Category: Nevin Manimala

Interdiscip Sci. 2023 Jun 30. doi: 10.1007/s12539-023-00566-y. Online ahead of print.

ABSTRACT

Diabetes mellitus significantly contributes to breast cancer progression, where hyperglycemia upregulates specific genes, leading to more aggressive tumor growth. In patients with BC that develop diabetes, neuregulin 1 (NRG1) and epidermal growth factor receptor 3 (ERBB3) overexpression exacerbate tumor growth and progression. Since the interaction between NRG1 and ERBB3 is critical for tumor growth, understanding the molecular mechanisms underlying NRG1-ERBB3 complex formation is essential for elucidating diabetes-assisted breast cancer progression. However, the key residues forming the NRG1-ERBB3 complex remain unknown. Here, we substituted specific residues in NRG1 with alanine and studied its interactions with ERBB3 using computational structural biology tools. We further screened the South African natural compounds database to target the complex’s interface residues to discover potential inhibitors. The conformational stability and dynamic features of NRG1-WT, -H2A, -L3A, and -K35A complexed with ERBB3 were subjected to 400 ns molecular dynamics simulations. The free binding energies of all NRG1-ERBB3 complexes were calculated using the molecular mechanics-generalized Born surface area (MM/GBSA). The H2 and L3 alanine substitutions caused a loss of interaction with ERBB3 residue D73, weakening the interaction with ERBB3. Screening 1300 natural compounds identified four (SANC00643, SANC00824, SANC00975, and SANC00335) with the best potential to inhibit ERRB3-NRG1 coupling. The binding free energies for each complex were – 48.55 kcal/mol for SANC00643, – 47.68 kcal/mol for SANC00824, – 46.04 kcal/mol for SANC00975, and – 45.29 kcal/mol for SANC00335, showing their overall stronger binding with ERBB3 than NRG1 and their potential to act as ERBB3-NRG1 complex inhibitors. In conclusion, this complex may represent a residue-specific drug target to inhibit BC progression.

PMID:37389721 | DOI:10.1007/s12539-023-00566-y

Psychiatr Q. 2023 Jun 30. doi: 10.1007/s11126-023-10040-z. Online ahead of print.

ABSTRACT

This study aimed to investigate the prevalence of anxiety and its associated factors among inpatients with type 2 diabetes mellitus (T2DM) in China. This study was a cross-sectional study. Inpatients with T2DM admitted to the Endocrinology Department of Xiangya Hospital, Central South University in Hunan Province of China from March 2021 to December 2021 were consecutively included in this study. Participants were interviewed to obtain the data on socio-demographic characteristics, lifestyle characteristics, T2DM-related information, and social support. Anxiety was measured using the Hospital Anxiety and Depression Scale-anxiety subscale by experienced physicians. Multivariable logistic regression analysis was used to estimate the independent contribution of each independent variable to anxiety. A total of 496 inpatients with T2DM were included in this study. The prevalence of anxiety was 21.8% (95% confidence interval [CI]: 18.1%-25.4%). The results of multivariable logistic regression analysis indicated that age of at least 60 (adjusted odd ratio [aOR] = 1.79, 95% CI: 1.04-3.08), and having diabetes specific complications (aOR = 4.78, 95% CI: 1.02-22.44) were risk factors for anxiety, and an educational level of high school or above (aOR = 0.55, 95% CI: 0.31-0.99), regular physical activity (aOR = 0.36, 95% CI: 0.22-0.58), and high social support (aOR = 0.30, 95% CI: 0.17-0.53) were protective factors for anxiety. A predictive model based on these five variables showed good performance (area under the curve = 0.80). Almost one in five inpatients with T2DM suffered from anxiety in China. Age, educational level, regular physical activity, diabetes specific complications, and social support were independently associated with anxiety.

PMID:37389720 | DOI:10.1007/s11126-023-10040-z

Eur J Orthop Surg Traumatol. 2023 Jun 30. doi: 10.1007/s00590-023-03628-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Tennis elbow management has primarily been conservative over the years with over 90% of the cases being managed conservatively. Surgical intervention may be necessary only for symptomatic recalcitrant cases of tennis elbow cases. However, there are gaps in the literature when it comes to comparison of the return to pre-operative return to their work and level of activities among patients who undergo arthroscopic management and those who receive conservative management.

