Uptake and safety of community-based "screen-and-treat" with thermal ablation preventive therapy for cervical cancer prevention in rural Lilongwe, Malawi.

Malawi has the highest invasive cervical cancer (ICC) mortality rate worldwide, and ICC is the leading cause of cancer death among women. In 2004, Malawi adopted visual inspection with acetic acid (VIA) and ablative treatment with cryotherapy. However, screening coverage has remained low (<30%) and few women (<50%) who require ablative treatment receive it. Additional barriers include long distances to health facilities and challenges with maintaining gas supplies. Thermal ablation is a safe and effective alternative to cryotherapy. We assessed the safety and uptake of community-based ICC screening with VIA and same-day treatment using a handheld thermocoagulator (HTU) in rural Malawi. We held educational talks alongside community leaders and conducted VIA screening in nonclinic community settings to nonpregnant women aged 25 to 49 years without history of hysterectomy or genital cancer/precancer. Eligible women received same-day thermal ablation and HIV testing/counseling. We collected cervical biopsies before treatment and followed up women at Weeks 6 and 12, with repeat biopsy at Week 12. Between July and August 2017, 408 (88%) of 463 eligible women underwent VIA. Overall, 7% (n = 30) of women had a positive VIA, of whom 93% (n = 28) underwent same-day thermal ablation. Among the 30 VIA-positive women, 5 had cervical intraepithelial neoplasia (CIN) 1, 4 had CIN 2/3 and 21 had benign histologic findings. Abnormal vaginal discharge (60%) and light vaginal bleeding (52%) were the most reported adverse events. There was high uptake of the community-based ICC screening in the study population and treatment was safe in this setting. Similar strategies that minimize false-positive results are urgently needed in Malawi.

Alcohol metabolite acetic acid activates BK channels in a pH-dependent manner and decreases calcium oscillations and exocytosis of secretory granules in rat pituitary GH3 cells.

Acetaldehyde and acetic acid/acetate, the active metabolites of alcohol (ethanol, EtOH), generate actions of their own ranging from behavioral, physiological, to pathological/cancerogenic effects. EtOH and acetaldehyde have been studied to some depth, whereas the effects of acetic acid have been less well explored. In this study, we investigated the effect of acetic acid on big conductance calcium-activated potassium (BK) channels present in GH3 rat pituitary tumor cells in more detail. In whole cell voltage clamp recordings, extracellular application of acetic acid increased total outward currents in a dose-dependent manner. This effect was prevented after the application of the specific BK channel blocker paxilline. Acetic acid action was pH-dependent-in whole cell current and single BK channel recordings, open probability (Po) was significantly increased by extracellular pH reduction and decreased by neutral or base pH. Acetic acid hyperpolarized the membrane potential, whereas acidic physiological solution had a depolarizing effect. Moreover, acetic acid reduced calcium (Ca2+) oscillations and exocytosis of growth hormone contained secretory granules from GH3 cells. These effects were partially prevented by BK inhibitors-tetraethylammonium or paxillin. In conclusion, our experiments indicate that acetic acid activates BK channels in GH3 cells which eventually contribute to acetic acid-induced membrane hyperpolarization, cessation of Ca2+ oscillations, and decrease of growth hormone release.

Short-term Cudrania tricuspidata fruit vinegar administration attenuates obesity in high-fat diet-fed mice by improving fat accumulation and metabolic parameters.

Previous studies have suggested that vinegar intake can help to reduce body fat and hyperglycemia. Therefore, this study aimed to evaluate the anti-obesity efficacy of vinegar fermented using Cudrania tricuspidata fruits (CTFV) and its main phenolic constituents and to analyze its molecular mechanism and changes in obesity-related metabolizing enzymatic activities. We found that HFD significantly caused hepatic steatosis; increases in body fats, feed efficiency, liver mass, lipids, insulin, oxidative parameters, cardiovascular-associated risk indices, lipase and α-amylase activities, whereas CTFV efficaciously attenuated HFD-induced oxidant stress, fat accumulation, obesity-related enzymatic activity, and the activation or reduction of obesity-related molecular reactions via improving metabolic parameters including phosphorylated insulin receptor substrate 1, protein tyrosine phosphatase 1B, phosphorylated phosphoinositide 3-kinase/protein kinase B, phosphorylated mitogen-activated protein kinases, sterol regulatory element-binding protein 1c, CCAAT/enhancer-binding protein, and fatty acid synthase; and decreases in adiponectin receptor 1, leptin receptor, adenosine monophosphate-activated protein kinase, acetyl-CoA carboxylase, and peroxisome proliferator-activated receptor, subsequently ameliorating HFD-induced obesity. Therefore, CTFV might provide a functional food resource or nutraceutical product for reducing body fat accumulation.

