Single-cell mapping of focused ultrasound-transfected brain.

Gene delivery via focused ultrasound (FUS) mediated blood-brain barrier (BBB) opening is a disruptive therapeutic modality. Unlocking its full potential will require an understanding of how FUS parameters (e.g., peak-negative pressure (PNP)) affect transfected cell populations. Following plasmid (mRuby) delivery across the BBB with 1 MHz FUS, we used single-cell RNA-sequencing to ascertain that distributions of transfected cell types were highly dependent on PNP. Cells of the BBB (i.e., endothelial cells, pericytes, and astrocytes) were enriched at 0.2 MPa PNP, while transfection of cells distal to the BBB (i.e., neurons, oligodendrocytes, and microglia) was augmented at 0.4 MPa PNP. PNP-dependent differential gene expression was observed for multiple cell types. Cell stress genes were upregulated proportional to PNP, independent of cell type. Our results underscore how FUS may be tuned to bias transfection toward specific brain cell types in vivo and predict how those cells will respond to transfection.

The pivotal role of Nrf2 activators in adipocyte biology.

Adipose tissue is instrumental in maintaining metabolic homeostasis by regulating energy storage in the form of triglycerides. In the case of over-nutrition, adipocytes favorably regulate lipogenesis over lipolysis and accumulate excess triglycerides, resulting in increased adipose tissue mass. An abnormal increase in hypertrophic adipocytes is associated with chronic complications such as insulin resistance, obesity, diabetes, atherosclerosis and nonalcoholic fatty liver disease. Experimental studies indicate the occurrence of oxidative stress in the pathogenesis of obesity. A common underlying link between increasing adipose tissue mass and oxidative stress is the Nuclear Factor Erythroid 2-related factor 2 (Nrf2), Keap1-Nrf2-ARE signaling, which plays an indispensable role in metabolic homeostasis by regulating oxidative and inflammatory responses. Additionally, Nrf2 also activates CCAAT/enhancer-binding protein α, (C/EBP-α), C/EBP-ß and peroxisome proliferator-activated receptor γ (PPARγ) the crucial pro-adipogenic factors that promote de novo adipogenesis. Hence, at the forefront of research is the quest for prospecting novel compounds to modulate Nrf2 activity in the context of adipogenesis and obesity. This review summarizes the molecular mechanism behind the activation of the Keap1-Nrf2-ARE signaling network and the role of Nrf2 activators in adipocyte pathophysiology.

Arytenoid asymmetry: Is it the most predictive parameter for arytenoid adduction in unilateral vocal fold paralysis?

OBJECTIVE: The aim of this study was to establish arytenoid asymmetry as a pre-operative predictive parameter for arytenoid adduction surgery in unilateral vocal fold paralysis and thereafter identify the most predictive parameter for arytenoid adduction among the established parameters. METHODS: A retrospective comparative study was undertaken. The 'arytenoid asymmetry angle' formed between skewed 'glottic' and 'interarytenoid' axes (traced along the plane of closure of the membranous and cartilaginous glottis, respectively) was quantified in pre-operative laryngoscopic images of 85 adults with unilateral vocal fold paralysis who underwent either type 1 thyroplasty (group 1) or type 1 thyroplasty with arytenoid adduction (group 2). The need for arytenoid adduction was determined intra-operatively based on subjective voice improvement and laryngoscopic results. RESULTS: Arytenoid asymmetry (p < 0.0001), posterior phonatory gap (p = 0.001) and vertical level difference (p = 0.004) were significantly greater in group 2 (descending order of parameters). Arytenoid asymmetry angle showed a significant positive correlation with the latter two parameters. CONCLUSION: Arytenoid asymmetry is the most predictive parameter for arytenoid adduction. An arytenoid asymmetry angle of more than or equal to 33.9° is an indication for arytenoid adduction. This aids in pre-operative planning of arytenoid adduction.

