Obstruction in Hypertrophic Cardiomyopathy: Many Faces.

Hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, exhibits left ventricular hypertrophy not secondary to other causes, with varied phenotypic expression. Enhanced actin-myosin interaction underlies excessive myocardial contraction, frequently resulting in dynamic obstruction within the left ventricle. Left ventricular outflow tract obstruction, occurring at rest or with provocation in 75% of HCM patients, portends adverse prognosis, contributes to symptoms, and is frequently a therapeutic target. Transthoracic echocardiography plays a crucial role in the screening, initial diagnosis, management, and risk stratification of HCM. Herein, we explore echocardiographic evaluation of HCM, emphasizing Doppler assessment for obstruction. Echocardiography informs management strategies through noninvasive hemodynamic assessment, which is frequently obtained with various provocative maneuvers. Recognition of obstructive HCM phenotypes and associated anatomical abnormalities guides therapeutic decision-making. Doppler echocardiography allows monitoring of therapeutic responses, whether it be medical therapies (including cardiac myosin inhibitor therapy) or septal reduction therapies, including surgical myectomy and alcohol septal ablation. This article discusses the hemodynamics of obstruction and practical application of Doppler assessment in HCM. In addition, it provides a visual atlas of obstruction in HCM, including high-quality figures and complementary videos that illustrate the many facets of dynamic obstruction.

Richer than Gold: the fungal biodiversity of Reserva Los Cedros, a threatened Andean cloud forest.

BACKGROUND: Globally, many undescribed fungal taxa reside in the hyperdiverse, yet undersampled, tropics. These species are under increasing threat from habitat destruction by expanding extractive industry, in addition to global climate change and other threats. Reserva Los Cedros is a primary cloud forest reserve of ~ 5256 ha, and is among the last unlogged watersheds on the western slope of the Ecuadorian Andes. No major fungal survey has been done there, presenting an opportunity to document fungi in primary forest in an underrepresented habitat and location. Above-ground surveys from 2008 to 2019 resulted in 1760 vouchered collections, cataloged and deposited at QCNE in Ecuador, mostly Agaricales sensu lato and Xylariales. We document diversity using a combination of ITS barcode sequencing and digital photography, and share the information via public repositories (GenBank & iNaturalist). RESULTS: Preliminary identifications indicate the presence of at least 727 unique fungal species within the Reserve, representing 4 phyla, 17 classes, 40 orders, 101 families, and 229 genera. Two taxa at Los Cedros have recently been recommended to the IUCN Fungal Red List Initiative (Thamnomyces chocöensis Læssøe and "Lactocollybia" aurantiaca Singer), and we add occurrence data for two others already under consideration (Hygrocybe aphylla Læssøe & Boertm. and Lamelloporus americanus Ryvarden). CONCLUSIONS: Plants and animals are known to exhibit exceptionally high diversity and endemism in the Chocó bioregion, as the fungi do as well. Our collections contribute to understanding this important driver of biodiversity in the Neotropics, as well as illustrating the importance and utility of such data to conservation efforts. RESUMEN: Antecedentes: A nivel mundial muchos taxones fúngicos no descritos residen en los trópicos hiper diversos aunque continúan submuestreados. Estas especies están cada vez más amenazadas por la destrucción del hábitat debido a la expansión de la industria extractivista además del cambio climático global y otras amenazas. Los Cedros es una reserva de bosque nublado primario de ~ 5256 ha y se encuentra entre las últimas cuencas hidrográficas no explotadas en la vertiente occidental de los Andes ecuatorianos. Nunca antes se ha realizado un estudio de diversidad micológica en el sitio, lo que significa una oportunidad para documentar hongos en el bosque primario, en hábitat y ubicación subrepresentatadas. El presente estudio recopila información entre el 2008 y 2019 muestreando material sobre todos los sustratos, reportando 1760 colecciones catalogadas y depositadas en el Fungario del QCNE de Ecuador, en su mayoría Agaricales sensu lato y Xylariales; además se documenta la diversidad mediante secuenciación de códigos de barras ITS y fotografía digital, la información está disponible en repositorios públicos digitales (GenBank e iNaturalist). RESULTADOS: La identificación preliminar indica la presencia de al menos 727 especies únicas de hongos dentro de la Reserva, que representan 4 filos, 17 clases, 40 órdenes, 101 familias y 229 géneros. Recientemente dos taxones en Los Cedros se recomendaron a la Iniciativa de Lista Roja de Hongos de la UICN (Thamnomyces chocöensis Læssøe y "Lactocollybia" aurantiaca Singer) y agregamos datos de presencia de otros dos que ya estaban bajo consideración (Hygrocybe aphylla Læssøe & Boertm. y Lamelloporus americanus Ryvarden). CONCLUSIONES: Se sabe que plantas y animales exhiben una diversidad y endemismo excepcionalmente altos en la bioregión del Chocó y los hongos no son la excepción. Nuestras colecciones contribuyen a comprender este importante promotor de la biodiversidad en el Neotrópico además de ilustrar la importancia y utilidad de dichos datos para los esfuerzos de conservación.

