Avaliação Cintilográfica e Ecocardiográfica em Portadores de Variantes Patogênicas ou Provavelmente Patogênicas do Gene TTR sem Envolvimento Cardíaco Manifesto / Scintigraphic and Echocardiographic Study of Patients with Pathogenic or Probably Pathogenic Variants of the TTR Gene without Overt Cardiac Involvement

Resumo Fundamento: A amiloidose por transtirretina (ATTR) é uma doença infiltrativa causada pela deposição anormal de proteína principalmente no coração e no sistema nervoso periférico. Quando acomete o coração, a doença manifesta-se como uma cardiomiopatia restritiva e, quando afeta o sistema nervoso periférico e autônomo, apresenta-se como uma polineuropatia, podendo ser chamada de Polineuropatia Amiloidótica Familiar (PAF). Existem dois subtipos de ATTR, a ATTR selvagem, em que não há variantes genéticas, e a ATTR hereditária, caracterizada por uma variante no gene que codifica a proteína transtirretina (T/TR). Em ambos os subtipos, o envolvimento cardíaco é o principal marcador prognóstico. Objetivos: Avaliar a prevalência do envolvimento cardíaco subclínico em uma amostra de pacientes com variantes genéticas no gene TTR usando a cintilografia com pirofosfato e o ecocardiograma com strain; comparar os achados cintilográficos e as medidas de strain; avaliar a associação entre PAF e o envolvimento subclínico; e analisar se existe uma associação entre uma variante genética específica e o envolvimento cardíaco. Métodos: Estudo transversal com carreadores de variantes no gene TTR sem sintomas cardiovasculares e sem alterações nos parâmetros da eletrocardiografia ou do ecocardiograma convencional. Todos os pacientes foram submetidos à cintilografia com pirofosfato e à ecocardiografia com análise de strain. O envolvimento cardíaco subclínico, definido como um escore de Perugini ≥ 2, razão Coração (C)/ Hemitórax Contralateral (CL) ≥ 1,5 em uma hora, C/CL ≥ 1,3 na terceira hora, ou um strain longitudinal global (SGL) ≤ −17%. Realizadas análises descritiva e analítica, e aplicados o teste exato de Fisher e o teste de Mann-Whitney. Um valor de p<0,05 foi considerado significativo. Resultados: Os 23 pacientes avaliados apresentavam uma idade mediana de 51 (37-57) anos, 15 (65,2%) eram do sexo feminino, 12 (52,2%) eram pardos, nove (39,1%) apresentavam hipertensão arterial sistêmica, e nove (39,1%) tinham um diagnóstico prévio de PAF. Dos nove pacientes com PAF, oito (34,8%) usavam tafamidis. As variantes genéticas identificadas foram Val142IIe, Val50Met e IIe127Val. O valor mediano do SGL foi −19% (-16% - −20%). Dos 23 pacientes, nove (39,1%; 95% CI = 29-49%) preencheram os critérios de envolvimento cardíaco, seis (26%) somente pelo critério do SGL. Não houve associação entre PAF e um carreador assintomático avaliado por ecocardiograma com análise de strain e pela cintilografia com pirofostato (p=0,19). A prevalência de hipertensão arterial sistêmica, diabetes mellitus, dislipidemia, tabagismo e SGL reduzido não foi diferente entre os grupos. A velocidade da onda e' septal foi a única variável que apresentou diferença significativa entre os indivíduos com e sem SGL reduzido, com uma área sob a curva ROC de 0,80 (IC95% = 0,61-0,98, p = 0,027). A melhor acurácia diagnóstica foi alcançada com uma velocidade e' septal ≤ 8,5 cm/s. Não houve associação entre o tipo de variante genética e o envolvimento cardíaco pré-clínico, nem entre o uso de tafamidis e este mesmo envolvimento (37,5% versus 40,0%, p = 0,90). Conclusão: O envolvimento cardíaco subclínico foi frequente em uma amostra de carreadores da variante genética do gene TTR. Um valor do SGL reduzido foi o achado mais comum. Não houve associação entre a presença de polineuropatia amiloidótica e o envolvimento subclínico. O tipo de variante genética não foi associado com envolvimento cardíaco precoce. Nesta amostra, o uso de tafamidis (20mg/dia) não foi associado com uma menor prevalência de envolvimento cardíaco subclínico.

