An augmented reality-guided biopsy system using a high-speed motion tracking and real-time registration platform.

Biopsies play a crucial role in diagnosis of various diseases including cancers. In this study, we developed an augmented reality (AR) system to improve biopsy procedures and increase targeting accuracy. Our AR-guided biopsy system uses a high-speed motion tracking technology and an AR headset to display a holographic representation of the organ, lesions, and other structures of interest superimposed on real physical objects. The first application of our AR system is prostate biopsy. By incorporating preoperative scans, such as computed tomography (CT) or magnetic resonance imaging (MRI), into real-time ultrasound-guided procedures, this innovative AR-guided system enables clinicians to see the lesion as well as the organs in real time. With the enhanced visualization of the prostate, lesion, and surrounding organs, surgeons can perform prostate biopsies with an increased accuracy. Our AR-guided biopsy system yielded an average targeting accuracy of 2.94 ± 1.04 mm and can be applied for real-time guidance of prostate biopsy as well as other biopsy procedures.

An augmented reality and high-speed optical tracking system for laparoscopic surgery.

While minimally invasive laparoscopic surgery can help reduce blood loss, reduce hospital time, and shorten recovery time compared to open surgery, it has the disadvantages of limited field of view and difficulty in locating subsurface targets. Our proposed solution applies an augmented reality (AR) system to overlay pre-operative images, such as those from magnetic resonance imaging (MRI), onto the target organ in the user's real-world environment. Our system can provide critical information regarding the location of subsurface lesions to guide surgical procedures in real time. An infrared motion tracking camera system was employed to obtain real-time position data of the patient and surgical instruments. To perform hologram registration, fiducial markers were used to track and map virtual coordinates to the real world. In this study, phantom models of each organ were constructed to test the reliability and accuracy of the AR-guided laparoscopic system. Root mean square error (RMSE) was used to evaluate the targeting accuracy of the laparoscopic interventional procedure. Our results demonstrated a registration error of 2.42 ± 0.79 mm and a procedural targeting error of 4.17 ± 1.63 mm using our AR-guided laparoscopic system that will be further refined for potential clinical procedures.

Anxiety, Depression, and Quality of Life in Women with Polycystic Ovarian Syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. Symptoms include amenorrhea, hirsutism, infertility, obesity, acne vulgaris, and androgenic alopecia. PCOS is a stigmatizing condition that affects a woman's identity, mental health and quality of life (QOL). This aspect has not received adequate attention in India. AIMS AND OBJECTIVES: (1) To study the prevalence of anxiety and depression among women suffering from PCOS (2) To determine if symptoms of PCOS were associated with psychiatric morbidity, and (3) To determine the impact of psychiatric morbidity on the QOL. MATERIALS AND METHODS: Seventy females in the reproductive age group (18-45 years) diagnosed with PCOS as per Rotterdam criteria and without any preexisting psychiatric illness were clinically interviewed for anxiety and depressive disorders which were then rated according to the Hamilton scales. QOL was assessed using the World Health Organization-QOL-BREF. Binary logistic regression was performed to study the association of the symptoms with the psychiatric morbidity. QOL scores of patients with and without psychiatric morbidity were compared using Mann-Whitney U-test. RESULTS AND CONCLUSIONS: The prevalence of anxiety and depression in our sample was 38.6% and 25.7%, respectively. Infertility and alopecia were associated with anxiety, while acne was associated with depression. Hirsutism was associated with a lower psychological QOL. Patients with psychiatric morbidity had a significantly lower QOL than those without.

Hepatic deletion of p110α and p85α results in insulin resistance despite sustained IRS1-associated phosphatidylinositol kinase activity.