Calcific Tendinopathy of the Rotator Cuff Treated With Acetic Acid Iontophoresis.

A 62-year-old right hand-dominant man with a 20-year history of left shoulder pain and 6-month insidious, progressively worsening symptoms was referred to physical therapy with clinical and radiographic evidence of left supraspinatus tendon calcification. Following examination, the patient was prescribed rest, isometrics, and pain-free range of motion. He was treated with iontophoresis for 3 visits per week for 5 weeks. Radiographs, repeated 1 week post treatment and 9 weeks since his initial radiographs, demonstrated marked resorption of the calcific deposit. J Orthop Sports Phys Ther 2020;50(11):650. doi:10.2519/jospt.2020.9270.

Targeted delivery of 5-fluorouracil-1-acetic acid (5-FA) to cancer cells overexpressing epithelial growth factor receptor (EGFR) using virus-like nanoparticles.

Chemotherapy is widely used in cancer treatments. However, non-specific distribution of chemotherapeutic agents to healthy tissues and normal cells in the human body always leads to adverse side effects and disappointing therapeutic outcomes. Therefore, the main aim of this study was to develop a targeted drug delivery system based on the hepatitis B virus-like nanoparticle (VLNP) for specific delivery of 5-fluorouracil-1-acetic acid (5-FA) to cancer cells expressing epithelial growth factor receptor (EGFR). 5-FA was synthesized from 5-fluorouracil (5-FU), and it was found to be less toxic than the latter in cancer cells expressing different levels of EGFR. The cytotoxicity of 5-FA increased significantly after being conjugated on the VLNP. A cell penetrating peptide (CPP) of EGFR was displayed on the VLNP via the nanoglue concept, for targeted delivery of 5-FA to A431, HT29 and HeLa cells. The results showed that the VLNP displaying the CPP and harboring 5-FA internalized the cancer cells and killed them in an EGFR-dependent manner. This study demonstrated that the VLNP can be used to deliver chemically modified 5-FU derivatives to cancer cells overexpressing EGFR, expanding the applications of the VLNP in targeted delivery of chemotherapeutic agents to cancer cells overexpressing this transmembrane receptor.

Beneficial Effects of Apple Vinegar on Hyperglycemia and Hyperlipidemia in Hypercaloric-Fed Rats.

The main objective of this study is to determine the effects of apple vinegar on the metabolic changes caused by hypercaloric diet in Wistar rats. Apple vinegar was first analyzed to find out the total acidity, the polyphenolic and flavonoid contents, the total antioxidant capacity, and the free radical scavenging activity. In vivo study on adult male and female Wistar rats was conducted by administering a drink containing either 10% D-glucose or water (control) for five weeks. Apple vinegar is administered daily by gavage (2 mL/kg) to rats fed D-glucose for 5 weeks. The results showed that the polyphenolic content in apple vinegar was 148.02 ± 10.16 mg GAE/100 mL, flavonoid content was 22.93 ± 0.73 QE/100 mL, and total antioxidant capacity was 13.4 ± 0.47 mg AAE/100 mL. Free radical IC50 apple vinegar scavenging activity (DPPH) was 0.74 ± 0.154 µL/mL. The total acidity was (3.24 ± 0.02 mg AAE/100 mL). The treatment during five weeks with D-glucose leads to increased plasma glucose, lipid profile, hepatic enzyme levels, urea, and creatinine. Simultaneous treatment with apple vinegar improves the parameters studied. These results clearly show that the daily consumption of vinegar can reduce the rise in blood sugar and lipid profile induced by hypercaloric diet in rats. Therefore, the use of apple vinegar would have a very beneficial effect in the prevention of metabolic disorders caused by high-caloric food.

