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Nevin Manimala Statistics

Social Media Use in COPD Patients in Germany and Switzerland

Pneumologie. 2021 May 7. doi: 10.1055/a-1481-0037. Online ahead of print.

ABSTRACT

Use of social media and the Internet has changed the information-seeking behaviour and exchange of experience and information by patients. Passive observation of such online interaction between patients (social media listening) is conducted in order to understand the burden of the disease, symptom perception, and expectations from a patient perspective. For most conditions, it remains to be established how representative the social media user community is for the overall patient population. In this study, we describe internet and social media use in a population of 570 COPD patients from Germany and Switzerland. This study population is a good representation of the overall patient population in Germany and Switzerland with regards to socioeconomic data. Patients were analyzed in an exploratory fashion whether usage of the Internet to obtain disease-specific information and exchanging on COPD via social media is associated with or is independent from certain socioeconomic criteria. About three-fourths of patients indicated using the Internet to search information about COPD and about a third of patients indicated using social media to exchange with others about their disease. Results indicated that among the patients using the Internet to seek information and among those sharing information via social media, patients with very severe COPD (GOLD stage 4) were overrepresented versus milder forms of the disease. Similarly, patients with more advanced educational background were also overrepresented in the groups using social media and Internet in relation to COPD. Differences in mean age were statistically significant, but surprisingly small between social media users and non-users. No relationship with regards to social media and Internet use for COPD were observed for domiciling situation and sex.

PMID:33962479 | DOI:10.1055/a-1481-0037

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Influence of estradiol on bovine trophectoderm and uterine gene transcripts around maternal recognition of pregnancy

Biol Reprod. 2021 May 7:ioab091. doi: 10.1093/biolre/ioab091. Online ahead of print.

ABSTRACT

Embryo survival and pregnancy success is increased among animals that exhibit estrus prior to fixed time artificial insemination (AI), but there are no differences in conceptus survival to d16. The objective of this study was to determine effects of preovulatory estradiol on uterine transcriptomes, select trophectoderm transcripts, and uterine luminal fluid (ULF) proteins. Beef cows/heifers were synchronized, artificially inseminated (d0), and grouped into either high (highE2) or low (lowE2) preovulatory estradiol. Uteri were flushed (d16); conceptuses and endometrial biopsies (n = 29) were collected. RNA sequencing was performed on endometrium. Real-Time PCR (RT-PCR) was performed on trophectoderm (TE; n = 21) RNA to measure relative abundance of IFNT, PTGS2, TM4SF1, C3, FGFR2, and GAPDH. Uterine fluid was analyzed using 2D LC-MS/MS based iTRAQ method. RT-PCR data were analyzed using the MIXED procedure in SAS. There were no differences in mRNA abundances in TE, but there were 432 differentially expressed genes (DEGs) (253 downregulated, 179 upregulated) in highE2/conceptus versus lowE2/conceptus groups. There were also 48 differentially expressed proteins (DEPs; 19 upregulated, 29 downregulated), 6 of these were differentially expressed (FDR < 0.10) at the mRNA level. Similar pathways for mRNA and proteins included: calcium signaling, protein kinase A signaling, and corticotropin releasing hormone (CRH) signaling. These differences in uterine function, may be preparing the conceptus for improved likelihood of survival after d16 among highE2 animals.

PMID:33962467 | DOI:10.1093/biolre/ioab091

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Microvesicles and Exosomes Released by Amnion Epithelial Cells Under Oxidative Stress Cause Inflammatory Changes in Uterine Cells

Biol Reprod. 2021 May 7:ioab088. doi: 10.1093/biolre/ioab088. Online ahead of print.

