Titin mutations: the fall of Goliath.

Titin (TTN), the largest protein in the human body, forms powerful elastic filaments along the sarcomere of cardiomyocytes. This multifunctional protein is involved in numerous cellular processes, including sarcomeric assembly, stabilization and mechanosensing. Along physiological sarcomere lengths, TTN is also the most important determinant of the passive tension of cardiac muscle. However, as the giant Goliath was brought down by David's slingshot, so single-base-pair mutations in the gene encoding TTN (TTN) can ultimately impair to some degree a normal cardiac function. Since the first report on the involvement of TTN mutations in the development of hypertrophic cardiomyopathy, in 1999, dozens of other mutations have been described and associated with the onset of cardiac disease. In this review, we aim to explore some of the mechanisms underlying the functions of TTN, as well as the pathophysiological consequences arising from the expression of abnormal TTN isoforms resulting from mutations located along TTN.

Does Platelet-Rich Plasma Promote Facial Rejuvenation? Revising the Latest Evidence in a Narrative Review.

Facial aging is characterized by progressive macroscopic, histological, and molecular changes. Due to its regenerative and rejuvenating properties, the use of platelet-rich plasma (PRP) as a facial antiaging agent has gained popularity over the last decade. In order to gather and evaluate the latest evidence focusing on the effect of PRP on facial skin rejuvenating, a search through MEDLINE (PubMed) using relevant keywords, inclusion, and exclusion criteria was performed. A total of 539 articles were initially retrieved, and from those, 16 were included in the review. Treatment protocols comprised the use of PRP both in monotherapy and in combination with other substances and by means of direct injection or topical application following skin permeation. The selected studies presented high variability regarding PRP preparation methods, administration protocols, and results assessment. In most studies, PRP seemed to improve to some degree the signs of facial aging, such has wrinkles, skin quality, and pigmentation, accompanied by significant histological and molecular responses. Optimizing treatment protocols should be the next step in assessing the full potential of PRP.

Unusual Extensive Physiologic Pigmentation of the Tongue: A Case Report.

The deposition of colored endogenous or exogenous substances in the tissues of the tongue may result in pigmented lesions of the lingual mucosa. The accurate identification of the underlying condition can be difficult to achieve and relies mainly on patient history and clinical and histological evaluation. We present the case of a 30-year-old male referred to our hospital with a chief complaint of extensive pigmentation of the lingual dorsum. A diagnosis of physiologic pigmentation based on clinical and histological findings was made. Since some life-threatening diseases may present solely as pigmented lesions of the tongue, an early diagnosis is of utmost importance.

Pilomatrixoma Recurring as Giant Form.

Pilomatrixoma is a benign skin tumor that originates from the hair matrix. It usually appears in children and young adults and is preferably in the head and neck region. It clinically presents as an asymptomatic firm, solitary subcutaneous mass of less than 3 cm. When located in the preauricular area, it is often misdiagnosed as benign or malignant parotids, skin tumors, or sebaceous cysts. Its treatment of choice is surgery, and recurrence is due to incomplete excision. We present a case of a male referred to our hospital with a diagnosis of recurrent pilomatrixoma in its giant form. The lesion was fully excised with no signs of recurrence and no functional impairment.

1-Year of covid-19 pandemic: changes in the epidemiology of maxillofacial trauma / 1 año de pandemia de COVID-19: cambios en la epidemiología del trauma maxilofacial

Objectives: Due to COVID-19 pandemic, social distancing policies were enacted worldwide, including by the Portuguese official authorities. However, the impact of these measures on maxillofacial trauma and fracture surgical repair remains poorly understood. The aim of this study was to evaluate and compare the incidence and aetiology of facial fractures submitted to surgical repair during 1-year of COVID-19 pandemic versus the previous 4 years, in a level III Trauma Centre located in Lisbon, Portugal. Materials and methods: All emergency episodes registered in our hospital between March 2016 and February 2021 that resulted in patient admittance for surgical treatment of facial fracture were included. Comparative analysis was performed for variables such as fracture type and aetiology. Results: Analysis showed that surgeries performed during the 1st year of COVID-19 were reduced by 37.5 %. Considering only the 75-day lockdown period at the beginning of the pandemic, reduction was even more pronounced and reached -66.7 %. Significant diffe­rences in the aetiology were also found, with physical assault and sport accidents relative frequency decreasing. Moreover, despite being systematically the second most common cause of fracture, during lockdown, fall ranked first, over physical assault. The relative frequency of nasal fractures, the most common facial fracture treated in our hospital, decreased during both the 1st year of COVID-19 and the lockdown period, while mandible fractures ranked first during lockdown. (AU)