Abstract Background: Transthyretin amyloidosis (ATTR) is an infiltrative disease caused by abnormal protein deposition mainly in the heart and peripheral nervous system. When it affects the heart, the disease presents as restrictive cardiomyopathy; when it affects the peripheral and autonomic nervous system, it manifests as polyneuropathy, and is called familial amyloid polyneuropathy (FAP). There are two ATTR subtypes: wild-type ATTR, where there is no mutation, and mutant ATTR (ATTRm), which is characterized by a mutation in the gene encoding the transthyretin protein (TTR). In both subtypes, cardiac involvement is the major marker of poor prognosis. Objectives: To assess the prevalence of subclinical cardiac involvement in a sample of patients with TTR gene mutation by using pyrophosphate scintigraphy and strain echocardiography; to compare scintigraphy and strain findings; to evaluate the association between neurological manifestations (FAP) and subclinical cardiac involvement; and to analyze whether there is an association between any specific mutation and cardiac involvement. Methods: This is a cross-sectional study with carriers of the TTR gene mutation, without cardiovascular symptoms or changes in electrocardiographic or conventional echocardiographic parameters. All patients underwent pyrophosphate scintigraphy and strain echocardiography. Subclinical cardiac involvement was defined as a Perugini score ≥ 2, heart-to-contralateral lung (H/CL) ratio ≥ 1.5 at 1 h, H/CL ≥1.3 at 3 h, or global longitudinal strain (GLS) ≤ −17%. Descriptive and analytical analyses were performed and Fisher's exact test and Mann-Whitney test were applied. A value of p < 0.05 was considered significant. Results: The 23 patients evaluated had a median age of 51 years (IQR 37-57 years), 15 (65.2%) were female, 12 (52.2%) were Pardo, nine (39.1%) had systemic arterial hypertension, and nine (39.1%) had a previous diagnosis of FAP. Of the nine patients with FAP, 8 (34.8%) were on tafamidis. The associated mutations were Val142IIe, Val50Met, and IIe127Val. The median GLS in the sample was −19% (−16% to −20%). Of the 23 patients, nine (39.1%; 95% CI = 29-49%) met criteria for cardiac involvement, six (26%) by the GLS-based criteria only. There was no association between having FAP and being an asymptomatic carrier, as assessed by strain echocardiography and pyrophosphate scintigraphy (p = 0.19). The prevalence of systemic arterial hypertension, diabetes mellitus, dyslipidemia, smoking, and reduced GLS did not differ between groups. Septal e' wave velocity was the only variable that significantly differed between individuals with and without reduced GLS, with an area under the ROC curve of 0.80 (95% CI = 0.61-0.98, p = 0.027). The best diagnostic accuracy was achieved with a septal e' velocity ≤ 8.5 cm/s. There was no association between mutation type and preclinical cardiac involvement, nor between tafamidis use and lower degree of cardiac involvement (37.5% versus 40.0%, p = 0.90). Conclusion: Subclinical cardiac involvement was common in a sample of TTR mutation carriers without cardiac involvement. Reduced left ventricular GLS was the most frequent finding. There was no association between the presence of amyloid polyneuropathy and subclinical cardiac involvement. Type of mutation was not associated with early cardiac involvement. In this sample, the use of tafamidis 20 mg/day was not associated with a lower prevalence of subclinical cardiac involvement.

FVB/NJ strain as a mouse model for cutaneous leishmaniasis by Leishmania (L.) amazonensis

BACKGROUND Leishmaniases encompass a spectrum of neglected diseases caused by parasites of the genus Leishmania, grouped in two forms: tegumentary and visceral leishmaniasis. OBJECTIVES In this study, we propose Friend Virus B NIH Jackson (FVB/NJ) mouse strain as a new experimental model of infection with Leishmania (Leishmania) amazonensis, the second most prevalent agent of tegumentary leishmaniasis in Brazil. METHODS AND FINDINGS We performed in vitro infections of FVB/NJ macrophages and compared them with BALB/c macrophages, showing that BALB/c cells have higher infection percentages and a higher number of amastigotes/cell. Phagocytosis assays indicated that BALB/c and FVB/NJ macrophages have similar capacity to uptake parasites after 5 min incubations. We also investigated promastigotes' resistance to sera from FVB/NJ and BALB/c and observed no difference between the two sera, even though FVB/NJ has a deficiency in complement components. Finally, we subcutaneously infected FVB/NJ and BALB/c mice with 2 × 106 parasites expressing luciferase. Analysis of lesion development for 12 weeks showed that FVB/NJ and BALB/c mice have similar lesion profiles and parasite burdens. MAIN CONCLUSIONS This work characterises for the first time the FVB/NJ mouse as a new model for tegumentary leishmaniasis caused by Leishmania (L.) amazonensis.

Research progress on the stress-strain index of Corvis ST / 国际眼科杂志(Guoji Yanke Zazhi)

Corneal visualization Scheimpflug technology(Corvis ST)is currently the most commonly used clinical device for assessing in vivo corneal biomechanics. The new parameter stress-strain index(SSI)has been a hot topic of clinical research in recent years, which not only directly reflect corneal biomaterial stiffness, but also closely correlates with the progression of certain diseases. SSI was generated based on the predictions of corneal behavior using finite element(FE)numerical modeling to simulate the effects of intraocular pressure and Corvis ST jets. The SSI algorithm does not change with central corneal thickness(CCT), intraocular pressure, or biomechanically corrected intraocular pressure(BIOP), but it is clearly associated with altered collagen fibres in the corneosclera. The principles of SSI, the relationship between age and SSI, the relationship between axial length and SSI, the relationship between myopia and SSI, and the application of SSI are summarized and concluded.

Assessment of short forms of recurrent atrial extra systoles by echocardiography with left atrial strain in ambulatory patients without organic cardiopathy / Evaluación de formas cortas de extrasístoles auriculares recurrentes mediante ecocardiografía con deformación auricular izquierda en pacientes ambulatorios sin cardiopatía orgánica

Abstract Aim: To analyse the potential usefulness and clinical relevance of the assessment by echocardiography with left atrial strain, based on the myocardial atrial deformation curves with speckle-tracking velocity vector imaging (VVI), in the analysis of short-form recurrent atrial extra systoles in ambulatory patients not suffering from organic cardiopathy. Methods: We designed a descriptive, prospective, and observational study including 270 patients between the ages of 18 and 75 assessed during an outpatient cardiology consultation attended due to palpitations over a period of two years. Using ambulatory electrocardiographic monitoring, we selected cases with short forms of repetitive atrial extrasystole, isolated or recurrentatrial fibrillation and a control group formed by those patients without repetitive ectopia. All patients underwent a thorough echocardiographic study during their first cardiological visit. Results: The analysis of the dynamic curves segmental deformation generated after an atrial extrasystole can reveal different points of origin of the extrasystole and detect specific anatomical alterations in the interatrial conduction at the level of the Bachmann's fascicle showing different models of electro anatomical activation possibly involved in the appearance of repetitive forms. Higher values of dyssynchrony between the septal and lateral wall and elongation in the time of interatrial electromechanical conduction could also be related to the existence of repetitive ectopic beats. Conclusions: Our ambulatory study employing the left atrial longitudinal strain, particularly in its segmental analysis, provides new insights into its the usefulness and potential clinical relevance.

