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Nevin Manimala Statistics

Eco-evolutionary trade-offs in the dynamics of prion strain competition

Proc Biol Sci. 2023 Jul 12;290(2002):20230905. doi: 10.1098/rspb.2023.0905. Epub 2023 Jul 5.

ABSTRACT

Prion and prion-like molecules are a type of self-replicating aggregate protein that have been implicated in a variety of neurodegenerative diseases. Over recent decades, the molecular dynamics of prions have been characterized both empirically and through mathematical models, providing insights into the epidemiology of prion diseases and the impact of prions on the evolution of cellular processes. At the same time, a variety of evidence indicates that prions are themselves capable of a form of evolution, in which changes to their structure that impact their rate of growth or fragmentation are replicated, making such changes subject to natural selection. Here we study the role of such selection in shaping the characteristics of prions under the nucleated polymerization model (NPM). We show that fragmentation rates evolve to an evolutionary stable value which balances rapid reproduction of PrPSc aggregates with the need to produce stable polymers. We further show that this evolved fragmentation rate differs in general from the rate that optimizes transmission between cells. We find that under the NPM, prions that are both evolutionary stable and optimized for transmission have a characteristic length of three times the critical length below which they become unstable. Finally, we study the dynamics of inter-cellular competition between strains, and show that the eco-evolutionary trade-off between intra- and inter-cellular competition favours coexistence.

PMID:37403499 | DOI:10.1098/rspb.2023.0905

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Nevin Manimala Statistics

Molecular-scale substrate anisotropy, crowding and division drive collective behaviours in cell monolayers

J R Soc Interface. 2023 Jul;20(204):20230160. doi: 10.1098/rsif.2023.0160. Epub 2023 Jul 5.

ABSTRACT

The ability of cells to reorganize in response to external stimuli is important in areas ranging from morphogenesis to tissue engineering. While nematic order is common in biological tissues, it typically only extends to small regions of cells interacting via steric repulsion. On isotropic substrates, elongated cells can co-align due to steric effects, forming ordered but randomly oriented finite-size domains. However, we have discovered that flat substrates with nematic order can induce global nematic alignment of dense, spindle-like cells, thereby influencing cell organization and collective motion and driving alignment on the scale of the entire tissue. Remarkably, single cells are not sensitive to the substrate’s anisotropy. Rather, the emergence of global nematic order is a collective phenomenon that requires both steric effects and molecular-scale anisotropy of the substrate. To quantify the rich set of behaviours afforded by this system, we analyse velocity, positional and orientational correlations for several thousand cells over days. The establishment of global order is facilitated by enhanced cell division along the substrate’s nematic axis, and associated extensile stresses that restructure the cells’ actomyosin networks. Our work provides a new understanding of the dynamics of cellular remodelling and organization among weakly interacting cells.

PMID:37403487 | DOI:10.1098/rsif.2023.0160

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Nevin Manimala Statistics

Comparison of perineal urethrostomy versus augmentation urethroplasty in anterior urethral stricture disease

Urologia. 2023 Jul 4:3915603231178392. doi: 10.1177/03915603231178392. Online ahead of print.

ABSTRACT

PURPOSE: Perineal urethrostomy and urethroplasty are very good options for complex and long anterior urethral strictures. A perineal urethroplasty is usually a neglected option. To our knowledge, a comparative study between augmentation urethroplasty and perineal urethrostomy has been not conducted regarding subjective and patient reported outcome measures. We compared both these groups in a high volume tertiary care hospital.

MATERIALS AND METHODS: A prospective comparative study of augmentation urethroplasty and perineal urethroplasty for long anterior urethral stricture. it was defined by strictures of more than 3 cm. We compared demographic data, urinary and sexual function; and quality of life using validated PROMs (patient-reported outcome measures) between both above groups.

RESULTS: Both groups had 40 patients each. IPSS score improvement for PU and AUP were 20 and 19.6, respectively(p = 0.1223); IIEF-5 score improvement for PU and AUP at baseline and after 6 months were 14.3 and 16.7, respectively(p = 0.1433); QOL score improvement for PU and AUP were 3.45 and 3.05, respectively; which was statistically significant (p ⩽ 0.001).

