Nevin Manimala

Vet Sci. 2022 Jun 14;9(6):295. doi: 10.3390/vetsci9060295.

ABSTRACT

Chronic enteropathy (CE) is a severe multifactorial gastrointestinal disease that affects dogs and is driven by poorly characterized inflammatory pathways. Imbalance of pro-inflammatory response regulators, including IL-1R8, may be due to different factors, among which the infection with Helicobacteraceae is known to lead to a vicious circle in which excessive pro-inflammatory signaling and gastrointestinal injury reinforce each other and boost the disease. We investigated the expression of IL-1R8 in large intestine biopsies of dogs with or without clinical signs of CE and with previously assessed enterohepatic Helicobacter spp. colonization status by mean of quantitative real-time PCR. Our study revealed that IL-1R8 is downregulated in both acutely (p = 0.0074) and chronically (p = 0.0159) CE affected dogs compared to healthy controls. The data also showed that IL-1R8 expression tends to decrease with colonization by Helicobacter spp. Interestingly, a negative correlation was detected between the level of expression of IL-1R8 and the severity of macroscopic lesions identified by endoscopy and the crypt hyperplasia score. We further compared the expression levels between males and females and found no statistically significant difference between the two groups. No significant difference was observed in IL-1R8 expression profiles with the age of the animals either. Interestingly, an association was uncovered between IL-1R8 expression level and dog breed. Together, our data advance knowledge on gastrointestinal pathoimmunology in dogs and highlight the potential utilization of IL-1R8 as a diagnostic, prognostic and therapeutic biomarker for canine chronic enteropathy.

PMID:35737347 | DOI:10.3390/vetsci9060295

Vet Sci. 2022 Jun 7;9(6):277. doi: 10.3390/vetsci9060277.

ABSTRACT

Glucocorticoid administration is a common clinical practice that attempts to decrease the inflammation associated with and improve the resectability of canine mast cell tumors (MCTs). However, the impact of neoadjuvant glucocorticoids on the histological features and proliferation indices of canine MCTs is unknown. The objective of this study was to evaluate changes in tumor grade, mitotic count, Ki67, AgNOR, and AgNORxKi67 scores following short-course anti-inflammatory neoadjuvant prednisone in canine patients with MCTs. This was a prospective single-arm pilot study. Client-owned dogs with treatment-naïve cytologically confirmed MCTs were enrolled. Patients underwent an initial incisional biopsy followed by a 10-14-day course of anti-inflammatory prednisone and surgical resection. All histological samples were randomized, masked, and evaluated by a single pathologist. Unstained paired pre- and post-treatment samples were submitted to a commercial laboratory for Ki67 and AgNOR immunohistochemical analysis. There were 11 dogs enrolled with 11 tumors. There were no statistical differences between the pre- and post-treatment histological parameters of mitotic index, Ki67, AgNOR, or Ki67xAgNOR. There were no clinically significant alterations between pre-treatment and post-treatment in the assignment of tumor grades. A short course of anti-inflammatory prednisone does not appear to alter the histological parameters that affect grade determination or significantly alter the proliferation indices in canine MCTs.

PMID:35737330 | DOI:10.3390/vetsci9060277

Vet Sci. 2022 May 30;9(6):260. doi: 10.3390/vetsci9060260.

ABSTRACT

This study aimed to determine uterine blood flow indices by transabdominal Doppler ultrasound in sows (n = 18) under different conditions: (i) sows after estrus detection (day 0, D0); (ii) sows 2 h after artificial insemination (AI), performed 24 h after detection of estrus (day 1, D1); (iii) sows in early diestrus (day 5, D5). Moreover, three different types of seminal doses were used for AI depending on the ejaculate fraction included (F1: doses containing only the rich fraction of the ejaculate; F2: F1 + the transition fraction between rich and poor fractions; F3: F2 and poor fraction). The statistical analysis revealed significant differences in some indices regarding the period of analysis (D0, D1, and D5). Diastolic velocity and mean velocity showed lower values at D5 in comparison with D0 and D1 (p < 0.01). On the other hand, the pulsatility index and the relationship systolic velocity/diastolic velocity indicated higher values at D5 in comparison with D0 and D1 (p < 0.01). No differences were observed regarding the type of seminal dose used in any of the time points analyzed (p > 0.05). Neither insemination per se nor the type of ejaculate fraction used immediately modified the uterine vascularity, but some indices are affected by the stage of the estrus cycle (estrus vs. early diestrus).

