Acupuncture for tinnitus: a scoping review of clinical studies.

BACKGROUND: Acupuncture treatment for tinnitus has received attention owing to its potential as an alternative to conventional treatment modalities. We conducted a scoping review to identify detailed information on acupuncture treatment methods used in clinical studies and to provide useful information for practitioners, patients, and researchers. METHODS: 　Medline, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Oriental Medicine Advanced Searching Integrated System (OASIS), Korean Research Information Sharing Service (RISS), DataBase Periodical Information Academic (DBPIA), and the China National Knowledge Infrastructure (CNKI) were searched from their inception to December 2023. This review included single-arm trials, open-label randomized controlled trials (RCTs), and double-blind RCTs using needle-type acupuncture to treat tinnitus in English, Chinese, and Korean. We investigated basic and detailed information on the acupuncture treatment methods, assessment methods, and study outcomes. Network analysis was also conducted to evaluate the centrality between acupoints in the double-blind RCTs. RESULTS: We included 106 articles. There were 11 single-arm trials, 90 open-label RCTs, and 5 double-blind RCTs. Most (89.6%) of these studies were conducted in China. Manual acupuncture was the most common type of acupuncture in treatment group. A total of 119 acupuncture points were used 1,138 times. The most frequently used acupoints were local points around the ear (TE17, GB2, SI19, and TE21). Both local and distant acupoints were used simultaneously in these studies. The treatment duration of 20 to 39 days, 10 to 19 sessions of treatment, the mean acupuncture duration of 30 minutes, needle diameter of 0.30 mm x 40 mm, and needling depth over 30 mm and less than 50 mm were confirmed as the most common. CONCLUSION: This study outcomes will enable future acupuncture studies on tinnitus to perform more effective and standardized acupuncture treatments in selecting acupoints and procedures. Furthermore, the study has implications for informing clinicians and students about more impactful acupuncture strategies for addressing tinnitus.

A repeated cross-sectional and longitudinal study of mental health and wellbeing during COVID-19 lockdowns in Victoria, Australia.

BACKGROUND: Population surveys across the world have examined the impact of the COVID-19 pandemic on mental health. However, few have simultaneously examined independent cross-sectional data with longitudinal data, each of which have different strengths and weaknesses and facilitate the investigation of distinct research questions. This study aimed to investigate psychological distress and life satisfaction during the first and second lockdowns in the state of Victoria, Australia, and the social factors that may be affected by lockdowns and could affect mental health. METHODS: The VicHealth Victorian Coronavirus Wellbeing Impact Study included two 20-min opt-in online panel surveys conducted in May and September 2020 in Victoria, each with a sample of 2000 adults aged 18 + . A two-part study design was used: a repeated cross-sectional study of respondents who participated in Survey One and Survey Two, followed by a longitudinal nested cohort study. The primary exposures were social solidarity, social connectedness and staying connected with family and friends. Using logistic regression modelling, we explored the associations between our exposures and primary outcomes of psychological distress and life satisfaction with and without adjustment for covariates, both cross-sectionally and longitudinally. The results from the multivariable models were summarised using adjusted Odds Ratios (aOR), 95% Confidence Intervals (CI). RESULTS: Cross-sectional results indicated that the percentage of participants with low life satisfaction was significantly higher in the second survey sample (53%) compared to the first (47%). The percentage of participants with high psychological distress was higher but not significantly different between the two survey samples (14% first survey vs 16% second survey). Longitudinal study results indicated that lower social connectedness was significantly associated with higher psychological distress (aOR:3.3; 95% CI: 1.3-8.4) and lower life satisfaction (aOR:0.2; 95% CI: 0.1-0.4). Younger adults had higher psychological distress compared to older adults (aOR:6.8; 95% CI:1.5-31.1). Unemployment at the time of the first survey was significantly associated with lower life satisfaction at the second survey (aOR:0.5; 95% CI: 0.3-0.9). CONCLUSION: This study supports the findings of other international studies. It also highlights the need to promote increased social connection and maintain it at times of isolation and separation, particularly amongst younger adults.

