Nevin Manimala

Swiss Med Wkly. 2021 Mar 15;151:w20463. doi: 10.4414/smw.2021.20463. eCollection 2021 Mar 15.

ABSTRACT

BACKGROUND: During the last 20 years, treatment for chronic lymphocytic leukaemia (CLL) / small lymphocytic lymphoma (SLL) has advanced, with improved clinical outcomes in randomised controlled trials. Currently, no data have been published from Switzerland to assess effectiveness of recent healthcare advances in CLL/SLL on a population-based level. We aimed to estimate trends in incidence, mortality and survival for patients with CLL/SLL in Switzerland.

METHODS: We retrospectively studied registry data from the National Agency for Cancer Registration (NACR) database in Switzerland from 1997 to 2016. We investigated incidence, mortality and survival in consecutive 5-year periods. Age-specific rates were calculated for three age groups (<65 years, 65–74 years and ≥75 years).

RESULTS: We obtained 6301 cases with CLL/SLL. Median age at diagnosis was 72 years. From 7.0 per 100,000 person-years in 1997–2002, age-adjusted incidence rates peaked at 7.8 per 100,000 person-years in the second time period, 2002–2006, and declined afterwards to 6.4 per 100,000 person-years in 2012–2016. Mortality declined from 2.4 per 100,000 person-years in 1997–2002 to 2.0 per 100,000 in 2012–2016. Five- and 10-year age-standardised relative survival increased from 77.9% and 55.6%, respectively, in 1997–2001 to 83.6% (p = 0.009) and 64.2% (p = 0.005), respectively, in 2012–2016. Improvement in age-specific relative survival was only significant in the middle age group (65–74 years). Incidence and mortality were significantly higher in males. Females had better relative survival.

CONCLUSION: We found no clear down- or upward trend in age-adjusted incidence rates. Age-standardised survival improved over time, mainly in the two younger age-groups, but this improvement was statistically significant in those aged 65–74 years only. Males have higher incidence rates, higher mortality and shorter survival than females. Reporting delay and underreporting are major limitations in the interpretation of registry data from patients diagnosed with CLL/SLL.

PMID:33793959 | DOI:10.4414/smw.2021.20463

J Pharm Pharmacol. 2021 Mar 4;73(2):247-262. doi: 10.1093/jpp/rgaa022.

ABSTRACT

OBJECTIVES: To explore the intervention mechanism of combining Polygala tenuifolia (PT) with Magnolia officinalis (MO) on gastrointestinal motility disorders caused by PT.

METHODS: Urine and faeces of rats were collected; the effects of PT and MO on the gastric emptying and small intestine advancing rates in mice were analysed via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) to determine the potential metabolites. Changes in the metabolic profiles of the urine and faeces were revealed by untargeted metabolomics, followed by multivariate statistical analysis. The integration of urine and faeces was applied to reveal the intervention mechanism of PT-MO on PT-induced disorders.

KEY FINDINGS: PT + MO (1:2) improved the gastrointestinal function in mice suffering from PT-induced gastrointestinal motility disorder. Metabolomics indicated that the PT-MO mechanism was mainly associated with the regulations of 17 and 12 metabolites and 11 and 10 pathways in urine and faeces, respectively. The common metabolic pathways were those of tyrosine, purine, tricarboxylic acid cycle, pyruvate and gluconeogenesis, which were responsible for the PT-MO intervention mechanism.

CONCLUSIONS: The PT-MO (1:2) couple mechanism mitigated the PT-induced disorders, which were related to the energy, amino acid and fatty metabolisms.

PMID:33793803 | DOI:10.1093/jpp/rgaa022

Med Ultrason. 2021 Mar 14. doi: 10.11152/mu-2692. Online ahead of print.

ABSTRACT

AIMS: The aim of this study was to compare technical success and tolerability between hysterosalpingography (HSG) and hysterosalpingo-contrast ultrasonography (HyCoUs) as a first-line evaluation method in a single fertility center.

MATERIAL AND METHODS: The study included 56 infertile women: 27 patients underwent HSG and 29 patients underwent HyCoUs. Pain perception was measured by means of an 11-point visual analog scale (VAS) and the Stacy score. Side-effects, technical aspects, complications and variable correlations were documented.

RESULTS: The median VAS scale was 5 (4;6) for HSG and 1 (1;2) for HyCoUs. The median Stacy score was 2 (1;3) for HSG and 1 (0;1) for HyCoUs. The difference in pain perception was statistically significant for both pain scores (p<0.001). All patients undergoing HyCoUs reported a visual analog (VAS) pain score of <5 and 59.3% of patients undergoing an HSG reported a score of >5. Increased pain scores showed a statistically significant association with duration and total volume of substance infused. The type of procedure and volume infused were independently associated with the VAS scale. In the HSG group, 14.8% (4) of patients reported a vagal effect (p<0.001), one patient requiring hospitalization. No vagal effects were reported following HyCoUs and the method was technically successful in 100% (29) of cases. HSG was successful in 88.9% (24) of cases.

