Tag: statistics

Alzheimers Dement. 2021 Nov 11. doi: 10.1002/alz.12411. Online ahead of print.

ABSTRACT

INTRODUCTION: We examined the temporal sequence of the core features in probable dementia with Lewy bodies (DLB).

METHODS: In 488 patients with probable DLB, the onset of each core feature and time to diagnosis was determined for men and women, and a pathologic subgroup (n = 209).

RESULTS: REM sleep behavior disorder (RBD) developed before the other core features in men and women. Men were more likely to have RBD and were diagnosed with probable DLB earlier than women. Visual hallucinations developed after the other core features in men, but in women, they appeared earlier and concurrently with fluctuations and parkinsonism. Women were older and more cognitively impaired at first visit, were less likely to have RBD, more likely to be diagnosed with probable DLB later than men, and more likely to have neocortical tangles.

DISCUSSION: An earlier latency to probable DLB was associated with men, RBD, and Lewy body disease without neocortical tangles.

PMID:34761850 | DOI:10.1002/alz.12411

J Physiol. 2021 Nov 11. doi: 10.1113/JP282228. Online ahead of print.

ABSTRACT

KEY POINTS: Spatiotemporal contractility analysis of human induced pluripotent stem cell derived cardiomyocyte (hiPSC-CM) monolayers seeded on conventional, rigid surfaces (glass or plastic) revealed the presence of multiphasic contraction patterns across the monolayer with a high variability, despite action potentials recorded in the same areas being identical. These multiphasic patterns are not present in single cells, in detached monolayers or in monolayers seeded on soft substrates such as a hydrogel, where only ‘twitch’-like transients are observed. HiPSC-CM monolayers that display a high percentage of regions with multiphasic contraction have significantly increased contractile duration and a decreased lusotropic drug response. There is no indication that the multiphasic contraction patterns are associated with significant activation of the stress-activated NPPA or NPPB signalling pathways. A computational model of cell clusters supports the biological findings that the rigid surface and the differential cell-substrate adhesion underly multiphasic contractile behaviour of hiPSC-CMs.

ABSTRACT: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in monolayers interact mechanically via cell-cell and cell-substrate adhesion. Spatiotemporal features of contraction were analysed in hiPSC-CM monolayers 1) attached to glass or plastic (Young’s modulus (E) >1 GPa), 2) detached (substrate-free) and 3) attached to a flexible collagen hydrogel (E = 22 kPa). The effects of isoprenaline on contraction were compared between rigid and flexible substrates. To clarify underlying mechanisms, further gene expression and computational studies were performed. HiPSC-CM monolayers exhibited multi-phasic contractile profiles on rigid surfaces in contrast to hydrogels, substrate-free cultures or single cells where only simple twitch-like time-courses were observed. Isoprenaline did not change the contraction profile on either surface, but its lusitropic and chronotropic effects were greater in hydrogel compared to glass. There was no significant difference between stiff and flexible substrates in regard to expression of the stress activated genes NPPA and NPPB. A computational model of cell clusters demonstrated similar complex contractile interactions on stiff substrates as a consequence of cell-to-cell functional heterogeneity. Rigid biomaterial surfaces give rise to unphysiological, multi-phasic contractions in hiPSC-CM monolayers. Flexible substrates are necessary for normal twitch-like contractility kinetics and interpretation of inotropic interventions. This article is protected by copyright. All rights reserved.

PMID:34761809 | DOI:10.1113/JP282228

Curr Med Res Opin. 2021 Nov 11:1-15. doi: 10.1080/03007995.2021.2003671. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to characterize the risk of people living with HIV (PLHIV) in the UK progressing to pre-specified HIV-associated comorbidities, compared with matched, HIV-negative controls.

METHODS: Primary and secondary care records from the Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES) were used to identify PLHIV, and a matched cohort from the HIV-negative population. Kaplan Meier curves and cox proportional hazard models were used to evaluate the risk of developing comorbidities including central nervous system (CNS) disorders, end-stage renal disease, osteoporosis, diabetes, cardiovascular disease (CVD), hypertension, stroke, and cancer.

