Nevin Manimala

Environ Sci Pollut Res Int. 2022 Jun 28. doi: 10.1007/s11356-022-21615-x. Online ahead of print.

ABSTRACT

In this study we propose, a multi-step strategy of selection and characterization of long-term dataset of contaminant concentrations in different environmental matrices (i.e., water and sediment). Starting from a high quality and homogeneous dataset of chemical parameters, a selection of a usable refined dataset followed by statistical characterization and hazard assessment was performed. The database of chemical contamination data from monitoring activities in the coastal marine water area of the Campania Region (Italy) produced by the Regional Agency for Environmental Protection of Campania (ARPAC) between 2013 and 2019 was utilized. Descriptive and multivariate statistics were applied to the extracted data subset to describe spatial variability and to investigate the relationships between matrices and contaminants. In addition, the impact on the sediment matrix was considered using the contamination factor (Cf), the sediment quality guidelines (SQG), and the probability of exceedance (PoE) of given thresholds for metals and organic compounds. The results highlighted the main anthropogenic pressures between the Gulf of Pozzuoli and the Gulf of Napoli, and the potential hazard posed in particular by metals (i.e., Pb, C, and Hg), TBT, and PAHs. A wide range of As concentration along the Campania coastline and Ni occurrence in the southern part of the region, mainly attributable to geogenic origin, was also evidenced. This approach allows extracting new knowledge from large dataset systematically collected by ARPAC monitoring activity, to support possible actions of contamination control and mitigation.

PMID:35763141 | DOI:10.1007/s11356-022-21615-x

Environ Sci Pollut Res Int. 2022 Jun 28. doi: 10.1007/s11356-022-21205-x. Online ahead of print.

ABSTRACT

The Sahelian zone of Senegal experienced heat waves in the previous decades, such as 2013, 2016 and 2018 that were characterised by temperatures exceeding 45°C for up to 3 successive days. The health impacts of these heat waves are not yet analysed in Senegal although their negative effects have been shown in many countries. This study analyses the health impacts of observed extreme temperatures in the Sahelian zone of the country, focusing on morbidity and mortality by combining data from station observation, climate model projections, and household survey to investigate heat wave detection, occurrence of climate-sensitive diseases and risk factors for exposure. To do this, a set of climatic (temperatures) and health (morbidity, mortality) data were collected for the months of April, May and June from 2009 to 2019. These data have been completed with 1246 households’ surveys on risk factor exposure. Statistical methods were used to carry out univariate and bivariate analyses while cartographic techniques allowed mapping of the main climatic and health indicators. The results show an increase in temperatures compared to seasonal normal for the 1971-2000 reference period with threshold exceedances of the 90th percentiles (42°C) for the maxima and (27°C) the minima and higher temperatures during the months of May and June. From health perspective, it was noted an increase in cases of consultation in health facilities as well as a rise in declared morbidity by households especially in the departments of Kanel (17.7%), Ranérou (16.1 %), Matam (13.7%) and Bakel (13.7%). The heat waves of May 2013 were also associated with cases of death with a reported mortality (observed by medical staff) of 12.4% unequally distributed according to the departments with a higher number of deaths in Matam (25, 2%) and in Bakel (23.5%) than in Podor (8.4%) and Kanel (0.8%). The morbidity and mortality distribution according to gender shows that women (57%) were more affected than men (43%). These health risks have been associated with a number of factors including age, access to drinkable water, type of fuel, type of housing and construction materials, existence of fan and an air conditioner, and health history.The heat wave recurrence has led to a frequency in certain diseases sensitive to rising temperatures, which is increasingly a public health issue in the Sahelian zone of Senegal.

PMID:35763140 | DOI:10.1007/s11356-022-21205-x

Environ Sci Pollut Res Int. 2022 Jun 28. doi: 10.1007/s11356-022-21651-7. Online ahead of print.

ABSTRACT

Esophageal cancer is a very deadly disease ranking 8th most common cancer in terms of incidence and the 6th highest in terms of mortality both in the USA and around the world. A growing body of evidence indicated that changes in the concentrations of essential and toxic elements may affect/increase esophagus carcinoma risk. The aim of this study was to measure serum levels of essential and toxic (Fe, Na, Ca, K, Zn, Mg, Co, Se, Cu, Ni, Mn, Sr, Pb, Li, Sb, Cr, Ag, Cd, As, and Hg) elements in patients with esophagus carcinoma and controls. Atomic absorption spectroscopy was used to determine serum concentrations of essential and toxic elements by using nitric acid/perchloric acid-based wet digestion method. Mean levels of Cu, Ni, Cr, Cd, Pb, As, and Ag were exhibited to be significantly higher and mean Se, Co, Zn, Ca, Fe, Hg, Li, and Mg were noted lower in the serum of cancer patients than controls. The correlation coefficients among the elements in the cancerous patients revealed significantly dissimilar communal relationships than the controls. Furthermore, multivariate methods demonstrated considerably different apportionment between the elements in the cancerous patients and the controls. Significant inequalities in the elemental concentrations were also observed for esophagus cancer types (adenocarcinoma and squamous cell carcinoma) and stages (I, II, III, and IV) between the patients. Majority of the elements exposed perceptible disparities in their levels based on smoking habits, dietary habits, habitat, and gender of the esophagus cancer patients and controls. Multivariate analysis of the essential and toxic elemental data explained significantly divergent apportionment in the serum of esophagus cancer patients when compared to controls.