Resumen Objetivo: Analizar la utilidad y relevancia clínica de la evaluación mediante ecocardiografía basada en las curvas de deformación auricular miocárdica con imágenes vectoriales de velocidad (VVI) de speckle-tracking, en el análisis de las extrasístoles auriculares recurrentes de corta duración en pacientes ambulatorios sin cardiopatía orgánica. Métodos: Se diseñó un estudio descriptivo, prospectivo y observacional que incluyó a 270 pacientes de entre 18 y 75 años evaluados durante una consulta externa de cardiología a la que acudieron por palpitaciones durante un periodo de dos años. Mediante el uso de monitorización electrocardiográfica ambulatoria, se seleccionaron casos con formas cortas de extrasistolia auricular repetitiva, fibrilación auricular aislada o repetitiva y un grupo control formado por aquellos pacientes sin ectopia repetitiva. Todos los pacientes se sometieron a un estudio ecocardiográfico exhaustivo durante su primera visita cardiológica. Resultados: El análisis de las curvas dinámicas de deformación segmentaria generadas tras un extrasístole auricular diferentes modelos de activación electroanatómica posiblemente implicados en la aparición de formas repetitivas. Valores mayores de disincronía entre la pared septal y lateral y el alargamiento en el tiempo de conducción electromecánica intraauricular pudieran también relacionarse con la existencia de latidos ectópicos repetitivos. Conclusiones: Nuestro estudio ambulatorio empleando la deformación longitudinal auricular izquierda, particularmente en su análisis segmentario, proporciona nuevas perspectivas sobre su utilidad y potencial relevancia clínica.

Age-related variations in corneal stress-strain index in the Indian population

Purpose: To report age?related variations in corneal stress–strain index (SSI) in healthy Indians. Methods: It was a retrospective study where healthy Indian individuals aged between 11 and 70 years who had undergone corneal biomechanics assessment using Corvis ST between January 2017 and December 2021 were enrolled. Composite corneal biomechanical parameters and corneal SSI were abstracted from Corvis ST and compared across different age groups using one?way analysis of variance (ANOVA). Also, Pearson’s correlation was used to evaluate the association between age and SSI. Results: Nine hundred and thirty?six eyes of 936 patients with ages between 11 and 77 years with mean ± SD intraocular pressure (IOP) and pachymetry of 16.52 ± 2.10 mmHg and 541.13 ± 26.39 ?s, respectively. Composite corneal biomechanical parameters such as deformation amplitude ratio max at 1 mm (P < 0.001) and 2 mm (P < 0.001), biomechanically corrected IOP (P = 0.004), stiffness parameter at A1 (P < 0.001, Corvis biomechanical index (P < 0.018), and SSI (P < 0.001) were found to be significantly different as a function of age group. We noted a statistically significant positive association of SSI with age (P < 0.001), spherical equivalent refractive error (P < 0.001), and IOP (P < 0.001) and a significant negative association with anterior corneal astigmatism (P < 0.001) and Anterior chamber depth (ACD) (P < 0.001). Also, SSI was positively associated with SPA1 and bIOP, whereas negatively associated with integrated radius, max inverse radius, and Max Deformation amplitude (DA) ratio at 1 mm and 2 mm. Conclusion: We noted a positive association of corneal SSI with age in normal healthy Indian eyes. This information could be helpful for future corneal biomechanical research.

The 20/20/20 rule: Practicing pattern and associations with asthenopic symptoms

Purpose: The present work style and lifestyle have increased the digital device use. Therefore, an increase in digital eyestrain is to be expected. We undertook a survey during coronavirus disease 2019 (COVID?19) pandemic to investigate the practice of 20/20/20 rule and its association with digital device use and asthenopic symptoms. While this rule is commonly advised, little is known about its validity. Methods: An online survey form was disseminated through social media and emails. The questions for eye?related symptoms were similar to the convergence insufficiency symptom survey (CISS). Participants with age ?5 years were included, with parents completing the survey for children (?16 years). Results: A total of 432 participants (mean ± standard deviation [SD]: 26.06 ± 13.92 years) were enrolled, of which 125 responses were for children. The 20/20/20 rule was practiced only by 34% of the participants either regularly (n = 38) or occasionally (n = 109). Those who had complaints of burning sensation and headache tended to practice this rule. Among adult participants, more females (47%) practiced this rule when compared to males (23%). Also, adult females significantly (P = 0.04) had more symptoms score when compared to males. In children, no such gender difference was found. Conclusion: Only one?third of participants practice the 20/20/20 rule at least occasionally. More number of adult females being symptomatic and practicing in greater number could be due to higher prevalence of dry eye condition in females. While the symptom of burning sensation could be related to dry eye, that of headache could be related to refractive error or binocular vision dysfunctions

Subcostal right ventricular free wall strain in patients with pulmonary hypertension / Strain subcostal de la pared libre del ventriculo derecho en pacientes con hipertensión pulmonar

Abstract Right ventricular longitudinal strain (RVLS) is frequently used as a measure of right ventricular systolic function. Abnormal RV strain is associated with poor prognosis in patients with pulmonary hyper tension (PH); however, the measure is not always easy to obtain in patients with poor apical acoustic windows. Objective: This study aims to analyze the RVLS and determine if there is a difference when measured from the apical and subcostal views. Methods: In this cross-sectional study, we analyzed 22 adult outpatients (≥ 18 years old), 81% female, mean age 49.9 ± 17.3 years, with a diagnosis of PH using right heart catheterization, followed from January 2016 to January 2020. Results: RVLS measured in the RV free wall from the apical views was -15% (-19% to -10%) and subcostal views -14.5% (-18% to -11%) were highly correlated (Person's r = 0.969, p < 0.0001). Segment by segment analysis did not show significant differences either: basal four-chamber vs. sub costal view was -16.5% (-21% to -11%) vs. -15.5% (-20% to -11%), p = 0.99, mid four-chamber view vs. subcotal view was -16.5% (-21% to -12%) vs. -16.5% (-20% to -11%), p = 0.87, apical four-chamber view vs. subcostal view was -12% (-18% to -8%) vs. -13.5% (-19% to -10%), p = 0.93. Conclusion: Subcostal RVLS free wall is a feasible and accurate alternative to conventional RVLS free wall from the apical view in patients with pulmonary hypertension and could be useful in patients with poor acoustic apical four-chamber windows.

