Nevin Manimala

Photodiagnosis Photodyn Ther. 2022 Mar 6:102795. doi: 10.1016/j.pdpdt.2022.102795. Online ahead of print.

ABSTRACT

BACKGROUND: Photodynamic therapy (PDT) has shown satisfactory antibacterial effects. However, few information regarding the cytotoxicity potential of PDT using curcumin as a photosensitizer (PS) on fibroblasts are found. The aim of this in vitro study was to evaluate the cytotoxicity of root canal irrigating solutions and photodynamic therapy with curcumin PS on the L-929 cell line.

METHODS: Healthy mouse skin fibroblast cells were distributed into the following 7 experimental groups: G1 – culture medium DMEM (control group); G2 – 0.9% sodium chloride; G3 – 2.5% sodium hypochlorite (NaOCl); G4 – 5% NaOCl; G5 – PDT with curcumin PS at 500 mg/L + blue LED; G6 – PDT with curcumin PS at 750 mg/L + blue LED; and G7 – PDT with curcumin PS at 1000 mg/L + blue LED. All experimental groups which underwent PDT action were submitted to blue LED for 4 minutes, with a wavelength of 480 nm and energy fluency of 75 J/cm². The cultures were maintained under standard cell culture conditions (37°C, 100% humidity, 5% CO₂). Cell viability analysis was performed using the colorimetric method to evaluate the periods of 6, 24, and 48 hours. Data were subjected to the Kruskal-Wallis test, followed by the Dunn test to compare groups and Friedman test to compare periods (α = 0.05).

RESULTS: When comparing the periods, no significant differences were observed for any of the experimental groups analyzed (p > 0.05), except for the NaOCl_2.5 group that exhibited higher cell viability at 6 hours compared to the period of 48 hours (p = 0.0489). In the comparisons of the experimental groups, there were no statistically significant differences between the control group compared to all disinfection protocols, regardless of the period evaluated (p > 0.05), except for the PDT + C₁₀₀₀ group that showed lower cell viability (p < 0.05).

CONCLUSIONS: PDT with curcumin at 1000 mg/L was cytotoxic on L-929 fibroblast cell culture. However, laser-activated curcumin at a concentration of 500 mg/L presented no influence on L-929 fibroblast cell viability in in vitro conditions.

PMID:35263668 | DOI:10.1016/j.pdpdt.2022.102795

Clin Immunol. 2022 Mar 6:108965. doi: 10.1016/j.clim.2022.108965. Online ahead of print.

ABSTRACT

Rheumatoid arthritis (RA) etiopathogenesis still remains complex, but involvement of several immune cells is evident. Present study focusses on evaluation of polymorphonuclear neutrophils (PMNs) in RA patients and healthy controls. From generation of oxidative species, release of inflammatory cytokines and matrix-degrading proteases, PMNs possess the ability to mediate immunological responses. Intracellular and mitochondrial ROS in PMNs and other oxidative parameters including catalase, superoxide dismutase, glutathione peroxidase, reduced glutathione and lipid peroxidation were measured in PMNs and serum samples. Gene regulation studies involved in oxidative (Keap1 and Nrf2) and degradative pathways (MMP2 and MMP9) were done using DNA methylation analysis. Intracellular expression levels of Keap1, Nrf2, Dnmt1, MMP2, and MMP9 were analyzed using flowcytometry in patients and controls. Moreover, serum levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were also measured. Comparative measurements amongst patients and controls were statistically analyzed, and correlations were made with disease severity scores (DAS28 ESR).

PMID:35263664 | DOI:10.1016/j.clim.2022.108965

Comput Methods Programs Biomed. 2022 Feb 25;218:106714. doi: 10.1016/j.cmpb.2022.106714. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Abnormalities of the heart motion reveal the presence of a disease. However, a quantitative interpretation of the motion is still a challenge due to the complex dynamics of the heart. This work proposes a quantitative characterization of regional cardiac motion patterns in cine magnetic resonance imaging (MRI) by a novel spatio-temporal saliency descriptor.

METHOD: The strategy starts by dividing the cardiac sequence into a progression of scales which are in due turn mapped to a feature space of regional orientation changes, mimicking the multi-resolution decomposition of oriented primitive changes of visual systems. These changes are estimated as the difference between a particular time and the rest of the sequence. This decomposition is then temporarily and regionally integrated for a particular orientation and then for the set of different orientations. A final spatio-temporal 4D saliency map is obtained as the summation of the previously integrated information for the available scales. The saliency dispersion of this map was computed in standard cardiac locations as a measure of the regional motion pattern and was applied to discriminate control and hypertrophic cardiomyopathy (HCM) subjects during the diastolic phase.