Minimal Lateral Internal Sphincterotomy (LIS): Is It Enough to Cut Less Than the Conventional Tailored LIS?

PURPOSE: Anal fissure is a common anorectal condition, yet its pathogenesis remains unclear. Lateral internal sphincterotomy (LIS) is the gold standard treatment for chronic anal fissures that do not respond to conservative treatment; however, it has a risk of anal incontinence. We believe that fibrosis of the internal anal sphincter is an important factor in the pathogenesis of chronic anal fissure. In this study, we describe the minimal LIS method, a minimally invasive method where only the fibrotic portion of the internal anal sphincter is cut. We also describe the outcomes of this method. METHODS: We performed a retrospective review of 468 patients (270 male and 198 female) who underwent minimal LIS for chronic anal fissure in 2017 at Seoul Song Do Hospital. We analyzed the patients' clinical characteristics, manometry data, complications, and outcomes of minimal LIS. The outcomes of the surgery were assessed via questionnaires during the postoperative outpatient visits, beginning 2 weeks postoperatively. RESULTS: The overall complication rate was 4.0% (19 patients). Delayed healing occurred in 14 patients (3.0%), perianal abscess was present in 3 patients (0.6%), and gas incontinence occurred in 2 patients (0.4%). All complications were improved with conservative treatment. Recurrence, defined as the recurrence of anal fissure more than 4 weeks after healing, was present in 6 patients (1.3%). CONCLUSION: Minimal LIS is a safe and effective treatment option for patients with chronic anal fissure. Postoperative complications, especially incontinence and recurrence, are rare.

Association between TP53 genetic polymorphisms and the methylation and expression of miR-34a, 34b/c in colorectal cancer tissues.

Colorectal cancer (CRC) is one of the most common types of cancers, as evidenced by the >1.2 million patient diagnoses and 600,000 mortalities globally each year. Recently, the microRNA (miR/miRNA)-34 miRNA precursor family was revealed to participate in the tumor protein (TP)-53 pathway, which is frequently involved in CRC. Furthermore, the expression of miR-34 is reportedly regulated by DNA methylation. Accordingly, the present study investigated the correlation between the methylation status of miR-34 miRNAs and miR-34 expression in paired CRC tumor and normal tissues. The methylation status of miR-34a and miR-34b/c was determined using the MethyLight assay, and the expression of miR-34a and miR-34b/c in the same paired tissues was analyzed by reverse transcription-quantitative polymerase chain reaction. The results revealed significantly elevated miR-34a (P=0.012) and miR-34b/c (P<0.0001) methylation levels in tumor tissues when compared with normal tissues, whereas only the expression of miR-34b/c differed (P=0.005) between the paired tissues. In addition, an association between TP53 haplotypes and miR-34 family expression levels was observed. The miR-34a methylation levels in the TP53 PIN A1A1 (48.56±36.49) and TP53 MSP GG (49.00±36.44) genotypes were increased in the tumor tissues when compared with normal tissues. In conclusion, it was determined that miR-34 promoter methylation and TP53 polymorphisms may be associated with CRC pathogenesis.

Effects of Local Muscle Vibration on the Displacement of Center of Pressure during Quiet Standing.

[Purpose] The purpose of this study was to investigate the effect of local vibration stimuli on body balance (trace area, trace length, and velocity) in healthy adults during double-leg standing. [Subjects and Methods] Thirty-nine subjects (10 male, 29 female) participated in this study. They were asked to keep their balance while holding four positions: standing with their eyes open, with and without vibration stimuli, and standing with their eyes closed, with and without vibration stimuli. The vibration stimuli, which had a duration of 30 sec, and a frequency of 60-80 Hz, were applied to the tibialis anterior and gastrocnemius muscle belly during double-leg standing. Balance measurement was performed using the Balance Trainer 4 (HUR Labs Oy, Tampere, Finland). All subjects provided informed consent prior to participation in this study. [Results] In the open-eyes position, there were no significant differences in trace area, trace length, and velocity of the center of pressure (COP) either with or without vibration stimuli. However, in the closed-eyes position, the vibration stimuli significantly decreased trace area, trace length, and velocity of the COP compared with when no vibration stimuli were applied. [Conclusion] These results suggest that vibration stimuli applied to the lower leg improve balance when a person's eyes are closed during double-leg quiet standing.

