Nevin Manimala

Geospat Health. 2021 Nov 3;16(2). doi: 10.4081/gh.2021.981.

ABSTRACT

Hepatitis-A virus is a worldwide healthcare problem, mainly affecting countries with poor sanitary and socioeconomic conditions. This communication evaluates the spatiotemporal variability of the disease’s socioepidemiological profile in one of the endemic Brazilian regions (Pará State) prior to (2008-2013) and after (2014-2017) the launch of the national public vaccination programme. Hepatitis-A epidemiological reports concerning Pará State – Brazil – were used for this study including municipalitylevel data of the disease’s reported positive notification cases (PNCs). The analyses involved socioepidemiological profiling and space-time scan statistics. A total of 5500 PNCs were reported in the study period. On average, PNCs decreased over time throughout the state, with strongest drops after 2015. The PNCs were specific for gender, race/ethnic origin and age group. The predominant gender and race/ethnic groups was male and brown, respectively. While children were the most susceptible age group prior to 2015, there was a shift towards older ages (young and adults) in later years. Those found to be the most affected by the disease, as shown by space-time scan statistics, were people in densely populated municipalities with unsatisfactory sanitary conditions and also less well covered by the public vaccination programme. Despite drops in the number of hepatitis-A PNCs, thanks to the national vaccination programme, the disease still persists in Pará State and elsewhere in Brazil. The present study reinforces the need of continuous prevention and control strategies for effective control and erradication of hepatitis-A.

PMID:34730318 | DOI:10.4081/gh.2021.981

Pol J Vet Sci. 2021 Sep;24(3):409-414. doi: 10.24425/pjvs.2021.138732.

ABSTRACT

Distribution of tripeptidyl peptidase I (TPPI) activity in the structures of porcine lumbar spinal ganglia (LSG) was studied by enzyme histochemistry on cryostat sections from all the ganglia using the substrate glycyl-L-prolyl-L-methionyl-5-chloro-1-anthraquinonyl hydrazide (GPM-CAH) and 4-nitrobenzaldehyde (NBA) as visualization factor. Light microscopic observations showed TPPI activity in almost all the LSG structures. The enzyme reaction in different cell types was compared semi-quantitatively. Strong reaction was observed in the small neurons, satellite ganglia cells and some nerve fibers. Weak reactivity was found in the large sensory somatic neurons, whereas moderate reaction for TPPI was determined in the middle sensory somatic neurons and some nerve fibers. Statistical analysis by one-way ANOVA showed no significance of difference (when p⟨0.05) for the number of TPPI positive neurons per mm2. The original data obtained by the enzyme histochemistry method give us a reason to presume that TPPI actively participates in the functions of all the neuronal structures in porcine LSG. According to our results, it could be suggested that TPPI activity is important for the functions of autonomic and somatic sensory neurons.

PMID:34730302 | DOI:10.24425/pjvs.2021.138732

Pol J Vet Sci. 2021 Sep;24(3):433-437. doi: 10.24425/pjvs.2021.138735.

ABSTRACT

The study was carried out in 5 dairy herds of Polish Holstein-Friesian cows. The average milk yield was about 9000 kg per year. For each herd, the following fertility parameters were calculated at the start of the program and 4 years later: first- service conception rate, services per conception, length of inter-calving period and culling rate due to infertility. The incidence of silent heat, ovarian cysts, ovarian afunction, retained placenta and clinical endometritis was also recorded. Four years after implementation of the program, the average first-service conception rate increased from 43.2% to 51.2%. In three herds the differences were statistically significant (p⟨0.05). There was also a decrease in the number of services per pregnancy and in the culling rate due to infertility. Fertility performance was maintained in two herds. The average incidence of silent heat decreased from 38.1% to 29.7% and the difference was statistically significant (p⟨0.05) in three herds. There was no significant reduction in incidence of other reproductive disorders during the 4 years except for clinical endometritis in one herd. The average milk yield increased from 9300 kg to 9530 kg milk per cow per year. In conclusion, the results indicate that the implementation of the integrated veterinary herd health program improved or maintained fertility performance despite an increase in milk yield.

