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Duchenne muscular dystrophy is a devastating neuromuscular disorder characterized by the loss of dystrophin, inevitably leading to cardiomyopathy. Despite publications on prophylaxis and treatment with cardiac medications to mitigate cardiomyopathy progression, gaps remain in the specifics of medication initiation and optimization.
Method:
This document is an expert opinion statement, addressing a critical gap in cardiac care for Duchenne muscular dystrophy. It provides thorough recommendations for the initiation and titration of cardiac medications based on disease progression and patient response. Recommendations are derived from the expertise of the Advance Cardiac Therapies Improving Outcomes Network and are informed by established guidelines from the American Heart Association, American College of Cardiology, and Duchenne Muscular Dystrophy Care Considerations. These expert-derived recommendations aim to navigate the complexities of Duchenne muscular dystrophy-related cardiac care.
Results:
Comprehensive recommendations for initiation, titration, and optimization of critical cardiac medications are provided to address Duchenne muscular dystrophy-associated cardiomyopathy.
Discussion:
The management of Duchenne muscular dystrophy requires a multidisciplinary approach. However, the diversity of healthcare providers involved in Duchenne muscular dystrophy can result in variations in cardiac care, complicating treatment standardization and patient outcomes. The aim of this report is to provide a roadmap for managing Duchenne muscular dystrophy-associated cardiomyopathy, by elucidating timing and dosage nuances crucial for optimal therapeutic efficacy, ultimately improving cardiac outcomes, and improving the quality of life for individuals with Duchenne muscular dystrophy.
Conclusion:
This document seeks to establish a standardized framework for cardiac care in Duchenne muscular dystrophy, aiming to improve cardiac prognosis.
Patients with Fontan failure are high-risk candidates for heart transplantation and other advanced therapies. Understanding the outcomes following initial heart failure consultation can help define appropriate timing of referral for advanced heart failure care.
Methods:
This is a survey study of heart failure providers seeing any Fontan patient for initial heart failure care. Part 1 of the survey captured data on clinical characteristics at the time of heart failure consultation, and Part 2, completed 30 days later, captured outcomes (death, transplant evaluation outcome, and other interventions). Patients were classified as “too late” (death or declined for transplant due to being too sick) and/or “care escalation” (ventricular assist device implanted, inotrope initiated, and/or listed for transplant), within 30 days. “Late referral” was defined as those referred too late and/or had care escalation.
Results:
Between 7/2020 and 7/2022, 77 Fontan patients (52% inpatient) had an initial heart failure consultation. Ten per cent were referred too late (6 were too sick for heart transplantation with one subsequent death, and two others died without heart transplantation evaluation, within 30 days), and 36% had care escalation (21 listed ± 5 ventricular assist device implanted ± 6 inotrope initiated). Overall, 42% were late referrals. Heart failure consultation < 1 year after Fontan surgery was strongly associated with late referral (OR 6.2, 95% CI 1.8–21.5, p=0.004).
Conclusions:
Over 40% of Fontan patients seen for an initial heart failure consultation were late referrals, with 10% dying or being declined for transplant within a month of consultation. Earlier referral, particularly for those with heart failure soon after Fontan surgery, should be encouraged.
We conducted a scientific survey of paediatric practitioners who manage heart failure with dilated cardiomyopathy in children. The survey covered management from diagnosis to treatment to monitoring, totalling 63 questions. There were 54 respondents from 40 institutions and 3 countries. There were diverse selections of management options by the respondents in general, but also unanimity in some management options. Variation in practice is likely due to the relative paucity of scientific data in this field and lack of strong evidence-based recommendations from guidelines, which presents an opportunity for future research and quality improvement efforts as the evidence base continues to grow.
