Background: Human immunodeficiency virus (HIV) is a retrovirus that integrates its genetic material into the host genome and establishes as a permanent chronic infection. HIV-1 infected individuals develop antibodies to gp41and the immune response varies from early to chronic stage of infection. We, therefore, performed studies to identify epitopes in the gp41 proteins that could potentially serve as biomarkers for changes in epitope recognition during disease progression. Method: Peptides of 20-mer with an overlap of 10 amino acids having two extra lysine at the N-terminus were synthesized for gp41 and were coated on to 96 well microplate. These peptides were evaluated using a europium nanoparticle-based immunoassay (ENIA) for binding of antibodies from patients who had recent or longstanding HIV -1 infection. We tested HIV-negative plasma control and calculated the signal ratio between negative and positive plasmas. Results and conclusion: We identified three contiguous gp41 peptides gp16, gp17 and gp18, which elicit strong antibody reactivity with plasma from persons with long standing infection and little or low reactivity with recent infections. These three gp41 peptides showed consistent positive reactivity in different sets of well characterized long standing HIV infected patient Plasmas and negative or very low response in recently infected plasma.

Automatic Violence Detection and Classification (AVDC) with deep learning has garnered significant attention in computer vision research. This paper presents a novel approach to combining a custom Deep Convolutional Neural Network (DCNN) with a Gated Recurrent Unit (GRU) in developing a new AVDC model called BrutNet. Specifically, we develop a time-distributed DCNN (TD-DCNN) to generate a compact 2D representation with 512 spatial features per frame from a set of equally-spaced frames of dimension 160×90 in short video segments. Further to leverage the temporal information, a GRU layer is utilised, generating a condensed 1D vector that enables binary classification of violent or non-violent content through multiple dense layers. Overfitting is addressed by incorporating dropout layers with a rate of 0.5, while the hidden and output layers employ rectified linear unit (ReLU) and sigmoid activations, respectively. The model is trained on the NVIDIA Tesla K80 GPU through Google Colab, demonstrating superior performance compared to existing models across various video datasets, including hockey fights, movie fights, AVD, and RWF-2000. Notably, our model stands out by requiring only 3.416 million parameters and achieving impressive test accuracies of 97.62%, 100%, 97.22%, and 86.43% on the respective datasets. Thus, BrutNet exhibits the potential to emerge as a highly efficient and robust AVDC model in support of greater public safety, content moderation and censorship, computer-aided investigations, and law enforcement.

A 15-year-old Warmblood gelding was presented with macroscopic hematuria and stranguria symptoms for two months. Cystoscopy revealed a pedunculated cauliflower-like mass, flowing from the right ureteral orifice into the bladder. Ureteroscopy showed a right dilated ureter (2.3 mm). The ureteral lumen mucosa was smooth and the mass had its origin approximately 10 cm cranial from the orifice. The right kidney was macroscopically on ultrasound within normal range. The mass was removed transendoscopically by means of a cautery snare leaving a small part at the base. Histopathological analysis identified it as a mucosal polyp. Recovery was uncomplicated and the gelding was discharged three days after surgery. A follow up 5 months later showed no signs of inflammation and the remaining small stalk in the right ureter.

Purpose Evaluate the potential risk for long-term complications related to cancer therapy among childhood cancer survivors who completed treatment in Tanzania at Bugando Medical Centre (BMC), and compare the relative risk assessment of BMC survivor cohort and British Childhood Cancer Survivor Study (BCCSS) cohort. Methods Files of all patients age <18 yo with an oncologic diagnosis who received and completed their treatment at BMC from 2016 to 2022 were retrospectively reviewed. Extracted data included patient demographics, primary disease diagnosis and site, treatment received, and cumulative treatment doses. BCCSS risk assessment was assigned. Predicted long term follow up surveillance needs were extrapolated from published Children’s Oncology Group Long-Term Follow-Up Guidelines. Results A total of 173 patients were included in the survivor cohort (47% female, average age =7). The most common diagnoses were Burkitt lymphoma (26%, n=45) and Wilms (30%, n=52). Within the cohort, 98% received chemotherapy (n=170), 49% (n=73) underwent tumor resection, and 18% (n=32) received radiation. Distribution of BCCSS late effect risk assessment included 6% low risk (n=10), 80% moderate risk (n=139) and 14% (n=24) high risk. Based on treatment received, the late effects with highest potential risk were cardiomyopathy (57% of patients, n=98), bladder and urinary tract toxicity (50%, n=87), and ototoxicity (22%, n=38). Conclusion Childhood cancer survivors at BMC have a higher risk of late effects as compared to published survivor cohorts in high-income countries. There is a need to develop and improve long-term follow-up care for survivors by enhancing patient and provider education to promote early detection of late effects.[1](#fn-0002)

