Tag: nevin manimala

Genes Environ. 2022 May 9;44(1):14. doi: 10.1186/s41021-022-00243-4.

ABSTRACT

BACKGROUND: In eye-drop drug development, the additional genotoxicity tests in some cases might be necessary to assess genotoxicity in the ocular surface since the ocular surface is exposed directly to high drug concentrations. Recently, an in vivo comet assay using corneal epithelial cells in rabbits following single ocular instillation was developed as an assay to evaluate genotoxicity in ocular tissues. In this study, we investigated the time-course changes in DNA damage after ocular instillation of genotoxic compounds to evaluate the optimal sampling timing for in vivo comet assay of the ocular surface tissue. Ethidium bromide (EtBr), methyl methanesulfonate (MMS), and 4-nitroquinoline 1-oxide (4-NQO) were administered to the eyes of the rabbits. Corneas were collected at 0.5, 2, 4, 6, and 24 h after administration, and the comet assay was performed. In addition, the in vitro comet assay was performed to assess the time-course changes in DNA damage induced by short-time exposure to the genotoxic compounds.

RESULTS: The mean % tail DNA, which is an indicator for DNA damage, in the corneal epithelial cells treated with all compounds exhibited statistically significant increases compared with those in the negative controls of saline at 0.5, 2, 4, and 6 h. There was a difference in the DNA damage response between EtBr and the other two compounds. In the 3% MMS- and 1% 4-NQO-treated eyes, the values of the % tail DNA were the highest at 0.5 h and then decreased gradually. In contrast, in the 1% EtBr-treated eyes, the highest value was noted at 4 h. The results of the in vitro comet assay showed that the % tail DNA increased in all groups. A further increase in the % tail DNA occurred in the EtBr-treated cells even after removing the compound but not in the MMS- and 4-NQO-treated cells.

CONCLUSION: Relatively high values of the % tail DNA were maintained from 0.5 to 6 h after administration, suggesting that the optimal sampling time is any one point from 0.5 to 6 h in the comet assay of the corneal surface.

PMID:35527291 | DOI:10.1186/s41021-022-00243-4

BMC Med. 2022 May 9;20(1):169. doi: 10.1186/s12916-022-02363-8.

ABSTRACT

BACKGROUND: Identifying the causal genes at the risk loci and elucidating their roles in schizophrenia (SCZ) pathogenesis remain significant challenges. To explore risk variants associated with gene expression in the human brain and to identify genes whose expression change may contribute to the susceptibility of SCZ, here we report a comprehensive integrative study on SCZ.

METHODS: We systematically integrated the genetic associations from a large-scale SCZ GWAS (N = 56,418) and brain expression quantitative trait loci (eQTL) data (N = 175) using a Bayesian statistical framework (Sherlock) and Summary data-based Mendelian Randomization (SMR). We also measured brain structure of 86 first-episode antipsychotic-naive schizophrenia patients and 152 healthy controls with the structural MRI.

RESULTS: Both Sherlock (P = 3. 38 × 10^-6) and SMR (P = 1. 90 × 10^-8) analyses showed that TYW5 mRNA expression was significantly associated with risk of SCZ. Brain-based studies also identified a significant association between TYW5 protein abundance and SCZ. The single-nucleotide polymorphism rs203772 showed significant association with SCZ and the risk allele is associated with higher transcriptional level of TYW5 in the prefrontal cortex. We further found that TYW5 was significantly upregulated in the brain tissues of SCZ cases compared with controls. In addition, TYW5 expression was also significantly higher in neurons induced from pluripotent stem cells of schizophrenia cases compared with controls. Finally, combining analysis of genotyping and MRI data showed that rs203772 was significantly associated with gray matter volume of the right middle frontal gyrus and left precuneus.

CONCLUSIONS: We confirmed that TYW5 is a risk gene for SCZ. Our results provide useful information toward a better understanding of the genetic mechanism of TYW5 in risk of SCZ.

PMID:35527273 | DOI:10.1186/s12916-022-02363-8

J Egypt Natl Canc Inst. 2022 May 9;34(1):20. doi: 10.1186/s43046-022-00116-5.

ABSTRACT

CONTEXT: Treatment-related toxicities in DLBCL (diffuse large B cell lymphoma) patients are higher in the initial phase of treatment (first cycle effect). Implementation of pre-phase treatment before definitive chemotherapy had been shown to alleviate some of these side-effects in a non-randomized study conducted earlier in our institute (Lakshmaiah et. al., Eur J Haematol 100:644-8, 2018).