PMID:35737312 | DOI:10.3390/vetsci9060260

J Clin Pharm Ther. 2022 Jun 23. doi: 10.1111/jcpt.13714. Online ahead of print.

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: There are no validated self-report measures to assess extent of and reasons for medication nonadherence in the Turkish language. The aim of this study is to evaluate validity and reliability of the Domains of Subjective Extent of Nonadherence Scale, which assesses extent of and reasons for nonadherence in Turkish patients with hypertension, diabetes mellitus and/or dyslipidaemia in community pharmacy settings.

METHODS: The Turkish version of the DOSE-Nonadherence scale was developed through translation and cultural adaption. Psychometric properties of the scale were evaluated in a cross-sectional study among 203 patients who visited six community pharmacies located in Istanbul, Turkey between November 2020 and March 2021. For the extent of nonadherence domain, reliability was estimated through Cronbach’s alpha, and convergent validity was evaluated with Spearman’s rank correlation with the validated Turkish version of the Medication Adherence Report Scale (MARS). Reasons for nonadherence were characterized among participants reporting nonadherence to the extent of nonadherence items. The measure was administered at baseline and 2 weeks later to 30 patients to estimate stability of extent scores using the Wilcoxon test and intraclass correlation coefficient. p < 0.05 was set as the level of statistical significance.

RESULTS: Among the 203 participants (65 male), the median (25th-75th percentiles) age was 59.0 years [51.0-67.0]. Cronbach’s alpha for the extent of nonadherence scale was 0.86. A moderate negative correlation (r = -0.58; p < 0.001) was found between the extent of nonadherence scores and MARS, supporting convergent validity. The most common reasons for medication nonadherence were forgetfulness (22.5%) and mismatch between the patients’ daily routine and medication taking (17.5%). The intraclass correlation coefficient was 0.97 for extent of nonadherence scores at baseline and 2 weeks (p < 0.001).

WHAT IS NEW AND CONCLUSION: The DOSE-Nonadherence Scale could be used to identify nonadherent patients and their reasons for nonadherence in Turkish patients with chronic cardiometabolic conditions. This scale can be used to evaluate clinical pharmacist-led services to reduce medication nonadherence. Nonadherence could be recorded longitudinally in electronic health records to provide a more accurate picture of medication use. Pharmacists or other providers could administer interventions tailored to patients’ reasons for nonadherence.

PMID:35735120 | DOI:10.1111/jcpt.13714

Aging Ment Health. 2022 Jun 23:1-9. doi: 10.1080/13607863.2022.2089628. Online ahead of print.

ABSTRACT

OBJECTIVES: Previous investigations of cognitive aging have mainly focused on structural aspects of social relations (e.g. network size and composition), thereby neglecting the role of qualitative aspects of social relations. The current longitudinal study examined sex-specific differences in verbal memory decline by measures of perceived relationship quality (social support/strain) by relationship type.

METHOD: In the English Longitudinal Study of Ageing (ELSA), 10,109 participants aged 50-89 years were assessed at wave 1 (baseline: 2002-03) and followed to wave 9 (2017-18). Verbal memory was assessed by immediate and delayed word-recall tasks. Social support/strain was measured by relationship type (spouse; children; family; friends). Random effects within-between (REWB) modelling was used to separate between- and within-person effects. We estimated associations between social support/strain and (1) baseline levels of memory (main effects), and (2) rate of decline in memory (interaction with time-since-baseline).

RESULTS: Longitudinal associations were most prominent for men, specific to relationship type, and showed between- rather than within-person effects. Among men, higher spousal strain was associated with faster memory decline (β_{between-effect×time} = -0.043; 95% CI [-0.084, -0.002]; p = .039), whilst greater support from children was associated with slower decline (β_{between-effect×time} = 0.020; 95% CI [0.002, 0.039]; p = .033). Men with higher strain from friends showed lower baseline memory (β_{between-effect} = -0.382; 95% CI [-0.627, -0.137]; p=.002) and faster decline (β_{between-effect×time} = -0.047; 95% CI [-0.095, 0.000]; p = .051).

CONCLUSION: Between-person differences in social support/strain were modestly associated with memory decline, especially among men.