CONCLUSIONS: Perineal urethrostomy is a good but neglected option for complex and long anterior urethral strictures and it should be considered one of the reliable treatment option for patients with long-segment urethral strictures.

PMID:37403482 | DOI:10.1177/03915603231178392

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Nevin Manimala Statistics

The effect of nutrition on sleeve gastrectomy patients’ weight loss, biochemical measurements, and comorbids: A clinical study

Nutr Health. 2023 Jul 4:2601060231186847. doi: 10.1177/02601060231186847. Online ahead of print.

ABSTRACT

BACKGROUND: This study investigates the effect of a nutrition program applied to patients as per bariatric surgery protocol at the sixth month postoperative. The study also compares and contrasts the postoperative findings with preoperative data.

METHODS: Twenty severely obese sleeve gastrectomy patients between the ages of 18-65 participated in the study. Energy requirements were calculated as 22 kcal/ideal body weight (kg/day) and protein requirements as 1.5 g/ideal body weight (kg/day). The study evaluates patients’ anthropometric and biochemical measurements, body mass index, waist circumference, fat mass (%), weight loss (%), excess weight loss (%), comorbids, and dietary habits at the third and sixth months preoperative and postoperative. Patients’ daily macro-micronutrient intake was also calculated. The Friedman Test and Cochran’s Q test were performed to determine statistically significant data (p < 0.05).

RESULTS: During the first 6 months postoperative, patients lost 34 kg of weight and 16.7% of fat mass, and their percent excess weight loss was measured at 60.2% (<0.0001). Biochemical measurements of the patients revealed that fasting blood glucose, low-density lipoprotein cholesterol, total cholesterol, triglyceride, and calcium levels, which were above the reference range in the preoperative period, were within this range in the postoperative period (<0.0001). Thirteen out of 21 comorbidities, including type 2 diabetes, hypertension, hyperlipidemia, pulmonary problems, and sleep apnea, improved at different rates in the sixth month postoperative.

CONCLUSIONS: Thanks to the nutrition program applied as per bariatric surgery protocol, patients lost weight, and their biochemical measurements and comorbids have improved following sleeve gastrectomy.

PMID:37403480 | DOI:10.1177/02601060231186847

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Nevin Manimala Statistics

Understanding the Relationship Between Decreases in Social Security Benefits and Intergenerational Inequalities in Mental Health

Int J Soc Determinants Health Health Serv. 2023 Jul 4:27551938231185948. doi: 10.1177/27551938231185948. Online ahead of print.

ABSTRACT

It is well-established that mental health follows similar patterns across generations. However, little is known how structural factors, such as those related to social security reforms, may impact this relationship. Our aim was to quantify the strength of association in mental health between parents and their adolescent children, and to explore how much of this correlation is explained by decreases in benefits. We used data from U.K. Household Longitudinal Study (2009-2019) from which we matched youth data to their parents, and split the sample into single- and dual-parent households. To estimate the intergenerational correlations, we estimated a series of unit- and rank-based regression models of standardized and time-averaged mental health measures for adolescents and their parents. Our findings suggest that there are statistically significant intergenerational associations in mental health between parents and children for both single- and dual-parent households, with the relationship being stronger for single-mother households. Benefit losses explain a small proportion of this association, for both single-mother and dual-parent households. Nevertheless, they are negatively associated with the mental health of adolescents in dual-parent households-independently of both adolescent and parental characteristics. Such negative effects should be considered when designing and evaluating future social security benefit policies.

PMID:37403462 | DOI:10.1177/27551938231185948

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Nevin Manimala Statistics

Interventional approaches to symptomatic Tarlov cysts: a 15-year institutional experience

J Neurointerv Surg. 2023 Jul 4:jnis-2023-020564. doi: 10.1136/jnis-2023-020564. Online ahead of print.

ABSTRACT

BACKGROUND: Tarlov cysts are perineural collections of cerebrospinal fluid most often affecting sacral nerve roots, which may cause back pain, extremity paresthesias and weakness, bladder/bowel dysfunction, and/or sexual dysfunction. The most effective treatment of symptomatic Tarlov cysts, with options including non-surgical management, cyst aspiration and injection of fibrin glue, cyst fenestration, and nerve root imbrication, is debated.

