EphA2 overexpression minimizes H2O2induced damage of lens epithelial tissue
Forward genetics is used to identify the genetic basis for a phenotype. The approach involves identifying a mutant organism exhibiting a phenotype of interest and then mapping the causative locus or gene. Bulked-segregant analysis (BSA) is a quick and effective approach to map mutants using pools of mutants and wild-type plants from a segregating population to identify linkage of the mutant phenotype, and this approach has been successfully used in plants. Traditional linkage mapping approaches are outdated and time intensive, and can be very difficult. With the highly evolved development and reduction in cost of high-throughput sequencing, this new approach combined with BSA has become extremely effective in multiple plant species, including Zea mays (maize). While the approach is incredibly powerful, careful experimental design, bioinformatic mapping techniques, and interpretation of results are important to obtain the desired results in an effective and timely manner. Poor design of a mapping population, l Periodicals LLC. Basic Protocol Bulked-segregant analysis and high-throughput sequencing to map maize mutants.Criminological theories and widespread assumptions about crime suggest that the modus operandi involved in sexual crimes should have changed over time given various contextual changes, such as better criminological knowledge (e.g., forensic awareness) as well as improved investigative techniques (e.g., forensic evidence analysis). The aim of this study was to test whether the modus operandi patterns of individuals having committed a sexual assault against female strangers have changed over time during the period of 2003-2017. More specifically, the study has identified changes in the trends of monthly counts and (relative) participations for sexual assaults during the study period in France. The measure of participations - a concept borrowed from the field of criminal career - was used to overcome the inherent limitations associated with this type of data. Results show that despite some significant changes in the modus operandi involved in sexual crimes, overall the modus operandi patterns appear to be fairly stable over time. The findings are discussed in light of their theoretical and practical implications.A common conundrum faced by clinicians is whether to go for fresh transfer or culture the embryos for future frozen transfer in a case of slow-growing embryo. This case report describes a successful pregnancy with the fresh transfer of a single day 3- 6-cell grade B embryo in a patient with poor ovarian reserve. Although more research is needed in this context, the fresh transfer can be considered as a treatment option in patients with optimal endometrium and well-controlled progesterone levels with slow-growing embryos.
To investigate the effect of endometriosis and its different stages over Intracytoplasmic Sperm Injection (ICSI) outcomes among infertile women without previous history of ovarian surgery.
A total of 440 women enrolled in ICSI cycles were recruited and divided into two groups endometriosis (n=220) and control group (n=220). Endometriosis patients without previous surgical treatment and with diagnostic laparoscopy were further stratified based on disease stage. Clinical and laboratory parameters, ovarian reserve markers, the number and quality of oocytes and embryos and fertilization rate were analyzed and compared among the various severity grades of endometriosis and the control group.
Patients with advanced endometriosis had significantly fewer retrieved oocytes with small effect size (p<0.001, η2=0.04), lower metaphase II oocytes (p<0.001, η2=0.09) and fewer total numbers of embryos (p<0.001, η2=0.11) compared with less severe disease or women with tubal factor infertility. The fertilization rate in women with severe endometriosis was similar to that of the control group and in those with minimal/mild endometriosis (p=0.187).
Severe endometriosis negatively affects ovarian response, oocyte quality and embryos. However, fertilization rate is not different among the various stages of endometriosis.