PMID:35735097 | DOI:10.1080/13607863.2022.2089628

Aging Ment Health. 2022 Jun 23:1-8. doi: 10.1080/13607863.2022.2087207. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate whether latent subgroups with distinct patterns of factors associated with self-rated successful aging can be identified in community-dwelling adults, and how such patterns obtained from analysis of quantitative data are associated with lay perspectives on successful aging obtained from qualitative responses.

METHODS: Cross-sectional data were collected from 1,510 community-dwelling Americans aged 21-99 years. Latent class regression was used to identify subgroups that explained the associations of self-rated successful aging with measures of physical, cognitive, and mental health as well as psychological measures related to resilience and wisdom. Natural language processing was used to extract important themes from qualitative responses to open-ended questions, including the participants’ definitions of successful aging.

RESULTS: Two latent subgroups were identified, and their main difference was that the wisdom scale was positively associated with self-rated successful aging in only one subgroup. This subgroup had significantly lower self-rated successful aging and worse scores for all health and psychological measures. In the subgroup’s qualitative responses, the theme of wisdom was only mentioned by 10.6%; this proportion was not statistically different from the other subgroup, for which the wisdom scale was not statistically associated with the self-rated successful aging.

CONCLUSION: Our results showed heterogeneous patterns in the factors underpinning successful aging even in community-dwelling adults. We found the existence of a latent subgroup with lower self-rated successful aging as well as worse health and psychological scores, and we suggest a potential role of wisdom in promoting successful aging for this subgroup, even though individuals may not explicitly recognize wisdom as important for successful aging.

PMID:35735096 | DOI:10.1080/13607863.2022.2087207

Biomed J. 2021 Dec;44(6S1):S119-S125. doi: 10.1016/j.bj.2020.08.002. Epub 2020 Aug 8.

ABSTRACT

BACKGROUND: No previous study has investigated the relationship between middle cerebral artery (MCA) flow velocity and the severity of hypoxic ischemic encephalopathy (HIE) evaluated by magnetic resonance imaging (MRI). The aim of this study was to assess the correlation between cerebral blood flow as assessed by transcranial Doppler sonography and the severity of MRI brain injury in asphyxiated neonates with clinical HIE who received therapeutic hypothermia.

METHODS: This retrospective cohort study was conducted in the neonatal intensive care unit at Chang Gung Memorial Hospital between April 2011 and May 2014. All neonates with HIE who received therapeutic hypothermia, transcranial Doppler examinations, and brain MRI were eligible. Brain MRI was performed at 11 days of age (interquartile range: 8.5-15 days) and the severity of MRI brain injuries was evaluated using the MR scoring system proposed by Barkovich et al. Serial transcranial Doppler examinations were performed in pre-hypothermia, hypothermia, and post-hypothermia phases.

RESULTS: Twenty-six neonates met the eligibility criteria for this study. Neonates with an abnormal MCA mean flow velocity (MFV) during the hypothermia phase had a higher risk of brain MRI abnormalities (77.8% vs. 22.2%, p = 0.017) and neonates with abnormal high MFV of MCA had higher MR scores of basal ganglia (p = 0.022). However, there were no statistical differences between abnormal MFV of MCA and brain MRI abnormalities during pre- and post-hypothermia phases.

CONCLUSIONS: During therapeutic hypothermia, mean cerebral blood flow velocity of the MCA was associated with the severity of MRI brain injury in the neonates with clinical HIE.

PMID:35735081 | DOI:10.1016/j.bj.2020.08.002

Mult Scler. 2022 Jun 23:13524585221100401. doi: 10.1177/13524585221100401. Online ahead of print.

ABSTRACT

Randomised controlled trials (RCTs) play an important role in multiple sclerosis (MS) research, ensuring that new interventions are safe and efficacious before their introduction into clinical practice. Trials have been evolving to improve the robustness of their designs and the efficiency of their conduct. Advances in digital and mobile technologies in recent years have facilitated this process and the first RCTs with decentralised elements became possible. Decentralised clinical trials (DCTs) are conducted remotely, enabling participation of a more heterogeneous population who can participate in research activities from different locations and at their convenience. DCTs also rely on digital and mobile technologies which allows for more flexible and frequent assessments. While hospitals quickly adapted to e-health and telehealth assessments during the COVID-19 pandemic, the conduct of conventional RCTs was profoundly disrupted. In this paper, we review the existing evidence and gaps in knowledge in the design and conduct of DCTs in MS.