RESULTS: 2,945 PLHIV were matched to a cohort of 5,890 HIV-negative controls. PLHIV demonstrated an increased hazard ratio (HR) for time to development of incident sleep disorders, depression, osteoporosis, stroke, cancer and renal disease when compared with their matched HIV-negative control. The HRs for anxiety, hypertension, diabetes, and CVD were not significantly increased.

CONCLUSIONS: PLHIV in the UK were at a higher risk of developing a number of comorbid conditions, highlighting the need for regular attendance of health reviews such as the annual health reviews recommended by the British HIV Associations (BHIVA) quality standard for care, which are currently not uniformly conducted.

PMID:34761727 | DOI:10.1080/03007995.2021.2003671

Chem Commun (Camb). 2021 Nov 11. doi: 10.1039/d1cc03756k. Online ahead of print.

ABSTRACT

Fluorescence lifetime imaging (FLIM) was used to study the behaviour of a BODIPY dye in a giant unilamellar vesicle (GUV) in the presence of an electric field. The modulation of the electric field resulted in distinctive fluorescence lifetime changes in line with environment alterations within the membrane mimic.

PMID:34761753 | DOI:10.1039/d1cc03756k

Acc Chem Res. 2021 Nov 11. doi: 10.1021/acs.accounts.1c00575. Online ahead of print.

ABSTRACT

ConspectusHomogeneous metal-mediated organometallic reactions represent a very large and diverse reaction class. Density functional theory calculations are now routinely carried out and reported for analyzing organometallic mechanisms and reaction pathways. While density functional theory calculations are extremely powerful to understand the energy and structure of organometallic reactions, there are several assumptions in their use and interpretation to define reaction mechanisms and to analyze reaction selectivity. Almost always it is assumed that potential energy structures calculated with density functional theory adequately describe mechanisms and selectivity within the framework of statistical theories, for example, transition state theory and RRKM theory. However, these static structures and corresponding energy landscapes do not provide atomic motion information during reactions that could reveal nonstatistical intermediates without complete intramolecular vibrational redistribution and nonintrinsic reaction coordinate (non-IRC) pathways. While nonstatistical intermediates and non-IRC reaction pathways are now relatively well established for organic reactions, these dynamic effects have heretofore been highly underexplored in organometallic reactions. Through a series of quasiclassical density functional theory direct dynamics trajectory studies, my group has recently demonstrated that dynamic effects occur in a variety of fundamental organometallic reactions, especially bond activation reactions. For example, in the C-H activation reaction between methane and [Cp*(PMe₃)Ir^III(CH₃)]⁺, while the density functional theory energy landscape showed a two-step oxidative cleavage and reductive coupling mechanism, trajectories revealed a mixture of this two-step mechanism and a dynamic one-step mechanism that skipped the [Cp*(PMe₃)Ir^V(H)(CH₃)₂]⁺ intermediate. This study also showed that despite a methane σ-complex being located on the density functional theory surface before oxidative cleavage and after reductive coupling, this intermediate is always skipped and should not be considered an intermediate during reactive trajectories. For non-IRC reaction pathways, quasiclassical direct dynamics trajectories showed that for the isomerization of [Tp(NO)(PMe₃)W(η²-benzene)] to [Tp(NO)(PMe₃)W(H)(Ph)], there are many dynamic reaction pathway connections due to a relatively flat energy landscape and π coordination is not necessary for C-H bond activation through oxidative cleavage. Trajectories also showed that dynamic effects are important in selectivity for ethylene C-H activation versus π coordination in reaction with Cp(PMe₃)₂Re, and trajectories provide a more quantitative model of selectivity than transition state theory. Quasiclassical trajectories examining Au-catalyzed monoallylic diol cyclizations showed dynamic coupling of several reaction steps that include alkoxylation π bond addition, proton shuttling, and water elimination reaction steps. Overall, these studies highlight the need to use direct dynamics trajectory simulations to consider atomic motion during reactions to understand organometallic reaction mechanisms and selectivity.