Occurrence of drought under rainfed conditions is the foremost factor responsible for yield reduction in soybean. Developing soybean cultivars with an inherent ability to withstand drought would immensely benefit the soybean production in rainfed areas. In the present study, F2 derived mapping populations were developed by crossing drought tolerant (PK 1180, SL 46) and susceptible (UPSL 298, PK 1169) genotypes to investigate the inheritance of seedling survival drought mechanisms and to identify simple-sequence repeat (SSR) markers associated with them, using bulked segregant analysis. Parents as well as a F2 derived mapping population were screened for drought tolerance based on seedling survivability under controlled conditions. Segregation analysis of F2 population derived from a cross between PK 1180 × UPSL 298 was previously shown to have a 3:1 tolerant to susceptible ratio and a probability of 0.61 at a χ2(3:1) value of 0.258. This was confirmed in another F2 population derived from a cross between PK 1169 × SL 46 with a χ2(3:1) value of 0.145 obtained at a probability of 0.70. One SSR marker Satt277 showed polymorphism between contracting bulks (tolerant and susceptible) out of 50 polymorphic markers identified during parental polymorphism. Single marker analysis suggested that the marker, Satt277 is linked to seedling survival drought tolerance and is located on chromosome linkage group C2 (chr 6) with a map distance of 3.40 cM. The tolerant genotypes identified could be used as a donor in soybean improvement programs. The marker identified can be used in marker-assisted selection while screening large collection of germplasm.
Terminal heat stress leads to sizeable yield loss in late-sown wheat in tropical environments. Several synthetic compounds are known to counteract plant stress emanating from abiotic factors. A field experiment was conducted in Sabour (eastern India) during 2013–2016 to investigate the field efficacy of two synthetic compounds, calcium chloride (CaCl2) and arginine, for improving grain yield of two contrasting wheat cultivars (DBW 14 and K 307) facing terminal heat stress. For this, foliar spray of 18.0 mM CaCl2 at booting (CCB) or anthesis (CCA), 9.0 mM CaCl2 at both booting and anthesis (CCB+A), 2.5 mM arginine at booting (ARGB) or anthesis (ARGA) and 1.25 mM arginine at both booting and anthesis (ARGB+A) treatments along with no-spray and water-spray treatments were evaluated in late-sown wheat. The highest grain yield was recorded in treatment CCB+A, followed by CCA and ARGB+A. However, the effect of these compounds was marginal on grain yield when applied only at the booting stage. Grains/ear and thousand-grain weight were found to be the critical determinants for yield in late-sown wheat. During the anthesis to grain filling period, flag-leaf chlorophyll degradation and increase in relative permeability in no-spray treatment were 34–36% and 29–52%, respectively, but these values were reduced considerably in CCB+A treatment followed CCA. Thus, foliar spray of 9.0 mM CaCl2 both at booting and anthesis stages may be recommended for alleviating the negative impacts of terminal heat stress in late-sown wheat and improving its productivity (>13%).
Salmonellosis is a leading cause of hospitalisation due to gastroenteritis in Australia. A previous source attribution analysis for a temperate state in Australia attributed most infections to chicken meat or eggs. Queensland is in northern Australia and includes subtropical and tropical climate zones. We analysed Queensland notifications for salmonellosis and conducted source attribution to compare reservoir sources with those in southern Australia. In contrast to temperate Australia, most infections were due to non-Typhimurium serotypes, with particularly high incidence in children under 5 years and strong seasonality, peaking in summer. We attributed 65.3% (95% credible interval (CrI) 60.6–73.2) of cases to either chicken meat or eggs and 15.5% (95% CrI 7.0–19.5) to nuts. The subtypes with the strongest associations with nuts were Salmonella Aberdeen, S. Birkenhead, S. Hvittingfoss, S. Potsdam and S. Waycross. All five subtypes had high rates of illness in children under 5 years (ranging from 4/100 000 to 23/100 000), suggesting that nuts may be serving as a proxy for environmental transmission in the model. Australia's climatic range allows us to conduct source attribution in different climate zones with similar food consumption patterns. This attribution provides evidence for environment-mediated transmission of salmonellosis in sub-tropical regions.
The staurolite-bearing schists of the area were metamorphosed in the staurolite-kyanite zone of the amphibolite facies. The various assemblages of the pelitic schists are represented in the AKF and Thompson's AFM diagrams. Within the PT conditions of stability of staurolite, this mineral develops in pelitic schists that have a high Al2O3 (excess)/(K2O+FeO+MgO) ratio so that the plots of analyses lie above the muscovite-garnet join in the AKF diagram. The three-phase field of staurolite-kyanite-biotite in the AFM diagram migrates towards the lower FeO/MgO side with increasing oxidation ratio and thus staurolite-bearing rocks are not necessarily restricted to pelitic schists with high FeO/MgO ratio as is commonly believed. On the other hand, the three-phase field shifts towards the higher FeO/MgO side with increasing grade of metamorphism assuming oxidation ratio and pressure to be constant, thus reducing the composition field of staurolite schists in the AFM diagram.
