Category: Nevin Manimala

Nutrition. 2021 Mar 26;90:111250. doi: 10.1016/j.nut.2021.111250. Online ahead of print.

ABSTRACT

OBJECTIVES: Folic acid (FA) is crucial before and during early pregnancy. FA deficiency can occur because dietary FA intake is low in mothers at the time of conception. Likewise, various ocular pathologies are related to the alteration of extracellular matrices. The present study aimed to investigate the association between maternal FA deficiency and congenital eye defects. We also investigated whether maternal diet deficient in FA alters the expression of collagen IV and laminin-1 as a possible mechanism responsible for the appearance of ocular malformations. Both proteins are the main components of the basal lamina, and form an interlaced network that creates a relevant scaffold basement membrane. Basal laminae are involved in tissues maintenance and implicated in regulating many cellular processes.

METHODS: A total of 57 mouse embryos were classified into the following groups: Control group, (mothers were fed a standard rodent diet), and D2 and D8 groups (mothers were fed FA-deficient [FAD] diet for 2 or 8 wk, respectively). Female mice from group D2 were fed a FAD diet (0 mg/kg diet + 1% succinyl sulfathiazole used to block the synthesis of FA) for 2 wk from the day after mating until day 14.5 of gestation (E14.5). On the other hand, female mice from group D8 were fed a FAD diet for 8 wk (6 wk before conception and during the first 2 wk of pregnancy). For the data analysis, we first estimated the incidence of malformations in each group. Then, the statistical analysis was performed using IBM SPSS Statistics, version 25.0. Expression patterns of collagen IV and laminin-1 were examined with the immunohistochemical technique.

RESULTS: Our results showed that mice born to FA-deficient mothers had several congenital eye abnormalities. Embryos from dams fed a short-term FAD diet were found to have many significant abnormalities in both anterior and posterior segments, as well as choroidal vessel abnormalities. However, embryos from dams fed a long-term FAD diet had a significantly higher incidence of eye defects. Finally, maternal FA deficiency increased the expression of both collagen IV and laminin-1. Likewise, changes in the spatial localization and organization of collagen IV were observed.

CONCLUSIONS: A maternal FAD diet for a short-term period causes eye developmental defects and induces overexpression of both collagen IV and laminin-1. The malformations observed are probably related to alterations in the expression of basement membrane proteins.

PMID:33962364 | DOI:10.1016/j.nut.2021.111250

J Neurosurg. 2021 May 7:1-8. doi: 10.3171/2020.10.JNS203236. Online ahead of print.

ABSTRACT

OBJECTIVE: Silent corticotroph adenomas (SCAs) are a distinct subtype of nonfunctioning pituitary adenomas (NFAs) that demonstrate positive immunohistochemistry for adrenocorticotropic hormone (ACTH) without causing Cushing’s disease. SCAs are hypothesized to exhibit more aggressive behavior than standard NFAs. The authors analyzed their institution’s surgical experience with SCAs in an effort to characterize rates of invasion, postoperative clinical outcomes, and patterns of disease recurrence and progression. The secondary objectives were to define the best treatment strategies in the event of tumor recurrence and progression.

METHODS: A retrospective analysis of patients treated at the authors’ institution identified 100 patients with SCAs and 841 patients with NFAs of other subtypes who were treated surgically from 2000 to 2019. Patient demographics, tumor characteristics, surgical and neuroimaging data, rates of endocrinopathy, and neurological outcomes were recorded. Cohorts of patients with SCAs and patients with standard NFAs were compared with regard to these characteristics and outcomes.

