Nevin Manimala

Eur J Obstet Gynecol Reprod Biol. 2021 Apr 12;261:25-28. doi: 10.1016/j.ejogrb.2021.04.006. Online ahead of print.

ABSTRACT

OBJECTIVE: Our objective was to identify non-obstetric risk factors for pelvic organ prolapse in women attending a urogynecology clinic.

STUDY DESIGN: A retrospective study of 662 women referred for pelvic floor dysfunction between January 2017 and August 2018. Participants underwent a standardized interview, clinical exam including Pelvic Organ Prolapse Qualification (POP-Q) assessment, and four-dimensional transperineal ultrasound. They were questioned about smoking, asthma, heavy lifting and family history of pelvic organ prolapse, as well as prolapse symptoms. Significant clinical prolapse was defined as POP-Q stage ≥2 for anterior and posterior compartments and stage ≥1 for apical prolapse. Offline analysis of volume data was performed blinded against all other data. Statistical analysis included logistic regression with multivariable models adjusted for age, body mass index, vaginal parity, levator hiatal area and levator avulsion.

RESULTS: Participating women were assessed at a mean age of 58 (SD 13.3) years with a mean body mass index of 28.93 kg/m² (standard deviation 5.98). The vast majority were vaginally parous (88.2 %) with a median of two vaginal deliveries (range 0-7). Previous hysterectomy was reported by 29.3 % of women (n = 194) and previous prolapse repair by 17.2 % (n = 114). Past or current smoking was reported by 300 (45.6 %) women, 113 (17.2 %) reported asthma, 246 (37.6 %) heavy lifting and 186 (28.6 %) a family history of pelvic organ prolapse. Heavy lifting was associated with sonographic prolapse (odds ratio 1.71, 95 % confidence interval 1.2-2.4), confirmed on multivariable analysis (P = 0.046). Heavy lifting was positively associated with symptoms (P = 0.053) and clinical signs of pelvic organ prolapse (P = 0.056) on univariate analysis; however, this became non-significant on multivariable analysis. No associations were found for individual compartments except for a trend towards more posterior compartment prolapse with heavy lifting.

CONCLUSIONS: Smoking, asthma and family history of prolapse were not found to be a significant risk factor for prolapse in our study population. Heavy lifting may be a potential risk factor, in particular for posterior compartment prolapse.

PMID:33873084 | DOI:10.1016/j.ejogrb.2021.04.006

Am J Otolaryngol. 2021 Apr 13;42(5):103014. doi: 10.1016/j.amjoto.2021.103014. Online ahead of print.

ABSTRACT

BACKGROUND: Smell dysfunction has been recognized as an early symptom of SARS-CoV-2 infection, often occurring before the onset of core symptoms of the respiratory tract, fever or muscle pain. In most cases, olfactory dysfunction is accompanied by reduced sense of taste, is partial (microsmia) and seems to normalize after several weeks, however, especially in cases of virus-induced complete smell loss (anosmia), there are indications of persisting deficits even 2 months after recovery from the acute disease, pointing towards the possibility of chronic or even permanent smell reduction for a significant part of the patient population. To date, we have no knowledge on the specificity of anosmia towards specific odorants or chemicals and about the longer-term timeline of its persistence or reversal.

METHODS: In this longitudinal study, 70 participants from a community in Lower Austria that had been tested positive for either IgG or IgM SARS-CoV-2 titers in June 2020 and a healthy control cohort (N = 348) underwent smell testing with a 12-item Cross-Cultural Smell Identification Test (CC-SIT), based upon items from the University of Pennsylvania Smell Identification Test (UPSIT). The test was performed in October 2020, i.e. 4 months after initial diagnosis via antibody testing. Results were analyzed using statistical tests for contingency for each smell individually in order to detect whether reacquisition of smell is dependent on specific odorant types.

RESULTS: For all odorants tested, except the odor “smoke”, even 4 months or more after acute SARS-CoV-2 infection, participants with a positive antibody titer had a reduced sense of smell when compared to the control group. On average, while the control cohort detected a set of 12 different smells with 88.0% accuracy, the antibody-positive group detected 80.0% of tested odorants. A reduction of accuracy of detection by 9.1% in the antibody-positive cohort was detected. Recovery of the ability to smell was particularly delayed for three odorants: strawberry (encoded by the aldehyde ethylmethylphenylglycidate), lemon (encoded by citronellal, a monoterpenoid aldehyde), and soap (alkali metal salts of the fatty acids plus odorous additives) exhibit a sensitivity of detection of an infection with SARS-CoV-2 of 31.0%, 41.0% and 40.0%, respectively.