The research was investigated in mice. The mice were acclimatized and randomly divided into two groups namely the control and treated groups (n=10) respectively. The treated mice were supplied ciprofloxacin antibiotic 50ppm drinking water ad libitum for a consecutive period of one year. The body weight of treated mice was found significantly higher from 3rd month onwards. The pattern of body weight was highest in the 10th month followed by decreasing in pattern but was significant until the day of sacrifice. Treated mice showed a decreased number of lymphocytes, neutrophils & monocyte. Both ALT and AST enzymes up-regulated in treated mice. Liver histopathology showed steatosis, enlarged central vein, and infiltration of inflammatory cells into the central vein. Kidney histopathology demonstrated atrophy, fragmentation of glomeruli, degeneration & necrosis. TLC analysis revealed ciprofloxacin antibiotic residue further deposited antibiotic residue in the liver, kidney, spleen, intestine, breast muscle, and thigh muscle.

Introduction The elbow is a complex joint consisting of ulnohumeral, proximal radioulnar, and radiocapitellar articulation. The elbow joint is the second most commonly dislocated joint in adults after dislocation of the shoulder. The annual incidence of simple and complex elbow dislocations is 6.1 per 100,000 (1) and they are classified as pure or complex as they are associated with fracture.Diverse mechanisms are reported as causes of elbow dislocation such as hyperextension, direct impact, axial varus-supination-compression, and axial valgus-supination-Compression. (2). Radial head fractures are the most frequent ones in the elbow (3). They are caused by axial mechanisms with the upper limb in extension and the forearm in pronation (posture in which pressure is more strongly transmitted through the radius). In divergent dislocations, the proximal radius and ulna are wedged apart by the humerus.The severity of radial head fractures is the presence of associated injuries. Most common injuries associated with radial head fractures into 5 patterns: a)fracture of the radial head and rupture of the interosseous ligament of the forearm (Essex-Lopresti) (4); b) Fracture of the radial head and rupture of the medial collateral ligament (MCL) or capitellar fracture; c) Fracture of the radial head and posterior dislocation of the elbow; d) Terrible triad injuries (posterior dislocation of the elbow with fractures of the radial head and coronoid process); and e) posterior olecranon fracture dislocations (posterior Monteggia pattern injuries) (5).Mason’s classification divides radial head fractures into: type I: non-displaced or <2mm-displaced fractures; type II: displaced fractures; type III: comminute fractures; and type IV: fractures associated with dislocation (6).We present a patient who suffered an elbow dislocation associated with fracture of the radial head

All authors have no conflict of interest to declareNo funding sourcesPatients signed informed consent regarding publishing their data and photographsAbstract :The occurrence of superficial vein aneurysms is uncommon. This report includes three lower extremity cases: a 38-year-old man with a Great saphenous vein aneurysm mimicking an inguinal hernia, a 40-year-old woman with a Small saphenous vein aneurysm at the back of her knee, and a 35-year-old smoker man with a dorsal foot mass confirmed as a medial marginal vein aneurysm on doplex sonography. All patients denied any prior trauma. All patients denied a history of trauma. and all of them had no medical history. all aneurysms were excised and their postoperative evaluation were uneventful. This article may increase awareness and encourage surgeons and radiologists to consider venous aneurysm as a differential diagnosis among all lower limb lesions, from the groin to the foot.Key Words : Lower Extremity, Aneurysm, Veins, Venous Thrombosis, saphenous veinIntroduction :The superficial venous system is a complicated web of collecting veins and thicker-walled truncal veins that run between the skin and the muscle fascia. They serve as large-capacitance reservoirs and are responsible for venous drainage from the skin and subcutaneous tissue(1). Superficial venous aneurysms can be misinterpreted as several soft tissue tumors and hernias dependent on the location of the aneurysm. In case of the lower extremity, distinguishing between varicose veins and venous aneurysms is also important. Because of their distinct pathophysiology, the management strategies for these two clinical entities differ(2). Although uncommon, thrombosis and concomitant embolism have been reported in association with vein aneurysms (3-5). This paper summarizes three rare cases of superficial vein aneurysms in diverse locations of the lower limb, with their presentation, chief complaint, and management. all patients presented to the Shohadaye Tajrish hospital’s outpatient clinic.Case 1:A 38-year-old man arrived with a compressible mass at the groin region (figure 1). he never had any episodes of pain and denied trauma to the area. He first noticed swelling about a year ago, it varied with position and was easily repressed by hand pressure (Figure2). The patient was a smoker with no history of DVT, malignancy, or other complications. Physical examination revealed a 4 × 5 cm2soft mass with no discomfort. His left leg had a moderate amount of varicosities. Doppler sonography verified the diagnosis. A Right oblique inguinal incision was performed under spinal anesthesia, the aneurysm of great saphenous vein (GSV) was excised, distal and proximal veins were ligated.Case 2:A 40-year-old woman presented with a painless mass at the back of her knee during the past 6 months. There are no additional comorbidities, and she has never smoked. There was no history of leg trauma, DVT, edema. On exam, the patient had an erythematous non-pulsatile, 4 × 1 cm2 mass that was non-tender to palpation. Doppler sonography confirmed the diagnosis. In the operating room, the aneurysm was excised and the proximal and distal continuation of the small saphenous vein (SSV) were ligated(Figure 3). The patient tolerated the procedure well and was discharged home on postoperative day 1Case 3:A 45-year-old man with a complaint of a mass on the medial of his right foot that made him uncomfortable when he wore shoes. He had no other significant medical or smoking history. On physical examination, a soft lesion measuring 3 × 4 cm2 was found on the top of the foot (Figure 4). The diagnosis was confirmed by Doppler ultrasound. Ligation and simple excision was the utilized technique in the surgery. The patient was operated under local anesthesia with lidocaine solution. Via longitudinal skin incision, the sac of aneurysm was visualized and has been dissected from the surrounding tissues

