Tag: pubmed

J Vet Intern Med. 2022 Feb 17. doi: 10.1111/jvim.16360. Online ahead of print.

ABSTRACT

BACKGROUND: Use of diets with increased concentrations of dietary fiber is thought to be beneficial in the management of dogs with large bowel diarrhea.

OBJECTIVE: To determine whether feeding a diet with high concentrations of soluble and insoluble fiber to dogs with acute colitis would be superior to feeding a diet with typical fiber levels.

ANIMALS: A total of 52 dogs with acute signs of large bowel diarrhea housed in an animal shelter were entered into the study; 11 dogs per diet completed the protocol.

METHODS: In this randomized, prospective study, dogs with a fecal score of 4, 5, 6, or 7 and signs of acute colitis were fed a high fiber diet (4.54% soluble; 15.16% insoluble fiber) or a standard diet (0.6% soluble; 5.33% insoluble fiber) and fecal scores compared over the course of the study with significance defined as P < .05.

RESULTS: All dogs fed the high fiber diet (11/11; 100%) had a fecal score <5 on the day of adoption or day 9, which was statistically different (P < .04) than dogs fed the standard diet (6/11 dogs; 55%; 95% CI: 23-83). The proportions of stools with a fecal score >4 were greater (P = .0001) in the dogs fed the standard diet (29/48 samples; 60%; 95% CI: 45-74) compared to the high fiber diet (8/50 samples; 16%; 95% CI: 7-29).

CONCLUSIONS AND CLINICAL IMPORTANCE: The results support feeding the high fiber diet described herein to dogs with acute large bowel diarrhea.

PMID:35174561 | DOI:10.1111/jvim.16360

Br J Clin Pharmacol. 2022 Feb 16. doi: 10.1111/bcp.15280. Online ahead of print.

ABSTRACT

Several cases of herpes zoster (HZ) following mRNA COVID-19 vaccination (BNT162b2 and mRNA-1273) have been reported, and first epidemiological evidences suggest an increased risk. We used the worldwide pharmacovigilance database VigiBase to describe HZ cases following mRNA COVID-19 vaccination. We performed disproportionality analyses (case/non-case statistical approach) to assess the relative risk of HZ reporting in mRNA COVID-19 vaccine recipients compared to influenza vaccine recipients and according to patient age. Until 30^th June 2021, of 716,928 reports with mRNA COVID-19 vaccines, we found 7,728 HZ cases. When compared to influenza vaccines, mRNA COVID-19 vaccines were associated with a significantly higher reporting of HZ (reporting odds-ratio 1.9, 95%CI [1.8-2.1]). Furthermore, we found a reduced risk of reporting HZ among under 40 year-old persons compared to older persons (reporting odds-ratio 0.39, 95%CI [0.36-0.41]). Mild and infrequent HZ reactions may occur shortly after mRNA COVID-19 vaccination, at higher frequency than reported with influenza vaccination, especially in patients over 40 year-old. Further analyses are needed to confirm this risk.

PMID:35174524 | DOI:10.1111/bcp.15280

Clin Endocrinol (Oxf). 2022 Feb 16. doi: 10.1111/cen.14698. Online ahead of print.

ABSTRACT

OBJECTIVE: Thyrotropin (TSH) suppression therapy is standard treatment after surgery for differentiated thyroid carcinoma (DTC). It may be associated with osteoporosis in postmenopausal women. However, there are no guidelines for bone mineral density (BMD) testing intervals to screen for osteoporosis in these patients. Therefore, we evaluated the timing of repeated BMD testing in DTC patients with TSH suppression according to baseline T-scores.

DESIGN, PATIENTS, AND MEASUREMENT: We retrospectively evaluated 658 DTC patients who underwent BMD testing more than twice between January 2007 and January 2020. A 1:3 propensity score matching was conducted to compare the timing of repeated BMD tests between the DTC and non-DTC groups. We stratified the participants into four groups based on their baseline T-scores: normal (-1.00 or higher), mild osteopenia (-1.01 to -1.49), moderate osteopenia (-1.50 to -1.99), and severe osteopenia (-2.00 to -2.49). Additionally, the 10% of patients in each group that transitioned to osteoporosis were analyzed.