CONCLUSION: Four months or more after acute infection, smell performance of SARS-CoV-2 positive patients with mild or no symptoms is not fully recovered, whereby the ability to detect certain odors (strawberry, lemon and soap) is particularly affected, suggesting the possibility that these sensitivity to these smells may not only be lagging behind but may be more permanently affected.

PMID:33873048 | DOI:10.1016/j.amjoto.2021.103014

Parkinsonism Relat Disord. 2021 Apr 11;86:74-77. doi: 10.1016/j.parkreldis.2021.04.003. Online ahead of print.

ABSTRACT

OBJECTIVE: To study the association between impulse control disorders (ICDs) in Parkinson’s disease (PD) and genetic risk scores (GRS) for 40 known or putative risk factors (e.g. depression, personality traits).

BACKGROUND: In absence of published genome-wide association studies (GWAS), little is known about the genetics of ICDs in PD. GRS of related phenotypes, for which large GWAS are available, may help shed light on the genetic contributors of ICDs in PD.

METHODS: We searched for GWAS on European ancestry populations with summary statistics publicly available for a broad range of phenotypes, including other psychiatric disorders, personality traits, and simple phenotypes. We separately tested their predictive ability in two of the largest PD cohorts with clinical and genetic available: the Parkinson’s Progression Markers Initiative database (N = 368, 33% female, age range = [33-84]) and the Drug Interaction With Genes in Parkinson’s Disease study (N = 373, 40% female, age range = [29-85]).

RESULTS: We considered 40 known or putative risk factors for ICDs in PD for which large GWAS had been published. After Bonferroni correction for multiple comparisons, no GRS or the combination of the 40 GRS were significantly associated with ICDs from the analyses in each cohort separately and from the meta-analysis.

CONCLUSION: Albeit unsuccessful, our approach will gain power in the coming years with increasing availability of genotypes in clinical cohorts of PD, but also from future increase in GWAS sample sizes of the phenotypes we considered. Our approach may be applied to other complex disorders, for which GWAS are not available or limited.

PMID:33872999 | DOI:10.1016/j.parkreldis.2021.04.003

Comput Biol Med. 2021 Apr 15;133:104380. doi: 10.1016/j.compbiomed.2021.104380. Online ahead of print.

ABSTRACT

Immune evasion is one of the unique characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attributed to its ORF8 protein. This protein modulates the adaptive host immunity through down-regulation of MHC-1 (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the host’s interferon-mediated antiviral response. To understand the host’s immune perspective concerning the ORF8 protein, a comprehensive study of the ORF8 protein and mutations possessed by it have been performed. Chemical and structural properties of ORF8 proteins from different hosts, such as human, bat, and pangolin, suggest that the ORF8 of SARS-CoV-2 is much closer to ORF8 of Bat RaTG13-CoV than to that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 in SARS-CoV-2 can be grouped into four classes based on their predicted effects (Hussain et al., 2021) [1]. Based on the geo-locations and timescale of sample collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were found upon sequence similarity analyses and consideration of the amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of the rapidly evolving SARS-CoV-2 through the ORF8.

PMID:33872970 | DOI:10.1016/j.compbiomed.2021.104380

Comput Biol Med. 2021 Apr 16;133:104396. doi: 10.1016/j.compbiomed.2021.104396. Online ahead of print.

ABSTRACT

BACKGROUND: Pacing artifacts must be excluded from the analysis of paced ECG waveform. This study aimed to develop and validate an algorithm to identify and remove the pacing artifacts on ECG and vectorcardiogram (VCG).

METHODS: We developed a semi-automatic algorithm that identifies the onset and offset of a pacing artifact based on the VCG signal slope steepness and designed a graphical user interface that permits quality control and fine-tuning the constraining threshold values. We used 1054 ECGs from the retrospective, multicenter cohort study “Global Electrical Heterogeneity and Clinical Outcomes,” including 3825 atrial and 10,031 ventricular pacing artifacts for the algorithm development and 22 ECGs including 108 atrial and 241 ventricular pacing artifacts for validation. Validation was performed per digital sample. We used the kappa-statistic of interrater agreement between manually labeled sample (ground-truth) and automated detection.