PMID:34730301 | DOI:10.24425/pjvs.2021.138735

Pol J Vet Sci. 2021 Sep;24(3):415-423. doi: 10.24425/pjvs.2021.138733.

ABSTRACT

PURPOSE: To assess the initial therapy of chronic superficial keratitis (CSK) in dogs with the use of dexamethasone and cyclosporine/ dimethyl sulfoxide combination eye drops.

METHODS: The study was conducted on 41 dogs – 16 males and 25 females, aged 2 to 9 years, diagnosed with CSK. The disease was treated with two kinds of eye drops containing 0.1% dexamethasone and 0.75% cyclosporine in combination with 30% DMSO, administered three times a day. Prior to the treatment and after 5 weeks of therapy, depigmentation of the third eyelid margin, corneal neovascularization and pigmentation were assessed. The percentage of the corneal surface afflicted with inflammatory processes was calculated with the use of IsoCalc.com’s Get Area software for CorelDRAW12.

RESULTS: The administered therapy resulted in a significant decrease in the mean number of quadrants affected by corneal neovascularization in the right eye from 2.63 prior to treatment to 0.24 after treatment (p⟨0.001), and the left eye from 2.66 to 0.59 (p⟨0.001), respectively. Mean corneal surface afflicted with inflammatory processes was statistically significantly reduced from 53.5% to 26.3% (p⟨0.001) in the case of right corneas, and from 54.5% to 30.2% (p⟨0.001) in the case of left corneas. Of 77 corneas diagnosed with pigmentation, pigmentation reduction was observed in 54 and pigmentation increase in 27.

CONCLUSIONS: Using dexamethasone and cyclosporine/DMSO combination eye drops proved to be a viable initial therapy against CSK, which facilitates reduction of inflammatory processes and neovascularization atrophy, but in many cases does not inhibit the progress of pigmentation.

PMID:34730300 | DOI:10.24425/pjvs.2021.138733

Mol Syst Biol. 2021 Nov;17(11):e10323. doi: 10.15252/msb.202110323.

ABSTRACT

Recent advances in genome-wide technologies have enabled analyses using small cell numbers of even single cells. However, obtaining tissue epigenomes with cell-type resolution from large organs and tissues still remains challenging, especially when the available material is limited. Here, we present a ChIL-based approach for analyzing the diverse cellular dynamics at the tissue level using high-depth epigenomic data. “ChIL for tissues” allows the analysis of a single tissue section and can reproducibly generate epigenomic profiles from several tissue types, based on the distribution of target epigenomic states, tissue morphology, and number of cells. The proposed method enabled the independent evaluation of changes in cell populations and gene activation in cells from regenerating skeletal muscle tissues, using a statistical model of RNA polymerase II distribution on gene loci. Thus, the integrative analyses performed using ChIL can elucidate in vivo cell-type dynamics of tissues.

PMID:34730297 | DOI:10.15252/msb.202110323

Arthritis Rheumatol. 2021 Nov 3. doi: 10.1002/art.42001. Online ahead of print.

ABSTRACT

OBJECTIVE: The effect of physical activity (PA) on the risk of developing knee osteoarthritis (OA) is unclear. Our aim was to examine the relationship between recreational PA and incident knee OA outcomes using comparable PA and OA definitions.

METHODS: Data were acquired from six global, community-based cohorts of participants with/without knee OA. Eligible participants had no evidence of knee OA and rheumatoid arthritis (RA) at baseline. Participants were followed for 5-12 years for incident outcomes including: i) radiographic knee OA (ROA) (Kellgren Lawrence (KL) ≥2), ii) painful radiographic knee OA (PROA) (ROA with knee pain) and iii) OA-related knee pain. Self-reported recreational PA included sport and walking/cycling activities was quantified at baseline as metabolic equivalents of tasks (METS) in days per week (days/wk). Risk ratios (RR) were calculated and pooled using Individual Participant Data (IPD) meta-analysis. Secondary analysis assessed the association between PA, defined as time (hrs/wk) spent in recreational PA and incident knee OA outcomes.