Acid exposure disrupts mucus secretion and impairs mucociliary transport in neonatal piglet airways.

Tenacious mucus produced by tracheal and bronchial submucosal glands is a defining feature of several airway diseases, including cystic fibrosis (CF). Airway acidification as a driving force of CF airway pathology has been controversial. Here we tested the hypothesis that transient airway acidification produces pathologic mucus and impairs mucociliary transport. We studied pigs challenged with intra-airway acid. Acid had a minimal effect on mucus properties under basal conditions. However, cholinergic stimulation in acid-challenged pigs revealed retention of mucin 5B (MUC5B) in the submucosal glands, decreased concentrations of MUC5B in the lung lavage fluid, and airway obstruction. To more closely mimic a CF-like environment, we also examined mucus secretion and transport following cholinergic stimulation under diminished bicarbonate and chloride transport conditions ex vivo. Under these conditions, airways from acid-challenged pigs displayed extensive mucus films and decreased mucociliary transport. Pretreatment with diminazene aceturate, a small molecule with ability to inhibit acid detection through blockade of the acid-sensing ion channel (ASIC) at the doses provided, did not prevent acid-induced pathologic mucus or transport defects but did mitigate airway obstruction. These findings suggest that transient airway acidification early in life has significant impacts on mucus secretion and transport properties. Furthermore, they highlight diminazene aceturate as an agent that might be beneficial in alleviating airway obstruction.

Modulation effects of black-vinegar-based supplement against a high-fat dietary habit: antiobesity/hypolipidemic, antioxidative, and energy-metabolism effects.

BACKGROUND: An imbalanced fat or excess energy intake always results in obesity and increased serum/liver lipids, thus leading to metabolic syndromes. Given the bioactive components in black vinegar (BV), such as branched amino acids, phenolic profile, and mineral contents, we investigated the antiobesity effects of BV-based supplements in rats fed a high-fat diet (HFD). RESULTS: HFD (30% fat, w/w) feeding increased (P < 0.05) body weight, weight gains, weights of livers and mesenteric, epididymal, and perirenal adipose tissues, and serum/liver triglyceride levels relative to those of rats fed a normal diet (4% fat, w/w; CON). These increased values were ameliorated (P < 0.05) by supplementing with BV-based supplements but were still higher (P < 0.05) than those of CON rats. The increased areas of perirenal adipocytes in rats fed with an HFD were also decreased (P < 0.05) by supplementing with BV-based supplements, which might result from an upregulation (P < 0.05) of 5'-adenosine monophosphate-activated protein kinase (AMPK), carnitine palmitoyltransferase-1 (CPT1), and uncoupling protein-2 (UCP2) in the perirenal adipose tissues. A similar effect was observed for AMPK, peroxisome proliferator-activated receptor alpha, retinoid X receptor alpha, CPT1, and UCP2 gene and protein levels in livers (P < 0.05). Generally, BV-based supplements increased the fecal triglyceride, cholesterol, and bile acid levels of rats fed with an HFD, which partially contribute to the lipid-lowering effects. Furthermore, BV-based supplements increased (P < 0.05) hepatic Trolox equivalent antioxidant capacity and lowered (P < 0.05) serum/liver thiobarbituric acid reactive substances values in HFD-fed rats. CONCLUSION: In a chronic high-fat dietary habit, the food-grade BV-based supplement is a good daily choice to ameliorate obesity and its associated comorbidities. © 2020 Society of Chemical Industry.

How long is too long? Application of acetic acid during colposcopy: a prospective study.