Resumen El strain longitudinal del ventrículo derecho (SLVD) permite medir la función sistólica del ventrículo derecho (VD). La disminución del strain (deformación) del VD se asocia con mal pronóstico en pacientes con hipertensión pulmonar (HP), pero no siempre es fácil de obtener en pacientes con mala ventana acústica apical. Objetivo: Este estudio tiene como objetivo analizar el SLVD y determinar si las vistas apical y subcostal son comparables. Métodos: En este estudio transversal, se incluyeron 22 pacientes adultos ambulatorios (≥18 años), 81% mujeres, edad promedio 49.9 ± 17.3 años, con diagnóstico de HP mediante cateterismo cardíaco derecho, seguidos desde enero de 2016 hasta enero de 2020. Se midió la deformación de la pared libre del ventrículo derecho desde las vistas de cuatro cámaras apical y cuatro cámaras subcostal. Resultados: El SLVD medido en la pared libre del VD desde la vista apical fue -15% (-19% a -10%) vs. -14.5% (-18% a -11%) cuando se midió desde la vista subcostal (p = 0,99). El análisis segmento por s egmento tampoco mostró diferencias significativas: el segmento basal apical vs. subcostal fue -16.5% (-21% a -11%) vs. -15.5% (-20% a -11%), p = 0.99, el segmento medio apical vs. la vista subcotal fue -16.5% (-21% a -12%) vs. a -16.5% (-20% a -11%), p = 0.87, el segmento apical vs. la vista subcostal fue -12% (-18% a -8%) frente a -13.5% (-19% a -10%), p = 0.93. Conclusión: En pacientes con HP, el SLVD obtenido en la pared libre subcostal es una alternativa útil en los casos con ventana acústica apical subóptima.

A study on correlation of computer vision syndrome and dry eye disease and knowledge regarding its associated factors amongst health professionals

Purpose: To know the magnitude and determinants of dry eye syndrome among health professionals and to study the correlation of computer vision syndrome with dry eye disease. Methods: In total, 501 participants took part in the study, which included history followed by baseline ocular examination, which included visual acuity using Snellen’s chart and anterior segment examination using a slit lamp. Later, a questionnaire was administered to health professionals to be filled out for analysis in the present study. Results: The symptoms reported occasionally were burning (35.5%), itching (34.5%), foreign body sensation 22.6%, and tearing (35.3%). The majority of participants used mobiles and laptops (56.1%) as a display. Also, 53.3% of participants have heard about dry eye syndrome, and the source of information was from friends and doctors in 17% of participants. One hundred twenty?one participants (24.2%) had taken the consultation for ocular symptoms. Eighty?six participants had mild, 29 participants had moderate, and 6 participants had severe dry eye disease, respectively. Conclusion: The pandemic effect, and the drastic shift of educational media from the classroom to the digital platform have increased the use of mobiles, laptops, or other digital pads for learning. This has increased the risk for health professionals.

Phenotypic and molecular characterization of Staphylococcus aureus isolates conducted in nares of psoriatic patients attending a public hospital in Argentina / Caracterización fenotípica y molecular de aislamientos de Staphylococcus aureus portados en narinas de pacientes con psoriasis que concurren a un hospital público en Argentina

Abstract Although Staphylococcus aureus increases its relative abundance in psoriasis when compared with the microbiome of healthy subjects, it is not the most important microorganism underlying this disease. However, there is scant data on the role and molecular features of S. aureus strains in psoriasis; therefore, the aim of this study was to evaluate nasal carriage of this microorganism, its phenotypic and molecular characteristics as well as the impact of host factors on its carriage in psoriatic patients. The presence of S. aureus was analyzed in nasal swabs from 46 healthy volunteers and 50 psoriatic patients by conventional microbiology techniques. Nasal carriage of S. aureus was higher in psoriatic patients than in the control group (37.24% vs 22.98%, respectively), being associated to sex (male), age (adults) and severity of the disease (more frequent in moderate and severe cases). Determination of antibiotic resistance detected 12% of (-lactam resistant isolates, with variable accompanying resistance to macrolides, aminoglycosides and fluoroquinolones. No resistance to rifampicin, vancomycin, mupirocin or trimethoprim/sulfamethoxazole was found. A preliminary molecular characterization of the isolates was performed by PCR amplification of virulence genes. Molecular characterization of the strains did not reveal a predominant strain in psoriatic patients. Although we established host factors related to increased carriage of S. aureus in psoriatic patients, we could not establish the predominance of one type of strain. Genomic and transcriptomic analysis of the isolated strains would be necessary to address this point.

Resumen A pesar de que Staphylococcus aureus incrementa su abundancia relativa en la psoriasis cuando se compara con el microbioma de personas sanas, no es el microorganismo más importante subyacente a la enfermedad. Sin embargo, existen pocos datos sobre el papel y las características moleculares de las cepas de S. aureus en pacientes con psoriasis. Nuestro objetivo fue evaluar la portación nasal de este microorganismo, sus características fenotípicas y moleculares, y el impacto de factores del hospedador sobre dicha portación en estos pacientes. Se analizó la presencia de S. aureus en hisopados nasales de 46 voluntarios sanos y 50 pacientes con psoriasis mediante técnicas microbiológicas convencionales. Se encontró mayor portación en pacientes con psoriasis que en el grupo control (37,24% vs. 22,98%, respectivamente) y esta estuvo asociada al sexo (masculino), la edad (adultos) y la gravedad de la enfermedad (más frecuente en casos moderados a graves). El 12% de los aislamientos de S. aureus mostraron resistencia a betalactámicos, con resistencia acompañante a macrólidos, aminoglucósidos y fluoroquinolonas en grado variable. No se encontró resistencia a rifampicina, vancomicina, mupirocina o trimetroprima/sulfametoxazol. Se realizó una caracterización molecular preliminar de los aislamientos por amplificación de genes de virulencia mediante PCR. Si bien se identificaron factores relacionados con el hospedador que incrementan la portación nasal de S. aureus en pacientes con psoriasis, la caracterización molecular de las cepas no reveló ninguna característica genotípica predominante asociada a esta afección. Se necesitan más estudios genómicos y transcriptómicos para profundizar en esta caracterización.