Objetivos: Debido a la pandemia por COVID-19, se establecieron políticas de confinamiento social mundial, incluso por parte de las autoridades oficiales portuguesas. Sin embargo, el impacto de estas medidas sobre la cirugía originada por traumatismo maxilofacial sigue siendo poco conocida. El objetivo del presente estudio ha sido evaluar y comparar la incidencia sobre la etiología de las fracturas faciales quirúrgicas, durante 1 año de pandemia de COVID-19 versus los 4 años anteriores, en un Centro de Traumatología (nivel III) ubicado en Lisboa, Portugal. Materiales y métodos: Se incluyeron todos los registros de urgencia en nuestro hospital, entre marzo de 2016 y febrero de 2021, que cursaron con el ingreso de pacientes diagnosticados de fractura facial y su correspondiente tratamiento quirúrgico. Se realizó un análisis comparativo de variables cualitativas como el tipo de fractura y la etiología de las mismas. Resultados: El análisis mostró que las cirugías realizadas durante el primer año por COVID-19 se redujeron en un 37,5 %. Teniendo en cuenta solo el periodo de confinamiento de 75 días al comienzo de la pandemia, la reducción fue aún más pronunciada y alcanzó el 66,7 %. Se encontraron diferencias significativas en la etiología_ disminuyendo la frecuencia relativa de agresiones físicas y accidentes deportivos. A pesar de ser sistemáticamente la segunda causa más frecuente de fractura durante el confinamiento, la caída ocupó el primer lugar, por encima de las agresiones físicas. La frecuencia relativa de las fracturas nasales, fractura facial tratada con mayor incidencia en nuestro hospital, disminuyó tanto durante el primer año por COVID-19 así como durante el periodo de confinamiento, mientras que las fracturas maxilares ocuparon el primer lugar durante el confinamiento. (AU)

Acute Myocardial Response to Stretch: What We (don't) Know.

Myocardial stretch, as result of acute hemodynamic overload, is one of the most frequent challenges to the heart and the ability of the heart to intrinsically adapt to it is essential to prevent circulatory congestion. In this review, we highlight the historical background, the currently known mechanisms, as well as the gaps in the understanding of this physiological response. The systolic adaptation to stretch is well-known for over 100 years, being dependent on an immediate increase in contractility-known as the Frank-Starling mechanism-and a further progressive increase-the slow force response. On the other hand, its diastolic counterpart remains largely unstudied. Mechanosensors are structures capable of perceiving mechanical signals and activating pathways that allow their transduction into biochemical responses. Although the connection between these structures and stretch activated pathways remains elusive, we emphasize those most likely responsible for the initiation of the acute response. Calcium-dependent pathways, including angiotensin- and endothelin-related pathways; and cGMP-dependent pathways, comprising the effects of nitric oxide and cardiac natriuretic hormones, embody downstream signaling. The ischemic setting, a paradigmatic situation of acute hemodynamic overload, is also touched upon. Despite the relevant knowledge accumulated, there is much that we still do not know. The quest for further understanding the myocardial response to acute stretch may provide new insights, not only in its physiological importance, but also in the prevention and treatment of cardiovascular diseases.

Revisiting the slow force response: the role of the PKG signaling pathway in the normal and the ischemic heart.

INTRODUCTION: The myocardial response to acute stretch consists of a two-phase increase in contractility: an acute increase by the Frank-Starling mechanism and a gradual and time-dependent increase in force generated known as the slow force response (SFR). The SFR is actively modulated by different signaling pathways, but the role of protein kinase G (PKG) signaling is unknown. In this study we aim to characterize the role of the PKG signaling pathway in the SFR under normal and ischemic conditions. METHODS: Rabbit papillary muscles were stretched from 92 to 100% of maximum length (Lmax) under basal conditions, in the absence (1) or presence of: a PKG agonist (2) and a PKG inhibitor (3); under ischemic conditions in the absence (4) or presence of: a PKG agonist (5); a nitric oxide (NO) donor (6) and a phosphodiesterase 5 (PDE5) inhibitor (7). RESULTS: Under normoxia, the SFR was significantly attenuated by inhibition of PKG and remained unaltered with PKG activation. Ischemia induced a progressive decrease in myocardial contractility after stretch. Neither the PKG agonist nor the NO donor altered the myocardial response to stretch under ischemic conditions. However, the use of a PDE5 inhibitor in ischemia partially reversed the progressive deterioration in contractility. CONCLUSIONS: PKG activity is essential for the SFR. During ischemia, a progressive decline in the force is observed in response to acute myocardial stretch. This dysfunctional response can be partially reversed by the use of PDE5 inhibitors.

The effects of angiotensin II signaling pathway in the systolic response to acute stretch in the normal and ischemic myocardium.

Acute myocardial stretch elicits a biphasic increase in contractility: an immediate increase, known as Frank-Starling mechanism (FSM), followed by a progressive increase, regarded as slow force response (SFR). In this study, we characterized the contractile response to acute stretch from 92 to 100% Lmax in rabbit papillary muscles (n=86) under normoxic and ischemic conditions, and its modulation by angiotensin II signaling pathway. Under normoxia, the FSM was independent of Na(+)/H(+)-exchanger, reverse mode of Na(+)/Ca(2+)-exchanger (r-NCX), AT1 receptor, AT2 receptor and PKC. Regarding the SFR, it was mediated by AT1 receptor activation and its downstream effectors PKC, Na(+)/H(+)-exchanger and r-NCX. Ischemia negatively impacted on the FSM and abolished the SFR, with the muscles exhibiting a time-dependent decline in contractility. Under ischemic conditions, FSM was not influenced by AT1 and AT2 receptors or PKC activation. AT1 receptor antagonism rescued the progressive deterioration in contractility, an effect partially dependent on AT2 receptor activation.