Tale of two hearts: a TNNT2 hypertrophic cardiomyopathy case report.

Hypertrophic cardiomyopathy (HCM) is a heritable cardiomyopathy that is predominantly caused by pathogenic mutations in sarcomeric proteins. Here we report two individuals, a mother and her daughter, both heterozygous carriers of the same HCM-causing mutation in cardiac Troponin T (TNNT2). Despite sharing an identical pathogenic variant, the two individuals had very different manifestations of the disease. While one patient presented with sudden cardiac death, recurrent tachyarrhythmia, and findings of massive left ventricular hypertrophy, the other patient manifested with extensive abnormal myocardial delayed enhancement despite normal ventricular wall thickness and has remained relatively asymptomatic. Recognition of the marked incomplete penetrance and variable expressivity possible in a single TNNT2-positive family has potential to guide HCM patient care.

High-Sensitivity Cardiac Troponin T Elevation in Hypertrophic Cardiomyopathy Is Associated With Ventricular Arrhythmias.

OBJECTIVE: To investigate the relationship between high-sensitivity cardiac troponin T (hs-cTnT) levels and sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). METHODS: A referral HCM population with prospectively obtained hs-cTnT concentration from March 1, 2018, to April 23, 2020, was reviewed. Patients with end-stage renal disease or an abnormal hs-cTnT level not collected in an outpatient protocolled fashion were excluded. The hs-cTnT level was compared with demographic characteristics, comorbidities, conventional HCM-associated SCD risk factors, imaging, exercise testing, and prior cardiac events. RESULTS: Of 112 included patients, 69 (62%) had an elevated hs-cTnT concentration. The level of hs-cTnT correlated with known risk factors for SCD, including nonsustained ventricular tachycardia (P=.049) and septal thickness (P=.02). When patients were stratified by having a normal vs an elevated hs-cTnT concentration, patients with elevated hs-cTnT concentration were more likely to have experienced an implantable cardioverter-defibrillator discharge for ventricular arrhythmia, ventricular arrhythmia with hemodynamic instability, or cardiac arrest (incidence rate ratio, 2.96; 95% CI, 1.11 to 10.2). When sex-specific hs-cTnT cutoffs were removed, this association was no longer present (incidence rate ratio, 1.50; 95% CI, 0.66 to 3.60). CONCLUSION: In a protocolized, outpatient HCM population, hs-cTnT elevations were common and were associated with more arrhythmic expressivity of the HCM substrate as indicated by previous ventricular arrhythmias and appropriate implantable cardioverter-defibrillator shocks only when sex-specific hs-cTnT cutoffs were used. Further research should use different hs-cTnT reference values by sex to determine whether an elevated hs-cTnT value is an independent risk factor for SCD in patients with HCM.

Postmenopausal women's adherence to pelvic floor muscle exercises over 2 years.

OBJECTIVE: This study aimed to investigate women's adherence patterns to pelvic floor muscle exercises (PFME), their associated factors and within-pattern changes. METHODS: This was a secondary analysis using data collected from 647 women aged 55 years and older in the USA. Women were randomly assigned to either a 2-h class group or an equivalent content 20-min DVD group to receive PFME complemented with adherence enhancement strategies. Adherence was assessed at 3, 12 and 24 months using three self-reported items matching PFME parameters. The k-mean clustering and multinomial logistic regression were used to investigate adherence patterns and their associated factors, respectively. Descriptive statistics were used for within-pattern changes over time. RESULTS: Four adherence patterns, A, B, C and D, were identified. Women who displayed optimal adherence to all three aforementioned items, i.e. adherence pattern A, constituted 49.1%, 38.2% and 37.2% of women at 3, 12 and 24 months, respectively. Women with income > US$100,000 were more likely to display adherence pattern A within 12 months. Of women who had adherence pattern A at 3 months, 63.9% and 49.2% continued in this pattern at 12 and 24 months. CONCLUSIONS: Fewer than half of women displayed adherence pattern A for 2 years. Early optimal adherence predicted women's subsequent optimal adherence.