RESULTS: The SCA cohort presented with cranial neuropathy (13% vs 5.7%, p = 0.0051) and headache (53% vs 42.3%, p = 0.042) compared to the NFA cohort, despite similar rates of apoplexy. The SCA cohort included a higher proportion of women (SCA 60% vs NFA 45.8%, p = 0.0071) and younger age at presentation (SCA 50.5 ± 13.3 vs NFA 54.6 ± 14.9 years of age, p = 0.0082). Reoperations were comparable between the cohorts (SCA 16% vs NFA 15.7%, p = 0.98). Preoperative pituitary function was comparable between the cohorts with the exception of higher rates of preoperative panhypopituitarism in NFA patients (2% vs 6.1%, respectively; p = 0.0033). The mean tumor diameter in SCA patients was 24 ± 10.8 mm compared to 26 ± 11.3 mm in NFA patients (p = 0.05). Rates of cavernous sinus invasion were higher in the SCA group (56% vs 49.7%), although this result did not reach statistical significance. There were no significant differences in extent of resection, intraoperative CSF leak rates, endocrine or neurological outcomes, or postoperative complications. Ki-67 rates were significantly increased in the SCA cohort (2.88 ± 2.79) compared to the NFA cohort (1.94 ± 1.99) (p = 0.015). Although no differences in overall rates of progression or recurrence were noted, SCAs had a significantly lower progression-free survival (24.5 vs 51.1 months, p = 0.0011). Among the SCA cohort, progression was noted despite the use of adjuvant radiosurgery in 33% (n = 4/12) of treated tumors. Adequate tumor control was not achieved in half (n = 6) of the SCA progression cohort despite radiosurgery or multiple resections.

CONCLUSIONS: In this study, to the authors’ knowledge the largest surgical series to assess outcomes in SCAs to date, the findings suggest that SCAs are more biologically aggressive tumors than standard NFAs. The progression-free survival duration of patients with SCAs is only about half that of patients with other NFAs. Therefore, close neuroimaging and clinical follow-up are warranted in patients with SCAs, and residual disease should be considered for early postoperative adjuvant radiosurgery, particularly in younger patients.

PMID:33962375 | DOI:10.3171/2020.10.JNS203236

J Neurosurg. 2021 May 7:1-10. doi: 10.3171/2020.9.JNS201558. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to 1) compare the safety and efficacy of acute targeted embolization of angiographic weak points in ruptured brain arteriovenous malformations (bAVMs) versus delayed treatment, and 2) explore the angioarchitectural changes that follow this intervention.

METHODS: The authors conducted a retrospective analysis of a prospectively acquired database of ruptured bAVMs. Three hundred sixteen patients with ruptured bAVMs who presented to the hospital within 48 hours of ictus were included in the analysis. The first analysis compared clinical and functional outcomes of acutely embolized patients to those with delayed management paradigms. The second analysis compared these outcomes of patients with acute embolization to those with angiographic targets who did not undergo acute embolization. Finally, a subset of 20 patients with immediate postembolization angiograms and follow-up angiograms within 6 weeks of treatment were studied to determine the angioarchitectural changes after acute targeted embolization. Kaplan-Meier curves for survival between the groups were devised. Multivariate logistical regression analysis was conducted.

RESULTS: There were three deaths (0.9%) and an overall rerupture rate of 4.8% per year. There was no statistical difference in demographic variables, mortality, and rerupture rate between patients with acute embolization and those with delayed management. Patients with acute embolization were more likely to present functionally worse (46.9% vs 69.8%, modified Rankin Scale score 0-2, p = 0.018) and to require an adjuvant therapy (71.9% vs 26.4%, p < 0.001). When comparing acutely embolized patients to those nonacutely embolized angiographic targets, there was a significant protective effect of acute targeted therapy on rerupture rate (annual risk 1.2% vs 4.3%, p = 0.025) and no difference in treatment complications. Differences in the survival curves for rerupture were statistically significant. Multivariate analyses significantly predicted lower rerupture in acute targeted treatment and higher rerupture in those with associated aneurysms, deep venous anatomy, and higher Spetzler-Martin grade. All patients with acute embolization experienced complete obliteration of the angiographic weak point with various degrees of resolution of the nidus; however, some had spontaneous recurrence of their bAVM, while others had spontaneous resolution over time. No patients developed new angiographic weak points.