Value of the strain ratio in the differential diagnosis of intraocular tumors by elastosonography: A retrospective case-control study

Purpose: To examine the role of the strain ratio in elastosonography for the differential diagnosis of common intraocular tumors such as choroidal melanoma, choroidal hemangioma, choroidal metastatic carcinoma, and retinoblastoma. Methods: This study included patients suffering from intraocular space?occupying lesions and who visited Beijing Tongren Eye Center of Beijing Tongren Hospital affiliated to Capital Medical University from June 2016 to March 2020. All patients underwent a physical examination, fundus examination with mydriasis, color Doppler ultrasonography, elastosonography, magnetic resonance imaging (MRI), and fundus angiography within 1 week. All patients were grouped as choroidal melanoma, choroidal metastatic carcinoma, retinoblastoma, choroidal hemangioma, and optic disk melanocytoma. A receiver operating characteristic (ROC) curve analysis was performed to assess the strain ratio for diagnosing malignant intraocular tumors. Results: A total of 155 patients (161 eyes) were recruited. The strain ratios measured were 39.59 ± 15.92 for choroidal melanoma, 36.85 ± 13.64 for choroidal metastatic carcinoma, 38.93 ± 17.27 for retinoblastoma, 13.42 ± 10.93 for choroidal hemangioma, and 3.84 ± 1.32 for optic disk melanocytoma. The strain ratios of the three malignant lesions were significantly higher than those of the two benign lesions (all P < 0.001). The area under the ROC curve was 0.95 ± 0.028. The optimal cutoff point was 22.67, with 85.7% sensitivity and 96.4% specificity. Conclusion: There were significant differences in elasticity between the malignant and benign intraocular tumors. The strain ratio using elastosonography could serve as an important auxiliary examination to distinguish between benign and malignant intraocular tumors

Strain echocardiography in predicting LV dysfunction in RV apical pacing

Right ventricular (RV) pacing is associated with a reduction in left ventricular (LV) systolic function, thought to be mediated by pacing-induced ventricular dyssynchrony. The prevalence of heart failure after RV pacing is reported to range from 31±3%. We studied 60 subjects with high-grade atrioventricular block and Complete Heart Block (CHB) scheduled to undergo right ventricular apical pacing. 2D echocardiography was done at baseline, 1 month and 12 months. Pacing-induced cardiomyopathy was defined as a reduction in LVEF to <45%. Strain was evaluated off-line from digitally stored images using all advanced software package (cardiac wall motion quantification (CMQ); Toshiba Medical Systems). Longitudinal strain for individual myocardial segments was measured from the apical four-chamber, two-chamber and long axis views (16 segment AHA/ASE model). None had LV dysfunction at baseline based on 2D and strain echo imaging. Subsequently 18 patients were detected to develop low GLS score (less than -14.5) at 1 month. On subsequent follow up at 1 year, all 18 patients developed LV dysfunction on 2D Echocardiography. Thus Strain imaging with GLS score helped in early detection of LV dysfunction in RV apical pacing subjects. Pacing-induced cardiomyopathy had significant association with high grade AV block with pacemaker dependency. It had no significant associations with other comorbidities like diabetes, hypertension, ischemic heart disease or with the type of medication intake. However there was a statistically significant association with heart failure

Prevalence of subclinical systolic dysfunction in Takayasu's arteritis and its association with disease activity: a cross-sectional study

Abstract Background Takayasu's arteritis (TA) is a vasculitis that affects the aorta and its branches and causes stenosis, occlusion, and aneurysms. Up to 60% of TA patients are associated with cardiac involvement which confers a poor prognosis. Global longitudinal strain (GLS) analysis is an echocardiographic technique that can detect the presence of subclinical systolic dysfunction. Hence, this study aimed to describe the prevalence of subclinical systolic dysfunction in patients with TA using the GLS method and to correlate this finding with disease activity using the ITAS-2010 (Indian Takayasu Activity Score). Methods Thirty patients over 18 years of age who met the American College of Rheumatology (ACR) 1990 criteria for TA were included. The sample was submitted for medical record review, clinical and echocardiographic evaluation, and application of ITAS-2010. The cutoff for systolic dysfunction was GLS > - 20%. Results Of the 30 patients analyzed, 25 (83.3%) were female, and the mean age was 42.6 years (± 13.2). The median time since diagnosis was 7.5 years [range, 3-16.6 years], and the type V angiographic classification was the most prevalent (56.7%). Regarding echocardiographic findings, the median ejection fraction (EF) was 66% [61-71%] and the GLS was - 19.5% [-21.3 to -15.8%]. Although half of the participants had reduced GLS, only two had reduced EF. Eleven patients (33.%) met the criteria for activity. An association was found between disease activity and reduced GLS in eight patients (P = 0.02) using the chi-square test. Conclusion GLS seems to be an instrument capable of the early detection of systolic dysfunction in TA. The association between GLS and disease activity in this study should be confirmed in a study with a larger sample size.