RESULTS: Based on a total of N=5065 participants, pooled risk ratio estimates for MET days/wk and PROA (1.02, 95% CI 0.93, 1.12), ROA (1.00, 95% CI 0.94, 1.07) and OA-related knee pain (1.00, 95% CI 0.96, 1.04) were non-significant, respectively. Similarly, analysis of hours per week spent in PA also showed no significant associations for all outcomes.

CONCLUSIONS: Our findings suggest that whole-body, physiological energy expenditure during recreational activities and time spent in physical activity were not associated with incident knee OA outcomes.

PMID:34730279 | DOI:10.1002/art.42001

Compr Rev Food Sci Food Saf. 2021 Nov 3. doi: 10.1111/1541-4337.12860. Online ahead of print.

ABSTRACT

Systematic review and meta-analysis were conducted to quantify the effects of processing stages and interventions on the prevalence and concentration of Campylobacter on broiler carcasses. To comprehensively capture relevant evidence, six databases were searched using the keywords “Campylobacter” and “broiler chicken.” The literature search yielded 10,450 unique citations, and after applying predetermined inclusion and exclusion criteria, 72 and 53 relevant citations were included in meta-analyses for processing stages and interventions, respectively. As the two primary outcomes, log reduction and prevalence changes were estimated for each stage or intervention using a random-effects meta-analysis approach whenever possible. The outcome-level quality assessment was conducted following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The analysis revealed that scalding and chilling majorly reduces the prevalence and concentration of Campylobacter. Immersion chilling reduces the concentration regardless of chemical additives, but its effect on prevalence is not conclusive. The effects of carcass washing applications remain uncertain due to the inconsistency and imprecision of both outcomes. Defeathering and evisceration were identified as stages that can increase both prevalence and concentration. Both chemical and physical processing interventions provide limited efficacy in concentration and prevalence reduction. Major limitations of the review were inconsistency and imprecision at the outcome level and reporting issues and data gaps at the study level. The results are expected to inform quantitative microbial risk assessment model development and support evidence-based decision-making.

PMID:34730272 | DOI:10.1111/1541-4337.12860

Eur J Heart Fail. 2021 Nov 3. doi: 10.1002/ejhf.2375. Online ahead of print.

ABSTRACT

AIMS: To evaluate the performance of the WATCH-DM risk score, a clinical risk score for heart failure (HF), in patients with dysglycemia and in combination with natriuretic peptides (NP).

METHODS AND RESULTS: Adults with diabetes/pre-diabetes free of HF at baseline from 4 cohort studies (ARIC, CHS, FHS, and MESA) were included. The machine learning- [WATCH-DM(ml)] and integer-based [WATCH-DM(i)] scores were used to estimate the 5-year risk of incident HF. Discrimination was assessed by Harrell’s concordance index (C-index) and calibration by the Greenwood-Nam-D’Agostino (GND) statistic. Improvement in model performance with the addition of NP-levels was assessed by C-index and continuous net reclassification improvement (NRI). Of the 8938 participants included, 3554 (39.8%) had diabetes and 432 (4.8%) developed HF within 5-years. The WATCH-DM(ml) and WATCH-DM (i) scores demonstrated high discrimination for predicting HF risk among individuals with dysglycemia (C-indices = 0.80 and 0.71) respectively, with no evidence of miscalibration (GND P-value ≥0.10). The C-index of elevated NP-levels alone for predicting incident HF among individuals with dysglycemia was significantly higher among participants with low/intermediate (<13) vs. high (≥13) WATCH-DM(i) scores [0.71(95%CI = 0.68-0.74) vs. 0.64(95%CI = 0.61-0.66)]. When NP-levels were combined with the WATCH-DM(i) score, HF risk discrimination improvement and NRI varied across the spectrum of risk with greater improvement observed at low/intermediate risk (WATCH-DM(i) < 13) vs. high risk (WATCH-DM(i) ≥13) (C-index = 0.73 vs. 0.71; NRI = 0.45 vs. 0.17, respectively).