RESULTS: The estimated BMD testing interval for 10% of patients who developed osteoporosis was 85 months for patients with initially mild osteopenia, 65 months for those with moderate osteopenia, and 15 months for those with severe osteopenia in the DTC group. In the non-DTC group, the testing intervals for mild, moderate, and severe osteopenia were 98, 57, and 13 months, respectively. On multivariate analysis, baseline T-score (mild osteopenia: hazard ratio [HR] 5.91, p = 0.105; moderate osteopenia: HR 25.27, p = 0.02; and severe osteopenia: HR 134.82, p < 0.001) and duration of TSH suppression (tertile 2: HR 2.25, p = 0.005; tertile 3: 1.78, p = 0.033) were independent risk factors for osteoporosis in the DTC group.

CONCLUSION: This study provides guidance for the timing of repeated BMD tests in women over 50 years of age with TSH suppression. The rescreening interval for BMD testing can be modified based on the baseline T-score. The appropriate BMD testing intervals in female DTC patients were similar to those in non-DTC females. This article is protected by copyright. All rights reserved.

PMID:35174522 | DOI:10.1111/cen.14698

J Med Virol. 2022 Feb 16. doi: 10.1002/jmv.27663. Online ahead of print.

ABSTRACT

The COVID-19 pandemic continues to have a threatening impact on a global scale, largely due to the emergence of newly SARS-CoV-2 variants. The Mu (PANGO lineage B.1.621), was first identified in Colombia in January 2021 and was classified as a variant of interest (VOI) in August 2021, due to a constellation of mutations that likely-mediate an unexpectedly enhanced immune resistance to inactivated vaccine-elicited antibodies. Despite if recently studies suggested that the Mu variant appear to have a less infectivity than the Delta variant, here we examined the structural effect of the Mu spike protein mutations and predicted the potential impact on infectivity of the Mu variant compared with the Delta and Delta plus spike protein. This article is protected by copyright. All rights reserved.

PMID:35174519 | DOI:10.1002/jmv.27663

Epilepsia. 2022 Feb 17. doi: 10.1111/epi.17193. Online ahead of print.

ABSTRACT

OBJECTIVE: A broad spectrum of emotional-behavioral problems have been reported in pediatric temporal lobe epilepsy (TLE), but with considerable variability in their presence and nature of expression, which hampers precise identification and treatment. The present study aimed to empirically identify latent patterns or behavioral phenotypes and their correlates.

METHODS: Data included parental ratings of emotional-behavioral status on the Behavior Assessment System for Children, 2nd Edition (BASC-2) of 81 children (mean age = 11.79, standard deviation [SD] = 3.93) with TLE. The nine clinical subscales were subjected to unsupervised machine learning to identify behavioral subgroups. To explore concurrent validity and the underlying composition of the identified clusters, we examined demographic factors, seizure characteristics, psychosocial factors, neuropsychological performance, psychiatric status, and health-related quality of life (HRQoL).

RESULTS: Three behavioral phenotypes were identified, which included no behavioral concerns (Cluster 1, 43% of sample), externalizing problems (Cluster 2, 41% of sample), and internalizing problems (Cluster 3, 16% of sample). Behavioral phenotypes were characterized by important differences across clinical seizure variables, psychosocial/familial factors, everyday executive functioning, and HRQoL. Cluster 2 was associated with younger child age, lower maternal education, and higher rate of single-parent households. Cluster 3 was associated with older age at epilepsy onset and higher rates of hippocampal sclerosis and parental psychiatric history. Both Cluster 2 and 3 demonstrated elevated family stress. Concurrent validity was demonstrated through the association of psychiatric (i.e., rate of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) disorders and psychotropic medication) and parent-rated HRQoL variables.

SIGNIFICANCE: Youth with TLE present with three distinct behavioral phenotypes that correspond with important clinical and sociodemographic markers. The current findings demonstrate the variability of behavioral presentations in youth with TLE and provide a preliminary framework for screening and targeting intervention to enhance support for youth with TLE and their families.

PMID:35174484 | DOI:10.1111/epi.17193

Epilepsia. 2022 Feb 17. doi: 10.1111/epi.17195. Online ahead of print.