Inhibition of dextran sulfate sodium (DSS)-induced intestinal inflammation via enhanced IL-10 and TGF-beta production by galectin-9 homologues isolated from intestinal parasites.

We isolated a galectin-9 (Gal-9) homologue gene (Tl-gal) from an adult worm of the canine gastrointestinal nematode parasite, Toxascaris leonina, via random cDNA library sequencing. The deduced amino acid sequence of the Tl-gal genes evidenced an identity of 89% with the galectin of Dirofilaria immitis, 87% identity with the galectin of Brugia malayi, and 35% identity with the human GAL-9 gene. To evaluate immune modulate function of Tl-GAL in host inflammatory response, we constructed recombinant Tl-GAL (rTl-GAL) using an Escherichia coli expression vector system and treated to intestinal inflammation mice. Although the carbohydrate-binding ability of rTl-GAL was less than that of rat galectin, we confirmed that recombinant rTl-GAL has carbohydrate-binding activity. The clinical symptoms of dextran sulfate sodium (DSS)-treated mice after rTl-GAL pre-treatment were found to be minimized, or less profound, as compared to those of the rTl-GAL untreated group. Additionally, the DSS-treated mice exhibited a significant shortening of the colon, but the large intestines of the rTl-GAL pre-treated mice were longer than those of the control group (P<0.05). Additionally, the rTl-GAL treated group exhibited significantly increased the levels of TGF-beta and IL-10 (P<0.05). The production of these regulatory cytokines may ameliorate intestinal inflammation. These findings demonstrate that rTl-GAL could inhibit inflammation reactions via the inhibition of Th1 and Th2 cytokine production by increasing the production of TGF-beta and IL-10 cytokines. The rTl-GAL may induce TGF-beta expression, primarily via the activation of the p38 pathway. In conclusion, rTl-GAL may function like a host galectin, thus functioning as a regulatory molecule in the host immune system; rTl-GAL may prove useful in the design of novel therapeutic intervention strategies for the treatment of allergic and immune diseases.

Identification of host immune regulation candidate genes of Toxascaris leonina by expression sequenced tags (ESTs) analysis.

Toxascaris leonina adult worms live in the gastrointestinal tract of dog, cat, and fox, releasing eggs which enter the environment by the fecal route. Previously, we reported that T. leonina adult worm derived protein was able to inhibit OVA-specific Th2 responses, and in particular, immunization with parasite proteins exerts a more profound protective effect than allergen treatment. In order to gain greater insight into the relevant immune evasion mechanisms as well as basic scientific information, we have generated ESTs of T. leonina adult female worm and investigated their functions using euKaryotic Orthologous Groups (KOG) database analysis. From the randomly selected plasmids containing DNA inserts, a total of 487 reads were collected from the T. leonina adult worm cDNA library. The annotated ESTs were classified into 25 KOG categories; the most of ESTs (7.90%) were annotated with energy production and conversion, and the second highly annotated category is translation, ribosomal structure and biogenesis related ESTs (7.69%). We also identified many host-parasite immune related genes including C-type lectin, galectin, SXP, and cathepsin L-like cysteine protease coding genes. It is necessary to get more information regarding these genes for understanding about the mechanisms of immune evasion of Toxascaris.

Macrophage migration inhibitory factor homologs of anisakis simplex suppress Th2 response in allergic airway inflammation model via CD4+CD25+Foxp3+ T cell recruitment.