BACKGROUND: Application of acetic acid to the cervix followed by colposcopic assessment with or without colposcopically directed biopsy is the standard test used to detect dysplastic lesions of the cervix. However, there is no evidence-based common standard defining how exactly to perform this test. OBJECTIVE: To prospectively define the optimal timing for the colposcopic assessment of acetowhite lesions. MATERIALS AND METHODS: Consecutive women referred to our colposcopy unit were recruited. Using a standardized colposcopy protocol, we recorded the most severe colposcopic lesion 1, 3, and 5 minutes after application of acetic acid (primary study end point). The time to first appearance of the most severe colposcopic lesion, highest staining intensity, and fading of the most severe colposcopic lesion were video documented (secondary study end points, assessed independently by 3 raters). Results were compared using parametric and nonparametric tests. RESULTS: A total of 300 women were included. After 1 minute, 290 of 300 patients (96.7%) were diagnosed with the most severe colposcopic lesion. This proportion did not improve after 3 minutes (290/300 [96.7%]) or after 5 minutes (233/264 [88.3%]). The proportion of minor and major changes continuously declined over time from 142 in 300 (47.3%; 1 minute) to 107 in 264 (40.5%; 5 minutes) and from 110 in 300 (36.7%) to 91 in 264 (34.5%), respectively. The median time until the first appearance of the most severe colposcopic lesion was 13.5 (interquartile range, 3-27.25) seconds and was significantly lower in high-grade squamous intraepithelial lesion (7 [interquartile range, 1-20] seconds) compared to low-grade squamous intraepithelial lesion (19 [interquartile range, 9-39.5] seconds; P < .001). We observed fading of acetowhite lesions in 78% of cases, occurring at a median of 191 (interquartile range, 120-295) seconds after application of acetic acid. Fading started earlier in high-grade squamous intraepithelial lesion compared to low-grade squamous intraepithelial lesion (179.5 [interquartile range, 110- 253.25] versus 212.5 [interquartile range, 146.5-300]; P = .044). Overall, the net difference between colposcopic assessments at 3 minutes versus at 1 minute was 1 more high-grade squamous intraepithelial lesion and 1 less low-grade squamous intraepithelial lesion. CONCLUSION: It is reasonable to conclude that the best time to identify lesions is 1 minute after the application of acetic acid. Continued evaluation for up to 3 minutes may be considered reasonable for an optimal high-grade squamous intraepithelial lesion yield. However, fading of acetowhite lesions is common, especially in high-grade squamous intraepithelial lesions, and supports a recommendation of not prolonging colposcopy beyond 3 minutes.

Acetic acid versus radiofrequency ablation for the treatment of hepatocellular carcinoma: A randomized controlled trial.

PURPOSE: The purpose of this prospective study was to compare the efficacy of percutaneous acetic acid (PAAI) to that of radiofrequency ablation (RFA) in the treatment of small (≤5cm) hepatocellular carcinoma (HCC) using a randomized trial. MATERIAL AND METHODS: Consecutive patients with small HCC underwent clinical, biochemical, and imaging evaluation. Those fulfilling the inclusion criteria (Child's A/B cirrhosis, less than 5 HCC nodules, HCC nodules≤5cm diameter, no extrahepatic disease, patent portal vein, normal coagulation profile with informed consent) were randomly assigned to receive RFA or PAAI. Tumor response and survival rate were estimated. Non-inferiority margin of 10% difference was taken for effectivity of PAAI compared to RFA. RESULTS: Of the 86 patients screened, 55 patients with 67 HCC nodules were included. There were 40 men and 15 women with a mean age of 54.3±10.5 (SD) years (range: 28-71years). Of these, 26 patients had PAAI and 29 had RFA. The clinical, demographic and imaging profiles of the two groups were similar. Complete response was non-inferior to RFA [PAAI 75% and RFA 83.3%, difference 8.3% CI (-12.5% to 29.2%)]. Lower limit of this 95% CI (-12.5%) was lower than the 10% non-inferiority margin difference (8.3%). Survival rates were similar at 12months (PAAI, 81.6% vs. RFA, 71.9%; P=0.68) and at 30months (PAAI, 54.4% vs. RFA, 52%; P=0.50). CONCLUSION: PAAI and RFA have similar efficacy in treating small HCC. PAAI could thus be a cost-effective alternative in situations where RFA is either unavailable or unaffordable.