Severe endometriosis negatively affects ovarian response, oocyte quality and embryos. However, fertilization rate is not different among the various stages of endometriosis.Obesity is a multifactorial metabolic disorder, growing in an alarming rate across the world. Amongst the numerous targets explored for obesity management, inhibition of pancreatic lipase (PL) is considered as one of the promising approaches. Orlistat is the only PL inhibitory drug approved for long term treatment of obesity. However, it is reported to possess hepatotoxicity and nephrotoxicity. Thus, novel drug candidates that act through PL inhibition are considered the hour's need. Based on this aim, a series of quinazolinone hybrid analogues have been synthesized, characterized and evaluated for their PL inhibitory potential. The physicochemical properties and toxicity parameters suggested that these parameters are in an acceptable range for the screened analogues. Amongst the synthesised analogues, QH-25 exerted potential PL inhibition (IC50 = 16.99 ± 0.54 µM). Further, enzyme inhibition studies suggested a reversible competitive inhibition. Molecular docking of these analogues was in line with in vitro results, wherein the obtained MolDock scores exhibited a significant correlation with their inhibitory activity (Pearson's r = 0.6629). To further confirm the stability of the QH-25-PL complex in a dynamic environment, a molecular dynamics study (100 ns) was carried out and the results suggested that this complex is stable at dynamic conditions. Overall, these results shed light on the quinazolinone hybrids as potential PL inhibitors. Further structural modification may result in the development of potent anti-obesity agents which acts through PL inhibition.Communicated by Ramaswamy H. Sarma.Drug-target residence time has emerged as a key selection factor in drug discovery since the binding duration of a drug molecule to its protein target can significantly impact its in vivo efficacy. The challenge in studying the residence time, in early drug discovery stages, lies in how to cost-effectively determine the residence time for the systematic assessment of compounds. Currently, there is still a lack of computational protocols to quickly estimate such a measure, particularly for large and flexible protein targets and drugs. Here, we report an efficient computational protocol, based on targeted molecular dynamics, to rank drug candidates by their residence time and to obtain insights into ligand-target dissociation mechanisms. The method was assessed on a dataset of 10 arylpyrazole inhibitors of CDK8, a large, flexible, and clinically important target, for which the experimental residence time of the inhibitors ranges from minutes to hours. The compounds were correctly ranked according to their estimated residence time scores compared to their experimental values. The analysis of protein-ligand interactions along the dissociation trajectories highlighted the favorable contribution of hydrophobic contacts to residence time and revealed key residues that strongly affect compound residence time.
Mental health first aid programs show promise in reducing stigma and increasing help-seeking. However, the success of these and other mental health interventions are likely affected by health literacy. Yet, health literacy is understudied in the mental health literature and rarely considered in mental health interventions.
This study explored the relationship between health literacy and mental health stigma, aversion to mental health help-seeking, and willingness to interact with individuals with mental illnesses.
Adults (
= 601, mean age = 45.64) completed online surveys of their health literacy and mental health attitudes and beliefs. Hierarchal linear regression models were estimated to examine the relationship between health literacy and mental health attitudes and beliefs. Path models were estimated to determine if stigma mediated the relationship between health literacy and (1) aversion to help-seeking and (2) willingness to interact with individuals with mental illnesses.
Adults with higher fformation had fewer negative opinions and were more willing to interact with others with mental health problems. Improving those skills may reduce negative opinions about mental health and seeking help.
Results support including health literacy in mental health interventions and reiterate addressing stigma in community and clinical settings. [HLRP Health Literacy Research and Practice. 2022;6(4)e270-e279.] Plain Language Summary Many adults with mental health problems do not get help because of negative beliefs about mental health. We found that adults with more skills for accessing, understanding, and using health information had fewer negative opinions and were more willing to interact with others with mental health problems. Improving those skills may reduce negative opinions about mental health and seeking help.
Hypertension is the main risk factor for cardiovascular disease. Low level of health literacy is more common in people with hypertension. Evidence suggests that hypertension is preventable and can be controlled by modifying lifestyle and improving self-care behaviors.
This study aimed to determine the relationship between health literacy, self-efficacy, and self-care behaviors in older adults with hypertension.
The present study was a cross-sectional study conducted with 150 older adult patients with hypertension admitted to the Cardiac Care Unit (CCU) and post-CCU wards in East Guilan public hospitals in the north of Iran in 2020. Sampling was conducted using a convenience method based on inclusion criteria (age 60 years and older, high blood pressure and taking antihypertensive drugs for at least 6 months, ability to speak and communicate, having the suitable physical condition (not ill) to participate in research and answer questions, and having informed consent to participate in the study). The resecacy and self-care behaviors.
Stressors related to social determinants of health (SDH), such as housing and food insecurity, are implicated in chronic disease risk. Maladaptive strategies for coping with these stressors may exacerbate risk.
Given the limited research on SDH-related stressors and maladaptive coping, this study examined the relationship between two SDH-related stressors (housing and food insecurity) and maladaptive coping behaviors (i.e., emotional eating and stress-related cigarette and alcohol use) in adults. check details Further, because health literacy (HL), another SDH, may be a protective factor, this study explored whether HL moderated these relationships.
Data were collected from adults (
= 500, Mean age = 49.01 years, standard deviation = 16.36; 40% White) in the United States. A series of hierarchical logistic regressions predicting maladaptive coping behaviors from demographics, SDH-related stressors (i.e., housing or food insecurity), and HL variables were estimated.
Housing insecurity was associated with increasedress-related cigarette and alcohol use). Adults who experienced housing and food insecurity were more likely to report emotional eating and using cigarettes and alcohol when stressed. Adults with higher functional health literacy were less likely to report emotional eating.