Squat-to-stand provocation of dynamic left ventricular outflow tract obstruction in hypertrophic cardiomyopathy: a case report.

BACKGROUND: Left ventricular outflow tract (LVOT) obstruction is an important determinant of the management of hypertrophic cardiomyopathy (HCM). With a nationwide shortage of amyl nitrite in 2019, we implemented a 'repetitive squat-to-stand' manoeuvre to provoke LVOT obstruction during echocardiography. CASE SUMMARY: A 64-year-old female was referred with symptomatic HCM refractory to pharmacologic therapy. Transthoracic echocardiography showed minor LVOT obstruction with conventional imaging at rest and during Valsalva manoeuvre, but severe obstruction was confirmed with the repetitive squat-to-stand manoeuvre. Alcohol septal ablation via the first septal perforator was performed with subsequent resolution of symptoms. DISCUSSION: Due to the dynamic nature of LVOT obstruction, a series of provocative manoeuvres including Valsalva manoeuvre, inhalation of amyl nitrite, and exercise are often necessary to maximally augment ventricular obstruction. The recent unavailability of amyl nitrite during a nationwide shortage prompted the implementation of a protocol of repetitive squat-to-stand manoeuvre in our echocardiography laboratory. Rising from the squatting position decreases preload and afterload, both of which augment dynamic LVOT obstruction. Repetition of squatting and standing appears to enhance the sensitivity of the manoeuvre, particularly when exertional symptoms are reproduced. In this case, repetitive squat-to-stand manoeuvre led to the identification of severe LVOT obstruction which may not have been diagnosed otherwise, alteration of treatment to septal reduction therapy, and subsequent resolution of symptoms.

Montgomery and informed consent during Covid-19: Pneumatic retinopexy versus pars plana vitrectomy or scleral buckling for retinal detachment repair.

Recent reports suggest that the use of an outpatient-based procedure (pneumatic retinopexy, PR) for retinal detachment repair should be encouraged within the UK, especially in light of Covid-19 and possible restrictions/competing demands on access to operating theatres. It is therefore essential that patients receive comprehensive information about the risks and benefits of this approach compared with a formal surgical repair either by pars plana vitrectomy (PPV) and/or scleral buckling (SB). We report a retrospective case series of retinal detachments (RD) satisfying the strict selection criteria for PR but who were managed with formal surgery. Single-operation success rate for PPV/SB at six months follow-up was 93.8% in our study, higher than published primary success rates for PR (60-80%). When counselling patients for possible PR, the ease, speed and potentially reduced co-morbidity of an outpatient-based procedure needs to be balanced against its significantly higher failure rate in comparison with primary PPV/SB.

BCG vaccination early in life does not improve COVID-19 outcome of elderly populations, based on nationally reported data.

The reported numbers of Covid-19 cases and deaths were compared for 18 countries (14 in Western Europe, plus Australia, Brazil, Israel and the USA) to assess the effect of historic and current national BCG immunizations. In view of the high death rate for Covid-19 patients over 70 years of age, and given the fact that BCG vaccination is typically given early in life, we compared countries that had introduced BCG in the 1950s with those that had not. No effect on Covid-19 case fatality rate (CFR) or number of deaths per population could be demonstrated. Since some countries test for Covid-19 more than others, the effect of tests performed per million population on reported deaths per million was also assessed, but again did not demonstrate an effect of BCG vaccination in the 1950s. Whether countries had never used the vaccine, had historically used it but since ceased to do so, or were presently vaccinating with BCG did not correlate with national total number of deaths or CFR. We conclude that there is currently no evidence for a beneficial effect of BCG vaccination on Covid-19 reported cases or fatalities.

Upregulation of virulence genes promotes Vibrio cholerae biofilm hyperinfectivity.

