Category: Nevin Manimala

Mol Ther. 2022 May 6:S1525-0016(22)00299-4. doi: 10.1016/j.ymthe.2022.05.002. Online ahead of print.

ABSTRACT

A promising treatment for β-hemoglobinopathies is the de-repression of γ-globin expression leading to increased fetal hemoglobin (HbF) by targeting BCL11A. Here, we aim to improve a lentivirus vector (LV) containing a single BCL11A shmiR (SS) to further increase γ-globin induction. We engineered a novel LV to express two shmiRs simultaneously targeting BCL11A and the γ-globin repressor, ZNF410. Erythroid cells derived from human HSCs transduced with the double shmiR (DS) showed up to 70% reduction of both BCL11A and ZNF410 proteins. There was a consistent and significant additional 10% increase in HbF compared to targeting BCL11A alone in erythroid cells. Erythrocytes differentiated from SCD HSCs transduced with the DS demonstrated significantly reduced in vitro sickling phenotype compared to the SS. Erythrocytes differentiated from transduced HSCs from β-thalassemia major patients demonstrated improved globin chain balance by increased γ-globin with reduced microcytosis. Reconstitution of DS-transduced cells from Berkeley SCD mice was associated with a statistically larger reduction in peripheral blood hemolysis markers compared with the SS vector. Overall, these results indicate that the DS LV targeting BCL11A and ZNF410 can enhance HbF induction for treating β-hemoglobinopathies and could be used as a model to simultaneously and efficiently target multiple gene products.

PMID:35526095 | DOI:10.1016/j.ymthe.2022.05.002

J Clin Nurs. 2022 May 7. doi: 10.1111/jocn.16343. Online ahead of print.

ABSTRACT

AIM AND OBJECTIVES: To describe nurses with substance use disorder (SUD) in authority disciplinary actions.

BACKGROUND: Nurses with SUD risk patient safety. Research evidence on the identification of nurses’ SUD and related management procedures is currently sparse.

DESIGN: Retrospective document analysis of decisions related to SUD in nurses’ disciplinary actions.

METHOD: Decisions on nurses (N = 171) made by the Finnish National Supervisory Authority for Welfare and Health in Finland during 2007-2016 were used as data. An electronic extraction sheet was developed for data collection including variables (N = 34), of which 18 were analysed in this study with descriptive statistical methods and chi-squared statistics. The study reported in accordance with the STROBE checklist for cross-sectional studies.

RESULTS: The mean age of the nurses was 43 years (SD 8.7). The most mentioned reasons for notifications leading to disciplinary actions were substance abuse with working while intoxicated and drug theft. The most mentioned intoxicants used were medicines and alcohol. On average, the first disciplinary decision was given at 6.4 months (SD 3.9) and the final decision was given at 17.9 months (SD 13.1). The most common decision was restriction of the right to practice.

CONCLUSION: The results supported findings from previous decades and different continents, showing similar trends are prevalent globally and continue today. In future studies, countries’ registers of nurses with SUD could be used to clarify the profile of nurses and develop appropriate procedures. Qualitative studies could be conducted to investigate to shed light on concealment of the phenomenon.

RELEVANCE TO CLINICAL PRACTICE: There is a need for early identification, intervention and referral to treatment as well as effective protocols for reducing nurses’ risks of disciplinary actions related to SUD. It is important to be aware of the signs and symptoms of SUD and training for this is needed.

PMID:35526092 | DOI:10.1111/jocn.16343

J Health Popul Nutr. 2022 May 7;41(1):17. doi: 10.1186/s41043-022-00296-9.

ABSTRACT

BACKGROUND: Balanced nutrition is crucial for adolescent’s proper physical and mental development. Dietary habits change significantly with a child’s development. Along with increasing age and the shift towards adolescence, unhealthy diet-related habits become more common. The objective of the survey study was to determine the differences in nutritional habits between children and adolescents according to their age and body mass index (BMI).

METHODS: “Let’s get the kids moving” campaign (pol. “Uruchamiamy dzieciaki”) was launched in 2016. Within the campaign, the survey study was conducted in 2913 participants between 6 and 17 years old from primary and junior high schools in Wroclaw (Poland). The survey was anonymous, and its supplement was voluntary. Participants were divided into age groups. The study group of 2913 consisted of 29.8% of 6-9-year-olds, 32.7% of 10-12-year-olds, and 37.5% of 13-17-year-olds. Body mass index (BMI) was calculated and further interpreted as a BMI z-scores depending on children’s age and gender.