PMID:35735014 | DOI:10.1177/13524585221100401

Stroke. 2022 Jun 23:101161STROKEAHA121038659. doi: 10.1161/STROKEAHA.121.038659. Online ahead of print.

ABSTRACT

BACKGROUND: Millions of women worldwide use exogenous hormones as oral contraceptives or hormone replacement therapy. Still, time-dependent and long-term consequences of exogenous hormones on stroke risk remains unclear.

METHODS: We examined the association between self-reported oral contraceptive and hormone replacement therapy use and stroke risk in 257 194 women from the UK Biobank, born between 1939 and 1970. Outcomes included any type of stroke, ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Exposures were analyzed as time-varying variables in Cox regression models.

RESULTS: During first year of oral contraceptive use, an increased event rate of any stroke was observed (hazard ratio [HR], 2.49 [95% CI, 1.44-4.30]), while the hazards were found to be comparable during remaining years of use (HR, 1.00 [95% CI, 0.86-1.14]), compared with nonusers. Similarly, first year of hormone replacement therapy use was associated with higher hazard rates of any stroke (HR, 2.12 [95% CI, 1.66-2.70]), as well as cause-specific stroke, including ischemic stroke (HR, 1.93 [95% CI, 1.05-3.57]) and subarachnoid hemorrhage (HR, 2.17 [95% CI, 1.25-3.78]), which remained increased for any stroke during remaining years of use (HR, 1.18 [95% CI, 1.05-1.31]), and after discontinuation (HR, 1.16 [95% CI, 1.02-1.32]).

CONCLUSIONS: Oral contraceptive use and hormone replacement therapy were associated with an increased risk of stroke, especially during the first year of use, possibly due to immediate changes in hemostatic balance. This study provides new insights on the effects of hormone exposure on stroke risk and provide evidence of not only an overall risk but also a pronounced effects seen in the beginning of treatment.

PMID:35735009 | DOI:10.1161/STROKEAHA.121.038659

Circulation. 2022 Jun 23:101161CIRCULATIONAHA121058389. doi: 10.1161/CIRCULATIONAHA.121.058389. Online ahead of print.

ABSTRACT

BACKGROUND: Genome-wide association studies have identified many genetic loci that are robustly associated with coronary artery disease (CAD). However, the underlying biological mechanisms are still unknown for most of these loci, hindering the progress to medical translation. Evidence suggests that the genetic influence on CAD susceptibility may act partly through vascular smooth muscle cells (VSMCs).

METHODS: We undertook genotyping, RNA sequencing, and cell behavior assays on a large bank of VSMCs (n>1499). Expression quantitative trait locus and splicing quantitative trait locus analyses were performed to identify genes with an expression that was influenced by CAD-associated variants. To identify candidate causal genes for CAD, we ascertained colocalizations of VSMC expression quantitative trait locus signals with CAD association signals by performing causal variants identification in associated regions analysis and the summary data-based mendelian randomization test. Druggability analysis was then performed on the candidate causal genes. CAD risk variants were tested for associations with VSMC proliferation, migration, and apoptosis. Collective effects of multiple CAD-associated variants on VSMC behavior were estimated by polygenic scores.

RESULTS: Approximately 60% of the known CAD-associated variants showed statistically significant expression quantitative trait locus or splicing quantitative trait locus effects in VSMCs. Colocalization analyses identified 84 genes with expression quantitative trait locus signals that significantly colocalized with CAD association signals, identifying them as candidate causal genes. Druggability analysis indicated that 38 of the candidate causal genes were druggable, and 13 had evidence of drug-gene interactions. Of the CAD-associated variants tested, 139 showed suggestive associations with VSMC proliferation, migration, or apoptosis. A polygenic score model explained up to 5.94% of variation in several VSMC behavior parameters, consistent with polygenic influences on VSMC behavior.

CONCLUSIONS: This comprehensive analysis shows that a large percentage of CAD loci can modulate gene expression in VSMCs and influence VSMC behavior. Several candidate causal genes identified are likely to be druggable and thus represent potential therapeutic targets.

PMID:35735005 | DOI:10.1161/CIRCULATIONAHA.121.058389