Treatment of Axillary Hyperhidrosis/Bromidrosis Using VASER Ultrasound

Background  Current methods of treatment for axillary hyperhidrosis and/or bromidrosis are palliative (use of topical aluminum chloride or injections of botulinum toxin type A) or surgically based for more permanence (excisional surgery, endoscopic transthoracic sympathectomy, liposuction/curettage). The surgical approaches have mixed effectiveness and incur the risk of significant side effects and complications. Methods  Thirteen patients (3 males, 10 females) with significant axillary hyperhidrosis and/or bromidrosis were recruited, treated with the VASER ultrasound, and followed for 6 months. Preoperative assessment of the impact of hyperhidrosis and/or bromidrosis on lifestyle and the degree of sweat/odor were completed. Postoperative assessment of changes relative to lifestyle and degree of sweat/odor reduction and patient and surgeon satisfaction were completed. Results  Eleven of 13 patients had significant reduction in sweat/odor and had no recurrence of significant symptoms at 6 months. Two patients had a reduction in sweat/odor but not to the degree desired by the patients. No significant complications were noted. A simple amplitude and time protocol was established that provides consistent and predictable therapy. The complete procedure takes less than 1 h to treat two axillae using local anesthetic. Conclusion  The VASER is safe and effective for treatment of axillary hyperhidrosis/bromidrosis. The method is minimally invasive with immediate return to basic activities and only temporary minor restriction of arm movement. At 6 months the treatment appears to be long-lasting, but further follow-up is required for verification of permanence. This method has become the standard of care for the treatment of axillary hyperhidrosis/bromidrosis in the authors’ practice. This study was investigator-initiated and did not have sponsorship from any business or organization. Institutional Review Board and facility fees were paid for by Sound Surgical Technologies.     

Linkage-to-Care Following Community-Based HBV and HCV Screening Among Immigrants from the Washington–Baltimore Metropolitan Area, 2016–2019

Journal of Immigrant and Minority Health - Understanding characteristics that impact linkage-to-care (LTC) among individuals living with HBV and/or HCV can enhance public health efforts to provide...     

Genome-wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk

Genome-wide association studies (GWAS) have identified 45 susceptibility loci associated with lung cancer. Only less than SNPs, small insertions and deletions (INDELs) are the second most abundant genetic polymorphisms in the human genome. INDELs are highly associated with multiple human diseases, including lung cancer. However, limited studies with large-scale samples have been available to systematically evaluate the effects of INDELs on lung cancer risk. Here, we performed a large-scale meta-analysis to evaluate INDELs and their risk for lung cancer in 23,202 cases and 19,048 controls. Functional annotations were performed to further explore the potential function of lung cancer risk INDELs. Conditional analysis was used to clarify the relationship between INDELs and SNPs. Four new risk loci were identified in genome-wide INDEL analysis (1p13.2: rs5777156, Insertion, OR = 0.92, p = 9.10 × 10⁻⁸; 4q28.2: rs58404727, Deletion, OR = 1.19, p = 5.25 × 10⁻⁷; 12p13.31: rs71450133, Deletion, OR = 1.09, p = 8.83 × 10⁻⁷; and 14q22.3: rs34057993, Deletion, OR = 0.90, p = 7.64 × 10⁻⁸). The eQTL analysis and functional annotation suggested that INDELs might affect lung cancer susceptibility by regulating the expression of target genes. After conducting conditional analysis on potential causal SNPs, the INDELs in the new loci were still nominally significant. Our findings indicate that INDELs could be potentially functional genetic variants for lung cancer risk. Further functional experiments are needed to better understand INDEL mechanisms in carcinogenesis.     

Carcinogen exposure and gene promoter hypermethylation in bladder cancer

Tobacco smoking, certain occupational exposures, and exposure to inorganic arsenic in drinking water have been associated with the occurrence of bladder cancer. However, in these tumors the exposure-associated pattern of somatic alterations in genes in the causal pathway for disease has been poorly characterized. In particular, the mechanism by which arsenic induces bladder cancer and the effects of lower environmental levels of exposure remain uncertain. Animal and in-vitro studies have suggested that arsenic and other exposures may act through epigenetic mechanisms. We, therefore, examined, in a population-based study of human bladder cancer, the relationship between epigenetic silencing of three tumor suppressor genes, p16(INK4A), RASSF1A and PRSS3, and exposure to both tobacco and arsenic in bladder cancer. Promoter methylation of each of these genes occurred in approximately 30% of bladder cancers, and both RASSF1A and PRSS3 promoter methylation were associated with advanced tumor stage (P<0.001 and P<0.04, respectively). Arsenic exposure, measured as toenail arsenic, was associated with RASSF1A (P<0.02) and PRSS3 (P<0.1) but not p16INK4A promoter methylation, in models adjusted for stage and other factors. Cigarette smoking was associated with a >2-fold increased risk of promoter methylation of the p16INK4A gene only, with greater risk seen in patients with exposures more recent to disease diagnosis. These results, from human bladder tumors, add to the body of animal and in vitro evidence that suggests a role in epigenetic alterations for bladder carcinogens.     