We have cloned the macrophage migration inhibitory factor (MIF)-like protein (Anisakis simplex (As)-MIF) from larvae of the whale worm (Anisakis simplex third-stage larvae). Asthma was induced in the mice using OVA/alum, with or without various concentrations of rAs-MIF treatment before OVA/alum challenge. Treatment with rAs-MIF coupled with OVA/alum during the challenge period induced a complete inhibition of eosinophilia and goblet cell hyperplasia within the lung and profoundly ameliorated the development of lung hyperreactivity. Also, rAs-MIF was shown to reduce profoundly the quantity of Th2-related cytokines (IL-4, IL-5, and IL-13) in the bronchial alveolar lavage fluid and allergen-specific IgG2a in sera. IL-10 and TGF-beta levels in the bronchoalveolar lavage fluid of the rAs-MIF-treated group were significantly higher than in the other groups. Additionally, CD4(+)CD25(+)Foxp3(+) T cells (regulatory T) were recruited to the spleen and lungs of the rAs-MIF-treated mice, but this recruitment was inhibited by anti-rAs-MIF Ab.

Immunization of proteins from Toxascaris leonina adult worm inhibits allergic specific Th2 response.

Recently, the influence of parasitic infections on the incidence of allergic diseases has become the focus of increased attention. In order to ascertain whether parasite-derived proteins could inhibit the allergic specific Th2 response, we applied excretory-secretory protein (Tl-ES) or total protein (Tl-TP) of the adult worm Toxascaris leonina to asthma model mice prior to or simultaneously with OVA challenge, after which we assessed the OVA-specific Th2 responses. The group subjected to immunization with Tl-ES and Tl-TP (immunized group) evidenced a thinning of the bronchial epithelial and muscle layer, a disruption and shedding of epithelial cells, a reduction in the number of goblet cells, and a reduction in mucus production as compared to the group treated with Tl-ES coupled with OVA challenge (challenge with OVA groups) and the OVA-induced asthma group. The administration of Tl-ES and Tl-TP, regardless of injection time, was shown to inhibit the recruitment of inflammatory cells into the airway, and in particular, macrophages, neutrophils, and lymphocytes were significantly reduced as the result of the parasite proteins. However, the total number of eosinophils was slightly reduced as the result of the administration of parasite proteins. Sensitization and OVA challenge was shown to accelerate the secretion of Th2 cytokines (IL-4 and IL-5) within the lung, but in the immunized groups, those levels were lower. The administration of Tl-TP and OVA challenge group also evidenced a significant reduction in IL-4 levels as compared to the OVA-challenged group. The concentrations of Th2 cytokines in the Tl-ES and OVA challenge group were more similar to those observed in the OVA-challenged group. The concentration of IL-10 and TGF-beta in the lung was decreased substantially in the OVA-only challenge group, but the Tl-TP immunized group exhibited significantly induced IL-10 cytokine. OVA-specific IgG2a, IgG1, and IgE levels in the immunized groups were significantly lower than those detected in the OVA-challenged group. In conclusion, parasite-derived protein is able to inhibit OVA-specific Th2 responses, and in particular, immunization with parasite proteins exerts a more profound protective effect than is seen with the treatment of allergic reactions. The results of our study are encouraging in terms of our further understanding of the molecular basis of immune evasion by nematodes.

Acanthamoeba: keratopathogenicity of isolates from domestic tap water in Korea.

In a previous study, we reported on the contamination rate of free living amoeba, including Acanthamoeba, isolated from contact lens storage cases (CLSC) and domestic tap water in Korea. In an effort to evaluate the potential kerato-pathogenicity of 5 isolates from CLSC and 17 isolates from domestic tap water, we have conducted an investigation into the morphological features, mitochondrial DNA (mtDNA) restriction fragment length polymorphism (RFLP) phenotypes, 18S rDNA sequences, and drug sensitivities of these isolates, and have compared the results with those of 20 amoebic keratitis (AK) isolates from Korea, as well as 14 reference strains. Cysts from 22 isolates obtained from CLSC and domestic tap water showed typical characteristics of morphological group 2. A total of three and five mtDNA RFLP patterns generated by EcoRI were found in 5 of the isolates from CLSC and 17 of the isolates from domestic tap water, respectively. The mtDNA RFLP patterns of four of the five isolates from the CLSC were found to be identical to those of the isolates from domestic tap water of students who had contaminated CLSC. The majority had mtDNA RFLP patterns identical to those of AK isolates in Korea. The results of 18S rDNA sequencing analysis were also shown to coincide with the results of mtDNA RFLP analysis. KA/WP12 was determined to be profoundly sensitive to chlorhexidine (MCC; 6.25microg/ml), and KAWP2 was the most sensitive strain to polyhexamethylene biguanide (PHMB) (MCC; 4.69microg/ml). Some difference in the cytopathic effects of isolates against human corneal epithelial cells was observed according to their mtDNA genotypes. In conclusion, domestic tap water may constitute a source of Acanthamoeba contamination of CLSC, and most isolates from CLSC and domestic tap water appear to be potentially keratopathogenic.