Cordierite commonly alters to chlorite-sericite, called pinite. Besides pinite alteration, cordierite from the Fishtail Lake shows textural evidence indicating retrogression to kyanite, andalusite, and coarse flakes of chlorite. This is consistent with the experimental data on the stability of cordierite and may be expected to be limited to potash-deficient rocks, such as the cordierite-garnetgedrite bearing gneisses of the area. In common potash-bearing pelitic rocks, retrogression of cordierite results in the formation of sericite and chlorite. In gneisses containing sillimanite and cordierite, the breakdown of cordierite in this way results in the association of the three aluminosilicates (kyanite, andalusite, and sillimanite) in the same rock. The association of kyanite-andalusite in equilibrium probably suggests that the retrogression of cordierite took place close to the univariant line of kyanite-andalusite.
Scheelite mineralization in the granulite-facies supracrustal sequences of the Kerala Khondalite Belt, southern India is reported. The supracrustal sequences where the mineralization is found comprise granulite-grade metasediments which underwent metamorphism at ∼550 Ma. The mineralization is assumed to have formed by late-stage metasomatism that overprinted the regional metamorphism of the country rock (garnet-biotite gneiss) and occurs along a quartz vein that intrudes the regional foliation. The paragenetic data from the vein demonstrate unambiguously a separate cycle of hydrothermal activity, resulting in metasomatism and mineralization. Scheelite is found in both the altered host rock along the foliation plane and in the quartz vein. Fluid inclusions preserved in the vein suggest that the mineralizing fluids were saline-aqueous in composition, while those in the country rocks were predominantly CO2-rich. The mineral chemistry and bulk-rock chemical composition of the mineralized domain reveal the unusual enrichment of Ca in the mineralised zone with the depletion of K. We propose that fluid discharging from a crystallizing deep-seated magma, mixing with deep circulating Ca-bearing palaeo-groundwater gave rise to the deposition of scheelite. The scheelite mineralization and the quartz vein emplacement occurred after the Pan-African regional metamorphism.
Weed management is the major challenge to the success of boro rice (rice grown during Dec–Jan to May–Jun, also known as summer rice) in Southern Asia. Herbicide seems to be a cost effective and strategic tool from an agronomic view point to control weeds; however, herbicide application can potentially interfere with soil enzyme activity and microbial biomass carbon (MBC). A field study was conducted in 2012/13 and 2013/14 to evaluate the performance of sole and combined application of different pre-emergence herbicides in comparison to manual weeding in boro rice. Lowest weed density, biomass and highest weed control efficiency (~83%) were recorded with the pyrazosulfuron ethyl, causing higher grain yield (6.7 Mg ha−1 in 2012/13 and 4.5 Mg ha−1 in 2013/14) than treatments with chlorimuron + metsulfuron-methyl, bensulfuron methyl + pretilachlor, butachlor fb 2,4D, butachlor and cono-weeder. Among, the herbicidal treatments butachlor caused lower grain yield and higher weed density and biomass when compared to the others. Although grain yield was highest in weed-free treatments but net returns and (B:C) benefit cost ratio was highest for pyrazosulfuron ethyl due to high cost of hand weeding. After 15 days of herbicide application, lowest microbial biomass carbon was recorded with bensulfuron methyl + pretilachlor, whereas lower values of dehydrogenase and fluorescein diacetate activities were observed with the application of chlorimuron + metsulfuron-methyl at 15 days after herbicide application. Our results suggest that pyrazosulfuron ethyl is one broad-spectrum and economically effective herbicide for controlling weeds as an alternative to labour consuming hand weeding in boro rice cultivation.