Doxorubicin cardiotoxicity and Camellia sinensis cardioprotection determined by speckle-tracking echocardiography

Abstract Doxorubicin (Dox) is a medication used in the treatment of cancerous tumors and hematologic malignancies with potentially serious side effects, including the risk of cardiotoxicity. Flavonoids are plant metabolites with antioxidant properties and can be extracted from Camellia sinensis (CS). The aim of this study is to evaluate the possible cardioprotective effect of CS against injuries induced by Dox in rats. A total of 32 animals were distributed into four groups: (1) control - intraperitoneal injection (I.P.) of 0.5 mL saline weekly and 1.0 mL water by gavage daily; (2) CS - 0.5 mL saline I.P. weekly and 200 mg/kg CS by gavage daily; (3) Dox - 5.0 mg/kg Dox I.P. weekly and 1.0 mL water by gavage daily; and (4) Dox+CS -5.0 mg/kg Dox I.P. weekly and 200 mg/kg CS by gavage daily. Clinical examinations, blood profiles, electrocardiograms, echocardiograms, and histological analyses of hearts were performed over 25 days. The animals in the Dox group showed changes in body weight and in erythrogram, leukogram, electrocardiography, and echocardiography readings. However, animals from the dox+CS group had significantly less change in body weight, improved cardiac function, and showed more preserved cardiac tissue. This study demonstrated that CS prevents dox-induced cardiotoxicity, despite enhancing the cytotoxic effect on blood cells

The predictive value of left ventricular global longitudinal strain in normotensive critically ill septic patients / Valor preditivo do strain longitudinal global do ventrículo esquerdo em pacientes críticos normotensos com sepse

ABSTRACT Objective: Evaluation of left ventricular systolic function using speckle tracking echocardiography is more sensitive than conventional echocardiographic measurement in detecting subtle left ventricular dysfunction in septic patients. Our purpose was to investigate the predictive significance of left ventricular global longitudinal strain in normotensive septic intensive care patients. Methods: This observational, prospective cohort study included septic normotensive adults admitted to the intensive care unit between June 1, 2021, and August 31, 2021. Left ventricular systolic function was measured using speckle-tracking echocardiography within 24 hours of admission. Results: One hundred fifty-two patients were enrolled. The intensive care unit mortality rate was 27%. Left ventricular global longitudinal strain was less negative, which indicated worse left ventricular function in non-survivors than survivors (median [interquartile range], -15.2 [-17.2 - -12.5] versus -17.3 [-18.8 - -15.5]; p < 0.001). The optimal cutoff value for left ventricular global longitudinal strain was -17% in predicting intensive care unit mortality (area under the curve, 0.728). Patients with left ventricular global longitudinal strain > -17% (less negative than -17%, which indicated worse left ventricular function) showed a significantly higher mortality rate (39.2% versus 13.7%; p < 0.001). According to multivariate analysis, left ventricular global longitudinal strain was an independent predictor of intensive care unit mortality [OR (95%CI), 1.326 (1.038 - 1.693); p = 0.024], along with invasive mechanical ventilation and Glasgow coma scale, APACHE II, and SOFA risk scores. Conclusion: Impaired left ventricular global longitudinal strain is associated with mortality and provided predictive data in normotensive septic intensive care patients.

RESUMO Objetivo: A avaliação da função sistólica do ventrículo esquerdo utilizando ecocardiografia com speckle tracking é mais sensível do que a medição ecocardiográfica convencional na detecção de disfunções sutis do ventrículo esquerdo em pacientes sépticos. Nosso objetivo foi investigar a significância preditora do strain longitudinal global do ventrículo esquerdo em pacientes sépticos normotensos internados em unidades de terapia intensiva. Métodos: Este estudo de coorte observacional e prospectivo incluiu adultos sépticos normotensos internados em uma unidade de terapia intensiva entre 1° de junho de 2021 e 31 de agosto de 2021. A função sistólica do ventrículo esquerdo foi mensurada utilizando a ecocardiografia com speckle tracking nas primeiras 24 horas após a internação. Resultados: Foram recrutados 152 pacientes. A taxa de mortalidade na unidade de terapia intensiva foi de 27%. O strain longitudinal global do ventrículo esquerdo foi menos negativo, o que indicou pior função do ventrículo esquerdo em não sobreviventes do que em sobreviventes (mediana [intervalo interquartil] -15,2 [-17,2 - -12,5] versus -17,3 [-18,8 - -15,5]; p < 0,001). O valor de corte ótimo para o strain longitudinal global do ventrículo esquerdo foi -17% para prever a mortalidade na unidade de terapia intensiva (área sob a curva de 0,728). Pacientes com strain longitudinal global do ventrículo esquerdo > -17% (menos negativo do que -17%, o que indicou pior função do ventrículo esquerdo) apresentaram taxa de mortalidade significativamente maior (39,2% versus 13,7%; p < 0,001). De acordo com a análise multivariada, o strain longitudinal global do ventrículo esquerdo foi um preditor independente de mortalidade na unidade de terapia intensiva [RC (IC95%), 1,326 (1,038 - 1,693); p = 0,024], com ventilação mecânica invasiva e os escores de risco da escala de coma de Glasgow, APACHE II e SOFA. Conclusão: Alterações do strain longitudinal global do ventrículo esquerdo estão associadas a mortalidade e podem fornecer dados preditivos em pacientes sépticos normotensos internados em unidades de terapia intensiva.

Aportes del ecocardiograma y las técnicas de deformación miocárdica en la amiloidosis cardíaca: bases de la técnica y hallazgos de utilidad diagnóstica / Contributions of echocardiography and myocardial deformation techniques in cardiac amyloidosis: basis of the technique and diagnostically useful findings / Contribuições da ecocardiografia e das técnicas de deformação miocárdica na amiloidose cardíaca: base da técnica e resultados diagnosticamente úteis

La amiloidosis cardíaca es una miocardiopatía restrictiva infiltrativa secundaria al depósito extracelular de amiloide. Las diferentes técnicas de imagen cardíaca permiten la evaluación de forma no invasiva. El ecocardiograma juega un rol central en la evaluación diagnóstica, pronóstica y ayuda a guiar el tratamiento. El objetivo de este artículo de revisión es describir las diferentes herramientas que nos brinda la ecocardiografía, poniendo énfasis en el strain por speckle tracking y describir su rol en el diagnóstico de esta patología.