Conventional approaches on using hydroxylamine derivatives as single nitrogen sources, for the preparation of N-heterocyclic molecules, rely upon two chemical operations by involving sequential nucleophilic and electrophilic C−N bond formations. Here, we report a novel Suzuki reaction/C−H activation/amination sequence for building up a myriad of carbazoles, in a single transformation, using bifunctional secondary hydroxylamines. Noteworthy, the synthetic utility of this methodology is highlighted with the total synthesis of Clausine V and Glycoborine by incorporating the titled [2+2+1] cycloamination as the key step. Control experiments were performed to gain a better understanding of the reaction mechanism.

Herein, we synthesized two small molecules named as 4TBTCN and 6TBTCN with strongly electron-rich 4T and 6T as central unit and weak electron-withdrawing benzo[c][1,2,5]thiadiazole-4-carbonitrile as termini, which were connected by C-C single bond. Both mole-cules exhibited medium optical bandgap and high-lying frontier molecular orbital energy levels, which were matched with those of the representative low-cost polymer donor P3HT. Moreover, 4TBTCN and 6TBTCN showed high stability under continuous illumination and base condition, owing to a lack of exocyclic vinyl group between the central unit and end group. Compared to P3HT:6TBTCN, P3HT:4TBTCN blend system displayed lower miscibility and thus more distinct phase separation, leading to more efficient charge transport and collection. Although the LUMO energy level of 4TBTCN was 0.15 eV deeper than that of 6TBTCN, the energy loss for P3HT:4TBTCN based device was similar to that of P3HT:6TBTCN based device. As a result, P3HT:4TBTCN based device displayed a similar open-circuit voltage but higher fill factor and short-circuit current density, yielding a superior power conversion efficiency, in comparison to P3HT:6TBTCN based device. This work provides a new strategy for design of efficient and stable acceptor molecules.

Video capsule endoscopy (VCE) is a minimally invasive diagnostic technique that helps in the detection of various anomalies like polyps, ulcers, aphthae, etc, within the intestinal lumen. Due to the high no. of frames in VCE and the low doctor-to-patient ratio across the globe, the inspection time of VCE is about 2-4 hours. Research has shown that Artificial Intelligence (AI) has the potential to decrease the inspection time in VCE reading and improve upon the false-positive rates. However, the lack of AI data is a big hindrance to it. To address this issue, we present the VCE-AnomalyNet Dataset, a new AI dataset fueling AI precision in anomaly detection for VCE. The dataset comprises 108,832 accurately labeled frames with bounding box annotations in YOLO (You Only Look Once) format. These frames have been compiled from multiple open-source datasets, aiming to support research in automatic anomaly detection in VCE. The dataset is available at VCE-AnomalyNet Dataset (zenodo.org) .