The effect of L-tryptophan, a precursor of serotonin, and placebo were studied in eight patients with spasmodic torticollis. L-Tryptophan (5gpo as a single dose) which increased free plasma tryptophan 20-53 fold improved only one out of six patients. Two out of three patients, including the subject who improved following an oral load of tryptophan, improved with L-tryptophan combined with nicotinamide, a tryptophan pyrrolase inhibitor, when administered for 1-3 weeks. However, the magnitude of clinical improvement was not impressive. Our findings suggest that impairment of serotonergic function is not a general finding in spasmodic torticollis though it may play a minor role in the manifestation of this movement disorder in some patients. The present study emphasizes some of the difficulties in evaluating therapeutic response, namely, the intrinsic variability of the disorder, the response to placébo in some subjects and the limitations of methods for measuring change.
Background: Calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) has been extensively studied and characterized in normal mammalian tissues; however very little is known about this enzyme in human brain tumors. It has been established that high levels of this enzyme exist in non-central nervous system tumors, PDE inhibitors or cAMP analogues have been used to treat them. This study has examined the levels of CaMPDE in glioblastoma multiforme from six patients and has compared these to the levels of CaMPDE in four patients with normal cerebral tissue. In addition, an enzyme immune assay method (EIA) was developed in this study for the detection of CaMPDE in human cerebral tissue. This method is proposed to be used as an adjunct to the spectrophotometric method presently utilized. This would be beneficial in cases where small tissue samples, for example in stereotactic biopsy, are available. Methods: The CaMPDE activity and corresponding levels of expression in cerebral tissue from temporal lobectomies and both surgical extraction or stereotactic biopsy in patients with primary tumors were determined by spectophotometric and EIA, respectively. The EIA was developed from the production of a polyclonal antibody against bovine brain 60 kDa CaMPDE isozyme. Cross reactivity of the antibody with human was confirmed using transblot and immunohistochemistry. Results: Utilising the EIA, there was found to be significant reduction in both catalytic activity (p < 0.001) and in quantitative protein expression (p < 0.001) in glioblastoma multiforme from patients when compared to normal cerebral cortex. Immunoblotting experiments and immunohistochemistry demonstrated that CaMPDE in glioblastoma multiforme failed to react with a polyclonal antibody raised against bovine brain 60 kDa CaMPDE isozyme, whereas the enzyme from normal tissue reacted with antibody. Conclusions: Contrary to other studies on non-CNS tumors, the catalytic activity and the protein expression of CaMPDE is reduced in glioblastoma multiforme. The EIA method is a more sensitive in detecting CaMPDE than in the spectrophotometric method, especially when a small amount of tissue is available. Immunohistochemistry and the EIA may be useful in the future to use as markers for other types of brain tumors and not for glioblastoma multiforme as demonstrated.
In most mental illnesses, onset occurs before the age of 25 and the earliest stages are critical. The youth bear a large share of the burden of disease associated with mental illnesses. Yet, Canadian youths with mental health difficulties face delayed detection; long waiting lists; inaccessible, unengaging services; abrupt transitions between services; and, especially in remoter regions, even a complete lack of services. Responding to this crisis, the Canadian Institutes of Health Research announced a 5-year grant that was awarded to ACCESS, a pan-Canadian network of youths, families, clinicians, researchers, policymakers, community organisations and Indigenous communities. Using strategies developed collaboratively by all stakeholders, ACCESS will execute a youth mental healthcare transformation via early detection, rapid access and appropriate, high-quality care. The project includes an innovative, mixed-methods service research component. Similar in many respects to other national youth mental health initiatives, ACCESS also exhibits important differences of scale, scope and approach.
Large areas of rainfed lowlands of Asia annually experienced flash flooding during the rice-growing season, which is an important abiotic stress that adversely affect grain yield of rice (Oryza sativa L.) crop. Submergence stress is a common environmental challenge for agriculture sustainability in these areas because lack of high-yielding, flood-tolerant cultivars. In this study, IR64-Sub1 and IR64 were compared for their tolerance to submergence at active tillering (AT), panicle initiation (PI) and heading (H) stages with nitrogen and phosphorus application time. We evaluated the role of cultivars, stage of submergence and N and P application on phenology, leaf senescence (LS), photosynthetic (Pn) rate, yield attributes and yield. Under non-submerged conditions, no difference was observed in phenology, Pn rate and yield of both cultivars. Submergence substantially reduced biomass, Pn rate, yields attributes and yield across cultivars with more drastic reduction in IR64. Submergence at H stage proves to be most detrimental. Nitrogen application after desubmergence with basal P improved the Pn rate resulting in significantly higher yield and yield components. Nitrogen application before submergence resulted in increased LS and ethylene accumulation in shoots leading to drastic reduction in growth, Pn rate and yield. Crop establishment and productivity could therefore be enhanced in areas where untimely flooding is anticipated by avoiding N application before submergence and applying N after desubmergence with basal P (phosphorus).