CONCLUSION: The WATCH-DM risk score can accurately predict incident HF risk in community-based individuals with dysglycemia. The addition of NP-levels is associated with greater improvement in the HF risk prediction performance among individuals with low/intermediate risk than those with high risk. This article is protected by copyright. All rights reserved.

PMID:34730265 | DOI:10.1002/ejhf.2375

Stat Med. 2021 Nov 3. doi: 10.1002/sim.9242. Online ahead of print.

ABSTRACT

There is a growing trend to combine a new targeted or immunotherapy agent with the cancer-specific standard of care to treat different types of cancers. We propose a master-protocol-based, Bayesian phase I/II platform design to co-develop combination (BPCC) therapies in multiple indications. Under the BPCC design, only a single master protocol is needed, and the combined drug is evaluated in different indications in a concurrent or staggered fashion. For each indication, we jointly model dose-toxicity and -efficacy relationships and employ Bayesian hierarchical models to borrow information across them for more efficient indication-specific decision-making. To account for the characteristic of targeted or immunotherapy agents that their efficacy may not monotonically increase with the dose, and often plateau at high doses, we use the utility to quantify the risk-benefit tradeoff of the treatment. At each interim, we update the toxicity and efficacy model, as well as the estimate of the utility, based on the observed data across indications to inform the indication-specific decision of dose escalation and de-escalation and identify the optimal biological dose for each indication. Simulation study shows that the BPCC design has desirable operating characteristics, and that it provides an efficient approach to accelerate the development of combination therapies.

PMID:34730248 | DOI:10.1002/sim.9242

Epilepsia. 2021 Nov 3. doi: 10.1111/epi.17109. Online ahead of print.

ABSTRACT

OBJECTIVE: Psychogenic nonepileptic seizures (PNES) are characterized by multifocal and global abnormalities in brain function and connectivity. Only a few studies have examined neuroanatomic correlates of PNES. Traumatic brain injury (TBI) is reported in 83% of patients with PNES and may be a key component of PNES pathophysiology. In this study, we included patients with TBI preceding the onset of PNES (TBI-PNES) and TBI without PNES (TBI-only) to identify neuromorphometric abnormalities associated with PNES.

METHODS: Adults diagnosed with TBI-PNES (n = 62) or TBI-only (n = 59) completed psychological questionnaires and underwent 3-T magnetic resonance imaging. Imaging data were analyzed by voxel- and surface-based morphometry. Voxelwise general linear models computed group differences in gray matter volume, cortical thickness, sulcal depth, fractal dimension (FDf), and gyrification. Statistical models were assessed with permutation-based testing at 5000 iterations with the Threshold-Free Cluster Enhancement toolbox. Logarithmically scaled p-values corrected for multiple comparisons using familywise error were considered significant at p < .05. Post hoc analyses determined the association between structural and psychological measures (p < .05).

RESULTS: TBI-PNES participants demonstrated atrophy of the left inferior frontal gyrus and the right cerebellum VIII. Relative to TBI-only, TBI-PNES participants had decreased FDf in the right superior parietal gyrus and decreased sulcal depth in the left insular cortex. Significant clusters were positively correlated with global assessment of functioning scores, and demonstrated varying negative associations with measures of anxiety, depression, somatization, and global severity of symptoms.

SIGNIFICANCE: The diagnosis of PNES was associated with brain atrophy and reduced cortical folding in regions implicated in emotion processing, regulation, and response inhibition. Cortical folds primarily develop during the third trimester of pregnancy and remain relatively constant throughout the remainder of one’s life. Thus, the observed aberrations in FDf and sulcal depth could originate early in development. The convergence of environmental, developmental, and neurobiological factors may coalesce to reflect the neuropathophysiological substrate of PNES.

PMID:34730239 | DOI:10.1111/epi.17109