PMID:35763136 | DOI:10.1007/s11356-022-21651-7

Lifetime Data Anal. 2022 Jun 28. doi: 10.1007/s10985-022-09565-5. Online ahead of print.

ABSTRACT

Conventional semiparametric hazards regression models rely on the specification of particular model formulations, such as proportional-hazards feature and single-index structures. Instead of checking these modeling assumptions one-by-one, we proposed a class of dimension-reduced generalized Cox models, and then a consistent model selection procedure among this class to select covariates with proportional-hazards feature and a proper model formulation for non-proportional-hazards covariates. In this class, the non-proportional-hazards covariates are treated in a nonparametric manner, and a partial sufficient dimension reduction is introduced to reduce the curse of dimensionality. A semiparametric efficient estimation is proposed to estimate these models. Based on the proposed estimation, we further constructed a cross-validation type criterion to consistently select the correct model among this class. Most importantly, this class of hazards regression models contains the fully nonparametric hazards regression model as the most saturated submodel, and hence no further model diagnosis is required. Overall speaking, this model selection approach is more effective than performing a sequence of conventional model checking. The proposed method is illustrated by simulation studies and a data example.

PMID:35763127 | DOI:10.1007/s10985-022-09565-5

Bull Math Biol. 2022 Jun 28;84(8):78. doi: 10.1007/s11538-022-01028-0.

ABSTRACT

A compartmental epidemiological model with distributed recovery and death rates is proposed. In some particular cases, the model can be reduced to the conventional SIR model. However, in general, the dynamics of epidemic progression in this model is different. Distributed recovery and death rates are evaluated from COVID-19 data. The model is validated by the epidemiological data for different countries, and it shows better agreement with the data than the SIR model. The time-dependent disease transmission rate is estimated.

PMID:35763126 | DOI:10.1007/s11538-022-01028-0

Transgenic Res. 2022 Jun 28. doi: 10.1007/s11248-022-00312-y. Online ahead of print.

ABSTRACT

Two conserved Glycine max (soybean) mitogen activated protein kinase 3 (MAPK3) paralogs function in defense to the parasitic soybean cyst nematode Heterodera glycines. Gene Ontology analyses of RNA seq data obtained from MAPK3-1-overexpressing (OE) and MAPK3-2-OE roots compared to their control, as well as MAPK3-1-RNA interference (RNAi) and MAPK3-2-RNAi compared to their control, hierarchically orders the induced and suppressed genes, strengthening the hypothesis that their heterologous expression in Gossypium hirsutum (upland cotton) would impair parasitism by the root knot nematode (RKN) Meloidogyne incognita. MAPK3-1 expression (E) in G. hirsutum suppresses the production of M. incognita root galls, egg masses, and second stage juveniles (J2s) by 80.32%, 82.37%, and 88.21%, respectfully. Unexpectedly, egg number increases by 28.99% but J2s are inviable. MAPK3-2-E effects are identical, statistically. MAPK3-1-E and MAPK3-2-E decreases root mass 1.49-fold and 1.55-fold, respectively, as compared to the pRAP15-ccdB-E control. The reproductive factor (RF) of M. incognita for G. hirsutum roots expressing MAPK3-1-E or MAPK3-2-E decreases 60.39% and 50.46%, respectively, compared to controls. The results are consistent with upstream pathogen activated molecular pattern (PAMP) triggered immunity (PTI) and effector triggered immunity (ETI) functioning in defense to H. glycines. The experiments showcase the feasibility of employing MAPK3, through heterologous expression, to combat M. incognita parasitism, possibly overcoming impediments otherwise making G. hirsutum’s defense platform deficient. MAPK homologs are identified in other important crop species for future functional analyses.

PMID:35763120 | DOI:10.1007/s11248-022-00312-y

J Neurol. 2022 Jun 28. doi: 10.1007/s00415-022-11231-7. Online ahead of print.