Vibrio cholerae remains a major global health threat, disproportionately impacting parts of the world without adequate infrastructure and sanitation resources. In aquatic environments, V. cholerae exists both as planktonic cells and as biofilms, which are held together by an extracellular matrix. V. cholerae biofilms have been shown to be hyperinfective, but the mechanism of hyperinfectivity is unclear. Here we show that biofilm-grown cells, irrespective of the surfaces on which they are formed, are able to markedly outcompete planktonic-grown cells in the infant mouse. Using an imaging technique designed to render intestinal tissue optically transparent and preserve the spatial integrity of infected intestines, we reveal and compare three-dimensional V. cholerae colonization patterns of planktonic-grown and biofilm-grown cells. Quantitative image analyses show that V. cholerae colonizes mainly the medial portion of the small intestine and that both the abundance and localization patterns of biofilm-grown cells differ from that of planktonic-grown cells. In vitro biofilm-grown cells activate expression of the virulence cascade, including the toxin coregulated pilus (TCP), and are able to acquire the cholera toxin-carrying CTXФ phage. Overall, virulence factor gene expression is also higher in vivo when infected with biofilm-grown cells, and modulation of their regulation is sufficient to cause the biofilm hyperinfectivity phenotype. Together, these results indicate that the altered biogeography of biofilm-grown cells and their enhanced production of virulence factors in the intestine underpin the biofilm hyperinfectivity phenotype.

Characteristics Associated With Clinically Important Treatment Responses in Women Undergoing Nonsurgical Therapy for Fecal Incontinence.

OBJECTIVE: To identify baseline clinical and demographic characteristics associated with clinically important treatment responses in a randomized trial of nonsurgical therapies for fecal incontinence (FI). METHODS: Women (N = 296) with FI were randomized to loperamide or placebo- and manometry-assisted biofeedback exercises or educational pamphlet in a 2 × 2 factorial design. Treatment response was defined in 3 ways from baseline to 24 weeks: minimal clinically important difference (MID) of -5 points in St. Mark's score, ≥50% reduction in FI episodes, and combined St. Mark's MID and ≥50% reduction FI episodes. Multivariable logistic regression models included baseline characteristics and treatment groups with and without controlling for drug and exercise adherence. RESULTS: Treatment response defined by St. Mark's MID was associated with higher symptom severity (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.11-1.28) and being overweight vs normal/underweight (aOR 2.15, 95% CI 1.07-4.34); these predictors remained controlling for adherence. Fifty percent reduction in FI episodes was associated with the combined loperamide/biofeedback group compared with placebo/pamphlet (aOR 4.04, 95% CI 1.36-11.98), St. Mark's score in the placebo/pamphlet group (aOR 1.29, 95% CI 1.01-1.65), FI subtype of urge vs urge plus passive FI (aOR 2.39, 95% CI 1.09-5.25), and passive vs urge plus passive FI (aOR 3.26, 95% CI 1.48-7.17). Controlling for adherence, associations remained, except St. Mark's score. DISCUSSION: Higher severity of FI symptoms, being overweight, drug adherence, FI subtype, and combined biofeedback and medication treatment were associated with clinically important treatment responses. This information may assist in counseling patients, regarding efficacy and expectations of nonsurgical treatments of FI.

Energy Flux Densities near the Electron Dissipation Region in Asymmetric Magnetopause Reconnection.

Magnetic reconnection is of fundamental importance to plasmas because of its role in releasing and repartitioning stored magnetic energy. Previous results suggest that this energy is predominantly released as ion enthalpy flux along the reconnection outflow. Using Magnetospheric Multiscale data we find the existence of very significant electron energy flux densities in the vicinity of the magnetopause electron dissipation region, orthogonal to the ion energy outflow. These may significantly impact models of electron transport, wave generation, and particle acceleration.

Hemizygosity for the gene encoding glycoprotein Ibß is not responsible for macrothrombocytopenia and bleeding in patients with 22q11 deletion syndrome.