METHODS: Retrospective chart review was conducted for 220 patients with Tarlov cysts seen at our institution between 2006 and 2021. Logistic regression analysis was conducted to determine the association between treatment modality, patient characteristics, and clinical outcome.

RESULTS: Seventy-two (43.1%) patients with symptomatic Tarlov cysts were managed non-surgically. Of the 95 patients managed interventionally, 71 (74.7%) underwent CT-guided aspiration of the cyst with injection of fibrin glue; 17 (17.9%) underwent cyst aspiration alone; 5 (5.3%) underwent blood patching; and 2 (2.1%) underwent more than one of the aforementioned procedures. Sixty-six percent of treated patients saw improvement in one or more symptoms, with the most improvement in patients after aspiration of cyst with injection of fibrin glue; however, this association was not statistically significant on logistic regression analysis.

CONCLUSION: Although the subtype of percutaneous treatment was not significantly associated with optimal or suboptimal patient outcomes, cyst aspiration both with and without injection of fibrin glue may serve as a useful diagnostic tool to (1) determine symptom etiology and (2) identify patients who might have achieved temporary improvement between the time of cyst aspiration and refill with cerebrospinal fluid as potential candidates for neurosurgical intervention of cyst fenestration and nerve root imbrication.

PMID:37402574 | DOI:10.1136/jnis-2023-020564

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Nevin Manimala Statistics

Morphology of middle cerebral artery using computed tomography angiographic study in a tertiary care hospital

Anat Cell Biol. 2023 Jul 5. doi: 10.5115/acb.22.242. Online ahead of print.

ABSTRACT

Increased tortuosity of vessel is associated with high incidence of plaque formation leading to atherosclerosis. Surgical procedures are done after analyzing morphology of middle cerebral artery (MCA). However, literature describing MCA morphology using computed tomography angiography (CTA) is limited, so this study was planned to determine its incidence in Indian population. Datasets of CTA from 289 patients (180 males and 109 females), average age: 49.29±16.16 years (range: 11 to 85 years), from a tertiary care hospital were systematically reviewed for morphology of MCA. Cases involving aneurysms and infarcts were excluded. Four shapes of MCA were recognized: straight, U, inverted U, and S-shaped. MCA was straight in 44% (254/578), U-shaped in 37% (215/578), S shaped in 15% (89/578) and inverted U-shaped in 3% (20/578) cases. In males, MCA was straight in 46% (166/360), U-shaped in 37% (134/360), S-shaped in 16% (58/360) and inverted U-shaped in 4% (14/360) cases. In females, MCA was straight in 42% cases (92/218), U-shaped in 37% (81/218), S-shaped in 17% (36/218) and inverted U-shaped in 4% (9/218). On comparing shape with various age groups using chi square test, U shaped (P≤0.001) and S-shaped (P=0.003) MCA were found to be statistically significant. The incidence of straight shape was higher in advanced age group (>60 years). Knowledge of MCA shape will be useful for clinicians and surgeons in successful endovascular recanalization. Also, this data would help surgeons during neurointerventional procedures.

PMID:37402565 | DOI:10.5115/acb.22.242

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Nevin Manimala Statistics

Association of age with death and withdrawal of life-sustaining therapy after severe traumatic brain injury

Can J Surg. 2023 Jul 4;66(4):E348-E355. doi: 10.1503/cjs.013721. Print 2023 Jul-Aug.

ABSTRACT

BACKGROUND: Compared to younger age, older age (≥ 65 yr) is associated with worse outcomes after severe traumatic brain injury (TBI). We sought to describe the association of older age with in-hospital death and aggressiveness of intervention.

METHODS: We conducted a retrospective cohort study of adult (age ≥ 16 yr) patients with severe TBI admitted to a single academic tertiary care neurotrauma centre between January 2014 and December 2015. We collected data through chart review as well as from our institutional administrative database. We provided descriptive statistics and used multivariable logistic regression to evaluate the independent association of age with the primary outcome, in-hospital death. The secondary outcome was early withdrawal of life-sustaining therapy.