A new way was used to modify the thermal, electrical, optical, and antimicrobial properties of polyaniline by embedding a nanosized metal in the polymeric matrix. The sequence of fabrication was as follows: first, preparing a silver colloid by gamma-irradiating the precursor and then, aniline was polymerized in the colloid using different molarities of dopant and silver. The obtained Ag colloid and the polymer / Ag nanocomposites (NCs) were studied for their properties using TGA, electrical measurements, UV-Vis spectroscopy, FTIR, TEM, SEM, DLS, SAED, and EDX. The particle size of the Ag colloid is ranged from 7 to 17 nm. The conductivity of NCs increased with increasing dopant, while an unexpected reduction of conductivity was obtained with the increase of Ag content due to some agglomerations. All the prepared NCs exhibited medium to high antibacterial activity against Escherichia coli and Staphylococcus aureus reaching the maximum efficiency at PANI: Ag: dopant molar ratio of 1:1:0.83. Also, an electrostatic interaction has been generated between the polyaniline chains and the free electrons around Ag NPs leading to a conjugating electron cloud in the produced NCs. This electronic behavior facilitates the use of the prepared NCs as supercapacitors, sensors, photocatalysts, or antibacterial materials.

Key clinical message:This is the image of dentigerous cyst detected in the medial wall of maxillary sinus, a rare location for the mentioned cyst, which emphasizes the superiority of radiographic features from the site of the lesion. Moreover, the present case showed no facial asymmetry despite the extension of the lesion.Keywords:Dentigerous cyst, impacted third molar, maxillary sinusCase description:A 22-year-old woman was referred to the private radiographic center for a cone beam computed tomography (CBCT) scan due to a lesion discovered in a previous panoramic radiography. The patient chief complaint was pus drainage at the distal portion of upper left last tooth. No facial asymmetries or other clinical features were identified, and the patient did not report any other complications including airway obstruction. No medical history was also reported.The evaluation of CBCT scan, including axial, coronal, sagittal and 3-dimensional reconstructed aspects, revealed an extensive lesion surrounding the coronal part of the impacted ectopic tooth no. 16, locating in the left maxillary sinus. The border of the lesion was well-defined and corticated. Double cortex view was visible in coronal, sagittal and axial aspects. The internal structure of the lesion was unilocular and radiolucent. However, it was responsible for the opacity observed in the left maxillary sinus. The dimensions of the lesion were 41 mm vertically, 36 mm antero-posteriorly and 25 mm medio-laterally.The lesion displaced tooth no. 16, pushing it towards nasal fossa. It had also occupied the entire left maxillary sinus, caused displacement and thinning of the left maxillary sinus walls. Bony perforation was visible at the distal site of the tooth no. 15, probably responsible for the pus drainage at the distal portion of tooth no. 15. Additionally, severe displacement of the medial wall of left maxillary sinus to the midline with prolapse into the ethmoidal air cells and nasal fossa, narrowing of left nasal airway, and obstruction of the left maxillary sinus ostium were visible.The lesion was attached to the tooth via cementoenamel junction as seen in figure 1.Among differential diagnoses including unicystic ameloblastoma and dentigerous cyst, based on these radiographic findings, the diagnosis of a dentigerous cyst was made. The patient was then referred to an oral and maxillofacial surgeon for further management of the lesion, which may include marsupialization or enucleation, as well as pathological evaluations.Dentigerous cyst (DC) also called follicular cyst, is the most common noninflammatory and also the second most common odontogenic cyst originating from the reduced enamel epithelium, which is proliferated due to the osmotic pressure resulting from a fluid filled sac (1, 2). It is more frequent in males and the incidence of the aforementioned cyst is approximately 70% in the mandible and its occurrence in the maxilla is rare (2, 3). In cases with the diagnosis of DC in the maxilla, the impacted canine is usually the responsible tooth and the diagnosis of DC involving a maxillary impacted third molar is very rare (3). Radiographically, DC is a radiolucent lesion, presenting either unilocular or scalloping multilocular pattern (2). The important diagnostic key is the engagement of the cyst’s well-defined and corticated periphery to the cementoenamel junction of the involved tooth (1).Author contributionsMaryam Mohebiniya: Conceptualization, investigation, project administration, supervision, visualization, writing – review & editing. Soheila Jadidi: writing – original draft, writing – review & editing.Conflict of interestsNoneDeclaration of patient consentThe patient has given her consent for her clinical information to be reported in the journal.AcknowledgmentNoneReferences1. Sanjay Mallya EL. White and Pharoah’s Oral Radiology. 8th ed2018.2. Motamedi MHK, Talesh KT. Management of extensive dentigerous cysts. British Dental Journal. 2005;198(4):203-6.3. Asnani S, Mahindra U, Rudagi B, Kini Y, Kharkar V. Dentigerous cyst with an impacted third molar obliterating complete maxillary sinus: Official Publication of Indian Society for Dental Research. Indian Journal of Dental Research. 2012;23(6):833-5.Figure LegendsFigure 1: (a) axial and (b) coronal CBCT scan revealing an extensive lesion surrounding the coronal part of the impacted ectopic tooth no. 16, locating in the left maxillary sinus. Note the attachment of the lesion to the tooth via cementoenamel junction.