METHODS: A retrospective observational study was conducted to compare 23 patients receiving continued intensive conservative (CIC) management in group 1 with 24 patients undergoing arthroscopic release of the extensor carpi radialis brevis and lateral epicondyle decortication (ARD) in group 2. The study had a minimum follow-up period of 3.5 years. The researchers compared the groups in terms of return to work (RTW) at the same intensity or lower level and any changes in their previous work. Objective grip strength and patient-reported outcome measures, such as post-intervention satisfaction level (rated on a scale of 0-100) and visual analog scale (VAS) for residual elbow pain, were also compared between the two groups.

RESULTS: Return to work (RTW) occurred significantly earlier in group 2 (mean 6.13 months) compared to group 1 (mean 4.64 months), and a greater number of patients in group 2 (13/24, 54.2%) were able to return to the same of work. Although not statistically significant, the ARD group exhibited comparable patient satisfaction (p = 0.62) and visual analog scale (VAS) scores for residual elbow pain (p = 0.67). Grip strength was comparable (p = 0.084, 0.121) between the affected and unaffected sides of the bilateral upper extremities and among both groups of patients.

CONCLUSION: The use of ARD for RTE (recalcitrant tennis elbow) indicates a significantly earlier return to work (RTW) at the same or lower intensity level compared to the standard CIC therapy protocol. Objective grip strength was comparable to the non-affected side and among the two groups of patients receiving two different management modalities. Comparable patient-reported satisfaction and residual lateral elbow pain were also noted among both the groups.

LEVEL OF EVIDENCE: Retrospective, comparative study, level III.

PMID:37389708 | DOI:10.1007/s00590-023-03628-5

Immunol Med. 2023 Jun 30:1-7. doi: 10.1080/25785826.2023.2228074. Online ahead of print.

ABSTRACT

Metabolic syndromes including obesity and diabetes are the most common health issues due to insulin resistance, disturbance in glucose homeostasis, lack of exercise, and improper diet. The current study was planned to evaluate the potential effects of regular diet with fortified yogurt on blood glycemia and anthropometric responses. Plain yogurt was procured from the local market, and then it was fortified with calcium. Furthermore, the subsequent effect of fortified yogurt on blood glucose, insulin, and anthropometric measurements was assessed at different time intervals. A total of 40 healthy females and males aged about 20 years with a normal BMI range (20-24.9 kg/m²) were recruited within the Government College University Faisalabad. Participants filled out the habits Performa, stress factors questionnaire, and activity questionnaire. Blood glucose (BG) and visual analogous scale (VAS) performs were also taken in the fasting stage and then assigned treatment was given. After 15, 30, 45, 60, 90, and 120 min intervals VAS and BG estimation was carried out. The results shows that fortified yogurt contained a higher amount of calcium. Likewise, a similar trend was observed for the desire to eat, a feeling of fullness, palatability, physical comfort, and overall acceptability. The results obtained from various analyses were statistically evaluated.

PMID:37387250 | DOI:10.1080/25785826.2023.2228074

Palliat Support Care. 2023 Jun 30:1-10. doi: 10.1017/S1478951523000755. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aims to measure and explore the barriers to translating theoretical knowledge of palliative care into clinical practice.

METHODS: A mixed-method study, combining a cross-sectional survey and key interviews was conducted. The quantitative data were obtained from 173 nurses and the key interviews were conducted with 42 health professionals drawn from multiple settings. For quantitative data analysis, Statistical Package for the Social Sciences software were conducted, and a thematic analysis supported with NVivo software were used for analyzing qualitative data.

RESULTS: Of the 220 nurses invited, 173 completed the survey (79%). Most (78%) had a bachelor’s degree in nursing. Fewer than half, 69 (40%) scored 75% or more for the knowledge test; 173 (100%) scored 50% or greater for attitude; and only 32 (18.5%) scored 75% or greater for self-reported practice. While there was a small, positive correlation between palliative care attitudes and self-reported practice (r = 0.22, p = 0.003), the qualitative findings indicated that nurses had significant challenges in translating their theoretical knowledge into clinical practice. Limited clinical practice was linked to inadequate knowledge resulting from insufficient integration of palliative care content in undergraduate curricula and a lack of follow-up training. This was further exacerbated by shortages of medicine, staff, and financial resources and was linked to limited attention accorded to palliative care by the government.