PMID:34761673 | DOI:10.1021/acs.accounts.1c00575

Ann Med. 2021 Dec;53(1):2034-2040. doi: 10.1080/07853890.2021.1999490.

ABSTRACT

BACKGROUND: The bronchiectasis severity index (BSI) and FACED score are currently used in predicting outcomes of non-cystic fibrosis bronchiectasis (NCFB). Distance-saturation product (DSP), the product of distance walked, and lowest oxygen saturation during the 6-min walk test showed strong predictive power of mortality in non-CF bronchiectasis patients. This study aimed to compare the efficacy of these scores and DSP in predicting mortality.

METHODS AND PATIENTS: Our retrospective study included NCFB patients from January 2004 to December 2017. We recorded the basic data, pulmonary function, radiologic studies, sputum culture results, acute exacerbations (AE), emergency department (ED) visits, hospitalization, and mortality.

RESULTS: A total 130 NCFB patients were analysed. The mean BSI score, FACED score, and DSP were 8.8 ± 4.9, 3.4 ± 1.7, and 413.1 ± 101.5 m%, respectively. BSI and FACED scores had comparable predictive power for AE (p=.011; p=.010, respectively). The BSI score demonstrated a significant correlation with ED visits (p=.0003). There were 12 deaths. Patients were stratified using a DSP cut-off value of 345 m% according to the best area under receiver operator characteristic curve (AUC) value in mortality. DSP was not correlated with AE and ED visits. BSI, FACED scores, and DSP demonstrated statistically significant correlations with hospitalization (p<.0001; p<.0001; p=.0007, respectively). The AUC for overall mortality was similar for BSI, FACED score, and DSP (0.80 versus 0.85, p=.491; 0.85 versus 0.83, p=.831).

CONCLUSION: DSP had comparable predictive power for mortality as the well-validated BSI and FACED scores and is relatively easy to use in clinical practice.KEY MESSAGEDistance-saturation product (DSP) comprised with the product of distance walked, and lowest oxygen saturation during the 6-min walk test, which is common used in clinical practice.DSP demonstrated strong and comparable predictive power of mortality as the well-validated BSI and FACED scores in non-CF bronchiectasis patients.

PMID:34761709 | DOI:10.1080/07853890.2021.1999490

Allergol Immunopathol (Madr). 2021 Nov 1;49(6):48-55. doi: 10.15586/aei.v49i6.338. eCollection 2021.

ABSTRACT

INTRODUCTION: There is an increasing amount of data relating the dietetic pattern to health variables, although data concerning the child population are scarce. The aim of the study was to assess the effects of affinity to the Traditional Mediterranean Diet (TMD) pattern, together with breastfeeding, on the incidence of childhood asthma and other inflammatory and recurrent diseases (IRD) in children under 2 years of age.

METHODS: Single-group intervention study evaluating differences in results according to degree of adherence to TMD recommendations. According to their adhesion to the TMD-Breastfed Test, patients were classified into two groups: Group 1 (with greater adherence) and Group 2 (with less adherence). The incidence of childhood asthma and IRD was evaluated and compared with both groups.

RESULTS: The score of the TMD-Breastfed Test was optimal in Group 1 and good in Group 2. It shows a marked reduction in both consultation groups “on request” compared with “planned,” with low morbidity and low use of antibiotics. The incidence of infectious diseases and recurrent bacterial complications shows a clinically relevant difference between both groups. The incidence of childhood asthma was greater and statistically significant in Group 2, with less adherence to breastfeeding.

CONCLUSIONS: In these cohorts of breastfed patients with good adherence to TMD patterns, there was evidence of a low incidence of childhood asthma and the IRD, more pronounced in the highest adherence Group 1. Some non-TMD foods have been linked to the occurrence of childhood asthma and IRD, as their dietary limitations have contributed to decreasing morbidity.