RESULTS: The constraining parameter values were for onset threshold 13.06 ± 6.21 μV/ms, offset threshold 34.77 ± 17.80 μV/ms, and maximum window size 27.23 ± 3.53 ms. The automated algorithm detected a digital sample belonging to pacing artifact with a sensitivity of 74.5% and specificity of 99.6% and classified correctly 98.8% of digital samples (ROC AUC 0.871; 95%CI 0.853-0.878). The kappa-statistic was 0.785, indicating substantial agreement. The agreement was on 98.81% digital samples, significantly (P < 0.00001) larger than the random agreement on 94.43% of digital samples.

CONCLUSIONS: The semi-automated algorithm can detect and remove ECG pacing artifacts with high accuracy and provide a user-friendly interface for quality control.

PMID:33872969 | DOI:10.1016/j.compbiomed.2021.104396

Spectrochim Acta A Mol Biomol Spectrosc. 2021 Mar 24;257:119741. doi: 10.1016/j.saa.2021.119741. Online ahead of print.

ABSTRACT

When our liver does not work well, it can induce damage to other organs causing their dysfunction. With this background, we aim to study the effect of liver fibrosis on other organs such as heart, lungs, kidney and spleen by assessing the variations in the inherent emission property of the tissue, using fluorescence spectroscopy. Fluorescence emission spectra from excised organs of liver fibrosis induced rats were collected at excitation wavelengths 320 and 410 nm. Optical redox ratio derived from the spectral data supported by multivariate statistical analysis, principal component analysis followed by linear discriminant analysis (PCA-LDA) distinguished between control and fibrosis induced groups. The two different excitation wavelength provided variations in the endogenous flurophores collagen, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD), lipopigments and porphyrins. Additionally, evaluation of redox ratio provided variations in tissue metabolic activity of different organs. The PCA-LDA modelling yielded a sensitivity of 85 to 97% and specificity of 80 to 96% on 320 nm excitation and a sensitivity of 72 to 100% and specificity of 59 to 100% on 410 nm excitation. Fluorescence emission spectral study along with multivariate analysis paved way to identify the biochemical alterations caused to other organs due to the development of liver fibrosis, which could lead to their damage and dysfunction.

PMID:33872953 | DOI:10.1016/j.saa.2021.119741

Spectrochim Acta A Mol Biomol Spectrosc. 2021 Apr 1;257:119763. doi: 10.1016/j.saa.2021.119763. Online ahead of print.

ABSTRACT

Achieving good glycemic control in patients with type II diabetes mellitus is essential for preventing both microvascular and macrovascular complications. Combination therapy represents the principle strategy for successful long term control of type II diabetes mellitus with minimal complications. Two sensitive, precise and non-destructive spectroscopic methods were developed for the simultaneous estimation of two new co-formulated hypoglycemic drugs; canagliflozin/metformin (CAG/MEF) and empagliflozin/linagliptin (EMG/LIG) in tablets with no need of previous separation. The first method was amplitude modulation (a normalized spectra-based UV spectrophotometric method) for the analysis of (CAG/MEF) binary mixture. The amplitude of the constant at the plateau region at (264-310 nm) on the ratio spectrum was measured and used for the determination of CAG concentration in the mixture. On the other hand, MEF was estimated by subtracting the previously obtained amplitude from the total amplitude of CAG and MEF at the isosbestic point (λ_iso) at 250 nm. The second method was chemometric-assisted FTIR spectrophotometric method for the determination of (EMG/LIG) binary mixture. (EMG/LIG) mixture in chloroform was analyzed using FTIR in the region 4000-400 cm^-1. The spectral region 3900-2900 cm^-1 was selected for (EMG/LIG) determination using principal component regression and partial least squares chemometric methods. The methods were validated according to ICH guidelines. The studied drugs were successfully determined in tablets applying the developed methods. Validation parameters were in agreement with acceptance limits, ensuring methods accuracy and selectivity. Besides, no significant difference was obtained by statistically comparing the obtained results with the reported one.

PMID:33872950 | DOI:10.1016/j.saa.2021.119763

Int J Food Microbiol. 2021 Mar 26;347:109171. doi: 10.1016/j.ijfoodmicro.2021.109171. Online ahead of print.

