Transcranial focused ultrasound for the treatment of tremor: A preliminary case series.

BACKGROUND: Essential tremor (ET) can be debilitating. Treatments for ET include beta-blockers and surgical interventions. Low-intensity focused ultrasound (LIFU) may offer an office-based non-invasive alternative. OBJECTIVE: This pilot open label clinical trial explores safety, feasibility, and potential efficacy of LIFU in treatment of ET. METHODS: We report outcomes from the first 10 participants in this IRB-approved trial of LIFU for treatment of ET. The ventral intermediate nucleus of the thalamus (Vim) was targeted using structural and functional MRI. Participants underwent eight 10-min sessions of LIFU targeting the contralateral (Vim) to the most affected hand. Safety was closely monitored; Global Rating of Change (GRC) and The Essential Tremor Rating Scale (TETRAS) scores were collected. RESULTS: No adverse effects were reported. Eight participants reported a GRC ≥2. TETRAS performance subscale demonstrated clinically significant improvement in all participants. CONCLUSION: Preliminary findings support LIFU's safety and feasibility. The potential efficacy encourages additional sham-controlled studies.

Use of transcranial low-intensity focused ultrasound for targeted delivery of stem cell-derived exosomes to the brain.

The blood-brain barrier (BBB) presents a significant challenge for targeted drug delivery. A proposed method to improve drug delivery across the BBB is focused ultrasound (fUS), which delivers ultrasound waves to a targeted location in the brain and is hypothesized to open the BBB. Furthermore, stem cell-derived exosomes have been suggested as a possible anti-inflammatory molecule that may have neural benefits, if able to pass the BBB. In the present study, transcranial low-intensity focused ultrasound (LIFU), without the use of intravenous microbubbles, was assessed for both (1) its ability to influence the BBB, as well as (2) its ability to increase the localization of intravenously administered small molecules to a specific region in the brain. In vivo rat studies were conducted with a rodent-customized 2 MHz LIFU probe (peak pressure = 1.5 MPa), and injection of labeled stem cell-derived exosomes. The results suggested that LIFU (without microbubbles) did not appear to open the BBB after exposure times of 20, 40, or 60 min; instead, there appeared to be an increase in transcytosis of the dextran tracer. Furthermore, the imaging results of the exosome study showed an increase in exosome localization in the right hippocampus following 60 min of targeted LIFU.

Association between tumour necrosis-α gene polymorphisms and acne vulgaris in a Pakistani population.

BACKGROUND: The cytokine tumour necrosis factor (TNF)-α is a well-studied potent candidate mediator that is systemically involved in a variety of inflammatory diseases. Several single nucleotide polymorphisms (SNPs) of the TNF-α gene have been studied with regard the pathogenesis of acne vulgaris, but the results have been inconclusive. AIM: This case-control study investigated the association of the TNF -308 G>A and -238 G>A SNPs with acne vulgaris in a high-risk Pakistani population. METHODS: In total, 160 healthy controls and 140 patients with acne were enrolled in this study. Polymorphisms were determined by PCR and restriction fragment length polymorphism analysis. RESULTS: Our data showed that the TNF -308 G>A and TNF -238 G>A SNPs were present at a significantly higher rate in cases than in controls (P < 0.01 and P < 0.02; respectively). There was a significant difference between the G and A alleles from patients with acne and controls for -308 G>A (OR = 1.5, 95% CI = 1.07-2.19, P < 0.02) and -238 G>A (OR=1.6, 95% CI = 1.06-2.44, P = 0.02) genotype. Moreover, the severity of acne was significantly associated with TNF genotype (TNF -308 G>A: χ² = 34.6, P < 0.001; TNF -238 G>AL χ² = 12.9, P < 0.01). CONCLUSION: Our data suggest that the TNF -308 G>A and TNF -238 G>A SNPs may contribute to the pathogenesis of acne in the study population. Furthermore, patients with severe acne showed an increased frequency of mutant TNF genotypes at -308 and -238 compared with patients with less severe acne.

Sex differences in cocaine-stimulated motor behavior: disparate effects of gonadectomy.

Sex differences in biological substrates of drug use and addiction are poorly understood. The present study investigated sexual dimorphisms in motor behavior following acute cocaine administration (10, 20, or 40 mg/kg, i.p.). Cocaine increased stereotypy rating, horizontal and vertical activity in both sexes, and effects were always greater in females than males. A population analysis using data from multiple experiments indicated that horizontal activity scores were normally distributed in males but not in females. Gonadectomy induced disparate effects on cocaine-stimulated motor behavior. Population analysis indicated that castrated males exhibited more horizontal activity and stereotypy than shams. Ovariectomy did not affect cocaine-stimulated stereotypy but did attenuate horizontal activity in a subset of rats that had not been vaginally lavaged. In summary, gonadectomy effects were sex and behavioral topography specific and indicate that activational effects of gonadal hormones partially mediate the robust sex differences in cocaine-stimulated open-field behavior.