SIGNIFICANCE OF RESULTS: While the results showed the majority held positive views toward palliative care, improving palliative care practices requires, and enhancing nurses’ knowledge of palliative care. This requires changing teaching methods and engaging policymakers.

PMID:37387249 | DOI:10.1017/S1478951523000755

J Mater Chem B. 2023 Jun 30. doi: 10.1039/d3tb00878a. Online ahead of print.

ABSTRACT

In recent years, developing artificial cells of higher complexity has emerged as being key to simulating advanced life behaviors, among which coacervate microdroplets are a promising kind of model artificial cell. Constructing simple coacervate systems in vitro which can subsequently achieve specific responses to environmental stimuli to form coacervate microdroplet communities are fundamental for studying the interactions between liquid-liquid phase separated molecules and the way such interactions determine material properties, composition and phase behavior. Herein, we propose a membrane-free artificial cell based on recombinant spidroin, NT2RepCT, which utilizes the complex structure of spidroin to provide coacervate microdroplets with a unique population morphology in response to environmental stimuli. By changing the environmental conditions such as protein concentration, pH and temperature, the coacervate microdroplets of single-type, regular adhesion-type and irregular adhesion-type were statistically generalized, and it is highlighted that the adhesion-type of coacervate microdroplets depended on the α-helical percentage, complex folding degree of spidroin and internally hydrophobic environment of the coacervate, while it was inversely proportional to the surface hydrophobic environment. Much more interesting, regulation of the non-enzymatic polymerization reaction of oligonucleotides was successfully achieved by adjusting the population morphology of coacervate microdroplets.

PMID:37387245 | DOI:10.1039/d3tb00878a

Future Oncol. 2023 Jun 30. doi: 10.2217/fon-2022-1284. Online ahead of print.

ABSTRACT

Aims: Physicians determine the treatment regimen for metastatic colorectal cancer on a case-by-case bases, according to the individual disease characteristics. We retrospectively compared the baseline characteristics and efficacies of first-line treatment among patients with metastatic colorectal cancer who received intensive therapy involving fluoropyrimidine plus oxaliplatin and/or irinotecan, potentially with molecularly targeted agents as well, versus less intensive fluoropyrimidine and/or bevacizumab therapy. Materials & methods: Data were collected from a medical claims database. The efficacy outcomes were: time to treatment failure, time to first subsequent therapy and overall survival. Results: The less intensive therapy group (n = 633) had higher median age, lower daily activity levels and shorter time to treatment failure, time to first subsequent therapy and overall survival than the intensive therapy group (n = 3829). Combination therapy with molecularly targeted agents and bevacizumab improved treatment efficacy outcomes in the intensive and less intensive groups, respectively. Conclusion: Patient age and daily activity levels were important factors for determining treatment intensity.

PMID:37387237 | DOI:10.2217/fon-2022-1284

Rev Esp Salud Publica. 2023 Jun 22;97:e202306045.

ABSTRACT

OBJECTIVE: In Chile, the elderly represent 18% of the population. In women, the aging process impacts body composition, in addition to the coexistence of other pathologies such as chronic noncommunicable diseases (NCDs). The aim of the study was to relate body composition to the presence of chronic noncommunicable diseases in active older women in the city of Chillán.

METHODS: The sample consisted of 284 women belonging to senior centers in Chillán. Body composition was determined by bioimpedanciometry. Sociodemographic information, prevalent pathologies, geriatric syndromes and physical activity were determined by means of a validated questionnaire. Data were analyzed with descriptive and inferential statistics in STATA 15.0 software with an α<0.05.