AIMS: This study was aimed at validating the role of pre-phase treatment in newly diagnosed DLBCL patients.

SETTINGS AND DESIGN: All newly diagnosed patients with DLBCL above the age of 18 years were evaluated for eligibility and prospectively enrolled. A single-arm prospective study was conducted at the Department of Medical Oncology, in our institute from July 2015 to December 2019.

METHODS AND MATERIAL: Patients received vincristine and prednisolone as pre-phase treatment for 7 days after which definitive chemotherapy was instituted on day 1. They were followed up for 30 days post-first cycle chemotherapy.

STATISTICAL ANALYSIS USED: Paired Student’s t tests and Wilcoxon signed-ranks test were used for comparison of various clinical variables as appropriate. P value of less than 0.05 was considered significant.

RESULTS: Among the 180 patients who were included in study, performance status improvement was noted in significant number of patients (p < 0.001). 38.4% achieved an ECOG (Eastern Cooperative Oncology Group) performance status of 0 post-pre-phase therapy. Febrile neutropenia was observed in 12.8% in the present cohort as compared to the historical non-pre-phase cohort (34%).

CONCLUSIONS: Pre-phase therapy significantly improves the performance status and diminishes neutropenia rates in DLBCL patients.

PMID:35527285 | DOI:10.1186/s43046-022-00116-5

Reprod Health. 2022 May 8;19(1):114. doi: 10.1186/s12978-022-01408-8.

ABSTRACT

BACKGROUND: Parents’ communication on sexual and reproductive health issues with their adolescent plays a great role in preventing morbidity and mortality associated with sexual behavior. However lack of parent to adolescent communication was a serious problem in Ethiopia resulted in teenage pregnancy, unsafe abortions, sexually transmitted infections, school problems, and other sexual risk behaviors. Parents have high responsibility on cultivating their son and daughter regarding to sexual and reproductive health issues. Therefore, the objective of this study was to determine the magnitude of parent’s communication with their adolescents and affecting factors in Ethiopia.

METHODS: A community-based, cross-sectional study was conducted on 347 respondents. A systematic sampling method was used to select the study participants. Data were collected by trained interviewers using a structured questionnaire, entered into Epi-Info version 7.1.2 and exported to SPSS version 23 for analysis. Descriptive statistics, bivariate and multivariate logistic regression analyses were used. Variables at P-value < 0.05 were considered as significant associations.

RESULTS: Slightly more than one-fifth of the parents (21.3%) had communicated with their adolescents on sexual and reproductive health issues. Associated factors like: being knowledgeable [AOR = 3.08, 95% CI: 1.89-5.39] and being having positive attitudes [AOR 3.03, 95% CI: 1.37-6.70] towards sexual reproductive health issues were significantly associated with communication.

CONCLUSION: Overall a low proportion of parental communication with their children was identified on sexual and reproductive health issues. This was affected by multidimensional factors to determine their discussion. Thus, promotion of parent to adolescent communication, parents training and addressing the importance of parent to young people communication along with health care providers was important.

PMID:35527271 | DOI:10.1186/s12978-022-01408-8

Int J Exp Pathol. 2022 May 8. doi: 10.1111/iep.12443. Online ahead of print.

ABSTRACT

The purpose of the present study was to investigate the expression of α-SMA and SM22α in airway smooth muscle (ASM) of bronchioles from children younger than 14 years who died of acute interstitial pneumonia (AIP). This is based upon the hypothesis that as contractile marker proteins α-SMA and SM22α can serve as an index of the overcontractile phenotype of ASM that is seen in AIP. Lung tissue samples of children were obtained from autopsies and divided into the AIP group (55.9% male and 44.1% female, between 0.4 and 132 months old, n = 34) and the control group (60% male and 40% female, between 2 and 156 months old, n = 10). We recorded the post-mortem interval (PMI), height, clinical symptoms and abdominal fat thickness (AFT) of each case. Haematoxylin-and-eosin-stained sections were used to examine the luminal area and observe the morphological changes in the bronchioles. Immunohistochemistry and Masson’s trichrome staining were used to detect the expression of contractile marker proteins and the degree of pulmonary fibrosis respectively. Compared with the control group, the luminal areas of bronchioles in the AIP group were smaller (p < .001). The expression differences in α-SMA and SM22α between the two groups were statistically significant (p = .01 and p = .02 respectively). Also, there was no significant correlation of the contractile marker proteins expression with PMI, height, clinical symptoms and AFT. The collagen deposition difference in lung between the two groups was not statistically significant (p = .224). These findings suggest that enhancement of ASM contractile function appears to be involved in the death mechanism of children with AIP, which affords more insights into the understanding of AIP.