Cardiac amyloidosis is an infiltrative restrictive cardiomyopathy secondary to extracellular amyloid deposition. Different cardiac imaging techniques allow noninvasive evaluation. Echocardiography plays a central role in diagnostic and prognostic evaluation and helps to guide treatment. The aim of this review is to describe the different tools provided by echocardiography, with emphasis on speckle tracking strain and to describe its role in the diagnosis of this pathology.

A amiloidose cardíaca é uma cardiomiopatia restritiva infiltrativa secundária ao depósito de amiloide extracelular. Diferentes técnicas de imagem cardíaca permitem fazer uma análise não invasiva. A ecocardiografia desempenha um papel central no diagnóstico e na avaliação prognóstica e ajuda a orientar o tratamento. O objetivo deste artigo de revisão é descrever as diferentes ferramentas proporcionadas pela ecocardiografia, com ênfase no strain por speckle tracking, e descrever o seu papel no diagnóstico desta patologia.

Une double discordance cardiaque complexe décompensée, à propos d'un cas et revue de la littérature / A double cardiac discordance decompensated, about a case and review of the literature

La double discordance est une cardiopathie congénitale complexe extrêmement rare, elle se caractérise par une discordance auriculo-ventriculaire suivie d'une autre discordance ventriculo-artérielle. Son diagnostic est posé généralement à l'âge adulte par des examens d'imagerie. Son pronostic dépend essentiellement des autres malformations congénitales cardiaques associées, des arythmies et des troubles de la conduction, ainsi que de la fonction systolique du ventricule droit en position systémique. Nous rapportons le cas d'un patient âgé de 23 ans, porteur d'une cardiopathie congénitale complexe cyanogène. Il s'agit d'une double discordance associée à une large communication interventriculaire sous aortique avec un shunt inversé et une hypoplasie de l'artère pulmonaire. Ce diagnostic a été confirmé par l'imagerie multimodale. Non opéré, le patient a vu son stade fonctionnel s'aggraver rapidement avec une dyspnée qui est passée d'un stade I à un stade III-IV de la New York Heart Association (NYHA), et apparition de signes hypoxiques et congestifs. A travers cette observation, nous avons précisé les caractéristiques anatomocliniques de cette cardiopathie congénitale complexe cyanogène, son exploration, ses options thérapeutiques, ainsi que le rôle péjoratif de son association avec d'autres malformations congénitales.

Double discordance is an extremely rare complex congenital heart disease; It is characterized by atrioventricular discordance followed by another ventriculo-arterial discordance. Its diagnosis is usually made in adulthood by imaging examinations. Its prognosis depends mainly on other associated congenital heart defects, arrhythmias and disorders of the conduction, as well as systolic function of the right ventricle in the systemic position. We report the case of a 23-year-old patient with a complex cyanogen heart disease.It is a double discordance associated to an interventricular communication with reverse shunt and an hypoplasia of the pulmonary artery.This Diagnosis was confirmed in multimodal imaging. Non-operated, the patient saw his functional status worsen rapidly with dyspnea which went from stage I to stage III-IV of the New York Heart Association (NYHA), and appearance of hypoxic and congestive signs. Through this observation, we have clarified the anatomoclinical characteristics of this complex congenital cyanogens heart disease, the necessary explorations and the different therapeutic options, as well as the pejorative role of its association with other congenital malformations.

Left Ventricle Longitudinal Strain Parameters Are Effective for Differentiating Cardiac Amyloidosis from Primary Hypertensive Left Ventricular Hypertrophy / 中山大学学报(医学科学版)

ObjectiveTo clarify the value of the left ventricular longitudinal strain（LVLS）parameters in patients with cardiac amyloidosis （CA） and primary hypertension with left ventricular hypertrophy （HLVH）. MethodsForty-one patients confirmed with CA were selected and assigned to CA with hypertension group （n =14） and pure CA group （n=27） based on the initial diagnosis with or without hypertension. Twenty patients with primary hypertension-induced left ventricular hypertrophy （HLVH group） and twenty healthy controls were also selected， matching for gender， age， and body surface area. Clinical data， conventional echocardiography parameters were collected and LVLS parameters were measured. Within-group variations were compared among the four groups， and pairwise comparisons were conducted between groups. The sensitivity and specificity of each parameter in predicting CA were judged by the receiver operator characteristic （ROC） curvy in CA and HLVH patients with left ventricular ejection fraction （LVEF） preserved. ResultsAmong the conventional echocardiography parameters， LVEF and left ventricular end-diastolic diameter （LVEDD） were lower in the CA with hypertension group and pure CA group compared with the higher values in the HLVH group and control group. Whereas， left ventricular posterior wall thickness （LVPWT）， relative wall thickness （RWT）， and average E/e' were higher in the two CA groups compared with the HLVH group （all P＜0.05）.Among the LVLS parameters， Global longitudinal strain （GLS） was the worst in the CA with hypertension group so as pure CA group， modest in the HLVH group， and highest in the control group. On the contrary， relative longitudinal strain and ejection fraction strain ratio （EFSR） were the highest in the CA with hypertension group so as to pure CA group， modest in the HLVH group， and lowest in the control group （all P＜0.05）. ROC analysis showed that when LVEF was preserved， the absolute value of GLS less than 14.35% and EFSR higher than 4.28 could effectively distinguish CA from HLVH （all AUCs＞0.9，all P＜0.05）； meanwhile GLS showed high sensitivity（100%） and EFSR showed great specificity（95%）. There were not statistically significance in any parameter between CA with hypertension group and pure CA group（all P＞0.05）. ConclusionWhether CA was complicated with hypertension or not， there were statistically significance among routine echocardiography and LVLS parameters compared with HLVH. In particular， GLS and EFSR are accurate in predicting CA in patients with myocardial hypertrophy and preserved LVEF.

