PTEN regulates natural killer cell trafficking in vivo.

Phosphatase and tensin homolog (PTEN) is a critical negative regulator of the phosphoinositide-3 kinase pathway, members of which play integral roles in natural killer (NK) cell development and function. However, the functions of PTEN in NK cell biology remain unknown. Here, we used an NK cell-specific PTEN-deletion mouse model to define the ramifications of intrinsic NK cell PTEN loss in vivo. In these mice, there was a significant defect in NK cell numbers in the bone marrow and peripheral organs despite increased proliferation and intact peripheral NK cell maturation. Unexpectedly, we observed a significant expansion of peripheral blood NK cells and the premature egress of NK cells from the bone marrow. The altered trafficking of NK cells from peripheral organs into the blood was due to selective hyperresponsiveness to the blood localizing chemokine S1P. To address the importance of this trafficking defect to NK cell immune responses, we investigated the ability of PTEN-deficient NK cells to traffic to a site of tumor challenge. PTEN-deficient NK cells were defective at migrating to distal tumor sites but were more effective at clearing tumors actively introduced into the peripheral blood. Collectively, these data identify PTEN as an essential regulator of NK cell localization in vivo during both homeostasis and malignancy.

MicroRNA-15/16 Antagonizes Myb To Control NK Cell Maturation.

NK cells develop in the bone marrow and complete their maturation in peripheral organs, but the molecular events controlling maturation are incompletely understood. The miR-15/16 family of microRNA regulates key cellular processes and is abundantly expressed in NK cells. In this study, we identify a critical role for miR-15/16 in the normal maturation of NK cells using a mouse model of NK-specific deletion, in which immature NK cells accumulate in the absence of miR-15/16. The transcription factor c-Myb (Myb) is expressed preferentially by immature NK cells, is a direct target of miR-15/16, and is increased in 15a/16-1 floxed knockout NK cells. Importantly, maturation of 15a/16-1 floxed knockout NK cells was rescued by Myb knockdown. Moreover, Myb overexpression in wild-type NK cells caused a defective NK cell maturation phenotype similar to deletion of miR-15/16, and Myb overexpression enforces an immature NK cell transcriptional profile. Thus, miR-15/16 regulation of Myb controls the NK cell maturation program.

Yoga as an Adjuvant therapy in management of migraine- An open label randomised trial.

Introduction: Drug treatment is not very satisfactory in migraine and is associated with adverse effects. The effect of yoga as an add-on therapy in migraine was evaluated in the present study. Methods: Patients between the age of 18 and 60 years suffering from migraine were recruited from Internal Medicine and Neurology OPD. Migraine was diagnosed according to the International Headache Society, International Classification of Headache Disorders-3rd edition (IHS, ICHD-3). At baseline, clinical and autonomic parameters of patients were assessed, and consenting patients were randomized into two equal groups by using a computer-based random number generator program (version 1): conventional (C group) and conventional plus yoga (C+Y group). Both groups were given conventional therapy for migraine, and the C+Y group was given yoga as an add-on therapy. Yoga therapy was given for 5 days/week for 12 weeks, and a post-intervention assessment was done at the 14th week. Subjective variables such as frequency and average duration were assessed through headache diaries or telephonic conversation, while severity was assessed using the visual analog scale (VAS) and headache impact test (HIT-6). Statistical Analysis: Independent t test and Mann-Whitney U Test (Wilcoxon rank-sum test) were used for comparing normally and non-normally distributed endpoint outcomes after treatment (AT). Results: Out of 170 patients screened, 75 were diagnosed with migraine and only 34 patients completed the study (17 in each group). All clinical and autonomic parameters showed significant improvement in pre- and post-intervention values in both groups (P < 0.0001). On comparing the conventional (C) group and conventional + yoga (C+Y) group, the change in the VAS score was more in the C+Y group (P = 0.041) and heart rate variability showed more reduction in the C+Y group (P = 0.032). Conclusion: We did not find any significant difference in the clinical outcome by adding yoga therapy to conventional therapy, except reduction in VAS score and reduction in heart rate variability.

Type Va Duplication of the Common Bile Duct With Type IIIa Intrahepatic Bile Duct Anatomy: A Rare Combination of Dual Biliary Ductal Anomaly With Difficulty to Extract Common Bile Duct Stone.

Extrahepatic duplication of the common bile duct (CBD) is an extremely rare anatomic variation seen in the biliary tract. It represents failure of regression of the primitive duplicated biliary ductal system, resulting in five different subtypes of the duplicated CBD as described by Choi et al. To date, only few such cases have been reported in the literature. Associated variation in branching of intrahepatic bile ducts presenting as combined dual ductal anomaly is even rarer phenomena to be seen. We report a case of a 67-year-old man with chronic kidney disease and obstructive jaundice resulting from choledocholithiasis. Evaluation revealed type IIIa branching of intrahepatic bile ducts with type Va duplication of the CBD.

Yogic Pranayama and Diaphragmatic Breathing: Adjunct Therapy for Intraocular Pressure in Patients With Primary Open-angle Glaucoma: A Randomized Controlled Trial.

PRCIS: Yogic pranayama and diaphragmatic breathing are potential adjunctive therapies for patients with glaucoma; however, they are not substitutes for medicine or eye drops. PURPOSE: Currently, medical or surgical lowering of intraocular pressure is the only therapeutic approach for treating primary open-angle glaucoma. Intraocular pressure maintenance is influenced by autonomic activity (sympathetic and parasympathetic). "Yogic pranayama" and "diaphragmatic breathing" are exercises that can affect autonomic activity by stimulating a wakeful hypometabolic state of parasympathetic dominance. We aimed to assess the effect of yogic pranayama and diaphragmatic breathing on intraocular pressure to determine whether it can be recommended for individuals with established glaucoma in combination with glaucoma medication as an adjuvant therapy. MATERIALS AND METHODS: In this prospective, randomized trial, 90 patients with primary open-angle glaucoma (180 eyes, age: above 40 y) were assigned to either the control or yogic pranayama and diaphragmatic breathing exercise group. In the latter group, yogic pranayama and diaphragmatic breathing were practiced daily for 6 months. We measured the intraocular pressure at presentation and subsequently after 1, 3, and 6 months. RESULTS: Compared with the wait-list group, the yogic pranayama and diaphragmatic breathing exercise group had significantly lowered intraocular pressure (right eye: 20.85±3.39 to 14.90±2.86 mm Hg; left eye: 20.30±4.12 to 14.25±3.85 mm Hg; P<0.001). CONCLUSION: Yogic pranayama and diaphragmatic breathing exercises can reduce intraocular pressure in patients with primary open-angle glaucoma and can therefore be recommended as an adjuvant therapy.