RESULTS: Salient motion patterns were estimated from an experimental set, which consisted of 3D sequences acquired by MRI from 108 subjects (33 control, 35 HCM, 20 dilated cardiomyopathy (DCM), and 20 myocardial infarction (MINF) from heterogeneous datasets). HCM and control subjects were classified by an SVM that learned the salient motion patterns estimated from the presented strategy, by achieving a 94% AUC. In addition, statistical differences (test t-student, p<0.05) were found among groups of disease in the septal and anterior ventricular segments at both the ED and ES, with salient motion characteristics aligned with existing knowledge on the diseases.

CONCLUSIONS: Regional wall motion abnormality in the apical, anterior, basal, and inferior segments was associated with the saliency dispersion in HCM, DCM, and MINF compared to healthy controls during the systolic and diastolic phases. This saliency analysis may be used to detect subtle changes in heart function.

PMID:35263659 | DOI:10.1016/j.cmpb.2022.106714

Exp Eye Res. 2022 Mar 6:109019. doi: 10.1016/j.exer.2022.109019. Online ahead of print.

ABSTRACT

PURPOSE: Retinitis pigmentosa (RP) patients commonly experience negative psychological states due to their progressive and unpredictable loss of vision and visual variations related to stress. The aim of this study was to examine hair cortisol concentrations (HCCs), which is usually associated with chronic stress, pretending to unveil possible associations between underlying psychological factors and disease severity in RP patients.

METHODS: Seventy-eight RP patients and 148 healthy controls were included in this A complete ophthalmological exam was performed in all patients to grade into severity disease groups. Perceived stress and trait-anxiety were measured by the State-Trait Anxiety Inventory (STAI) questionnaire.

RESULTS: Fifty-two (67%) patients had severe RP and 26 (33%) mild-moderate RP. Fifty-eight (58,9%) patients reported severely levels of stress and 18 (23.,1%) highly levels assessed by STAI questionnaire. RP patients exhibited higher HCCs (500.04 ± 120.99 pg/mg) than in controls (136.17 ± 60.51 pg/mg; p < 0.001). Severe RP patients had significant higher HCCs than mild-moderate patients differing in 274.27pg/mg (p < 0.001). RP severity grade and perceived anxiety levels in the questionaries were not associated. Group differences were not affected by relevant covariates (age, grade of severity, stress status, and gender).

CONCLUSIONS: HCC seems an effective biomarker associated with chronic stress in RP patients. This study shows that HCC in patients with RP are elevated compared to population-based controls, and association between HCC and RP severity was found. Future research is needed to characterize the effect of untreated negative psychological states on progression of the disease if any.

PMID:35263654 | DOI:10.1016/j.exer.2022.109019

Contraception. 2022 Mar 6:S0010-7824(22)00059-2. doi: 10.1016/j.contraception.2022.02.011. Online ahead of print.

ABSTRACT

OBJECTIVE: The primary aim of this project was to facilitate access to contraception at the University of Wisconsin-Madison campus by offering telehealth as an alternative option to an in-person contraception visit. The secondary aim was to assess patient feedback regarding telehealth contraception encounters and generate descriptive statistics of the 366 unique telehealth patients.

STUDY DESIGN: We implemented this quality improvement project from August 20, 2018 through December 31, 2018 at the University Health Services (UHS) Women’s Health Clinic at the University of Wisconsin-Madison. Patients completed a health history form online and scheduled a 15 minute phone call appointment with a provider. Providers addressed concerns, contraindications, screening recommendations and prescribe a patient selected contraceptive method over the phone or schedule a LARC appointment. After the telehealth encounter, we invited patients to complete a confidential electronic patient satisfaction survey.

RESULTS: In the fall of 2018, there were 3,413 contraception visits, 371 (11%) of which were telehealth encounters, an overall 7.8% increase in total Women’s Health visits compared to the same time period in the previous year. The response rate of the satisfaction survey was 41%, with 97% of respondents reporting being very satisfied or satisfied with the telehealth option.

CONCLUSIONS: Offering telehealth as an option for contraceptive visits improved capacity by increasing the total number of available appointments, including both in-person and telehealth visits. Additionally, telehealth may reduce barriers to reproductive health care with high patient satisfaction assessed prior to pandemic restrictions.

IMPLICATION STATEMENT: This study supports telehealth as an option for health systems to improve capacity by increasing the total number of available appointments, as well as reduce barriers to reproductive health care. Our patients found value in telehealth for contraceptive appointments prior to the major shift to telehealth with the onset of the pandemic, suggesting that this value may likely remain in the post-pandemic future.