Silicon epitaxy is an essential building block in the manufacturing of complementary metal-oxide semiconductor (CMOS) devices. Accurate determination of epitaxial layer thickness is indispensable for a uniform and reproducible process. In this paper, we compare thickness values of the transition zone in silicon epitaxial wafers obtained by two of Semilab’s production-compatible electrical and optical characterization techniques: Fourier-transform infrared (FTIR) reflectometry and spreading resistance profiling (SRP). We demonstrate a high correlation between transition zone thicknesses obtained from the optical modelling of FTIR reflectance spectra and SRP profiles. The dependance of transition zone thickness change on the high-temperature annealing steps is also examined. FTIR reflectometry thus offers a quick, contactless alternative for obtaining structural parameters of an epitaxial layer, and these values can be well matched to those given by SRP.

Scientists have not always had freely accessible high-quality and high-resolution datasets relevant to their study systems. Today, early career researchers routinely confront a deluge of data that is relevant to their research questions. Early-career scientists face the combined challenges of using accessible yet powerful models, under high publication pressure, and with mixed guidance from scientists trained under an earlier era. There exists a temptation to reach for black-box analytical approaches to offer guidance through this wilderness of data. New complex models consisting of artificial intelligence and machine learning tools are poised to be co-opted by large numbers of early career researchers due to their modelling strength and easy, out-of-the-box usage. Just because we can use these new tools, does not mean we always should. I emphasise the role of complexity in the construction of our ecological models and suggest a new model planning process which early career researchers can use when trying to develop our understanding of the natural world.

Leukemia cutis revealing relapse of a chronic myeloid leukemia: a case report

Differentiation plays a crucial role in estimating system states, especially in embedded systems where direct measurements might be noisy or unavailable. This study delves into various differentiation techniques tailored for the Arduino platform, an archetype of embedded systems. Beginning with a first-order differentiation method, the research provides a clear path from fundamental principles to practical implementation. Progressing to a second-order differentiator, we examine the nuanced advantages and complexities it introduces, particularly in real-world applications. The exploration culminates in the discussion of high-gain observers, highlighting their potential in specific scenarios while emphasizing the challenges in noisy environments. Through theoretical derivations juxtaposed with experimental insights, this paper furnishes a holistic perspective on differentiation techniques for Arduino and analogous embedded platforms.

IntroductionCoronavirus disease 2019 (COVID-19) is a highly contagious respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus was first identified in Wuhan, China in December 2019 and has since spread globally, leading to a worldwide pandemic. The majority of individuals who contract COVID-19 experience mild to moderate symptoms and recover within a few weeks. However, a significant proportion of individuals continue to experience symptoms long after the acute phase of the illness has resolved, a condition known as Long-COVID or post-acute sequelae of SARS-CoV-2 infection (PASC).1 Long-COVID symptoms can be diverse and can range from mild to severe, and can include fatigue, depression, anxiety, joint pain, headaches, and cognitive impairment.There are currently no effective or broad treatment options for Long COVID, but some symptom-related management has been trialed. Traditional treatment options, including rehabilitation, physical therapy, and medications, may not be fully effective for all individuals.2 The pathophysiology of Long-COVID is still being elucidated and there is a need for alternative treatment options. A recent review has suggested that psilocybin and 3,4-Methyl​enedioxy​methamphetamine (MDMA) may be an effective treatment option for the mental health challenges associated with COVID.3 Psychedelics have been traditionally used in spiritual and religious practices, but in recent years, there has been a resurgence of research on the therapeutic potential of psychedelics.4 Psychedelics have shown promise in the treatment of various medical conditions such as depression, anxiety, PTSD, and addiction.4 This case report describes the experience of a 44-year-old female who developed Long-COVID symptoms after contracting COVID-19 and her experience managing her symptoms and using psychedelics as a treatment. To our knowledge, this is the first case report describing the potential efficacy of psychedelics for Long-COVID symptoms.