This Summary for Policymakers presents key findings from the Special Report on Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation (SREX). The SREX approaches the topic by assessing the scientific literature on issues that range from the relationship between climate change and extreme weather and climate events (‘climate extremes’) to the implications of these events for society and sustainable development. The assessment concerns the interaction of climatic, environmental, and human factors that can lead to impacts and disasters, options for managing the risks posed by impacts and disasters, and the important role that non-climatic factors play in determining impacts. Box SPM.1 defines concepts central to the SREX.
The character and severity of impacts from climate extremes depend not only on the extremes themselves but also on exposure and vulnerability. In this report, adverse impacts are considered disasters when they produce widespread damage and cause severe alterations in the normal functioning of communities or societies. Climate extremes, exposure, and vulnerability are influenced by a wide range of factors, including anthropogenic climate change, natural climate variability, and socioeconomic development (Figure SPM.1). Disaster risk management and adaptation to climate change focus on reducing exposure and vulnerability and increasing resilience to the potential adverse impacts of climate extremes, even though risks cannot fully be eliminated (Figure SPM.2). Although mitigation of climate change is not the focus of this report, adaptation and mitigation can complement each other and together can significantly reduce the risks of climate change. [SYR AR4, 5.3]
Here we discuss proteomic analyses of whole cell preparations of the mosquito stages of malaria parasite development (i.e. gametocytes, microgamete, ookinete, oocyst and sporozoite) of Plasmodium berghei. We also include critiques of the proteomes of two cell fractions from the purified ookinete, namely the micronemes and cell surface. Whereas we summarise key biological interpretations of the data, we also try to identify key methodological constraints we have met, only some of which we were able to resolve. Recognising the need to translate the potential of current genome sequencing into functional understanding, we report our efforts to develop more powerful combinations of methods for the in silico prediction of protein function and location. We have applied this analysis to the proteome of the male gamete, a cell whose very simple structural organisation facilitated interpretation of data. Some of the in silico predictions made have now been supported by ongoing protein tagging and genetic knockout studies. We hope this discussion may assist future studies.
The insect parasites bred out of Psyllid hosts, in the course of studying their biology in Scotland, belong to four families of Hymenoptera and one of Diptera, the total number of species encountered being seven. Of these one and possibly two more of the hymenopterous species are hyperparasites. The hosts involved include four species, of which only one, Psyllia mali race peregrina, may be said to have been fairly heavily parasitised. As observed by Ferrière (1926), species of Psyllidae, in spite of their nymphs leading a comparatively sedentary life, are less susceptible to attack by parasites than are the other Homoptera. As a rule the hymenopterous parasites attack them in the nymphal stage, while the dipterous species parasites the adults as well.
Field experiments made for 4 years between 1976–7 and 1979–80 in a semi-arid environment of north-west India showed that the productivity of dryland unirrigated wheat can be increased considerably by adjusting the date of sowing to conducive atmospheric temperatures. Sowing in the middle of November when daily mean temperatures ranged between 19 and 21 °C produced yields ranging between 2·6and 3·5t/ha (averaged over the 4 years) compared with 1·4–3·3 t/ha obtained from the crop sown by mid-October when the daily mean temperature ranged between 24 and 26 °C. The tall cultivar C 306, a derivative of winter x spring wheat cross, could withstand sowing at higher temperatures (mid-October) more than the spring wheats. High temperatures prevailing during the seedling stage of spring wheats shortened their vegetative growth and initiated early differentiation. Night temperatures above 13 °C coupled with day temperatures of 33–35 °C in the last fortnight of October adversely affected the tillering of spring wheats sown on 15 October and produced smaller spikes with few fertile spikelets.
A field experiment conducted for two cropping seasons (1976–7 and 1977–8) showed that a fodder crop of Egyptian clover (Trifolium alexandrinum) increased the grain yield of a subsequently grown maize crop. Lathyrus (Lathyrus sativus) and peas (Pisum sativum) were less effective in this regard.