PMID:35263651 | DOI:10.1016/j.contraception.2022.02.011

Am J Obstet Gynecol. 2022 Mar 6:S0002-9378(22)00170-3. doi: 10.1016/j.ajog.2022.02.042. Online ahead of print.

ABSTRACT

OBJECTIVES: This study investigated the efficacy and safety of pharmacological interventions to prevent vertical transmission of hepatitis B virus.

DATA SOURCE: Medline, Cochrane and Scopus databases were searched up to 28^th October 2020.

STUDY ELIGIBILITY CRITERIA: All randomized controlled trials reporting vertical hepatitis B virus transmission with pharmacological intervention were included.

STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias was assessed using the Cochrane Risk-of-Bias tool Version 2. Treatment efficacy was estimated using stratified network meta-analysis based on maternal hepatitis B envelope antigen status.

RESULTS: Nineteen studies were included for mothers positive for hepatitis B surface and envelope antigens. Pooling indicated a combination of hepatitis B vaccine and hepatitis B immunoglobulin in infants significantly reduced transmission risk compared to vaccine alone with a risk ratio of 0.52 (95% confidence interval 0.30, 0.91). Only the addition of maternal tenofovir disoproxil fumarate, but not telbivudine, lamivudine, or maternal hepatitis B immunoglobulin further reduced transmission risk compared to a combination of hepatitis B vaccine and hepatitis B immunoglobulin in infants, with a pooled risk ratio of 0.10 (0.03, 0.35). Twelve studies conducted in mothers with hepatitis B surface antigen positivity and mixed, unknown or negative hepatitis B envelope antigen status, provided limited evidence to suggest that maternal hepatitis B immunoglobulin combined with hepatitis B vaccine and immunoglobulin in infants was the likely best treatment, but this failed to reach statistical significance compared to a combination of hepatitis B vaccine and immunoglobulin in infants. Similarly, infant hepatitis B immunoglobulin, added to vaccination, likely provides additional benefit but again failed to reach statistical significance.

CONCLUSION: A combination of hepatitis B vaccine and immunoglobulin in infants is the cornerstone for prevention of vertical transmission for mothers double positive for both hepatitis B surface and envelope antigens. The addition of maternal tenofovir in this infant combination regimen was considered the likely most effective treatment. For infants of mothers with hepatitis B surface antigen positivity and mixed, unknown or negative hepatitis B envelop antigen status, no additional agents provided further benefit beyond hepatitis B vaccine alone.

PMID:35263648 | DOI:10.1016/j.ajog.2022.02.042

Toxicol In Vitro. 2022 Mar 6:105344. doi: 10.1016/j.tiv.2022.105344. Online ahead of print.

ABSTRACT

Bile acids (BA) are known to influence the susceptibility of hepatocytes to chemicals. We investigated the cytotoxicity of 18 compounds with known hepatotoxicity status and pharmacokinetics in cultivated primary human hepatocytes with and without the addition of a BA mix to the cell culture medium. This BA mix consisted of physiological ratios of the most abundant human BA at a cholestatic sum concentration of 0.5 mM, which corresponds to 50% of the EC₁₀ (cytotoxicity) of the mix. The BA mix decreased the EC₁₀ of 7 compounds by a factor greater than 1.5, but also increased the EC₁₀ of 5 compounds. The compounds with increased susceptibility include the known hepatotoxicants and BSEP/MRP2 inhibitors rifampicin, ketoconazole, atorvastatin, and cyclosporin A. However, the cytotoxicity of some non-hepatotoxic compounds was also enhanced, among them glucose, which is not known to be an inhibitor of canalicular bile acid export. A recently established technique to quantify how well hepatotoxic and non-hepatotoxic compounds are separated by an in vitro test indicated that the addition of the BA mix did not improve separation. In conclusion, the addition of BA to cultivated hepatocytes leads to a complex situation with increased and decreased susceptibilities depending on the specific compound.

PMID:35263627 | DOI:10.1016/j.tiv.2022.105344

Am J Hum Genet. 2022 Mar 3:S0002-9297(22)00064-7. doi: 10.1016/j.ajhg.2022.02.013. Online ahead of print.