CONCLUSIONS: This study demonstrates that acute targeted embolization of angiographic weak points, particularly aneurysms, is technically safe and protective in the early phase of recovery from ruptured bAVMs. Serial follow-up imaging is necessary to monitor the evolution of the nidus after targeted and definitive treatments. Larger prospective studies are needed to validate these findings.

PMID:33962377 | DOI:10.3171/2020.9.JNS201558

J Biomech. 2021 Apr 21;122:110456. doi: 10.1016/j.jbiomech.2021.110456. Online ahead of print.

ABSTRACT

Mechanomyography (MMG) is a non-invasive technique that records muscle contraction using sensors positioned on the skin’s surface. Therefore, it can have its signal attenuated due to the adipose tissue, directly influencing the results. This study evaluates the influence of different mass added to a sensor’s assembly and the adipose tissue on MMG signals of elbow flexor muscles. Test protocol consisted of skinfold thickness measurement of 22 volunteers, followed by applying 2-3 s electrical stimulation for muscle contraction during the acquisition of MMG signals. MMG signals were processed in the time domain, using the average of the absolute amplitude, and expressed in gravity values (G), termed here as MMG(G). Tests occurred four times with different sensor masses. MMG data were processed and analyzed statistically using Friedman and Kruskal-Wallis tests to determine the differences between the MMG signals measured with different sensor masses. The Mann-Whitney analysis indicated differences in the MMG signals between groups with different skinfold thickness. MMG(G) signals suffered attenuation with increasing sensor mass (0.4416 G to 0.94 g; 0.3902 G to 2.64 g; 0.3762 G to 5.44 g; 0.3762 G to 7.14 g) and adipose tissue.

PMID:33962326 | DOI:10.1016/j.jbiomech.2021.110456

Eur J Cancer. 2021 May 4;151:25-34. doi: 10.1016/j.ejca.2021.03.053. Online ahead of print.

ABSTRACT

OBJECTIVE: The gut microbiome plays an important role in systemic inflammation and immune response. Microbes can translocate and reside in tumour niches. However, it is unclear how the intratumour microbiome affects immunity in human cancer. The purpose of this study was to investigate the association between intratumour bacteria, infiltrating CD8+ T cells and patient survival in cutaneous melanoma.

METHODS: Using The Cancer Genome Altas’s cutaneous melanoma RNA sequencing data, levels of intratumour bacteria and infiltrating CD8+ T cells were determined. Correlation between intratumour bacteria and infiltrating CD8+ T cells or chemokine gene expression and survival analysis of infiltrating CD8+ T cells and Lachnoclostridium in cutaneous melanoma were performed.

RESULTS: Patients with low levels of CD8+ T cells have significantly shorter survival than those with high levels. The adjusted hazard ratio was 1.57 (low vs high) (95% confidence interval: 1.17-2.10, p = 0.002). Intratumour bacteria of the Lachnoclostridium genus ranked top in a positive association with infiltrating CD8+ T cells (correlation coefficient = 0.38, p = 9.4 × 10^-14), followed by Gelidibacter (0.31, p = 1.13 × 10^-9), Flammeovirga (0.29, p = 1.96 × 10^-8) and Acinetobacter (0.28, p = 8.94 × 10^-8). These intratumour genera positively correlated with chemokine CXCL9, CXCL10 and CCL5 expression. The high Lachnoclostridium load significantly reduced the mortality risk (p = 0.0003). However, no statistically significant correlation was observed between intratumour Lachnoclostridium abundance and the levels of either NK, B or CD4+ T cells.

CONCLUSION: Intratumour-residing gut microbiota could modulate chemokine levels and affect CD8+ T-cell infiltration, consequently influencing patient survival in cutaneous melanoma. Manipulating the intratumour gut microbiome may benefit patient outcomes for those undergoing immunotherapy.

PMID:33962358 | DOI:10.1016/j.ejca.2021.03.053

Drug Alcohol Depend. 2021 Apr 29;224:108727. doi: 10.1016/j.drugalcdep.2021.108727. Online ahead of print.