ABSTRACT

OBJECTIVE: Levetiracetam (LEV) is an antiseizure medication prescribed to women during childbearing age. The impact of LEV on placental transporters is poorly understood. This study aimed to assess the effect of LEV exposure on the messenger RNA (mRNA) expression of placental transporters for hormones and nutrients and to correlate their expression with the drug’s serum concentration in pregnant mice.

METHODS: Studies were conducted on gestational days (GD) 13 and 18, following oral treatment with 100 mg/kg LEV or the vehicle every 24 h after weaning. Serum LEV measurements were performed by High-performance liquid chromatography with a UV detector (HPLC-UV). The weight, height, and width of the fetuses were also analyzed. In addition, the placental expression of transporters xCt, Lat1, Oatp4a1, Fr-α, Rfc, and Snat4 was evaluated through semi-quantitative real-time polymerase chain reaction (qPCR). The Kruskal-Wallis and the Mann-Whitney U tests were used to determine the statistical significance (p < .05). The correlation between serum LEV concentration and placental gene expression was evaluated using the Spearman test.

RESULTS: The weight, height, and width were lower in the fetuses exposed to LEV compared with the control group (p < .05). The number of fetuses was lower in the LEV-exposed group than in the control GD 13 group (p < .001). No significant differences were detected in the mRNA expression level at GD 13. At GD 18, the expression of Lat1, Oatp4a1, xCT, and Snat4 was higher in the group treated with LEV compared with the control group (p < .05), whereas the expression of Rfc was lower (p < .05). No correlation was identified between serum LEV concentrations and gene expression levels.

SIGNIFICANCE: The repression of the Rfc transcript by LEV at GD 18 suggests that the protein expression would be abolished contributing to the observed intrauterine growth restriction (IUGR). Furthermore, the significant increase in mRNA of xCt, Snat4, Oatp4a1, and Lat1 might be a compensatory mechanism for fetal survival at GD 18.

PMID:35174498 | DOI:10.1111/epi.17195

Ann Nucl Med. 2022 Feb 16. doi: 10.1007/s12149-022-01725-9. Online ahead of print.

ABSTRACT

OBJECTIVE: Although previous studies have investigated age and gender effects on striatal subregional dopamine transporter (DaT) binding, these studies were mostly based on a conventional regions of interest-based analysis. Here, we investigated age and gender effects on striatal DaT binding at the voxel level, using a multicenter database of [(¹²³)I] N-omega-fluoropropyl-2beta-carbomethoxy-3beta-{4-iodophenyl}nortropane ([(¹²³)I] FP-CIT)-single photon emission computed tomography (SPECT) scans in 256 healthy Japanese adults.

METHODS: We used the Southampton method to calculate the specific binding ratios (SBRs) of each subject’s striatum and then converted the [¹²³I] FP-CIT SPECT images to quantitative SBRs images. To investigate the effects of age and gender effects on striatal DaT binding, we performed a voxel-based analysis using statistical parametric mapping. Gender differences were also compared between young to middle-aged subjects and elderly subjects (age threshold: 60 years).

RESULTS: When all subjects were explored as a group, DaT binding throughout the striatum decreased with advancing age. Among all subjects, the females showed higher DaT binding in the bilateral caudate compared to the males. In the young to middle-aged subjects, the females showed higher DaT binding throughout the striatum (with a slight caudate predominance) versus the males. In the elderly, there were no gender differences in striatal DaT binding.

CONCLUSION: Our findings of striatal subregional age- and gender-related differences may provide useful information to construct a more detailed DaT database in healthy Japanese subjects.

PMID:35174441 | DOI:10.1007/s12149-022-01725-9

Brain Struct Funct. 2022 Feb 17. doi: 10.1007/s00429-022-02464-3. Online ahead of print.