Anisakis simplex: analysis of expressed sequence tags (ESTs) of third-stage larva.

This study analyzed the expressed sequence tags (ESTs) of the third-stage larvae of Anisakis simplex, in an attempt to gain further insight into its genomic expression patterns. An A. simplex cDNA library was constructed using the Uni-ZAP XR expression vector. A total of 493 clones (insert DNA>400 bp) were sequenced out of 580 clones selected randomly from a cDNA library of the A. simplex third-stage larva. After BLAST search analyses, 154 (31.2%) ESTs were found to have very low similarity, or no match at all to any of the proteins and gene sequences in the published databases. Most matched clones (98 clones, 20.0%) were determined to be highly homologous with the genes or proteins of Caenorhabditis elegans. Ten (2.0%) ESTs matched the genes isolated from humans, and 21 (4.3%) ESTs matched with the previously reported A. simplex genes or proteins. Eighty-nine clones (18.0%) matched a total of 14 genera and 17 species of human parasites. These 339 ESTs identified could be grouped into 13 categories: allergens or antigens (4.1%), growth- and cell division-related proteins (3.2%), heat shock proteins or molecular chaperones (1.8%), membrane proteins (5.6%), metabolism-associated proteins (24.2%), mitochondrial proteins (9.4%), nuclear proteins (2.4%), proteases and protease inhibitors (3.5%), signal transduction proteins (2.4%), structural proteins (7.4%), transcription and translation machinery-associated proteins (20.1%), transporters and receptor proteins (3.8%), and other protein types (12.1%). The genetic information of Anisakis determined in this study might prove to be quite helpful in elucidating the pathogenetic mechanisms of anisakidosis, and might be useful in the development of therapeutic reagents specific to anisakidosis.

Acanthamoeba: could it be an environmental host of Shigella?

Shigellosis is a serious public health problem in Korea, because large outbreaks of Shigella sonnei infections were recorded in many parts of the country during the period 1998-2000. However, the epidemiological features of shigellosis are not well known. In this study, we devised conditions suitable for the growth and replication of Shigella in an amoebic intracellular environment, and investigate whether medium conditions affect the survival and replication of Shigella within Acanthamoeba. We evaluated the uptake rates of invasive and non invasive S. sonnei strains by three Acanthamoeba species, namely, A. castellanii Neff, A. astronyxis Ray & Hayes, and A. healyi OC-3A. When A. castellanii Neff was infected with S. sonnei 99OBS1 or 80DH248, shigellae was maintained for a longer time in cytoplasms than in other Acanthamoeba species. S. sonnei 99OBS1 strain (a virulent strain) was recovered in higher numbers than the non-virulent S. sonnei 80DH248 strain in all experiments. Moreover, S. sonnei was more easily engulfed by Acanthamoeba at 18 degrees C. The shigellae uptake rates of Neff strain, which was cultured in free-media (less nutrition), were higher (>10-fold) than those observed in original amoeba culture media (PYG medium) in all time points. S. sonnei 99OBS1 was localized, with an intact membrane, to the vacuoles of Acanthamoeba. We conclude that free-living amoebae more likely act as environmental hosts for shigellae, and thus, may have contributed to outbreaks of shigellosis in Korea.