Animal camouflage serves the dual purpose of enhancing predation or anti-predation efficiency through strategies such as background matching, disruptive coloration, countershading, masquerade, and motion dazzle. Although body size and shape determine the visual appearance of animals, potentially affecting their camouflage effectiveness, research over the past two centuries has primarily focused on animal coloration. Over the past two decades, attention has gradually shifted to the impact of body size and shape on camouflage. In this review, we analyze the impact of animal body size and shape on camouflage based on existing research and identify research issues and challenges. The results of existing studies indicate a negative correlation between background matching effectiveness and an animal’s body size, whereas flatter body shapes enhancing background matching. The effectiveness of disruptive coloration is also negatively correlated with body size, whereas irregular body shapes physically disrupt the body outline, reducing the visibility of true edges and making it challenging for predators to identify prey. Countershading is more likely to occur in larger mammal groups with smaller individuals, whereas body size is unrelated to countershading in smaller animal groups. Different body shapes also contribute to variations in countershading effectiveness. Animals employing masquerade achieve camouflage by resembling inanimate objects in their habitats in terms of body size and shape. The camouflaging effect of motion dazzle is negatively correlated with body size; however, the impact of body shape on motion dazzle remains unknown. A significant research gap exists in examining correlations between various camouflage strategies and body size and shape. Further, insufficient exploration of these strategies warrants thorough investigation in the future to better understand the mechanisms and evolutionary factors influencing camouflage in animals. Our review provides a theoretical foundation for the development of novel camouflage strategies.

Plant responses to environmental heterogeneity depend on life-history traits, which could relate to phenotypical and genetic characteristics. To elucidate this relationship, we examined the variation in population genetics and functional traits of short- and a long-lived Artemisia species that are co-occurring in the steppes of Mongolia. Mongolian steppes represent stressful, waterlimited habitats demanding phenotypic modifications in the short term and/or genetic adaptation in the long term. However, detailed knowledge is missing about both plant phenotypic and genetic differentiation and their inter-relationships in temperate grasslands. Here, we investigated 21 populations of the widely distributed subshrub A. frigida and the herbaceous biennial A. scoparia. Genetic variation was assessed with newly developed Simple Sequence Repeats (SSRs) markers. Functional trait data was collected from each individual, and data on environmental variables was collected for each population. We detected significantly higher genetic diversity in the biennial species (H E =0.86) compared to the perennial (H E =0.79). For both species, the largest share of genetic variation was partitioned within populations (96%). Population genetic structure in the biennial A. scoparia was weak, while the perennial A. frigida showed some spatial genetic structure, which was impacted by geographical factors, soil nutrients, and precipitation. Morphology-related functional traits (i.e., plant height) were predominantly associated with environmental variables rather than with genetic variation, while physiology-related traits (i.e., specific leaf area) were partly genetically determined.

A document by Robyn Granger. Click on the document to view its contents.