RESULTS: A total of 19.3% of participants consumed 3 meals a day or less. Children from the oldest age group (13-17) consumed statistically significantly fewer meals per day than younger children (p < 0.001). Children from the oldest age group (13-17) consumed breakfast statistically less often than children of age group 10-12 years (75.0% vs. 83.6%; p < 0.001) and children of age group 6-9 years (75.0% vs. 84.0%; p < 0.001). Severely thin children consumed breakfast significantly more often than overweight (85.8% vs. 76.3%; p = 0.004) and children with obesity (85.8% vs. 75.9%; p = 0.021). Children with obesity consumed vegetables significantly less often than severely thin (p < 0.008), thin (p < 0.001), and children with normal body weight (p < 0.007). The oldest children (13-17 years) consumed Coca-Cola and SSB (p < 0.001) and fruit-flavored beverages (p < 0.05) significantly more often than children from other age groups. Boys consumed carbonated beverages with added sugar significantly more often than girls (p < 0.01).

CONCLUSIONS: Unhealthy diet-related behaviors in children and adolescents may promote overweight and obesity and should be targeted in health promotion programs. Special attention should be paid to 13-17-year-olds, as adolescents from this group made more unhealthy choices than younger children.

PMID:35526064 | DOI:10.1186/s41043-022-00296-9

Chemphyschem. 2022 May 7. doi: 10.1002/cphc.202200205. Online ahead of print.

ABSTRACT

In this study, a series of tetrafluoroborates with non- π -conjugated [BF 4 ] tetrahedra are investigated systematically by utilizing the first-principles calculations. Theoretical studies demonstrate that tetrafluoroborates with alkali and/or alkaline-earth metals are more favorable for deep-ultraviolet transmission and are comparable to the classical deep-ultraviolet (deep-UV) material, MgF 2 . Furthermore, bandgap decrease with the increasing of ionic radii in alkali and/or alkaline-earth metals. Introducing highly polarizable cations with d 10 -configuration or cations with lone pair electrons into the structure will decrease the bandgaps. The birefringence and second harmonic generation effects are not large enough in tetrafluoroborates because polarizability anisotropy and hyperpolarizability in non- π -conjugated [BF 4 ] tetrahedra are much smaller than those in π -conjugated groups. However, the second harmonic generation effect for [BF 4 ] tetrahedra has a higher contribution in comparison with that due to birefringence. To effectively synthesize the borate fluorides or fluorooxoborates in the deep-UV region, raw materials with B-F bonds are preferred.

PMID:35524646 | DOI:10.1002/cphc.202200205

Alzheimers Res Ther. 2022 May 7;14(1):63. doi: 10.1186/s13195-022-00997-7.

ABSTRACT

BACKGROUND: The combined effects of increased life expectancy and the considerable number of persons reaching old age will magnify the dementia epidemic in the USA. Demonstration that subclinical atherosclerosis precedes and is associated with cognitive impairment suggests a modifiable risk factor for age-associated cognitive impairment and dementia. The purpose of this study is to determine whether subclinical atherosclerosis as measured by carotid artery intima-media thickness (CIMT) is associated with changes in cognitive function over time in older adults.

METHODS: This study combined longitudinal data from three clinical trials conducted between 2000 and 2013: the B-Vitamin Atherosclerosis Intervention Trial (BVAIT), the Women’s Isoflavone Soy Health (WISH) trial, and the Early versus Late Intervention Trial with Estradiol (ELITE). Participants were recruited from the general population in the Greater Los Angeles area and were free of cardiovascular disease and diabetes; no cognitive or psychiatric exclusion criteria were specified. The same standardized protocol for ultrasound image acquisition and measurement of CIMT was used in all trials. CIMT measurements performed at baseline and 2.5 years were used in these analyses. Cognitive function was assessed at baseline and 2.5 years using a battery of 14 standardized cognitive tests. All clinical trials were conducted at the University of Southern California Atherosclerosis Research Unit, Los Angeles, and had at least 2.5 years of cognitive follow-up.

RESULTS: A total of 308 men and 1187 women, mean age of 61 years, were included in the combined longitudinal dataset for the primary analysis. No associations were found between CIMT and cognitive function at baseline or at 2.5 years. There was a weak inverse association between CIMT measured at baseline and change in global cognition assessed over 2.5 years (β (SE) = – 0.056 (0.028) units per 0.1 mm CIMT, 95% CI – 0.110, – 0.001, p = 0.046). No associations between CIMT at baseline and changes in executive function, verbal memory, or visual memory were found.

CONCLUSIONS: In this sample of healthy older adults, our findings suggest an association between subclinical atherosclerosis and change in global cognitive function over 2.5 years. Stronger associations were observed longitudinally over 2.5 years than cross-sectionally. When analysis was stratified by age group (<65 and ≥65 years old), the inverse association remained statistically significant for participants in the older age group. Subclinical atherosclerosis of the carotid artery may be a modifiable correlate of cognitive decline in middle and older age.