ABSTRACT

One mechanism by which genetic factors influence complex traits and diseases is altering gene expression. Direct measurement of gene expression in relevant tissues is rarely tenable; however, genetically regulated gene expression (GReX) can be estimated using prediction models derived from large multi-omic datasets. These approaches have led to the discovery of many gene-trait associations, but whether models derived from predominantly European ancestry (EA) reference panels can map novel associations in ancestrally diverse populations remains unclear. We applied PrediXcan to impute GReX in 51,520 ancestrally diverse Population Architecture using Genomics and Epidemiology (PAGE) participants (35% African American, 45% Hispanic/Latino, 10% Asian, and 7% Hawaiian) across 25 key cardiometabolic traits and relevant tissues to identify 102 novel associations. We then compared associations in PAGE to those in a random subset of 50,000 White British participants from UK Biobank (UKBB_50k) for height and body mass index (BMI). We identified 517 associations across 47 tissues in PAGE but not UKBB_50k, demonstrating the importance of diverse samples in identifying trait-associated GReX. We observed that variants used in PrediXcan models were either more or less differentiated across continental-level populations than matched-control variants depending on the specific population reflecting sampling bias. Additionally, variants from identified genes specific to either PAGE or UKBB_50k analyses were more ancestrally differentiated than those in genes detected in both analyses, underlining the value of population-specific discoveries. This suggests that while EA-derived transcriptome imputation models can identify new associations in non-EA populations, models derived from closely matched reference panels may yield further insights. Our findings call for more diversity in reference datasets of tissue-specific gene expression.

PMID:35263625 | DOI:10.1016/j.ajhg.2022.02.013

Clin Exp Optom. 2022 Mar 9:1-6. doi: 10.1080/08164622.2022.2048174. Online ahead of print.

ABSTRACT

CLINICAL RELEVANCE: Practitioners can be reassured that this antihistamine-releasing contact lens has no additional effect on corneal epithelial integrity.

BACKGROUND: To evaluate the effect of an antihistamine-releasing soft contact lens on corneal epithelium integrity when worn on a daily disposable modality for 12 weeks.

METHODS: Two clinical trials using the same randomised, double-masked, placebo-controlled, parallel-group design enrolled healthy contact lens wearers. Participants wore either etafilcon A with 0.019 mg ketotifen (test; n = 374) or etafilcon A with no added drug (placebo; n = 186). Assessments were conducted at baseline, 1 week and 4, 8, and 12 weeks. Slit-lamp evaluations of corneal staining (using sodium fluorescein) in all regions of the corneas of both eyes were graded on a 0-4 scale. Data from all randomised participants were analysed.

RESULTS: Corneal staining was infrequent and, where present, was mild (Grade 2) or trace (Grade 1). There were no Grade 3 or 4 findings of corneal staining. The overall proportion of findings of Grade 0 corneal staining was 95.86% with the test lens and 95.88% with the placebo lens. The odds of no staining were not statistically different between the test and placebo lenses (Odds Ratio: 0.96, 95% Confidence Intervals: 0.76 to 1.20). There were no serious ocular adverse events or signs of ocular surface medicamentosa.

CONCLUSION: Both test and placebo lenses were well tolerated by subjects during the 3 months of wear. The antihistamine-releasing contact lens does not significantly impact corneal epithelial integrity.

PMID:35263558 | DOI:10.1080/08164622.2022.2048174

J Invest Surg. 2022 Mar 9:1-11. doi: 10.1080/08941939.2022.2046215. Online ahead of print.

ABSTRACT

OBJECTIVE: The hypothesis of this parallel group randomized trial testifies if TissuGlu is a safe and an effective alternative to the conventional drainage placement in regard to post-operative fluid management in the abdominal donor site for autologous (DIEP flap) breast reconstruction with a higher postoperative patient quality of life.

PATIENTS AND METHODS: Data was collected for 58 women who required to be at min.18 years old with a BMI < 30 and not taking any SSRIs (Selective Serotonin Reuptake Inhibitors).Exclusion criteria: Discharge with indwelling suction drains at the abdominal site or signs of wound infection during hospital stay.The patients were randomized into a study group (donor site closure with application of surgical adhesive without drains) and a control group (donor site closure with drains) using a randomly sorted sealed envelope system.Th e primary outcome was defined as the number of post-operative seroma formations.The secondary endpoint was the evaluation of patient satisfaction with both methods.

RESULTS: 58 patients underwent a DIEP reconstruction (29 in the control- and 29 in the study group).Both groups were homogenous. Rate of seroma was 17%(5/29) in the study group and 10%(3/29) in the control group which showed no statistical significance (p-value = 0.71).Smoking and previous abdominal surgery turned out to be a risk factor for seroma formation in the study group.Overall satisfaction was evaluated with a questionnaire and was higher in the study group.

CONCLUSION: The abdominal closure with the surgical adhesive seems to be a safe procedure that contributes to patient satisfaction and increases the independence upon discharge in patients with adequate inclusion criteria.

PMID:35263551 | DOI:10.1080/08941939.2022.2046215