THE ADDED VALUE OF LEFT ATRIAL STRAIN IN CANCER-THERAPY-RELATED CARDIAC DYSFUNCTIONByLaura Romero, MD and Michele Nanna, MDAlbert Einstein Coll of Med/ Cardiac Care and Vascular Medicine, Bronx, NYCorrespondence:Michele Nanna, MD,Associate Professor of Medicine, Albert Einstein College of Medicine/ Cardiac Care and Vascular Medicine1461 Astor Ave, Bronx, NY 10469, USAEmail: mnannamd@cardiovascularcare.orgCancer-therapy-related cardiac dysfunction (CTRCD) is an undesirable side effect of chemotherapy that occurs in approximately 10% of the patients [1]. Targeting early detection and advances in treatment increases cancer survivors [2]. The American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines recommend the use of Speckle-Tracking-derived LV Global Longitudinal Strain (LV-GLS) as a more objective and accurate method to identify subclinical LV deterioration in patient undergoing chemotherapy [3].In cancer patients, assessment of Left Atrium (LA) function by Speckle Tracking has emerged as a potential tool for predicting CTRCD and its associated morbid arrhythmias such as atrial fibrillation (AF), a frequent complication in this patient population [4-6].Early research work used volumetric approaches to derive LA function parameters. Volumetric parameters are widely used in standard clinical practice and current guidelines assigns prognostic value to end-systolic LA volume in patients with suspected LV diastolic dysfunction [3]. The relationship between LV filling and volumetric parameters is not linear and reduction in LV filling pressures reduces but rarely normalizes LA volumes. LA functional parameters, as measured by novel methods of deformation analysis, more reliably detect reductions in LV filling independent of LA volumes changes [7]. Speckle tracking echocardiography–derived analysis of LA strain provides quantitative parameters for all phases of LA function (reservoir, conduit, and booster pump) and carries similar prognostic significance to that provided by volumetric approaches, in different pathological conditions including cancer patients[5,8].Knowing the impact that LA functions has in detecting CTRCD the study by Lassen and colleagues has tested LA strain in the evaluation of CTRCD as a tool for early detection of myocardial damage induced by chemotherapy [9].In this retrospective cohort study a total of 170 women with HER2+ breast cancer (stage I-IV) undergoing treatment with trastuzumab were studied at baseline, 3 months into treatment and 1 year since treatment initiation. Of note, 77 (45.3%) of participants had prior exposure to anthracycline. Also of note, during the 1- year follow-up, 23 (13.5%) patients had trastuzumab held or stopped for either a decline in Left Ventricular Ejection Fraction (LVEF) in 82.6% of cases or other non-cardiac reasons in the remaining cases.A total of 36 patients developed CTRCD during follow-up. At 3-month follow-up, CTRCD patients had lower LVEF, LV-GLS, LA reservoir strain (LA εres), and LA conduit strain rate (LAεcon-sr) compared to patients that did not develop CTRCD. In the 36 patients developing CTRCD, there was a decline in LVEF from baseline to 3-months follow-up with partial recovery at 1-year follow- up. LV-GLS also declined at 3 months, however, contrary to LVEF a recovery did not occur at 1 year follow up. In the 134 patients who did not develop CTRCD during follow-up, LA Volume Index increased from baseline to 3-month follow-up and then modestly recovered at 1-year. LA strain parameters also declined during follow-up but to a lesser degree than in the CTRCD group suggesting its value as a more sensitive parameters of subtle functional changes. This study is one of the largest studies in patients with breast cancer that has assessed changes in LA strain parameters following treatment with transtuzumab.The new information provided by Lassen et al. is in demonstrating that cancer and its treatment with Transtuzumab may negatively affect atrial function and that measurements of LA strain can detect functional changes related to cardiotoxic effects of chemotherapy. Other studies also support the fact that cancer and chemotherapy can modified LA function earlier than LV function. For example, Laufer-Perl et al. identified that cancer itself caused LA εres to be 17% lower with a further 10% relative reduction in LA εres or a decrease in LA εres below 35% in half of a population of patients undergoing chemotherapy with anthracycline. [10]. Park et al. demonstrated that while both LA εres and LV-GLS were early markers in the detection of CTRCD, LA εres reduction was more sensitive and specific than LV-GLS in predicting CTRCD [6]. Similar abnormalities in LA function were demonstrated by Tadic et al. who showed that LA reservoir and conduit function were reduced, while booster pump function was increased in cancer patients [11]. Combined with the observation by Laufer- Perl and colleagues, this raises the question as to whether LV dysfunction is only the consequence of anti- cancer therapy or if cancer itself leads to abnormalities in function. Thus, both the pathology and the therapy for that pathology can lead to LA functional impairment, which is associated with a higher risk of AF, a frequent arrhythmia in cancer patients with an impact on prognosis [4, 12].Several limitations should be noted. CTRCD is a serious complication of anticancer therapy that can beclassified into Type I exemplified by anthracyline- induced cardiac dysfunction characterized by irreversible myocardial damage due to cumulative administered dose and type II exemplified bytrastuzumab- induced cardiac dysfunction that is dose independent and reversible. The mechanism of cardiac toxicity in both types is not well defined. Current ACC/AHA guidelines recommend that patients who develop Heart Failure (HF) while receiving potentially cardiotoxic therapies should have these therapies discontinued while a diagnostic workup is undertaken to