ABSTRACT

OBJECTIVES: Disparities in access to medication-assisted treatment are a major problem. This study estimated and compared drive time to the nearest opioid treatment program (OTP) and office-based buprenorphine treatment (OBBT) across the urban-rural continuum in the U.S.

METHODS: Drive time was calculated between the longitude and latitude of population weighted block group centroids and the longitude and latitude of the nearest OTP and OBBT. Rural-Urban Commuting Area (RUCA) codes were used for defining rurality. The Integrated Nested Laplace Approximation approach was used for statistical analysis.

RESULTS: The mean travel time to the nearest OBBT compared to OTP decreased by 7.18 min (95 % CI = 7.23-7.14) in metropolitan cores, 36.63 min (95 % CI = 37.12-36.15) in micropolitan cores, 38.84 min (95 % CI = 39.57-38.10) in small town cores, and 40.16 min (95 % CI = 40.81-39.50) in rural areas. Additionally, travel burden to the nearest OTP would be more than 60 min for 13,526,605 people and more than 90 min for 5,371,852 people. The travel burden to the nearest OBBT would be more than 60 min for 845,991 people and more than 90 min for 149,297 people.

CONCLUSIONS: The mean drive time to the closest OBBT was significantly smaller than the mean drive time to the closest OTP. Analysis of barriers to access is necessary to devising creative initiatives to improve access to critical opioid use disorder treatment services.

PMID:33962300 | DOI:10.1016/j.drugalcdep.2021.108727

Int J Paleopathol. 2021 May 4;33:170-181. doi: 10.1016/j.ijpp.2021.04.007. Online ahead of print.

ABSTRACT

OBJECTIVE: To estimate the prevalence rate of gout and to explore the social factors that contributed to its development in the various sub-populations in medieval Cambridge.

MATERIALS: 177 adult individuals from four medieval cemeteries located in and around Cambridge, UK.

METHODS: Lesions were assessed macroscopically and radiographically. Elements with lytic lesions were described and imaged using micro-computed tomography (μCT) to determine their morphology.

RESULTS: Gout was identified in 3 % of the population. Individuals buried in the friary had highest prevalence (14 %), with low prevalence rates in the Hospital (3 %) and town parish cemetery (2 %), with no cases in the rural parish cemetery. Gout was more prevalent during the 14th-15th centuries than the 10th-13th centuries.

CONCLUSION: The high prevalence rate of gout in the friary is at least partly explained by the consumption of alcohol and purine-rich diets by the friars and the wealthy townsfolk. Medieval medical texts from Cambridge show that gout (known as podagra) was sometimes treated with medications made from the root of the autumn crocus. This root contains colchicine, which is a medicine that is still used to treat gout today.

SIGNIFICANCE: This is one of the first studies to assess the epidemiology of gout in medieval England and suggests that gout varied with social status.

LIMITATIONS: Our sample size precludes statistical analysis.

SUGGESTIONS FOR FURTHER RESEARCH: Additional studies that assess the epidemiology of gout in medieval Europe is needed in order to be able to fully contextualize these findings.

PMID:33962231 | DOI:10.1016/j.ijpp.2021.04.007

Hum Mov Sci. 2021 May 4;78:102803. doi: 10.1016/j.humov.2021.102803. Online ahead of print.

ABSTRACT

OBJECTIVES: The present study aimed to clarify the mechanisms of postural control during standing in older adults and document the mechanisms of age-related motor control based on changes in muscle activities.

METHODS: A total of 26 healthy male adults (older adult group, ≥65-78 years: n = 16; younger adult group, 20-23 years: n = 10) participated in this study. Ground reaction force and kinematic data of the lower limbs (hip, knee, and ankle), and electromyographic data from 6 postural muscles on the right side were recorded and quantified for each motor phase during rapid voluntary center of pressure (COP) shift.