PMID:35527237 | DOI:10.1111/iep.12443

J Geriatr Oncol. 2022 May 5:S1879-4068(22)00103-5. doi: 10.1016/j.jgo.2022.04.011. Online ahead of print.

ABSTRACT

BACKGROUND: A decade ago, it was demonstrated that the difference in survival between older patients and younger patients with colorectal cancer (CRC) was mainly due to mortality in the first postoperative year. Over the last few years, improvements – especially in perioperative care – have increased survival. The current research investigates whether a survival gap between younger and older patients with CRC still exists on a national level in four European countries.

METHODS: Population-based data from Belgium, the Netherlands, Norway, and Sweden were collected from patients that underwent surgical resection for primary stage I-III CRC between 2007 and 2016. Relative survival and conditional relative survival (CS), with the condition of surviving the first postoperative year, were calculated for colon and rectal cancer separately, stratified for country and age category (<65, 65-75, ≥75 years). In addition, relative excess risk of death (RER) was estimated, and one-year excess mortality was calculated.

RESULTS: Data of 206,024 patients were analyzed. In general, compared to patients <65 years, patients ≥75 years had a worse survival during the first year after surgery, which was most pronounced in Belgium (RER colon cancer 2.5 [95% confidence interval (CI) 2.3-2.8] and RER rectal cancer 2.6 [95% CI 2.3-2.9]). After surviving the first year, CS was mostly not statistically different between patients <65 years and patients ≥75 years with stage I-II, with the exception of stage II colon cancer in Belgium. However, CS remained worse in the largest part of the patients ≥75 years with stage III colon or rectal cancer (except for rectal cancer in Norway).

CONCLUSIONS: Although differences exist between the countries, the survival gap between young and older patients is based mainly on early mortality and remains only for stage III disease after surviving the first year.

PMID:35527207 | DOI:10.1016/j.jgo.2022.04.011

Value Health. 2022 May 5:S1098-3015(22)00091-2. doi: 10.1016/j.jval.2022.01.015. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to identify the most commonly used internal validity tests in the discrete choice experiment (DCE) literature and establish their sensitivity and specificity.

METHODS: A structured literature review of recent DCE articles (2018-2020Q1) published in the health, marketing, transport economics, and environmental science literature was used to identify commonly used internal validity tests. The 2 most frequently used internal validity tests were incorporated in 4 new data collections. Respondent preferences in each application were summarized using a mixed logit model, which served as the benchmark for the subsequent sensitivity and specificity calculations. The performance of the internal validity tests was also compared with that of the root likelihood (RLH) test, which is a likelihood-based statistical validity test that is commonly used in marketing applications.

RESULTS: Dominant and repeated choice tasks were most commonly included in health-related DCE designs. Based on 4 applications, their specificity and sensitivity depend on the type of incorrect response pattern to be detected and on design characteristics such as the number of choice options per choice task and the number of internal validity tests as included in the experimental design. In all but one scenario, the performance of the dominant and repeated choice tasks was considerably worse than that of the RLH test.

CONCLUSIONS: Dominant and repeated choice tasks are unreliable screening tests and costly in terms of statistical power. The RLH test, which is a statistical test that does not require additional choice tasks to be included in the DCE design, provides a more reliable alternative.

PMID:35527163 | DOI:10.1016/j.jval.2022.01.015

Prim Care Diabetes. 2022 May 5:S1751-9918(22)00079-1. doi: 10.1016/j.pcd.2022.04.003. Online ahead of print.

ABSTRACT

BACKGROUND: Data on glycemic control and its determinants among Brazilian patients with type-2 diabetes (DM2) are scarce. The BrazIliaN Type 1 & 2 DiabetEs Disease Registry (BINDER) is a multicenter, longitudinal study, designed to investigate the glycemic control in a real-word scenario.

METHODS: 1142 patients participated in the five visits of the BINDER study between April/2017 and October/2019. For each visit, glycemic control was assessed using the last measure available for HbA1c. Sociodemographic and anthropometric characteristics were also analyzed.