ascertain the cause of HF [12, 13]. These guidelines acknowledge that, particularly in patients receiving trastuzumab, asymptomatic decreases in LVEF can occur in approximately 10% of patients, yet, a high recovery rate is observed and discontinuation of therapy is not always necessary. [13, 14].Accordingly, trastuzumab is often continued in patients deemed low risk while neurohormonal blockadeIs initiated usually with guideline directed medical therapy to improve LV function such as beta blockersand ACEi. While the authors report discontinuing or holding trastuzumab in 23 (13.5%) patients, they do not mention adjuvant treatment with neurohormonal blockade that might have influenced the results. Partial improvement of some parameters (LA εres and LVEF) at 12 months follow-up in patients who developed CTRCD raises the possibility that treatment with adjuvant therapy might be responsible for the beneficial changes. Another important limitation is the lack of additional echocardiographic parameters potentially related to LA function. A significant association exists between impaired LA strain and LV filling pressure (E/E′ ratio), pulmonary pressure (tricuspid regurgitation velocity), and RV systolic function (RVFAC) [15]. None of these parameters have been described in the manuscript.From a research perspective, future investigations should be mindful of the association between reduction in LV filling pressure and improvement in LA function as indicated by the improvement in LA strain and a more holistic approach should be used reporting echocardiographic parameters related toLV filling (i.e. E/E′ ratio, LA stiffness index or E/E′/LA reservoir strain). Although Strain and Strain Rate are increasingly used, deformation analysis of the LA offers unique challenges. Anatomic challenges as well as specific expertise and training required for accurate data acquisition and processing remain a significant impediment to a widespread clinical use. Advances in cardiac imaging in the field of speckle tracking echocardiography, including machine learning algorithms, may help overcome these obstacles and provide a more reliable and fast functional assessment of the LA.Despite the limitations the manuscript convincingly confirms previous reports that have demonstrated the added value of LA strain in the assessment of various pathologic conditions affecting LV function and reinforces the need for further work to establish its role in clinical applications such as risk stratification and decision-making strategies.BIBLIOGRAPHY1. Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015; 131(22):1981-8.2. de Moor JS, Mariotto AB, Parry C, et al. Cancer survivors in the United States: prevalence across the survivorship trajectory and implications for care. Cancer Epidemiol Biomarkers Prev. 2013; 22(4):561-70.3. Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016; 29(4):277-314.4. Galderisi M, Esposito R, Sorrentino R, et al. Atrial Fibrillation, Cancer and Echocardiography. J Cardiovasc Echogr. 2020; 30(Suppl 1):S33-S7.5. Sarvari SI, Haugaa KH, Stokke TM, et al. Strain echocardiographic assessment of left atrial function predicts recurrence of atrial fibrillation. Eur Heart J Cardiovasc Imaging. 2016; 17(6):660-7.6. Park H, Kim KH, Kim HY, et al. Left atrial longitudinal strain as a predictor of Cancer therapeutics-related cardiac dysfunction in patients with breast Cancer. Cardiovasc Ultrasound. 2020; 18(1):28.7. Huynh QL, Kalam K, Iannaccone A,et al. Functional and Anatomic Responses of the Left Atrium to Change in Estimated Left Ventricular Filling Pressure. J Am Soc Echocardiogr. 2015; 28(12):1428-33.e1.8. Donal E, Behagel A, Feneon D. Value of left atrial strain: a highly promising field of investigation. Eur Heart J Cardiovasc Imaging. 2015; 16(4):356-7.9. M C Lassen, F Arya, T Biering-Sørensen, et al. Left Atrial Strain is Reduced Following Trastuzumab in Breast Cancer Patients. Echocardiography (InPress).10. Laufer-Perl M, Arias O, Dorfman SS, et al. Left Atrial Strain changes in patients with breast cancer during anthracycline therapy. Int J Cardiol.2021; 330:238-44.11. Tadic M, Genger M, Cuspidi C, et al. Phasic Left Atrial Function in Cancer Patients Before Initiation of Anti-Cancer Therapy. J Clin Med.2019; 8(4).12. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022; 79(17):e263-e421.13. Guarneri V, Lenihan DJ, Valero V, et al. Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience. J Clin Oncol. 2006; 24(25):4107-15.14. Wang SY, Long JB, Hurria A, et al. Cardiovascular events, early discontinuation of trastuzumab, and their impact on survival. Breast Cancer ResTreat. 2014; 146(2):411-9.15. Santos AB, Roca GQ, Claggett B, et al. Prognostic Relevance of Left Atrial Dysfunction in Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2016; 9(4):e002763.

Aphasia is characterized by language impairments and deficits in oral expression and comprehension. Eye tracking is a promising technique to investigate language processing in complex cases, like aphasia. A paradigm supporting this idea demonstrates a temporal relationship between language processing and gaze. In this work, we developed a new resource to investigate auditory sentence processing by aphasic individuals in the Brazilian context. The solution was based on the application of a second version of a clinically validated method knownas the Test for Reception of Grammar (TROG-2). A pilot was conducted by a multidisciplinary team, where four individuals with aphasia, and four individuals without aphasia, participated. The data analysis showed that eye-tracking combined with the TROG-2 provides complementary information of individual insights which would lead to more personalized and assertive rehabilitation programs.

A synopsis of cutaneous adverse effects of TenofovirSamir Shrestha1, Kamal Acharya2, Archana Pandey3 Basanta Regmi4, Raksha Pathak5

A document by Niloufar Nowrouzi. Click on the document to view its contents.