ABSTRACT

Extracellular vesicles (EVs) play a crucial role in feto-maternal communication and provide an important paracrine signaling mechanism in pregnancy. We hypothesize that fetal cells-derived exosomes and microvesicles (MVs) under oxidative stress carry unique cargo and traffic through feto-maternal interface, which cause inflammation in uterine cells associated with parturition. Exosomes and MVs, from primary amnion epithelial cell (AEC) culture media under normal or oxidative stress (OS)-induced conditions, were isolated by optimized differential centrifugation method followed by characterization for size (nanoparticle tracking analyzer), shape (transmission electron microscopy), and protein markers (western blot and immunofluorescence). Cargo and canonical pathways were identified by mass spectroscopy and Ingenuity Pathway Analysis. Myometrial, decidual, and cervical cells were treated with 1×107 control/OS-derived exosomes/MVs. Pro-inflammatory cytokines were measured using a Luminex assay. Statistical significance was determined by paired T-test (p < 0.05). AEC produced cup-shaped exosomes of 90-150 nm and circular MVs of 160-400 nm. CD9, HSP-70, and Nanog were detected in exosomes while OCT-4, HLA-G, and calnexin were found in MVs. MVs, but not exosomes, were stained for phosphatidylserine. The protein profiles for control versus OS-derived exosomes and MVs were significantly different. Several inflammatory pathways related to OS were upregulated that were distinct between exosomes and MVs. Both OS-derived exosomes and MVs significantly increased pro-inflammatory cytokines (GMCSF, IL-6, and IL-8) in maternal cells compared to control (p < 0.05). Our findings suggest that fetal-derived exosomes and MVs under OS exhibited distinct characteristics and a synergistic inflammatory role in uterine cells associated with the initiation of parturition.

PMID:33962471 | DOI:10.1093/biolre/ioab088

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Contralateral Masking in the Measurement of Auditory Brainstem Responses with Air-Conducted Tone Burst Stimuli in Individuals with Unilateral Hearing Loss

J Am Acad Audiol. 2021 May 7. doi: 10.1055/s-0041-1722985. Online ahead of print.

ABSTRACT

BACKGROUND: Contralateral noise masking is an important aspect of auditory brainstem response (ABR) measurements.

PURPOSE: The primary aim of this study is to determine how contralateral white noise (WN) masking influences the amplitude and the latency of V wave generated during ABR measurements, using tone burst (TB), in adult ears with normal hearing (NH). The secondary aim of this study is to ascertain the need of contralateral masking in ABR measurements with the TB stimuli using a 3A insertion earphone, and to propose the applicability of WN masking in unilateral sensorineural hearing loss (USNHL).

RESEARCH DESIGN: It is a cross-sectional observational and descriptive study.

STUDY SAMPLE: Experiment 1: Thirty individuals, without any otologic, psychological, or neurological dysfunction, were selected. Experiment 2: Fifteen individuals with previous audiological diagnoses of severe and profound USNHL were considered.

INTERVENTION: The study involves ABR TB at specific frequencies of 0.5, 1, 2, and 4 kHz.

DATA COLLECTION AND ANALYSIS: Experiment 1: The evaluation was performed at the fixed intensity of 80 dB nHL (decibel normalized hearing level) on the tested ear, followed by the application of simultaneous masking to the nontested ear, intensity ranged from 0 to 80 dB. Experiment 2: ABR threshold measurements were first performed on the ear with hearing loss (HL) at the frequencies of 1, 2, and 4 kHz. The results were subsequently confirmed using contralateral masking.

RESULTS: Experiment 1: At any given frequency, there were no statistically significant differences in the amplitude and latency of V wave with increase in the intensities of WN masking. Experiment 2: Cross-hearing was observed at least once in all frequencies analyzed through the occurrence of V wave.

CONCLUSION: In conclusion, the contralateral WN masking at the maximum intensity of 80 dB does not affect the amplitude and latency of V wave of the ABR TB at 1, 2, and 4 kHz. Contralateral masking for the ABR TB presented using 3A insertion earphones is necessary at 1, 2, and 4 kHz in individuals with severe or profound degrees of USNHL and at intensities of 15, 20, and 10 dB above the ABR threshold of the nontested ear.

PMID:33962478 | DOI:10.1055/s-0041-1722985

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Gestational folic acid deficiency alters embryonic eye development: Possible role of basement membrane proteins in eye malformations

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

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Silent corticotroph pituitary adenomas: clinical characteristics, long-term outcomes, and management of disease recurrence

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

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The safety profile and angioarchitectural changes after acute targeted embolization of ruptured arteriovenous malformations

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

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Intratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma

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

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Access to medication-assisted treatment in the United States: Comparison of travel time to opioid treatment programs and office-based buprenorphine treatment

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

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Influence of sensor mass and adipose tissue on the mechanomyography signal of elbow flexor muscles

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