RESULTS: Of the sample, 63% were under seventy-five years of age, 77.5% had less than twelve years of schooling, the predominant socioeconomic level was low, and the poor perception of health was mainly referred to as well as the use of regular medication. Arterial hypertension (AHT) and hypercholesterolemia were prevalent with 70.4% and 48.2% respectively. Body mass index (BMI) was 29.7±4.8 and 71.8% had excess malnutrition. The group older than seventy-five years presented more body fat (BMF) and extracellular water (ECW). AHT was related to higher BMI, TGM, MBC (Mean Arm Circumference), PC (Calf Circumference) and ECW (p<0.05), while Diabetes mellitus was related to BMI and MBC.

CONCLUSIONS: Hypertension is the most frequent pathology and is related to higher BMI, MGT, CMB, CP and ECW, followed by DM2 which is related to BMI and CMB.

PMID:37387225

Scand J Public Health. 2023 Jun 30:14034948231182022. doi: 10.1177/14034948231182022. Online ahead of print.

ABSTRACT

AIM: The aim is to report the design and baseline data of the ‘National Surveillance of the Work Environment of Employees in Denmark’ study (NASWEED).

METHODS: NASWEED consist of (a) bi-annual cross-sectional samples, based on probability samples of wage earners of the general working population in Denmark from 2021 onwards (surveillance), (b) a prospective cohort of all previous respondents every two years (epidemiology, questionnaire follow-up) and (c) longitudinal follow-up in Danish registers about work and health (epidemiology, register follow-up). Between February and May 2021, a stratified (38 occupational industries) probability sample of 63,391 Danish residents aged 15-69 years who were employed for at least 34 hours per month received an invitation to participate, of whom 30,099 (47.5%) completed the questionnaire, 897 (1.4%) partially completed the questionnaire and 32,395 (51.1%) did not respond. Baseline was completed in June 2021. NASWEED covers various topics about the work environment (psychosocial, ergonomic, chemical, biological, safety, accidents, working from home, etc), health behaviours and somatic and mental health-related conditions. Statistical analyses will mainly build on survey procedures with model-assisted weights to ensure that the sample will yield representative estimates of the general working population.

DISCUSSION: NASWEED will monitor the development of the work environment and health in Denmark until 2030. The survey data will be included in epidemiological studies with repeated measurement of the work environment, health variables and covariates, and follow-ups in national registers to investigate the prospective association in the years and decades to come between the work environment and workers’ health and labour market participation.

PMID:37387222 | DOI:10.1177/14034948231182022

Bioinformatics. 2023 Jun 30;39(Supplement_1):i357-i367. doi: 10.1093/bioinformatics/btad251.

ABSTRACT

The tendency of an amino acid to adopt certain configurations in folded proteins is treated here as a statistical estimation problem. We model the joint distribution of the observed mainchain and sidechain dihedral angles (〈ϕ,ψ,χ1,χ2,…〉) of any amino acid by a mixture of a product of von Mises probability distributions. This mixture model maps any vector of dihedral angles to a point on a multi-dimensional torus. The continuous space it uses to specify the dihedral angles provides an alternative to the commonly used rotamer libraries. These rotamer libraries discretize the space of dihedral angles into coarse angular bins, and cluster combinations of sidechain dihedral angles (〈χ1,χ2,…〉) as a function of backbone 〈ϕ,ψ〉 conformations. A ‘good’ model is one that is both concise and explains (compresses) observed data. Competing models can be compared directly and in particular our model is shown to outperform the Dunbrack rotamer library in terms of model complexity (by three orders of magnitude) and its fidelity (on average 20% more compression) when losslessly explaining the observed dihedral angle data across experimental resolutions of structures. Our method is unsupervised (with parameters estimated automatically) and uses information theory to determine the optimal complexity of the statistical model, thus avoiding under/over-fitting, a common pitfall in model selection problems. Our models are computationally inexpensive to sample from and are geared to support a number of downstream studies, ranging from experimental structure refinement, de novo protein design, and protein structure prediction. We call our collection of mixture models as PhiSiCal (ϕψχal).

AVAILABILITY AND IMPLEMENTATION: PhiSiCal mixture models and programs to sample from them are available for download at http://lcb.infotech.monash.edu.au/phisical.

PMID:37387189 | DOI:10.1093/bioinformatics/btad251