Concordance of multiple analytical approaches demonstrates a complex relationship between DNA repair gene SNPs, smoking and bladder cancer susceptibility

Study results of single nucleotide polymorphisms (SNPs) and cancer susceptibility are often conflicting, possibly because of the analytic challenges of testing for multiple genetic and environmental risk factors using traditional analytic tools. We investigated the relationship between DNA repair gene SNPs, smoking, and bladder cancer susceptibility in 355 cases and 559 controls enrolled in a population-based study of bladder cancer in the US. Our multifaceted analytical approach included logistic regression, multifactor dimensionality reduction, and hierarchical interaction graphs for the analysis of gene-gene and gene-environment interactions followed by linkage disequilibrium and haplotype analysis. Overall, we did not find an association between any single DNA repair gene SNP and bladder cancer risk. We did find a marginally significant elevated risk of the XPD codon 751 homozygote variant among never smokers [adjusted odds ratio (OR) 2.5, 95% confidence interval (CI) 1.0-6.2]. In addition, the XRCC1 194 variant allele was associated with a reduced bladder cancer risk among heavy smokers [adjusted OR 0.4, 95% CI 0.2-0.9)]. The best predictors of bladder cancer included the XPD codon 751 and 312 SNPs along with smoking. Interpretation of this multifactor model revealed that the relationship between the XPD SNPs and bladder cancer is mostly non-additive while the effect of smoking is mostly additive. Since the two XPD SNPs are in significant linkage disequilibrium (D' = 0.52, P = 0.0001), we estimated XPD haplotypes. Individuals with variant XPD haplotypes were more susceptible to bladder cancer [e.g. adjusted OR 2.5, 95% CI 1.7-3.6] and the effect was magnified when smoking was considered. These results support the hypothesis that common polymorphisms in DNA repair genes modify bladder cancer risk and emphasize the need for a multifaceted statistical approach to identify gene-gene and gene-environment interactions.     

The effect of a physical activity education programme on physical activity, fitness, quality of life and attitudes to exercise in obese females

Obesity has reached epidemic proportions worldwide. Decline in physical activity has occurred simultaneously or before the increase in obesity. The aim of this pilot study was to investigate the effect of a physical activity group-based education programme delivered by a Physiotherapist on weight, physical activity, cardiovascular fitness, quality of life and attitudes to exercise in obese females. A sample of 18 obese Irish females (mean age 37.6 years, mean weight 117.9kg), took part in this study. The participants attended four physical activity education sessions in groups of 6-8, 1 month apart. Outcome measures were Cardiorespiratory fitness (CRF) measured by the Incremental Shuttle Walk test (ISWT) International Physical Activity Questionnaire-Short Form (IPAQ-Short) Impact of Weight on Quality of Life Questionnaire-Short Form (IWQOL-Lite), and a questionnaire adapted from the EU survey on Consumer Attitudes to Physical Activity. There were no significant decreases in participants' weight (p=0.444) and there were no significant improvements in IPAQ (p=0.496) and IWQOL-Lite scores (p=0.337). There were significant improvements in CRF (p<0.0002). Attitudes towards exercise improved as shown by decreased barriers to exercise, i.e. decreased shyness (17%) and increased energy (22%) and increased enjoyment (22%). A group education programme focusing on physical activity alone demonstrated a significant increase in CRF (ISWT) and had a positive influence on attitudes to exercise. Longer duration interventions may allow participants to make the necessary lifestyle changes to achieve weight loss.     

High concordance of drug-induced human hepatotoxicity with in vitro cytotoxicity measured in a novel cell-based model using high content screening

To develop and validate a practical, in vitro, cell-based model to assess human hepatotoxicity potential of drugs, we used the new technology of high content screening (HCS) and a novel combination of critical model features, including (1) use of live, human hepatocytes with drug metabolism capability, (2) preincubation of cells for 3 days with drugs at a range of concentrations up to at least 30 times the efficacious concentration or 100 μM, (3) measurement of multiple parameters that were (4) morphological and biochemical, (5) indicative of prelethal cytotoxic effects, (6) representative of different mechanisms of toxicity, (7) at the single cell level and (8) amenable to rapid throughput. HCS is based on automated epifluorescence microscopy and image analysis of cells in a microtiter plate format. The assay was applied to HepG2 human hepatocytes cultured in 96-well plates and loaded with four fluorescent dyes for: calcium (Fluo-4 AM), mitochondrial membrane potential (TMRM), DNA content (Hoechst 33342) to determine nuclear area and cell number and plasma membrane permeability (TOTO-3). Assay results were compared with those from 7 conventional, in vitro cytotoxicity assays that were applied to 611 compounds and shown to have low sensitivity (<25%), although high specificity (∼90%) for detection of toxic drugs. For 243 drugs with varying degrees of toxicity, the HCS, sublethal, cytotoxicity assay had a sensitivity of 93% and specificity of 98%. Drugs testing positive that did not cause hepatotoxicity produced other serious, human organ toxicities. For 201 positive assay results, 86% drugs affected cell number, 70% affected nuclear area and mitochondrial membrane potential and 45% affected membrane permeability and 41% intracellular calcium concentration. Cell number was the first parameter affected for 56% of these drugs, nuclear area for 34% and mitochondrial membrane potential for 29% and membrane permeability for 7% and intracellular calcium for 10%. Hormesis occurred for 48% of all drugs with positive response, for 26% of mitochondrial and 34% nuclear area changes and 12% of cell number changes. Pattern of change was dependent on the class of drug and mechanism of toxicity. The ratio of concentrations for in vitro cytotoxicity to maximal efficaciousness in humans was not different across groups (12±22). Human toxicity potential was detected with 80% sensitivity and 90% specificity at a concentration of 30× the maximal efficacious concentration or 100 μM when efficaciousness was not considered. We conclude that human hepatotoxicity is highly concordant with in vitro cytotoxicity in this novel model and as detected by HCS.