TRIAL REGISTRATION: BVAIT, NCT00114400 . WISH, NCT00118846 . ELITE, NCT00114517 .

PMID:35526057 | DOI:10.1186/s13195-022-00997-7

Eye Vis (Lond). 2022 May 7;9(1):18. doi: 10.1186/s40662-022-00289-z.

ABSTRACT

BACKGROUND: The ability to view the posterior segment in keratoprosthesis (Kpro) implanted patients is limited. The purpose of this retrospective, observational study was to investigate the use of ultra-wide field (UWF) scanning laser ophthalmoscopy imaging and its utility for serial evaluation of the retina and optic nerve in patients with either a Boston type I or II Kpro.

METHODS: A retrospective chart review was performed for patients with a Boston type I or II Kpro seen at The Ohio State University Wexner Medical Center. Images were graded for quality by two masked observers on a defined four-point scale (“Poor”, “Fair”, “Good”, or “Very good”) and assessed for visible posterior segment anatomy. Interobserver agreement was described using the Kappa statistic coefficient (κ) with 95% confidence intervals.

RESULTS: A total of 19 eyes from 17 patients were included in this study. Eighteen eyes had a type I Kpro, while one eye had a type II Kpro. UWF imaging from 41 patient visits were reviewed by two observers. Interobserver agreement between the two graders was fair for image quality (κ = 0.36), moderate for visibility of the macula with discernible details (κ = 0.59), moderate for visibility of the anterior retina with discernable details (κ = 0.60), and perfect agreement for visibility of the optic nerve with discernible details (κ = 1.0). In 6 eyes, UWF imaging was performed longitudinally (range 3-9 individual visits), allowing for long-term follow-up (range 3-46 months) of posterior segment clinical pathology.

CONCLUSIONS: UWF imaging provides adequate and reliable visualization of the posterior segment in Kpro implanted patients. This imaging modality allowed for noninvasive longitudinal monitoring of retinal and optic nerve disease in this selected patient population.

PMID:35526055 | DOI:10.1186/s40662-022-00289-z

Orphanet J Rare Dis. 2022 May 7;17(1):186. doi: 10.1186/s13023-022-02342-5.

ABSTRACT

BACKGROUND: Design and analysis of clinical trials for rare and ultra-rare disease pose unique challenges to the practitioners. Meeting conventional power requirements is infeasible for diseases where sample sizes are inherently very small. Moreover, rare disease populations are generally heterogeneous and widely dispersed, which complicates study enrollment and design. Leveraging all available information in rare and ultra-rare disease trials can improve both drug development and informed decision-making processes.

MAIN TEXT: Bayesian statistics provides a formal framework for combining all relevant information at all stages of the clinical trial, including trial design, execution, and analysis. This manuscript provides an overview of different Bayesian methods applicable to clinical trials in rare disease. We present real or hypothetical case studies that address the key needs of rare disease drug development highlighting several specific Bayesian examples of clinical trials. Advantages and hurdles of these approaches are discussed in detail. In addition, we emphasize the practical and regulatory aspects in the context of real-life applications.

CONCLUSION: The use of innovative trial designs such as master protocols and complex adaptive designs in conjunction with a Bayesian approach may help to reduce sample size, select the correct treatment and population, and accurately and reliably assess the treatment effect in the rare disease setting.

PMID:35526036 | DOI:10.1186/s13023-022-02342-5

BMC Musculoskelet Disord. 2022 May 7;23(1):430. doi: 10.1186/s12891-022-05370-1.

ABSTRACT

BACKGROUND: Fibrillin-1 (FBN1) is an extracellular matrix glycoprotein essential to the structural component of microfibrils and FBN1 gene polymorphisms can be associated with adolescent idiopathic scoliosis (AIS) susceptibility. This study aimed to evaluate the potential role of the FBN1 rs12916536 polymorphism in AIS development or severity and the variation in Cobb angle in relation to patient’s characteristics.

METHODS: DNA from 563 subjects (185 AIS patients and 378 controls) were genotyped using a validated TaqMan allelic discrimination assay. A multivariate logistic regression model evaluated the association between polymorphism and AIS, using the adjusted odds ratios (OR) with their respective 95% confidence intervals (95% CI). A linear regression analysis evaluated the variation in Cobb angle according to the patient’s age and body mass index (BMI).

RESULTS: Among the AIS group there was a predominance of females (12:1), low or normal BMI (90%), 58% had a Cobb angle greater than 45° and 74% were skeletally mature. Age was a risk factor (4-fold) for curve progression higher than BMI (P < 0.001). The allelic frequency of the rs12916536 G > A polymorphism was 40% in controls and 31% in AIS cases; and this difference was statistically significant (P = 0.004). FBN1 rs12916536 GA + AA genotypes were associated with a lower risk of AIS susceptibility (OR = 0.58 and 95% CI = 0.35-0.98), after adjustment for age, sex and BMI. However, no significant differences were detected in polymorphism distribution with the severity of the disease (Cobb < 45° or ≥ 45°).