Pharmacological Characterization and Raman Spectroscopy Evaluation of Oral and Maxillofacial Surgery-Related Carnoy´S Solution Modified by Different Viscosity Agents.

BACKGROUND: There are several lesions of odontogenic and non-odontogenic origin in the oral cavity, such as odontogenic keratocyst, as well as many treatment options for such lesions. In order to reduce recurrence due to conservative treatments and less aesthetic and functional impairment of the patient (radical therapies), Carnoy's solution has been used as an adjuvant to surgery, showing satisfactory results. Its application is not standardized, presenting risks to adjacent tissues. Thus, we characterized the Carnoy's solution with different viscosity agents to enhance its applicability. MATERIAL AND METHODS: All solutions prepared (Carnoy with and without chloroform) were added with viscosity agent: ethyl cellulose, propylene glycol, and glycerol totaling eight solutions. The pharmacological characterization of the solutions was performed by determining the mass density and relative density (using a clean and dry pycnometer), pH (using pH meter), and concentration of Fe3+ (using ultraviolet/visible spectroscopy). The analyses of the inorganic components were determined by Raman micro spectrometry. Data were analyzed with statistical program BIOESTAT 5.3. RESULTS: Solutions with ethyl cellulose were discarded due to precipitate formation and suspension of the viscosity agent. In the other solutions, viscosity increase (propylene glycol solutions) and acidic pH were observed mainly in the glycerol group. The ferric chloride characterized as a hemostatic agent had its concentration increased with the use of thickening agents, theoretically favoring its action. CONCLUSION: The similarity of the propylene glycol and glycerol molecules justifies the Raman spectra of these substances to be similar and the difficulty in obtaining a "fingerprint".
.

[Cervical cancer: Current situation and management in Morocco]. / Le cancer du col de l'utérus : état des lieux et prévention au Maroc.

With more than 3300 new cases and almost 2500 deaths each year, cervical cancer (CC) ranks second among female cancers in Moroccan women. The majority of cases occurs in women aged 50 and over. In absence of a national cancer registry, data published in Morocco are limited to the number of cases recorded in some oncology centers, so the incidence of this cancer is likely much higher than estimated. A Moroccan national program against CC based on the practice of visual inspection after application of acetic acid was set up in 2010, allowing both screening and possibly immediate treatment of (pre)cancerous lesions. However, this program has not been implemented in all regions of the country. The CC develops slowly and most often without any symptoms, and so it is diagnosed at an advanced stage of the disease. Virtually, all CC are associated with persistent infection of high risk human papillomavirus (HPV), particularly HPV16 and 18. For more than ten years, two prophylactic vaccines targeting these two HPV genotypes have been marketed. They have proved their excellent immunogenicity and efficacy and they are well tolerated. However, HPV vaccine is not yet recommended by health authorities in Morocco. In this literature review, we focused on the current situation of CC, the prevalence of HPV infection and the prevention strategies against CC in Morocco.

Vinegar (acetic acid) intake on glucose metabolism: A narrative review.

Vinegar intake is considered a food item that improves blood glucose in humans. This review aimed to discuss studies that investigated the impact of vinegar intake on the glycemic profile in humans and the putative mechanistic cellular pathways in both human and animal models. A search of literature was performed on the Cochrane, MEDLINE and Web of Science databases for articles published between 1995 and 2018. There is considerable support for vinegar having a positive acute effect on blood glucose levels when combined with carbohydrate-rich meals. Conversely, there are few chronic interventions analyzing the impact of vinegar intake on blood glucose. Based on available evidence, we hypothesize three pathways by which vinegar may improve blood glucose: The inhibition of α-amylase action; increased glucose uptake; and mediation by transcription factors. When evaluating the current body of literature, daily vinegar intake in amounts of ∼10-30 mL (∼2-6 tablespoons) appear to improve the glycemic response to carbohydrate-rich meals; however, there is a paucity of studies investigating chronic effects of vinegar intake.

Comparison of the diagnostic value of the visual inspection with acetic acid (VIA) and Pap smear in cervical cancer screening.