ABSTRACT

Visual disturbances are a common disease manifestation in multiple sclerosis (MS) due to lesions damaging white matter tracts involved in vision. Vertical occipital fasciculus (VOF), a tract located vertically in the occipital lobe, was neglected for more than a century. We hypothesize that VOF is involved in integrating information between dorsal and ventral visual streams. Thus, its damage in MS, as well as its probable role in visual processing (by using MS as a VOF damage model) needs to be clarified. To study fiber characteristics of VOF in MS, and their clinical and visual learning associations, 57 relapsing-remitting MS (RRMS) and 25 healthy controls (HC) were recruited. We acquired MS Functional Composite, Expanded Disability Status Scale (EDSS), and Brief Visuospatial Memory Test-Revised (BVMT-R), and diffusion MRI scans. Tractography of VOF and optic radiation (OR) was done. VOF’s metrics were statistically tested for between-group differences and clinical and visual tests associations. Along-tract analysis and laterality were also tested. RRMS patients had higher mean, axial, and radial diffusivity (nearly in all fiber points), and lower fractional anisotropy in bilateral VOFs compared to HC. No laterality was noted. These were associated with poor clinical outcomes, poor visual scores in EDSS, and lower total immediate and delayed recall in BVMT-R in RRMS, after adjusting for age, gender, and fiber metrics of OR. VOF damage is present in RRMS and is associated with visual symptoms and visuospatial learning impairments. It seems VOF is involved in integrating information between visual streams.

PMID:35174417 | DOI:10.1007/s00429-022-02464-3

Pharm Res. 2022 Feb 16. doi: 10.1007/s11095-022-03201-5. Online ahead of print.

ABSTRACT

Model-based meta-analysis (MBMA) is a quantitative approach that leverages published summary data along with internal data and can be applied to inform key drug development decisions, including the benefit-risk assessment of a treatment under investigation. These risk-benefit assessments may involve determining an optimal dose compared against historic external comparators of a particular disease indication. MBMA can provide a flexible framework for interpreting aggregated data from historic reference studies and therefore should be a standard tool for the model-informed drug development (MIDD) framework.In addition to pairwise and network meta-analyses, MBMA provides further contributions in the quantitative approaches with its ability to incorporate longitudinal data and the pharmacologic concept of dose-response relationship, as well as to combine individual- and summary-level data and routinely incorporate covariates in the analysis.A common application of MBMA is the selection of optimal dose and dosing regimen of the internal investigational molecule to evaluate external benchmarking and to support comparator selection. Two case studies provided examples in applications of MBMA in biologics (durvalumab + tremelimumab for safety) and small molecule (fenebrutinib for efficacy) to support drug development decision-making in two different but well-studied disease areas, i.e., oncology and rheumatoid arthritis, respectively.Important to the future directions of MBMA include additional recognition and engagement from drug development stakeholders for the MBMA approach, stronger collaboration between pharmacometrics and statistics, expanded data access, and the use of machine learning for database building. Timely, cost-effective, and successful application of MBMA should be part of providing an integrated view of MIDD.

PMID:35174432 | DOI:10.1007/s11095-022-03201-5

Acta Orthop Belg. 2021 Dec;87(4):761-764. doi: 10.52628/87.4.23.

ABSTRACT

Hindfoot deformities are often surgically corrected with calcaneal osteotomy. These are increasingly performed via a minimally invasive approach. Identifying a neurovascular “safe zone” for this approach is important in reducing iatrogenic injury. We aimed to identify a safe zone for minimally invasive calcaneal osteotomy without neurovascular injury. Three individuals independently assessed 100 con- secutive magnetic resonance imaging ankle studies. The distance of the medial neurovascular bundle from the level of the centre of the Achilles tendon insertion was measured. The points measured were centralised in three planes (axial, sagittal and coronal). The three sets of observations were statistically analysed with confidence intervals and intraclass correlation coefficient was calculated. The mean distance measured by the three observers were 22.91 mm (range 18.2-28.5 mm); 22.81 mm (range 18.7-26.7 mm); and 23.41 mm (range 19.2- 28.4 mm); overall mean 23.0 mm. The mean inter- observer variation was 1.1 mm. 95% confidence interval for observer 1 ranges from 22.45-23.25 mm, observer 2 ranges from 22.52-23.1 mm and observer 3 ranges from 22.97-23.65 mm. Overall 95% confidence interval ranges from 22.8-23.2 mm. Intraclass correlation coefficient for inter-observer reliability is 0.7, indicating strong agreement between the observers. This radiological study suggests an anatomical “safe zone” for minimally invasive medial calcaneal osteotomy is at least 18 mm (mean: 23 mm) from the level of insertion of the Achilles tendon. Individual variation between patients must be taken in to consideration during preoperative planning.

PMID:35172445 | DOI:10.52628/87.4.23