CONCLUSIONS: HyCoUs is a well-tolerated procedure with reduced frequency of adverse effects. Low pain perception is strongly correlated with a low volume infused. It is non-invasive and efficient in rendering good quality images.

PMID:33793700 | DOI:10.11152/mu-2692

Med Ultrason. 2021 Mar 14. doi: 10.11152/mu-2855. Online ahead of print.

ABSTRACT

AIM: To determine the early effects of excess weight on renal cortical stiffness in children and adolescents using point shear wave elastography (pSWE).

MATERIALS AND METHODS: One hundred and forty-six overweight and obese children (43.2% male; mean age, 12.6±2.9 years: range 4.3-18) and 48 lean children (27.1% male: mean age, 12.4±3.4: range 4.8-18.9) were included in the study and control group, respectively. pSWE measurements of the two kidneys were performed. The mean value of shear wave velocity was compared between groups.

RESULTS: The mean shear wave velocity was 2.79±0.53 m/s for the control subjects and 3.09±0.59 m/s for the overweight-obese subjects. The differences between the two groups were sta-tistically significant (p=0.001). There was no correlation between shear wave velocity and age or depth. A positive correlation was found between shear wave velocity and body mass index, body mass index-standard deviation score.

CONCLUSION: Renal cortical stiffness was higher in children with excess weight than in lean children. This study is the first attempt at applying pSWE to investigate the early adverse effects of excess weight.

PMID:33793699 | DOI:10.11152/mu-2855

PLoS One. 2021 Apr 1;16(4):e0249369. doi: 10.1371/journal.pone.0249369. eCollection 2021.

ABSTRACT

BACKGROUND: Tuberculosis (TB) is one of the major public health problems in Ethiopia. Determining treatment outcome of TB cases could help to understand the effectiveness of TB control efforts. The objective of this study was to assess TB treatment outcome and associated factors and determine the risk factors of death among TB cases who were on Directly Observed Treatment Short course (DOTS).

METHODOLOGY: We analyzed a retrospective data for TB cases who were on DOTS at Dilla Referral Hospital from July 2011- June 2016. The study population was TB cases with known HIV status and whose treatment outcome was evaluated at the Hospital. Data were entered, cleaned and analyzed using statistical package SPSS for windows, version 20.

RESULT: Out of 899 registered TB cases, 731 included in this analysis. Of these cases, 424 (58.0%) were male and 334 (45.7%) were in the age group of below 25 years. Treatment success rate of TB was 675 (92.3%) and death rate was 18 (2.5%). Treatment outcome showed statistically significant variation by HIV status (P < 0.001). HIV status of the TB cases and pretreatment weight were associated with TB treatment outcome. HIV status of the TB cases was associated with death of the TB cases (Adjusted Odds Ratio (AOR) 5.0; CI 95%: 1.8-13.5).

CONCLUSION: TB treatment success rate found in this study was high. Patient’s weight and HIV status were associated with treatment outcome. Moreover, HIV status predicted death of TB cases. Cautious treatment follow-up and defaulter tracing mechanisms for TB cases with these risk factors were suggested.

PMID:33793648 | DOI:10.1371/journal.pone.0249369

PLoS One. 2021 Apr 1;16(4):e0249412. doi: 10.1371/journal.pone.0249412. eCollection 2021.

ABSTRACT

BACKGROUND: Anemia has severe public health significance in sub-Saharan Africa. In Ethiopia, anemia has been increasing in the last two decades, reaching the highest national level in 2016, however, the geospatial distribution and determinants of anemia in children weren’t well explored at a national level.

METHODS: We used the Ethiopian Demographic and Health Survey(EDHS) data from 2005-2016. The data consists of samples of households (HHs) obtained through a two-stage stratified sampling procedure. Our analysis included 19,699 children. Descriptive statistics, geospatial analysis, and Generalized Linear Mixed Model (GLMMs) were used.

RESULTS: The overall prevalence of anemia was 51.5%; the spatial distribution of anemia significantly different across clusters in each survey. Children from 6 to 11 months had higher odds of anemia compared to 24-59 months (Adjusted Odds ratio (AOR) = 3.4, 95%Confidence level (CI): 2.99-3.76). Children with the first and second birth order were less likely to be anemic compared to fifth and above (AOR = 0.60, 95%CI: 0.38-0.95, and AOR = 0.83, 95%C: 0.73-0.93) respectively. Mothers’ age 15 to 24 years was associated with higher odds of anemia compared to 35 to 49 years (AOR = 1.37, 95%CI: 1.20-1.55). Children from HHs with the poorest and poorer wealth category showed a higher odds of anemia compared to the richest (AOR = 1.67, 95%CI: 1.45-1.93, and AOR = 1.25, 95%CI: 1.08-1.45) respectively. Moreover, children from HHs with one to two under-five children were less likely to be anemic compared to those three and more (AOR = 0.83, 95%CI: 0.76-0.91).