Effects of Cyclic Strain on Neural Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells / 医用生物力学

Objective To study the mechanical effects of cyclic strain on neural differentiation of rat bone marrow mesenchymal stem cells (rBMSCs). Methods The rBMSCs were subjected to cyclic strain for 24 hours andthen cultured for 5 days. The expression of neural markers and the phosphorylation of relative signaling pathway proteins were evaluated. The stress distribution on cell surface was analyzed by finite element method. The differentially expressed genes induced by strain were identified by RNA sequencing analysis. Results The 0. 5 Hz strain with 5% magnitude could significantly induce higher expression of neural markers and elevated phosphorylation level of extracellular-signal-regulated kinase (ERK), protein kinase B (AKT) and mammalian target of rapamycin ( mTOR). KEGG pathway analysis showed that the focal adhesion and ECM-receptor interaction were significantly enriched under cyclic strain. Conclusions Cyclic strain could change the interaction of cells with the extracellular matrix ( ECM) and enhance the AKT/ mTOR and ERK pathway, finally promote rBMSC neural differentiation. Knowledge about the impact of mechanical stimulation on BMSC neural differentiation is expected to improve the efficiency of stem cell differentiation, shed light on device design for tissue engineering, and promote clinical application of mesenchymal stem cells in neural issue repair and regeneration.

Genome sequencing and analysis of BCG strain for vaccine production in China / 上海预防医学

ObjectiveTo conduct the sequencing and preliminarily analysis of the whole genome of BCG Shanghai D2PB302 strain （hereinafter referred to as BCG Shanghai D2 strain）， which has been used exclusively for the vaccine production in China. MethodsThe DNA of of BCG Shanghai D2 strain （D2-JIA12-1） was extracted， and the whole genome was sequenced by Pacbio-RS Ⅱ. The sequence data was assembled by Smrtlink and polished with the illumina data. Genes， tRNA and rRNA were predicted based on the sequence data. The functional annotation of predicted genes was performed through BLASTP. The IVE-TB antigen gene and MTBVAC were selected as the target sequences to be compared with Mycobacterium tuberculosis H37Rv （NC_000962.3）. ResultsThe sequence length of BCG Shanghai D2 strain was 4 045 232 bp， and the GC content was 65.66%. A total of 4 259 protein-encoding genes were predicted， with an average gene size of 933 bp. 2 476 genes had biological functions and others were hypothetical proteins.144 virulence genes were obtained by comparing with the VFDB. There were 29 type Ⅶ secretion system genes and 10 PE/PPE protein family genes. ConclusionThe whole genome sequence of BCG Shanghai D2 strain is clarified. It lays a broad foundation for subsequent detection of the stability of major antigen genes.

Screening,identification,enzymatic characteristics and optimization of fermentation condition of a high alkaline xylanase-producing strain / 中国生物制品学杂志

@#ObjectiveTo screen a high alkaline xylanase-producing strain,subject to molecular identification and characterization of enzymatic property,and optimize its fermentation condition.MethodsThe farmland soil samples from Shanxi,Henan and Zhejiang Provinces were collected aseptically,from which the high xylanase-producing strains were screened by enrichment culture,isolation and identification of 16S r DNA,and determined for enzymatic properties.The carbon source(xylan,lactose,soluble starch,sucrose,bran and glucose),nitrogen source[ammonium oxalate,peptone,yeast powder,(NH_4)_2SO_4,NH_4Cl,Na NO_3,urea,beef extract,bean powder,KNO_3,(NH_4)_2HPO_4or random mixture of two of peptone,yeast powder,beef extract,(NH_4)_2HPO_4and bean powder],metal ion[CuCl_2,MgCl_2,ZnCl_2,Al_2(SO_4)_3,CoCl_2,MnCl_2,AgNO_3,NaCl,CaCl_2,FeCl_2,BaCl_2 and FeCl_3],pH value(3.0～10.0)in medium and the fermentation temperature(25,28,30,33,35,37 and 40℃)were optimized by single factor test,while the contents of components[xylan,(NH_4)_2HPO_4and bean powder]by response surface method.The high alkaline xylanase-producing strain was fermented by using the optimized medium under the optimized condition,and determined for xylanase activity,and the result was compared with that predicated in model.ResultsA high alkaline xylanase-producing strain named as SX6-18 was screened and identified as Paemibacillus based on 16s rDNA sequence analysis.The xylanase produced by the strain maintained more than 70%of relative activity at temperatures of 25～55℃and pH 6.0～10.0.Mg(2+)promoted while Fe(2+)promoted while Fe(3+),Mn(3+),Mn(2+)and Cu(2+)and Cu(2+)inhibited the activity of xylanase.The optimal carbon source,nitrogen source and metal ion of the medium were xylan,bean powder+(NH_4)_2HPO_4 and Fe(2+)inhibited the activity of xylanase.The optimal carbon source,nitrogen source and metal ion of the medium were xylan,bean powder+(NH_4)_2HPO_4 and Fe(3+),while the optimal p H value and temperature for fermentation were 8.0 and 30℃，respectively.However,the optimal component contents were 15.00 g/L xylan,3.03 g/L(NH_4)_2HPO_4and 3.28 g/L bean powder.The activity of xylanase cultured in optimized medium under opti-mized condition for fermentation reached 701.08 U/m L,which was closed to the expected value(693.96 U/m L).ConclusionA high alkaline xylanase-producing strain SX6-18 was successfully screened,which maintained relatively high enzyme activity in alkaline condition.This study laid a foundation of application of xylanase in papermaking and washing fields.