Aberrant SGK1 Transcription in LNCaP: A Novel Feed-back Mechanism of TGF-beta1 Regulation in Prostate Carcinogenesis

SGK1, a serum- and glucocorticoid-inducible kinase implicated in cancer, is regulated by TGF-beta1 and PI3-kinase. In a comparative study of different benign and cancerous breast and prostate cells, we demonstrate in this study that exon 11 deletion in SGK1 occurs only in LNCaP prostate cancer cells in association with the deficient TGF-beta1 mRNA message and FOXO3A-driven promoter activity. Using protein modeling approaches, we discovered that exon11 deletion in SGK1 could redistribute electrostatic surface potential around the major kinase domain and affect phosphorylation of SGK1 target proteins including FOXO3A. Concordantly, we found that LNCaP cells displayed FOXO3A hyperphosphorylation at the Ser218/321 (a site next to Ser315 with the marked SGK1 preference) along with changes in gene expression profile of TGF-beta relevant regulators (such as SMAD2/4, MAD4 and SKIP). Oncomine-interactome analysis further validated a possibility of reciprocal TGF-beta1 regulation by its transcriptional target SGK1 through alterations in FOXO/SMAD and steroid hormone nuclear receptor interactions

Bifurcation of the Brachial Artery into Brachioradial and Brachioulnar Arteries in the Proximal Arm: Case Report and Clinical Significance

During anatomical dissection of fifty donors in the 2020 undergraduate first-year anatomy course at the Uniformed Services University of the Health Sciences, a high origin of the radial and ulnar arteries, also known as a brachioradial artery and a brachioulnar artery, was observed on the left arm of a 90 year-old White female donor. The bifurcation of the brachial artery occurred in the proximal third of the arm. Both the left brachioradial and left brachioulnar arteries ran superficial and medial to the biceps brachii muscle. The brachioulnar artery continues as the UA in the forearm, ran superficial and lateral to the flexor carpi ulnaris muscle, traversed the flexor retinaculum, and continued to form the superficial arterial palmar arch. The brachioradial artery ran deep to the pronator teres muscle and continued as the RA in the forearm. It presented with an atypical branching pattern and was tortuous until it reached the hand. On the dorsum of the hand, the radial artery runs superficial to the first dorsal interosseous muscle, parallel to the first metacarpal bone. It also reached the palmar side of the hand in an unusual manner. Medical professionals, especially radiologists, orthopedic and vascular surgeons, need to be aware of these variations to avoid iatrogenic injuries during normal procedures, such as venipuncture and intravenous injections. Knowledge of these variations is also important during invasive procedures, such as elbow reconstructive surgery, percutaneous brachial catheterization, and when creating an arteriovenous fistula using the radial artery. When such variations are suspected, Doppler and angiogram studies are necessary

Accessory Lateral Head of the Right Gastrocnemius Muscle in a 65 year-old White Male Donor

The three muscles that form the calf muscle or triceps surae include the soleus muscle, the gastrocnemius muscle, and the plantaris muscle. Generally, the gastrocnemius muscle consists of a larger medial head and relatively smaller lateral head. It is responsible for plantar flexion of the foot. The lateral head arises from the posterior lateral femoral condyle and the larger medial head originates from the posterior medial femoral condyle. The medial and lateral heads of the gastrocnemius muscle along with the soleus muscle combine to form the Achilles tendon, which inserts onto the posterior surface of the calcaneus. Since the gastrocnemius muscle crosses three joints including the knee and subtalar joints, it can be vulnerable to injury, especially in mature athletes who experience sudden and swift changes in direction associated with muscular overstretching. Other causes of gastrocnemius muscle injury include maximal knee extension and full ankle dorsiflexion. Since the muscle is already prone to injury, anatomical variations of the gastrocnemius muscles may be symptomatic. With muscle variations, there are potential implications and effects on the other structures within the popliteal fossa. Many different anatomical variations have been identified during routine dissections and reported in the literature. Understanding details of these variations is important for diagnostic, surgical and clinical practice and patient management. Here we report on a 65-year-old White Male cadaveric donor with an accessory lateral head of the gastrocnemius muscle found incidentally during a routine dissection

Vínculo terapeútico en terapia ocupacional y oncología infantil

Tesis (Terapeuta Ocupacional)La investigación se basa en el desarrollo del vínculo terapéutico entre el Terapeuta Ocupacional y los niños, niñas y adolescentes (NNA) con cáncer que asisten a tratamiento, enfocándose en las estrategias y habilidades personales del profesional, en conjunto con factores que facilitan o interfieren con este lazo. La pregunta de investigación corresponde a: ¿Cuáles son las estrategias que han desarrollado los terapeutas ocupacionales para el desarrollo de un vínculo terapéutico entre Terapeuta Ocupacional y usuario de oncología infantil? La presente investigación será de metodología cualitativa y estará posicionada desde un paradigma fenomenológico, de carácter exploratorio, por ser un tema escasamente investigado. Siendo descriptiva con el fin de dar cuenta de características específicas que se dan en el vínculo terapéutico entre NNA con cáncer y el Terapeuta Ocupacional. En la investigación está incluido un diseño muestral de 6 profesionales que trabajan o han trabajado como Terapeutas Ocupacionales en Oncología infantil. Según lo investigado, se puede concluir que los profesionales requieren de un espacio y un apoyo para expresar sentimientos, emociones y dudas en relación con la forma de enfrentar los problemas y, así, evitar descargas de emociones negativas y/o sobre-involucramiento en el proceso interventivo. Es relevante reflexionar sobre la importancia del vínculo terapéutico, de manera que sea un medio auxiliar que permita, no solo el crecimiento emocional del profesional, sino también del usuario y como se ve reflejado en el tipo de vínculo positivo que guarden durante el proceso de la enfermedad y posterior a la misma. El fenómeno del vínculo terapéutico es multifactorial, abarcando al usuario, a la familia y a la sociedad, y cada una de estas partes funciona interdependiente con las otras