A prospective study of telephonic contact and subsequent physical follow-up of radically treated lung cancer patients.

BACKGROUND: We tested the hypothesis that telephonic follow-up (FU) may offer a convenient and equivalent alternative to physical FU of radically treated lung cancer patients. DESIGN: Prospective study carried out at a tertiary referral cancer care institute, Mumbai. MATERIALS AND METHODS: Two hundred consecutive lung cancer patients treated with curative intent were followed up regularly with telephonic interviews paired with their routine physical FU visits. Patient satisfaction with the telephonic call and the physical visit, the anxiety level of the patient after meeting the physician and the economic burden of the visit to the patient were noted in a descriptive manner. Kappa statistics was used to assess concurrence between the telephonic and physical impression of disease status. RESULTS: With a median FU duration of 21.5 months, the median satisfaction scores for telephonic and physical FU were 8 and 9, respectively. The prevalence and bias adjusted kappa (PABAK) score of the entire cohort of patients was 0.64 (95% confidence interval [CI] =0.58-0.70). Data analyzed up to first disease progression/relapse on FU had a PABAK score of 0.71 (95% CI = 0.64-0.77) indicating substantial agreement. Patients with disease controlled at the FU had a significant PABAK score of 0.88 (95% CI = 0.80-0.94) indicating excellent concurrence. On average, each patient spent Rs. 5117.10 on travel and Rs. 3079.06 on lodging per FU visit. CONCLUSION: Telephonic FU is substantially accurate in assessing disease status until the first relapse. In a resource-constrained country like India, it is worthwhile to further explore the benefits of such an alternative strategy.

On the antifeedant and anthellmintic potential of anacardium occidentale L.

The antifeedant and anthelmintic activities of crude extracts of the shells of Anacardium occidentale were studied by comparing it's activity with the activity of Azadirachta indica A Juss (Kernel), a commercial standard. The test extracts of A. occidentale in petroleum ether, dichloromethane: methanol showed better activities compared to A. Indica. To Study the anthelmintic activity, the addition of piperine to the formulation significantly enhances the activity. The phytochemical investigation of test extracts showed the presence of phenols namely cordol, cardanol and anacardic acid by TLC studies. The most potent extracts are non toxic to mice.

Effects of atrial natriuretic peptide in clinical acute renal failure.

Fifty-three consenting patients meeting clinical and urine composition criteria for established intrinsic ARF were assigned to two treatment groups. Group I patients were treated with human atrial natriuretic peptide (ANP) with or without diuretics. Groups II patients were treated with or without diuretics and with no ANP. Age, sex, etiology of ARF, entry serum creatinines (SCr) (Group I, 5.3 +/- 1.8; Group II, 5.1 +/- 2.1 mg/dl) and creatinine clearances (CCr) (Group I, 9.9 +/- 2.1; Group II, 9.2 +/- 2.1 ml/min) were similar. Thirty patients received ANP [0.20 micrograms/kg/min i.v. x 24 hr (N = 20) or 0.08 micrograms/kg/min i.a. x 8 hr (N = 10)] and furosemide, 0.5 mg/kg/hr x 24 hr or mannitol, 12.5 g every six hours x 4, or no diuretic; 23 Group II patients received diuretics as above or no diuretic in a similar distribution to Group I. CCr (verified with simultaneous inulin clearances x 12, r = 0.93, P < 0.001) increased significantly by eight hours of ANP treatment to 17.1 +/- 3.2 ml/min and by 24 hours after discontinuing ANP to 21.0 +/- 4.4 ml/min (both P < 0.05). There was no corresponding increase in CCr in Group II. Dialysis was required in 23% of Group I and in 52% of Group II patients (different at P < 0.05). Mortality rates of 17% for Group I and 35% for Group II were not significantly different (P = 0.11). It is concluded that parenteral ANP increases CCr and reduces need for dialysis in patients with established intrinsic ARF.