OBJECTIVE: This study aimed to compare the diagnostic value of VIA with Pap smear in screening for cervical cancer. MATERIALS AND METHODS: In this cross-sectional study, 440 women who had eligibility criteria, in Kashan city were assessed. All women underwent Pap smear test and then a visual inspection with acetic acid and colposcopy-biopsy (Gold Standard). Then, the diagnostic value indices including the specificity, sensitivity, positive and negative predictive values for the results of VIA and Pap smear were analyzed by SPSS V16 software. RESULTS: Finding showed that 29.9% of women had abnormal Pap smear. The false positive rate of Pap smear was 40.2%, and its false negative rate was 37.4%. For VIA, the false positive and false negative rates were 21.2% and 4.6%. The sensitivity, specificity, NPV and PPV of Pap smear was 29.7%, 85.5%, 59.8%, 62.6%, and these values for VIA was 94.6%, 81.6%, 78.8%, 95.4% respectively. Combination of Pap smear and VIA showed the sensitivity of 97.3% and 100% in low grade and high grade cervical lesions. CONCLUSION: VIA has a higher sensitivity than Pap smear in detection of low and high grade cervical lesions, however, its specificity is less than Pap smears. Therefore it is recommended to use of VIA along with Pap smear to reach a higher sensitivity.

Silagem de dourada Brachyplatystoma rousseauxii (Casteunal, 1855) a partir de diferentes concentrações de ácido acético e ácido sulfúrico / Silage of dourada Brachyplatystoma rousseauxii (Castelnau, 1855) from different concentrations of acetic acid and sulfuric acid

O objetivo deste trabalho foi analisar a estabilidade física e físico-química de silagens com diferentes concentrações de ácido acético e ácido sulfúrico, proferida com resíduos de Brachyplatystoma rousseauxii (Castelnau, 1855) (dourada). O método consistiu da adição de 0,5% de ácido sulfúrico; 3 e 5% de ácido acético (silos diferentes) em resíduos de Dourada. Durante a estocagem foram mensurados os parâmetros: pH, temperatura, umidade, cinzas e lipídios. Os tratamentos demonstraram poucas variações entre si, mantendo-se próximos ao do produto in natura, exceto para os níveis de umidade que apresentaram padrões decrescentes. Contudo, o silo contendo maior concentração de inoculante foi o que apresentou silagem com melhor estabilidade.

Performance of clinical screening algorithms comprising point-of-care HPV-DNA testing using self-collected vaginal specimens, and visual inspection of the cervix with acetic acid, for the detection of underlying high-grade squamous intraepithelial lesions in Papua New Guinea.

The performance of different clinical screening algorithms comprising point-of-care HPV-DNA testing using self-collected vaginal ('V') specimens, and visual inspection of the cervix with acetic acid (VIA) was evaluated in Papua New Guinea. Women aged 30-59 years provided V specimens that were tested at point-of-care using the Xpert HPV Test (Cepheid, Sunnyvale, CA). A clinician-collected cervical ('C') specimen was then collected for point-of-care Xpert testing, and liquid-based cytology (LBC). Following this, VIA examination was conducted, blind to HPV test results, and ablative cervical cryotherapy provided if indicated. Detection of high-grade squamous intraepithelial lesion (HSIL) by LBC was the reference standard used to evaluate clinical screening algorithms. Of 1005 women, 36 had HSIL+. Xpert HPV Test performance using V specimens (sensitivity 91.7%, specificity 87.0%, PPV 34.0%, NPV 99.3%) was superior to VIA examination alone (51.5%, 81.4%, 17.5%, 95.6% respectively) in predicting underlying HSIL+. A screening algorithm comprising V specimen HPV testing followed by VIA examination had low sensitivity (45.5%) but comparable specificity, PPV and NPV to HPV testing alone (96.3%, 45.5%, 96.3% respectively). A 'test-and-treat' screening algorithm based on point-of-care HPV testing of V specimens had superior performance compared with either VIA examination alone, or a combined screening algorithm comprising HPV testing plus VIA.