PMID:34761656 | DOI:10.15586/aei.v49i6.338

J BUON. 2021 Sep-Oct;26(5):2157-2168.

ABSTRACT

PURPOSE: To determine the relationship between inflammatory cell types in the microenvironment of papillary thyroid microcarcinoma (PTMC) and prognostic factors.

METHODS: The previous diagnoses and subtypes-variants of 163 patients with papillary thyroid microcarcinoma were re-evaluated according to the 2017 WHO classification. The peritumoral lymphocyte, plasma cell, neutrophil, eosinophil, and mast cell density were classified as none (0.24 mm2), mild (0-10/0.24 mm2), moderate (10-50/0.24 mm2), and severe (˃50/0.24 mm2) under 40x magnification and the relationship with prognostic factors was investigated.

RESULTS: There was a statistically significant relationship between tumor capsule invasion (p=0.024) and surgical margin (p=0.049) with mast cell infiltration. A statistically significant relationship was observed between tumor capsule invasion (p=0.0001) and the postoperative disease-free period (p=0.0001) with neutrophil cell infiltration. The postoperative disease-free period of those with neutrophil infiltration was statistically significantly shorter than that of those with no infiltration. The tumor diameter of those with no plasma cells was statistically significantly smaller than that of patients with plasma cells (p=0.003).

CONCLUSIONS: Closer follow-up of patients with neutrophils, mast cells, and plasma cells, which have been found to be associated with poor prognostic factors in terms of recurrence, lymph node involvement, and distant metastasis, may increase survival.

PMID:34761630

J BUON. 2021 Sep-Oct;26(5):2176-2182.

ABSTRACT

PURPOSE: To assess patient satisfaction from chemotherapy and investigate the effect of demographic factors, disease symptoms and treatment on satisfaction.

METHODS: A non-randomized cross-sectional survey was conducted on a sample of 100 patients undergoing chemotherapy at “Metaxa” Cancer Hospital, Piraeus, Greece for 6 months. A demographic data questionnaire, a Cancer Treatment Satisfaction Questionnaire (CTSQ) and visual analog scales were used to evaluate pain, anxiety, fatigue, and nausea while presence or absence of vomit were also assessed.

RESULTS: The majority of the patients in the sample were men (51%), with a mean age of 58.5 ± 10.82 years. The mean value of expectations from treatment was 60.55, from treatment’s satisfaction was 75.86 and from feelings about treatment’s side effects was 44.56. The most serious symptoms were fatigue and anxiety (7.2 ± 1.95 and 6.71 ± 2.5, respectively). Statistical tests have shown that sub-dimensions of CTSQ are associated with pain, anxiety, fatigue, and nausea.

CONCLUSIONS: Generally, chemotherapy meets patients’ expectations with cancer. Symptoms such as fatigue, anxiety, pain, and nausea affect their satisfaction. Treatment’s satisfaction can be improved by evaluating symptoms, which will lead to appropriate interventions.

PMID:34761632

J BUON. 2021 Sep-Oct;26(5):2106-2110.

ABSTRACT

PURPOSE: To evaluate the sexual functions of prostate cancer patients receiving radiotherapy (RT) with curative intent.

METHODS: Fifty patients with low-risk prostate cancer who responded to the international index of erectile function (IIEF) questionnaire before and after RT were included in the study Results: Statistically significant decline was observed in sexual functions by the end of RT. While the average sexual desire scores of the patients before RT was 6.24, it decreased to 3.62 (p=0.001) after RT. The average of sexual satisfaction scores dropped from 8.94 to 4.6 (p=0.001), the average of erection function scores dropped from 20.14 to 11.76 (p=0.001), orgasmic function scores dropped from 9.6 to 3.9 (p=0.001) and the average of overall satisfaction scores dropped from 7.48 to 4.36 (p=0.001).

CONCLUSION: Sexual functions evaluated by the IIEF questionnaire decrease by the end of RT.

PMID:34761623