CONCLUSIONS: The geospatial distribution of anemia among children varies in Ethiopia; it was highest in the East, Northeast, and Western regions of the country. Several factors were associated with anemia; therefore, interventions targeting the hotspots areas and specific determinant factors should be implemented by the concerned bodies to reduce the consequences of anemia on the generation.

PMID:33793640 | DOI:10.1371/journal.pone.0249412

PLoS One. 2021 Apr 1;16(4):e0249411. doi: 10.1371/journal.pone.0249411. eCollection 2021.

ABSTRACT

BACKGROUND: Preterm birth is a significant contributor of under-five and newborn deaths globally. Recent estimates indicated that, Tanzania ranks the tenth country with the highest preterm birth rates in the world, and shares 2.2% of the global proportion of all preterm births. Previous studies applied binary regression models to determine predictors of preterm birth by collapsing gestational age at birth to <37 weeks. For targeted interventions, this study aimed to determine predictors of preterm birth using multinomial regression models accounting for missing data.

METHODS: We carried out a secondary analysis of cohort data from the KCMC zonal referral hospital Medical Birth Registry for 44,117 women who gave birth to singletons between 2000-2015. KCMC is located in the Moshi Municipality, Kilimanjaro region, northern Tanzania. Data analysis was performed using Stata version 15.1. Assuming a nonmonotone pattern of missingness, data were imputed using a fully conditional specification (FCS) technique under the missing at random (MAR) assumption. Multinomial regression models with robust standard errors were used to determine predictors of moderately to late ([32,37) weeks of gestation) and very/extreme (<32 weeks of gestation) preterm birth.

RESULTS: The overall proportion of preterm births among singleton births was 11.7%. The trends of preterm birth were significantly rising between the years 2000-2015 by 22.2% (95%CI 12.2%, 32.1%, p<0.001) for moderately to late preterm and 4.6% (95%CI 2.2%, 7.0%, p = 0.001) for very/extremely preterm birth category. After imputation of missing values, higher odds of moderately to late preterm delivery were among adolescent mothers (OR = 1.23, 95%CI 1.09, 1.39), with primary education level (OR = 1.28, 95%CI 1.18, 1.39), referred for delivery (OR = 1.19, 95%CI 1.09, 1.29), with pre-eclampsia/eclampsia (OR = 1.77, 95%CI 1.54, 2.02), inadequate (<4) antenatal care (ANC) visits (OR = 2.55, 95%CI 2.37, 2.74), PROM (OR = 1.80, 95%CI 1.50, 2.17), abruption placenta (OR = 2.05, 95%CI 1.32, 3.18), placenta previa (OR = 4.35, 95%CI 2.58, 7.33), delivery through CS (OR = 1.16, 95%CI 1.08, 1.25), delivered LBW baby (OR = 8.08, 95%CI 7.46, 8.76), experienced perinatal death (OR = 2.09, 95%CI 1.83, 2.40), and delivered male children (OR = 1.11, 95%CI 1.04, 1.20). Maternal age, education level, abruption placenta, and CS delivery showed no statistically significant association with very/extremely preterm birth. The effect of (<4) ANC visits, placenta previa, LBW, and perinatal death were more pronounced on the very/extremely preterm compared to the moderately to late preterm birth. Notably, extremely higher odds of very/extreme preterm birth were among the LBW babies (OR = 38.34, 95%CI 31.87, 46.11).

CONCLUSIONS: The trends of preterm birth have increased over time in northern Tanzania. Policy decisions should intensify efforts to improve maternal and child care throughout the course of pregnancy and childbirth towards preterm birth prevention. For a positive pregnancy outcome, interventions to increase uptake and quality of ANC services should also be strengthened in Tanzania at all levels of care, where several interventions can easily be delivered to pregnant women, especially those at high-risk of experiencing adverse pregnancy outcomes.

PMID:33793638 | DOI:10.1371/journal.pone.0249411

PLoS One. 2021 Apr 1;16(4):e0248964. doi: 10.1371/journal.pone.0248964. eCollection 2021.