RESULTS: At baseline, the median HbA1c level was 7.1% (4.1-15.0%); 259 (31.4%) participants had HbA1c ≤ 6.5% and 396 (48.2%) had HbA1c ≤ 7.0%. Younger age (p = 0.014), low educational level (p = 0.025) and the type of healthcare service (public sector; p = 0.0058) were independently associated with the elevated HbA1c. After 2 years, there were no statistically significant differences in HbA1c median values in relation to baseline.

CONCLUSIONS: In this sample of DM2 patients, younger age, low educational level and being treated at the public service were associated with worse glycemic control. Over a 2-year follow-up, there was no significant change in the median HbA1c. These findings suggest that strategies are needed to improve glycemic control, especially in those treated in the public service.

PMID:35527171 | DOI:10.1016/j.pcd.2022.04.003

Mater Sci Eng C Mater Biol Appl. 2021 Nov 23:112559. doi: 10.1016/j.msec.2021.112559. Online ahead of print.

ABSTRACT

Hydrogels are a popular substrate for cell culture due to their mechanical properties closely resembling natural tissue. Stimuli-responsive hydrogels are a good platform for studying cell response to dynamic stimuli. Poly(N-isopropylacrylamide) (pNIPAM) is a thermo-responsive polymer that undergoes a volume-phase transition when heated to 32 °C. Conducting polymers can be incorporated into hydrogels to introduce electrically responsive properties. The conducting polymer, polypyrrole (PPy), has been widely studied as electrochemical actuators due to its electrochemical stability, fast actuation and high strains. We determine the volume-phase transition temperature of pNIPAM hydrogels with PPy electropolymerised with different salts as a film within the hydrogel network. We also investigate the electro-mechanical properties at the transition temperature (32 °C) and physiological temperature (37 °C). We show statistically significant differences in the Young’s modulus of the hybrid hydrogel at elevated temperatures upon electrochemical stimulation, with a 5 kPa difference at the transition temperature. Furthermore, we show a three-fold increase in actuation at transition temperature compared to room temperature and physiological temperature, attributed to the movement of ions in/out of the PPy film that induce the volume-phase transition of the pNIPAM hydrogel. Furthermore, cell adhesion to the hybrid hydrogel was demonstrated with mouse articular chondrocytes.

PMID:35527144 | DOI:10.1016/j.msec.2021.112559

Acad Radiol. 2022 May 5:S1076-6332(22)00207-0. doi: 10.1016/j.acra.2022.03.030. Online ahead of print.

ABSTRACT

RATIONALE AND OBJECTIVES: Female carriers of pathogenic sequence variants (PSVs) in the BRCA1 /BRCA2 (Breast Cancer gene – BRCA) genes are at a substantially high-risk for developing breast cancer (BC), hence are offered active surveillance scheme based on semiannual breast exam and imaging from age 25 years to facilitate BC early detection (mammography/breast ultrasound depending on the age, and MRI). However, there are not specific guidelines for screening in case of pregnancy or lactation. In the current study, we summarize the experience at the largest high-risk clinic in Israel.

MATERIALS AND METHODS: Data of consecutive BRCA-PSV carriers undergoing surveillance as well as diagnostic ultrasound at the Meirav high-risk clinic from January 2014 to 2021 who were pregnant and/or breastfeeding at time of follow-up were identified. Relevant clinical data including results of breast exam, breast ultrasonography, biopsies and histological results were retrieved. Percentage of biopsies with malignancy, cancer detection rate and positive predictive values were calculated. Data is presented in descriptive statistics.

RESULTS: A total of 263 BRCA-carriers were included. Of these, 593 breast-ultrasonograms were performed in 263 BRCA-carriers for 292 pregnancies and 409 breast-ultrasonograms for 175 breastfeeding carriers. Of 36 breast biopsies in 292 pregnancies, 4 (PPV = 11%) had BC diagnosed (high grade invasive). Of 175 breastfeeding women, 25 biopsies were performed and 2 (PPV = 8%) were high grade invasive BC. Five of 6 BC were diagnosed in BRCA1 carriers, and 4/6 were screen detected. The rate of pregnancy-associated breast cancer was 6/292 (2.05%).

CONCLUSION: The overall detection rate of pregnancy-associated BC in BRCA-carriers is relatively low (2.05%), but still much higher than that in the general population. Two thirds of the BC were detected by screening. Therefore, despite the changes of the glandular breast tissue at time of pregnancy and breastfeeding, screening plays an important role in early detection. Ultrasound should be considered as a screening tool during this period of life of high-risk patients.

PMID:35527100 | DOI:10.1016/j.acra.2022.03.030