated the feasibility of DGE placenta MRI at 3.0 Tesla.

Incidence and predictors of massive bleeding in children undergoing liver transplantation: A single-center retrospective analysis.

BACKGROUND: Liver transplantation represents a major surgery involving a highly vascular organ. Reports defining the scope of bleeding in pediatric liver transplants are few. AIMS: We conducted a retrospective analysis of liver transplants performed at our pediatric tertiary care center to quantify blood loss, blood product utilization, and to determine predictors for massive intraoperative bleeding. METHODS: Pediatric patients who underwent isolated liver transplantation at Boston Children's Hospital between 2011 and 2016 were included. The amount of blood product transfused in the perioperative period and the incidence of postoperative complications were reported. Univariable and multivariable logistic regressions were used to determine predictors for massive bleeding, defined as estimated blood loss exceeding one circulating blood volume within 24 hours. RESULTS: Sixty-eight children underwent liver transplantation during the study period and were included in the analysis. Multivariable logistic regression analysis identified the following independent predictors of massive bleeding: preoperative hemoglobin level <8.5 g/dL (OR 11.09, 95% CI 1.87-65.76), INR >1.5 (OR 11.62, 95% CI 2.36-57.26), platelet count <100 109 /L (OR 7.92, 95% CI 1.46-43.05), and surgery duration >600 minutes (OR 6.97, 95% CI 0.99-48.92). CONCLUSIONS: Pediatric liver transplantation is associated with substantial blood loss and a significant blood product transfusion burden. A 43% incidence of massive bleeding is reported. Further efforts are needed to improve bleeding management in this high-risk population.

Multivariable predictors of substantial blood loss in children undergoing craniosynostosis repair: implications for risk stratification.

BACKGROUND: Operative treatment of craniosynostosis is associated with substantial blood loss, often requiring transfusion of packed red blood cells (PRBC) and coagulation products. AIMS: The aim of this prospective study was to analyze thromboelastographic (TEG) parameters and platelet fibrinogen product to determine predictors of substantial blood loss, and the need for PRBC transfusion and coagulation products. METHODS: With IRB approval, we enrolled 120 children undergoing craniosynostosis repair with a standardized anesthetic, fluid management, and TEG measurements at predefined times. Outcomes of interest were intraoperative blood loss, and need for PRBC transfusion and coagulation products. Multivariable logistic regression and receiver operating characteristic (ROC) curve analysis was applied to determine independent predictors of substantial blood loss and need for coagulation products. RESULTS: One hundred and eighteen children were included in the analysis. Forty-four required PRBC transfusion (median 26 ml·kg(-1) ; IQR: 22-42) with median blood loss of 56 ml·kg(-1) (IQR: 43-83). Factors associated with the PRBC transfusion included type of surgery, duration of surgery, and three TEG parameters, α-angle, MA, and K-time (all P < 0.001). A predictive algorithm was developed by subgroup analysis of cranial vault reconstruction (CVR) patients for substantial intraoperative blood loss (defined as ≥60 ml·kg(-1) ) and need for coagulation products with ROC-derived cut-off values: platelet fibrinogen product, <343; α-angle, <62°; MA, <55 mm; K-time, >2.1 min. The best prognostic combination included at least two of these four predictors (sensitivity 89%, specificity 90%). Multivariable regression identified MA as the only independent predictor of coagulation product administration (P < 0.001) and ROC analysis identified MA <46 mm as the optimal cut-off (sensitivity 86%, specificity 94%). CONCLUSIONS: Risk for substantial intraoperative blood loss can be assessed using TEG parameters and platelet fibrinogen product, whereas the need for coagulation products is strongly related to low MA. Patients susceptible to substantial blood loss can be risk stratified based on their TEG/platelet fibrinogen product profile.

Predictors of clinically significant postoperative events after open craniosynostosis surgery.

BACKGROUND: Craniosynostosis surgery is associated with clinically significant postoperative events requiring intensive care unit (ICU) admission. The authors investigate specific variables, which might influence the risk for these events, and thereby make recommendations regarding the need for postoperative ICU admission. METHODS: A retrospective review of 225 children undergoing open craniosynostosis repair at a single center during a 10-yr period is reported. The primary outcome measure was the incidence of predefined clinically relevant postoperative cardiorespiratory and hematological events requiring ICU admission. RESULTS: The incidences of postoperative cardiorespiratory and hematological events requiring ICU care were 14.7% (95% CI, 10.5 to 20.1%) and 29.7% (95% CI, 24.0 to 36.3%), respectively. Independent predictors of cardiorespiratory events were body weight less than 10 kg, American Society of Anesthesiologists physical status 3 or 4, intraoperative transfusion of greater than 60 ml/kg packed erythrocytes, and the occurrence of an intraoperative complication. The independent predictors of hematological events were body weight less than 10 kg, American Society of Anesthesiologists physical status 3 or 4, intraoperative transfusion of greater than 60 ml/kg packed erythrocytes, transfusion of hemostatic products (fresh-frozen plasma, platelets, and/or cryoprecipitate), and tranexamic acid not administered. CONCLUSIONS: Children undergoing craniosynostosis surgery are at increased risk for clinically significant postoperative events requiring ICU admission if they are less than 10 kg body weight, American Society of Anesthesiologists physical status 3 or 4, require intraoperative transfusion of greater than 60 ml/kg of packed erythrocytes, receive hemostatic blood products, or if they develop a significant intraoperative complication. Tranexamic acid administration was associated with fewer postoperative events. A predictive clinical algorithm for pediatric patients having major craniosynostosis surgery was developed and validated to risk stratify these patients.