RESULTS: There were 126 adult patients (median age 67 yr [Q1-Q3, 33-80 yr]) with severe TBI during the study period who met our eligibility criteria. The most common mechanism was high-velocity blunt injury (55 patients [43.6%]). The median Marshall score was 4 (Q1-Q3, 2-6), and the median Injury Severity Score was 26 (Q1-Q3, 25-35). After controlling for confounders including clinical frailty, pre-existing comorbidity, injury severity, Marshall score and neurologic examination at admission, we observed that older patients were more likely than younger patients to die in hospital (odds ratio 5.10, 95% confidence interval 1.65-15.78). Older patients were also more likely to experience early withdrawal of life-sustaining therapy and less likely to receive invasive interventions.

CONCLUSION: After controlling for confounding factors relevant to older patients, we observed that age was an important and independent predictor of in-hospital death and early withdrawal of life-sustaining therapy. The mechanism by which age influences clinical decision-making independent of global and neurologic injury severity, clinical frailty and comorbidities remains unclear.

PMID:37402559 | DOI:10.1503/cjs.013721

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Nevin Manimala Statistics

G-estimation of structural nested mean models for interval-censored data using pseudo-observations

Stat Med. 2023 Jul 4. doi: 10.1002/sim.9838. Online ahead of print.

ABSTRACT

Two large-scale randomized clinical trials compared fenofibrate and placebo in diabetic patients with pre-existing retinopathy (FIELD study) or risk factors (ACCORD trial) on an intention-to-treat basis and reported a significant reduction in the progression of diabetic retinopathy in the fenofibrate arms. However, their analyses involved complications due to intercurrent events, that is, treatment-switching and interval-censoring. This article addresses these problems involved in estimation of causal effects of long-term use of fibrates in a cohort study that followed patients with type 2 diabetes for 8 years. We propose structural nested mean models (SNMMs) of time-varying treatment effects and pseudo-observation estimators for interval-censored data. The first estimator for SNMMs uses a nonparametric maximum likelihood estimator (MLE) as a pseudo-observation, while the second estimator is based on MLE under a parametric piecewise exponential distribution. Through numerical studies with real and simulated datasets, the pseudo-observations estimators of causal effects using the nonparametric Wellner-Zhan estimator perform well even under dependent interval-censoring. Its application to the diabetes study revealed that the use of fibrates in the first 4 years reduced the risk of diabetic retinopathy but did not support its efficacy beyond 4 years.

PMID:37402505 | DOI:10.1002/sim.9838

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Nevin Manimala Statistics

Correlates of delirium care competency among shift leader nurses in acute medical wards in Japan: A cross-sectional study

Jpn J Nurs Sci. 2023 Jul 4:e12551. doi: 10.1111/jjns.12551. Online ahead of print.

ABSTRACT

AIM: This study identified the correlates of delirium care competency among shift leader nurses in acute medical wards in Japan.

METHODS: A cross-sectional study was conducted from November 2019 to February 2020. We sent request letters to a random sample of 381 general acute care hospitals in Japan. Of these, 68 agreed to participate and distributed 735 self-administered questionnaires to shift leader nurses working in their acute medical wards. The questionnaire included the Self-rated Delirium Care Competency Scale for Shift Leader Nurses in Acute Medical Wards (DCSL-M), developed by the authors. It gathered data on the respondents’ demographics and delirium care competency, and investigated a total of 25 variables. We calculated descriptive statistics and examined associations between delirium care competency and the demographics using multiple logistic regression analysis.

RESULTS: Of the total, 301 (40.9%) questionnaires were returned. Delirium care competency was high among shift leader nurses who: (1) had experience as a clinical practice preceptor for nursing students; (2) had experience attending training related to dementia or delirium care; (3) worked at a hospital/ward that charged additional medical fees for dementia care; and (4) had access to consulting psychiatrists to refer patients with delirium.

CONCLUSIONS: The results suggest the need for efforts to improve delirium care competency among shift leader nurses who work in hospitals that do not charge additional medical fees for dementia care or that do not have consulting psychiatrists to refer patients with delirium.

PMID:37402502 | DOI:10.1111/jjns.12551