ABSTRACT

Potatoes contain several nutrients essential for fungal growth, making them an excellent component of media such as the popular Potato Dextrose Agar (PDA) medium. Commercially, PDA is available from multiple retailers offering virtually the same product. These media, however, could contain small differences in composition of nutrients affecting the expression of secondary metabolites. This study aims to investigate the use of four PDA media from different manufacturers (Fluka, Oxoid, Sigma, and VWR) and their effect on the metabolite profile of four species of Fusarium (F. fujikuroi, F. graminearum, F. pseudograminearum and F. avenaceum). Secondary metabolites were analysed using HPLC-HRMS, from which statistically significant differences in intensities were observed for 9 out of 10 metabolites.

PMID:33872940 | DOI:10.1016/j.ijfoodmicro.2021.109171

J Mech Behav Biomed Mater. 2021 Apr 16;119:104510. doi: 10.1016/j.jmbbm.2021.104510. Online ahead of print.

ABSTRACT

The present study elucidates the impact of detergent-based chemical decellularization on the micro-mechanical properties of porcine and rabbit corneas for the purpose of extracellular matrix (ECM) derived scaffolds. Aiming to optimize the decellularization process, different concentrations of Sodium Dodecyl Sulfate (SDS), Triton X-100 and CHAPS detergents were assessed on their ability to decellularize corneas from both bio-models at incubation periods of 12 and 24h. We evaluated the effect of decellularization on corneal ECM Young’s Modulus and various area’s roughness parameters (topography features) at a microscale by using Atomic Force Microscopy (AFM). Only SDS presented adequate decellularization properties at the selected concentrations (0.2, 0.5 and 1%) and incubation periods. All topography features displayed by native corneas were preserved after SDS treatments, while no statistically significant differences were identified for the average value of Young’s Modulus between the control samples and those treated with 0.2% SDS (rabbit corneas) and 0.5% SDS (porcine corneas) after 12h. In this sense, cornea decellularization procedures can be improved by simultaneously reducing SDS concentration and incubation period. AFM is a useful tool to perform biomechanical analysis of the effect of decellularization on scaffold micro-mechanics. Evaluation of the scaffold mechanical behavior at a microscale could help in understanding cell-scaffold interactions in terms of mechanotransduction, complementing macroscale techniques (e.g. tensile tests) relevant for tissue engineering quality control and decision-making.

PMID:33872923 | DOI:10.1016/j.jmbbm.2021.104510

Transbound Emerg Dis. 2021 Apr 19. doi: 10.1111/tbed.14108. Online ahead of print.

ABSTRACT

Bovine tuberculosis (TB) is a chronic disease caused mainly by Mycobacterium bovis, a zoonotic pathogen that has a worldwide distribution causing serious economic losses for milk and meat producers. In Chile the disease in dairy cattle has a heterogeneous distribution, where the Metropolitan Region concentrates the highest animal prevalence and the main challenge for the national control and eradication program. In this epidemiological context, vaccination with the M. bovis Bacillus Calmette-Guerin (BCG) vaccine might be a useful strategy for disease prevention and control. The objective of this study was to assess the efficacy and impacts on productivity and fertility of vaccination with the BCG Russia strain in 11-month-old heifers from a dairy farm, under a natural transmission condition. Sixty-two animals were vaccinated via the subcutaneous route with the equivalent of 1 human dose of BCG and 60 control animals received saline. Subsequently, blood sampling was performed at 3, 6, 9, 12, 15 and 18 months post inoculation, and infection status was determined using the IFNγ release assay (IGRA)with the DIVA (Differentiate Infected from Vaccinated Animals) antigens ESAT-6, CFP-10 and Rv3615c. Efficacy was calculated as the percentage of reduction in the incidence of infection attributable to vaccination, which showed a statistically significant level of overall protection of 66.5%. No adverse effects on fertility and production were recorded. In contrast, we observed beneficial effects of vaccination on several milk production parameters, with the milk yield in the first 100 days after calving in the BCG group significantly higher compared to unvaccinated heifers( p <0.05).These results suggest that BCG vaccination of heifers in a natural transmission setting might result in both sanitary and productive benefits, supporting its implementation as a new strategy for TB prevention in a high prevalence area of Chile.

PMID:33872473 | DOI:10.1111/tbed.14108