Essentials How thrombocytopenia relates to bleeding in 22q11 deletion syndrome (22q11DS) is not clear. Bleeding severity, platelet count and volume, and GPIBB were examined in patients with 22q11DS. Macrothrombocytopenia and bleeding typified imperfectly overlapping subsets of 22q11DS patients. GPIBB hemizygosity does not cause macrothrombocytopenia or bleeding in patients with 22q11DS. SUMMARY: Background and objectives Macrothrombocytopenia and bleeding are frequently associated with 22q11 deletion syndrome (22q11DS). GPIBB, which encodes the glycoprotein (GP) Ibß subunit of GPIb-IX-V, is commonly deleted in patients with 22q11DS. Absence of functional GPIb-IX-V causes Bernard-Soulier syndrome, which is a severe bleeding disorder characterized by macrothrombocytopenia. Patients with 22q11DS are often obligate hemizygotes for GPIBB, and those with only a pathogenically disrupted copy of GPIBB present with Bernard-Soulier syndrome. The objective of this study was to determine how GPIBB hemizygosity and sequence variation relate to macrothrombocytopenia and bleeding in patients with 22q11DS who do not have Bernard-Soulier syndrome. Patients/methods We thoroughly characterized bleeding severity, mean platelet volume, platelet count and GPIBB copy number and sequence in patients with 22q11DS. Results and conclusions Macrothrombocytopenia and mild bleeding were observed in incompletely overlapping subsets of patients, and GPIBB copy number and sequence variation did not correlate with either macrothrombocytopenia or bleeding in patients with 22q11DS. These findings indicate that GPIBB hemizygosity does not result in either macrothrombocytopenia or bleeding in these patients. Alternative genetic causes of macrothrombocytopenia, potential causes of acquired thrombocytopenia and bleeding and ways in which platelet size, platelet count and GPIBB sequence information can be used to aid in the diagnosis and management of patients with 22q11DS are discussed.

Modeling transport across the running-sandpile cellular automaton by means of fractional transport equations.

Fractional transport equations are used to build an effective model for transport across the running sandpile cellular automaton [Hwa et al., Phys. Rev. A 45, 7002 (1992)PLRAAN1050-294710.1103/PhysRevA.45.7002]. It is shown that both temporal and spatial fractional derivatives must be considered to properly reproduce the sandpile transport features, which are governed by self-organized criticality, at least over sufficiently long or large scales. In contrast to previous applications of fractional transport equations to other systems, the specifics of sand motion require in this case that the spatial fractional derivatives used for the running sandpile must be of the completely asymmetrical Riesz-Feller type. Appropriate values for the fractional exponents that define these derivatives in the case of the running sandpile are obtained numerically.

Predicting pork loin intramuscular fat using computer vision system.

The objective of this study was to investigate the ability of computer vision system to predict pork intramuscular fat percentage (IMF%). Center-cut loin samples (n = 85) were trimmed of subcutaneous fat and connective tissue. Images were acquired and pixels were segregated to estimate image IMF% and 18 image color features for each image. Subjective IMF% was determined by a trained grader. Ether extract IMF% was calculated using ether extract method. Image color features and image IMF% were used as predictors for stepwise regression and support vector machine models. Results showed that subjective IMF% had a correlation of 0.81 with ether extract IMF% while the image IMF% had a 0.66 correlation with ether extract IMF%. Accuracy rates for regression models were 0.63 for stepwise and 0.75 for support vector machine. Although subjective IMF% has shown to have better prediction, results from computer vision system demonstrates the potential of being used as a tool in predicting pork IMF% in the future.

Are there increased periprocedural complications with the MRI-conditional Medtronic Revo SureScan Pacing System? : A meta-analysis.

BACKGROUND: The use of magnetic resonance imaging (MRI)-conditional permanent pacemakers has increased significantly. In this meta-analysis, we examine the safety of MRI-conditional pacing systems in comparison with conventional systems. METHODS: An electronic search was performed using major databases, including studies that compared the outcomes of interest between patients receiving MRI-conditional pacemakers (MRI group) versus conventional pacemakers (control group). RESULTS: Six studies (5 retrospective and 1 prospective non-randomised) involving 2,118 adult patients were identified. The MRI-conditional pacemakers, deployed in 969 patients, were all from a single manufacturer (Medtronic Pacing System with 5086 leads). The rate of pacemaker lead dislodgement (atrial and ventricular) was significantly higher in the MRI group (3% vs. 1%, OR 2.47 (95% CI 1.26; 4.83), p = 0.008). The MRI group had a significantly higher rate of pericardial complications (2% vs. 1%, OR 4.23 (95% CI 1.18; 15.10), p = 0.03) and a numerically higher overall complication rate in comparison with the conventional group (6% vs. 3%, OR 2.02 (95% CI 0.88; 4.66), p = 0.10) but this was not statistically significant. CONCLUSIONS: In this meta-analysis, the rates of pacemaker lead dislodgement and pericardial complications were significantly higher with the Medtronic MRI-conditional pacing system.