RESULTS: Although hip strategy was more frequently observed in older adults than in young adults (56.3% vs. 20.0%), no muscle activity of hip agonists was observed in some (31.3%) older adults. Furthermore, older adults had a statistically significant delay in the inhibition of postural muscles during anticipatory postural adjustments (p < 0.05). After the onset of COP motion, the co-contraction time between agonists and antagonists was significantly prolonged in the older adults than in the younger adults (p < 0.05), and the reciprocal muscle pattern was unclear in the older adults. Prior to the termination of movement, agonist activity continued longer in the older adult group than in the younger adult group; that is, inhibition was insufficient in the older adult group.

CONCLUSION: A series of postural strategies during the voluntary movement task were altered in older adults, and this was significantly related not only with the activation but also the inhibition of postural muscles.

PMID:33962246 | DOI:10.1016/j.humov.2021.102803

Eur J Radiol. 2021 Apr 30;140:109744. doi: 10.1016/j.ejrad.2021.109744. Online ahead of print.

ABSTRACT

BACKGROUND: MRI based radiomics has the potential to better define tumor biology compared to qualitative MRI assessment and support decisions in patients affected by nasopharyngeal carcinoma. Aim of this review was to systematically evaluate the methodological quality of studies using MRI- radiomics for nasopharyngeal cancer patient evaluation.

METHODS: A systematic search was performed in PUBMED, WEB OF SCIENCE and SCOPUS using “MRI, magnetic resonance imaging, radiomic, texture analysis, nasopharyngeal carcinoma, nasopharyngeal cancer” in all possible combinations. The methodological quality of study included ( = 24) was evaluated according to the RQS (Radiomic quality score). Subgroup, for journal type (imaging/clinical) and biomarker (prognostic/predictive), and correlation, between RQS and journal Impact Factor, analyses were performed. Mann-Whitney U test and Spearman’s correlation were performed. P value < .05 were defined as statistically significant.

RESULTS: Overall, no studies reported a phantom study or a test re-test for assessing stability in image, biological correlation or open science data. Only 8% of them included external validation. Almost half of articles (45 %) performed multivariable analysis with non-radiomics features. Only 1 study was prospective (4%). The mean RQS was 7.5 ± 5.4. No significant differences were detected between articles published in clinical/imaging journal and between studies with a predictive or prognostic biomarker. No significant correlation was found between total RQS and Impact Factor of the year of publication (p always > 0.05).

CONCLUSIONS: Radiomic articles in nasopharyngeal cancer are mostly of low methodological quality. The greatest limitations are the lack of external validation, biological correlates, prospective design and open science.

PMID:33962253 | DOI:10.1016/j.ejrad.2021.109744

J Anxiety Disord. 2021 May 3;81:102415. doi: 10.1016/j.janxdis.2021.102415. Online ahead of print.

ABSTRACT

Since the outbreak of the coronavirus disease (COVID-19), several reports have shown that fear relating to COVID-19 has sharply increased. To measure fear of COVID-19, various questionnaires have been developed in parallel. However, fear concerning COVID-19 is not necessarily a uniform construct and the different questionnaires may cover diverse aspects. To examine the underlying structure of fear of COVID-19, we conducted structural equation modelling and network analyses on four scales in an online convenience sample (N = 829). Particularly, the Fear of COVID-19 Scale (Ahorsu et al., 2020), the Fear of the Coronavirus Questionnaire (Mertens et al., 2020), and the COVID Stress Scales (Taylor, Landry, Paluszek, Fergus et al., 2020, Taylor, Landry, Paluszek, Rachor et al., 2020) were included in our study, along with a new scale that also assessed socio-economic worries relating to COVID-19. We found that fear of COVID-19 was best classified into four clusters: Fear of health-related consequences, fear of supplies shortages and xenophobia, fear about socio-economic consequences, and symptoms of fear (e.g., compulsions, nightmares). We also find that a central cluster of items centered on fear of health, which likely represents the core of fear of COVID-19. These results help to characterize fear due to COVID-19 and inform future research.

PMID:33962142 | DOI:10.1016/j.janxdis.2021.102415