CONCLUSION: Age was a risk factor for progression of the scoliotic curve and FBN1 rs12916536 polymorphism a protective factor for AIS susceptibility.

PMID:35526034 | DOI:10.1186/s12891-022-05370-1

Arthritis Res Ther. 2022 May 7;24(1):102. doi: 10.1186/s13075-022-02788-9.

ABSTRACT

OBJECTIVE: Aortic valve involvement is not uncommon in patients with Takayasu arteritis (TAK) and leading to poor prognosis. The aim of our study was to explore the risk factors of aortic valve involvement and to evaluate the prognosis in TAK patients with aortic valve involvement.

METHOD: In this retrospective study, 172 TAK patients were divided into groups with or without aortic valve involvement to identify the risk factors. Patients who underwent aortic valve surgical treatment were followed up to assess cumulative incidence of postoperative adverse events.

RESULTS: A total of 92 TAK patients (53.49%) had aortic valvular lesion. The infiltration of inflammatory cells was found in surgical specimens of aortic valve. Numano type IIb, elevated high-sensitivity C-reactive protein (hs-CRP) level, and dilation of ascending aorta and aortic root were statistically associated with aortic valvular lesion in TAK patients (OR [95%CI] 6.853 [1.685-27.875], p=0.007; 4.896 [1.646-14.561], p=0.004; 4.509 [1.517-13.403], p=0.007; 9.340 [2.188-39.875], p=0.003). The 1-, 5-, and 7-year cumulative incidence of postoperative adverse events were 14.7%, 14.7%, and 31.8%, respectively. Surgical methods (p=0.024, hazard ratio (HR) 0.082) and postoperatively anti-inflammatory therapy (p=0.036, HR 0.144) were identified as potential predictors of postoperative adverse events.

CONCLUSIONS: Regularly echocardiogram screening is suggested in patients with Numano type IIb and aggressive treatment should be performed early in TAK patients. As for TAK patients with aortic valve surgery, aortic root replacement seems to be the preferred option and regular anti-inflammatory therapy may reduce the occurrence of adverse events of them.

PMID:35526024 | DOI:10.1186/s13075-022-02788-9

BMC Psychol. 2022 May 7;10(1):119. doi: 10.1186/s40359-022-00818-4.

ABSTRACT

BACKGROUND: Racial, ethnic, religious, and cultural diversity in Australia is rapidly increasing. Although Indigenous Australians account for only approximately 3.5% of the country’s population, over 50% of Australians were born overseas or have at least one migrant parent. Migration accounts for over 60% of Australia’s population growth, with migration from Asia, Sub-Saharan African and the Americas increasing by 500% in the last decade. Little is known about Australian mental health care practitioners’ attitudes toward this diversity and their level of cultural competence.

AIM: Given the relationship between practitioner cultural competence and the mental health outcomes of non-White clients, this study aimed to identify factors that influence non-White and White practitioners’ cultural competence.

METHODS: An online questionnaire was completed by 139 Australian mental health practitioners. The measures included: the Balanced Inventory of Desirable Responding (BIDR); the Multicultural Counselling Inventory (MCI); and the Color-blind Racial Attitudes Scale (CoBRAS). Descriptive statistics were used to summarise participants’ demographic characteristics. One-way ANOVA and Kruskal-Wallis tests were conducted to identify between-group differences (non-White compared to White practitioners) in cultural competence and racial and ethnic blindness. Correlation analyses were conducted to determine the association between participants’ gender or age and cultural competence. Hierarchical multiple regression analysis was conducted to predict cultural competence.

RESULTS: The study demonstrates that non-White mental health practitioners are more culturally aware and have better multicultural counselling relationships with non-White people than their White counterparts. Higher MCI total scores (measuring cultural competence) were associated with older age, greater attendance of cultural competence-related trainings and increased awareness of general and pervasive racial and/or ethnic discrimination. Practitioners with higher MCI total scores were also likely to think more highly of themselves (e.g., have higher self-deceptive positive enhancement scores on the BIDR) than those with lower MCI total scores.

CONCLUSION: The findings highlight that the current one-size-fits-all and skills-development approach to cultural competence training ignores the significant role that practitioner diversity and differences play. The recommendations from this study can inform clinical educators and supervisors about the importance of continuing professional development relevant to practitioners’ age, racial/ethnic background and practitioner engagement with prior cultural competence training.

PMID:35526020 | DOI:10.1186/s40359-022-00818-4