Overall Prevalence and Clinical Significance of a Retroesophageal Right Subclavian with a Non-Recurrent Right Laryngeal Nerve in an 83-year-old and a 93-year-old White Male Donor

Head and neck anatomic variations are common and generally go undetected, but may be clinically significant or have important surgical consequences. Knowledge of various abnormalities is important for clinical decision making and the avoidance of iatrogenic complications. Anomalies of the aortic arch and its various branches are relatively common. However, rare variations with profound clinical sequelae can occur. During recent cadaveric dissection, we identified an 83-year-old and a 93-year-old White male donor who both had a right retroesophageal subclavian artery with an associated non-recurrent right laryngeal nerve. Lack of knowledge of this anatomic variation can directly result in severe consequences for patients and lead to major morbidity. Understanding this variation and recognizing it will be important for anatomists, radiologists and surgeons

Palmaris Longus Inversus Muscle Present Bilaterally in an 82 Year-old White Female Cadaver and Unilaterally in a 68 Year-old White Female Cadaver

The palmaris longus muscle is one of the most variable muscles in the human body. Palmaris longus muscle anatomical variations include reversed (palmaris longus inversus muscle), duplicated, triplicated, bifid, hypertrophied, accessory (additional) slips, and/or complete absence. During anatomical dissection of fifty cadavers in the 2019 undergraduate first-year anatomy course at the Uniformed Services University of the Health Sciences, we found a palmaris longus inversus muscle bilaterally on an 82 year-old White female cadaver and a unilateral palmaris longus inversus muscle on the right forearm of a 68 year-old White female cadaver. Due to the prevalence of anatomical variations in the palmaris longus muscle, adequate knowledge of such prevalence and clinical significance is needed in multiple medical specialties for its reconstructive use, and the possibility and treatment of clinical syndromes. An accessory (additional) palmaris longus muscle, hypertrophied palmaris longus muscle, hypertrophied palmaris longus inversus muscle, or just the presence of a palmaris longus inversus muscle, can all cause compression to adjacent neurovascular structures, such as the median nerve, ulnar nerve, ulnar artery, and/or the anterior interosseous artery, in the distal forearm and wrist. Palmaris longus tendons are used as grafts in various surgeries, such as extensor tendon repair in rheumatoid arthritis patients, injuries of flexor tendons and repair, lip augmentation, reconstructive hand surgery, frontalis suspension sling in ptosis correction, plastic surgery, and pulley reconstructions. Surgeons, physicians, radiologists, and physiotherapists must be knowledgeable of the many PLM anatomical variations and their possible contributions to pathological processes

Diverse Effects of ANXA7 and p53 on LNCaP Prostate Cancer Cells Are Associated with Regulation of SGK1 Transcription and Phosphorylation of the SGK1 Target FOXO3A

Tumor suppressor function of the calcium/phospholipid-binding Annexin-A7 (ANXA7) has been shown in Anxa7-deficient mice and validated in human cancers. In the androgen-resistant prostate cancer cells, ANXA7 and p53 showed similar cytotoxicity levels. However, in the androgen-sensitive LNCaP, ANXA7 greatly exceeded the p53-induced cytotoxicity. We hypothesized that the p53 underperformance in LNCaP could be due to the involvement of p53-responsive SGK1 and FOXO3A. In this study, we show that p53 failed to match programmed cell death (PCD) and G1-arrest that were induced by ANXA7 in LNCaP. WT-ANXA7 preserved total FOXO3A expression with no hyperphosphorylation that could enable FOXO3A nuclear translocation and proapoptotic transcription. In contrast, in the p53-transfected LNCaP cells with maintained cell proliferation, the phosphorylated (but not total) FOXO3A fraction was increased implying a predominantly cytoplasmic localization and, subsequently, a lack of FOXO3A proapoptotic transcription. In addition, p53 reduced the expression of aberrant SGK1 protein form in LNCaP. Using Ingenuity Pathway Analysis and p53-signature genes, we elucidated the role of distinct SGK1/FOXO3A-associated regulation in p53 versus ANXA7 responses and proposed that aberrant SGK1 could affect reciprocal SGK1-FOXO3A-Akt regulation. Thus, the failure of the cell growth regulator p53 versus the phospholipid-binding ANXA7 could be potentially attributed to its diverse effects on SGK1-FOXO3A-Akt pathway in the PTEN-deficient LNCaP

Duplicated Inferior Vena Cava in a 69-Year-Old White Female Donor

While relatively uncommon, a duplication of the inferior vena cava is moderately well-discussed in the literature. This anatomical variation was noted in a 69-year-old white female donor. This variation is typically asymptomatic; however, it can be associated with complications, such as confusion with a mediastinal mass, increased risk for thromboembolism, and hemorrhage during surgery. It is also associated with a handful of comorbidities, including, but not limited to, congenital renal anomalies such as horseshoe kidney or fused crossed kidney. Research supports that the variation of a duplicated IVC (DIVC) can be due to a failure of the left supracardinal vein to regress during embryonic development

A Hepatogastrophrenic Trunk, Celiacomesenteric Trunk, and a Middle Mesenteric Artery in a 68-Year-Old White Male Donor

A detailed understanding of the enteric vascular supply is of great importance for pre-operative planning. In the case of this 68-year-old white male donor, the following variations were observed: a hepatogastrophrenic trunk, a celiacomesenteric trunk, and a middle mesenteric artery. Literature review was conducted to understand the frequency and clinical significance of these variations