BACKGROUND: Class IA phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) is an integral mediator of insulin signaling. The p110 catalytic and p85 regulatory subunits of PI3K are the products of separate genes, and while they come together to make the active heterodimer, they have opposing roles in insulin signaling and action. Deletion of hepatic p110α results in an impaired insulin signal and severe insulin resistance, whereas deletion of hepatic p85α results in improved insulin sensitivity due to sustained levels of phosphatidylinositol (3,4,5)-trisphosphate. Here, we created mice with combined hepatic deletion of p110α and p85α (L-DKO) to study the impact on insulin signaling and whole body glucose homeostasis. METHODS: Six-week old male flox control and L-DKO mice were studied over a period of 18 weeks, during which weight and glucose levels were monitored, and glucose tolerance tests, insulin tolerance test and pyruvate tolerance test were performed. Fasting insulin, insulin signaling mediators, PI3K activity and insulin receptor substrate (IRS)1-associated phosphatidylinositol kinase activity were examined at 10 weeks. Liver, muscle and white adipose tissue weight was recorded at 10 weeks and 25 weeks. RESULTS: The L-DKO mice showed a blunted insulin signal downstream of PI3K, developed markedly impaired glucose tolerance, hyperinsulinemia and had decreased liver and adipose tissue weights. Surprisingly, however, these mice displayed normal hepatic glucose production, normal insulin tolerance, and intact IRS1-associated phosphatidylinositol kinase activity without compensatory upregulated signaling of other classes of PI3K. CONCLUSIONS: The data demonstrate an unexpectedly overall mild metabolic phenotype of the L-DKO mice, suggesting that lipid kinases other than PI3Ks might partially compensate for the loss of p110α/p85α by signaling through other nodes than Akt/Protein Kinase B.

ARAP2 promotes GLUT1-mediated basal glucose uptake through regulation of sphingolipid metabolism.

Lipid droplet formation, which is driven by triglyceride synthesis, requires several droplet-associated proteins. We identified ARAP2 (an ADP-ribosylation factor 6 GTPase-activating protein) in the lipid droplet proteome of NIH-3T3 cells and showed that knockdown of ARAP2 resulted in decreased lipid droplet formation and triglyceride synthesis. We also showed that ARAP2 knockdown did not affect fatty acid uptake but reduced basal glucose uptake, total levels of the glucose transporter GLUT1, and GLUT1 levels in the plasma membrane and the lipid micro-domain fraction (a specialized plasma membrane domain enriched in sphingolipids). Microarray analysis showed that ARAP2 knockdown altered expression of genes involved in sphingolipid metabolism. Because sphingolipids are known to play a key role in cell signaling, we performed lipidomics to further investigate the relationship between ARAP2 and sphingolipids and potentially identify a link with glucose uptake. We found that ARAP2 knockdown increased glucosylceramide and lactosylceramide levels without affecting ceramide levels, and thus speculated that the rate-limiting enzyme in glycosphingolipid synthesis, namely glucosylceramide synthase (GCS), could be modified by ARAP2. In agreement with our hypothesis, we showed that the activity of GCS was increased by ARAP2 knockdown and reduced by ARAP2 overexpression. Furthermore, pharmacological inhibition of GCS resulted in increases in basal glucose uptake, total GLUT1 levels, triglyceride biosynthesis from glucose, and lipid droplet formation, indicating that the effects of GCS inhibition are the opposite to those resulting from ARAP2 knockdown. Taken together, our data suggest that ARAP2 promotes lipid droplet formation by modifying sphingolipid metabolism through GCS.

p110α Hot Spot Mutations E545K and H1047R Exert Metabolic Reprogramming Independently of p110α Kinase Activity.

The phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit p110α is the most frequently mutated kinase in human cancer, and the hot spot mutations E542K, E545K, and H1047R are the most common mutations in p110α. Very little is known about the metabolic consequences of the hot spot mutations of p110α in vivo. In this study, we used adenoviral gene transfer in mice to investigate the effects of the E545K and H1047R mutations on hepatic and whole-body glucose metabolism. We show that hepatic expression of these hot spot mutations results in rapid hepatic steatosis, paradoxically accompanied by increased glucose tolerance, and marked glycogen accumulation. In contrast, wild-type p110α expression does not lead to hepatic accumulation of lipids or glycogen despite similar degrees of upregulated glycolysis and expression of lipogenic genes. The reprogrammed metabolism of the E545K and H1047R p110α mutants was surprisingly not dependent on altered p110α lipid kinase activity.