Mandipropamid targets the cellulose synthase-like PiCesA3 to inhibit cell wall biosynthesis in the oomycete plant pathogen, Phytophthora infestans.

Oomycete plant pathogens cause a wide variety of economically and environmentally important plant diseases. Mandipropamid (MPD) is a carboxylic acid amide (CAA) effective against downy mildews, such as Plasmopara viticola on grapes and potato late blight caused by Phytophthora infestans. Historically, the identification of the mode of action of oomycete-specific control agents has been problematic. Here, we describe how a combination of biochemical and genetic techniques has been utilized to identify the molecular target of MPD in P. infestans. Phytophthora infestans germinating cysts treated with MPD produced swelling symptoms typical of cell wall synthesis inhibitors, and these effects were reversible after washing with H(2)O. Uptake studies with (14)C-labelled MPD showed that this oomycete control agent acts on the cell wall and does not enter the cell. Furthermore, (14)C glucose incorporation into cellulose was perturbed in the presence of MPD which, taken together, suggests that the inhibition of cellulose synthesis is the primary effect of MPD. Laboratory mutants, insensitive to MPD, were raised by ethyl methane sulphonate (EMS) mutagenesis, and gene sequence analysis of cellulose synthase genes in these mutants revealed two point mutations in the PiCesA3 gene, known to be involved in cellulose synthesis. Both mutations in the PiCesA3 gene result in a change to the same amino acid (glycine-1105) in the protein. The transformation and expression of a mutated PiCesA3 allele was carried out in a sensitive wild-type isolate to demonstrate that the mutations in PiCesA3 were responsible for the MPD insensitivity phenotype.

A novel Phytophthora infestans haustorium-specific membrane protein is required for infection of potato.

Phytophthora infestans causes late-blight, a devastating and re-emerging disease of potato crops. During the early stages of infection, P. infestans differentiates infection-specific structures such as appressoria for host epidermal cell penetration, followed by infection vesicles, and haustoria to establish a biotrophic phase of interaction. Here we report the cloning, from a suppression subtractive hybridization library, of a P. infestans gene called Pihmp1 encoding a putative glycosylated protein with four closely spaced trans-membrane helices. Pihmp1 expression is upregulated in germinating cysts and in germinating cysts with appressoria, and significantly upregulated throughout infection of potato. Transient gene silencing of Pihmp1 led to loss of pathogenicity and indicated involvement of this gene in the penetration and early infection processes of P. infestans. P. infestans transformants expressing a Pihmp1::monomeric red fluorescent protein (mRFP) fusion demonstrated that Pihmp1 was translated in germinating sporangia, germinating cysts and appressoria, accumulated in the appressorium, and was located at the haustorial membrane during infection. Furthermore, we discovered that haustorial structures are formed over a 3 h period, maturing for up to 12 h, and that their formation is initiated only at sites on the surface of intercellular hyphae where Pihmp1::mRFP is localized. We propose that Pihmp1 is an integral membrane protein that provides physical stability to the plasma membrane of P. infestans infection structures. We have provided the first evidence that the surface of oomycete haustoria possess proteins specific to these biotrophic structures, and that formation of biotrophic structures (infection vesicles and haustoria) is essential to successful host colonization by P. infestans.

Butt lengths differ by area deprivation level: a field study to explore intensive smoking.

We collected cigarette butts in a range of residential areas, to assess differences in the length of unburnt tobacco in the butts, and in proportions of roll-your-own (RYO) cigarettes. Two high, two medium, and two low deprivation areas, as classified by deciles of the New Zealand Deprivation Index, were selected for the Wellington region. Collected butts were systematically classified and measured. A mixed model of analysis, treating location clusters nested within deprivation level areas as a random effect, was used to assess differences in mean length of unburnt tobacco in the butts. A total of 6,262 cigarette butts and separate filters were collected, of which 3,509 (56.0%) were measurable manufactured cigarette butts, 1,069 were unmeasurable manufactured butts, 1,450 were RYO butts, and 236 were RYO filters. The RYO butts were not measured because of the extent of their degradation. The unburnt tobacco lengths in manufactured cigarette butts were significantly shorter in the most deprived areas, relative to the least deprived areas (p = .035). Deformed manufactured cigarette butts (i.e., that potentially were stubbed out) showed the same pattern (p = .011 between the most and least deprived areas). We found no significant difference between deprivation areas in the proportion of RYO material found. The shorter mean unburnt tobacco length in the most deprived areas is consistent with more intensive smoking among smokers in those areas. This finding is consistent with other evidence of increased price sensitivity among poorer smokers, and with basic economic theory. Further evidence on observed smoking behavior in the field is necessary to better interpret these preliminary findings.