ABSTRACT

Emerging studies indicate that APOA-I binding protein (AIBP) is a secreted protein and functions extracellularly to promote cellular cholesterol efflux, thereby disrupting lipid rafts on the plasma membrane. AIBP is also present in the mitochondria and acts as an epimerase, facilitating the repair of dysfunctional hydrated NAD(P)H, known as NAD(P)H(X). Importantly, AIBP deficiency contributes to lethal neurometabolic disorder, reminiscent of the Leigh syndrome in humans. Whereas cyclic NADPHX production is proposed to be the underlying cause, we hypothesize that an unbiased metabolic profiling may: 1) reveal new clues for the lethality, e.g., changes of mitochondrial metabolites., and 2) identify metabolites associated with new AIBP functions. To this end, we performed unbiased and profound metabolic studies of plasma obtained from adult AIBP knockout mice and control littermates of both genders. Our systemic metabolite profiling, encompassing 9 super pathways, identified a total of 640 compounds. Our studies demonstrate a surprising sexual dimorphism of metabolites affected by AIBP deletion, with more statistically significant changes in the AIBP knockout female vs male when compared with the corresponding controls. AIBP knockout trends to reduce cholesterol but increase the bile acid precursor 7-HOCA in female but not male. Complex lipids, phospholipids, sphingomyelin and plasmalogens were reduced, while monoacylglycerol, fatty acids and the lipid soluble vitamins E and carotene diol were elevated in AIBP knockout female but not male. NAD metabolites were not significantly different in AIBP knockout vs control mice but differed for male vs female mice. Metabolites associated with glycolysis and the Krebs cycle were unchanged by AIBP knockout. Importantly, polyamine spermidine, critical for many cellular functions including cerebral cortex synapses, was reduced in male but not female AIBP knockout. This is the first report of a systemic metabolite profile of plasma samples from AIBP knockout mice, and provides a metabolic basis for future studies of AIBP regulation of cellular metabolism and the pathophysiological presentation of AIBP deficiency in patients.

PMID:33793635 | DOI:10.1371/journal.pone.0248964

PLoS One. 2021 Apr 1;16(4):e0249071. doi: 10.1371/journal.pone.0249071. eCollection 2021.

ABSTRACT

Evidence-based STI (science, technology, and innovation) policy making requires accurate indicators of innovation in order to promote economic growth. However, traditional indicators from patents and questionnaire-based surveys often lack coverage, granularity as well as timeliness and may involve high data collection costs, especially when conducted at a large scale. Consequently, they struggle to provide policy makers and scientists with the full picture of the current state of the innovation system. In this paper, we propose a first approach on generating web-based innovation indicators which may have the potential to overcome some of the shortcomings of traditional indicators. Specifically, we develop a method to identify product innovator firms at a large scale and very low costs. We use traditional firm-level indicators from a questionnaire-based innovation survey (German Community Innovation Survey) to train an artificial neural network classification model on labelled (product innovator/no product innovator) web texts of surveyed firms. Subsequently, we apply this classification model to the web texts of hundreds of thousands of firms in Germany to predict whether they are product innovators or not. We then compare these predictions to firm-level patent statistics, survey extrapolation benchmark data, and regional innovation indicators. The results show that our approach produces reliable predictions and has the potential to be a valuable and highly cost-efficient addition to the existing set of innovation indicators, especially due to its coverage and regional granularity.

PMID:33793626 | DOI:10.1371/journal.pone.0249071

PLoS One. 2021 Apr 1;16(4):e0248905. doi: 10.1371/journal.pone.0248905. eCollection 2021.

ABSTRACT

Severe ulcerative colitis (UC) is a potentially life-threatening disease with a potential colorectal cancer (CRC) risk. The aim of this study was to explore the relationship between transcriptomic and genome-wide DNA methylation profiles in a well-stratified, treatment-naïve severe UC patient population in order to define specific epigenetic changes that could be responsible for the grade of disease severity. Mucosal biopsies from treatment-naïve severe UC patients (n = 8), treatment-naïve mild UC (n = 8), and healthy controls (n = 8) underwent both whole transcriptome RNA-Seq and genome-wide DNA bisulfite- sequencing, and principal component analysis (PCA), cell deconvolutions and diverse statistical methods were applied to obtain a dataset of significantly differentially expressed genes (DEGs) with correlation to DNA methylation for severe UC. DNA hypo-methylation correlated with approximately 80% of all DEGs in severe UC when compared to mild UC. Enriched pathways of annotated hypo-methylated genes revealed neutrophil degranulation, and immuno-regulatory interactions of the lymphoid system. Specifically, hypo-methylated anti-inflammatory genes found for severe UC were IL10, SIGLEC5, CD86, CLMP and members of inflammasomes NLRP3 and NLRC4. Hypo-methylation of anti-inflammatory genes during severe UC implies an interplay between the epithelium and lamina propria in order to mitigate inflammation in the gut. The specifically DNA hypo-methylated genes found for severe UC can potentially be useful biomarkers for determining disease severity and in the development of new targeted treatment strategies for severe UC patients.

PMID:33793617 | DOI:10.1371/journal.pone.0248905