ABSTRACT

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive disease where a deficient amount of SMN protein leads to progressive lower motor neuron degeneration. SMN-enhancing therapies are now available. Yet, fatigue and signs of impaired neuromuscular junction (NMJ) transmission could contribute to SMA phenotype. Amifampridine prolongs presynaptic NMJ terminal depolarization, enhancing neuromuscular transmission.

METHODS: SMA-001 was a phase 2, 1:1 randomized, double-blind, placebo-controlled crossover study. Ambulatory (walking unaided at least 30 m) SMA Type 3 patients, untreated with SMN-enhancing medications, entered a run-in phase where amifampridine was titrated up to an optimized stable dose. Patients achieving at least three points improvement in Hammersmith Functional Motor Score Expanded (HFMSE) were randomized to amifampridine or placebo, alternatively, in the 28-day double-blind crossover phase. Safety was evaluated by adverse events (AE) collection. Primary efficacy measure was the HFMSE change from randomization. Secondary outcomes included timed tests and quality of life assessment. Descriptive analyses and a mixed effects linear model were used for statistics.

RESULTS: From 14 January 2019, 13 patients, mean age 34.5 years (range 18-53), with 5/13 (38.5%) females, were included. No serious AE were reported. Transient paresthesia (33.3%) was the only amifampridine-related AE. Six patients for each treatment sequence were randomized. Amifampridine treatment led to a statistically significant improvement in HFMSE (mean difference 0.792; 95% CI from 0.22 to 1.37; p = 0.0083), compared to placebo, but not in secondary outcomes.

DISCUSSION: SMA-001 study provided Class II evidence that amifampridine was safe and effective in treating ambulatory SMA type 3 patients.

CLINICAL TRIAL REGISTRATION: NCT03781479; EUDRACT 2017-004,600-22.

PMID:35763114 | DOI:10.1007/s00415-022-11231-7

Eur Radiol. 2022 Jun 28. doi: 10.1007/s00330-022-08941-x. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess whether radiomic features could improve the accuracy of survival predictions of IDH-wildtype (IDHwt) histological lower-grade gliomas (LGGs) over clinicopathological features.

METHODS: Preoperative MRI data of 61 patients with IDHwt histological LGGs were included as the institutional training set. The test set consisted of 32 patients from The Cancer Genome Atlas. Radiomic features (n = 186) were extracted using conventional MRIs. The radiomics risk score (RRS) for overall survival (OS) was derived from the elastic net. Multivariable Cox regression analyses with clinicopathological features (including epidermal growth factor receptor [EGFR] amplification and telomerase reverse transcriptase promoter [TERTp] mutation status) and the RRS were performed. The integrated area under the receiver operating curves (iAUCs) from the models with and without the RRS were compared. The net reclassification index (NRI) for 1-year OS was also calculated. The prognostic value of the RRS was evaluated using the external validation set.

RESULTS: The RRS independently predicted OS (hazard ratio = 48.08; p = 0.001). Compared with the clinicopathological model alone, adding the RRS had a better OS prediction performance (iAUCs 0.775 vs. 0.910), which was internally validated (iAUCs 0.726 vs. 0.884, 1-year OS NRI = 0.497), and a similar trend was found on external validation (iAUCs 0.683 vs. 0.705, 1-year OS NRI = 0.733). The prognostic significance of the RRS was confirmed in the external validation set (p = 0.001).

CONCLUSIONS: Integrating radiomics with clinicopathological features (including EGFR amplification and TERTp mutation status) can improve survival prediction in patients with IDHwt LGGs.

KEY POINTS: • Radiomics risk score has the potential to improve survival prediction when added to clinicopathological features (iAUCs increased from 0.775 to 0.910). • NRIs for 1-year OS showed that the radiomics risk score had incremental value over the clinicopathological model. • The prognostic significance of the radiomics risk score was confirmed in the external validation set (p = 0.001).

PMID:35763095 | DOI:10.1007/s00330-022-08941-x

Oncologist. 2022 Jun 28:oyac117. doi: 10.1093/oncolo/oyac117. Online ahead of print.

ABSTRACT

BACKGROUND: Patient-reported adverse events may be a useful adjunct for assessing a drug’s tolerability in dose-finding oncology trials (DFOT). We conducted surveys of international stakeholders and the National Cancer Research Institute (NCRI) Consumer Forum to understand attitudes about patient-reported outcome (PRO) use in DFOT.

METHODS: A 35-question survey of clinicians, trial managers, statisticians, funders, and regulators of DFOT was distributed via professional bodies examining experience using PROs, benefits/barriers, and their potential role in defining tolerable doses. An 8-question survey of the NCRI Consumer Forum explored similar themes.

RESULTS: International survey: 112 responses from 15 September-30 November 2020; 103 trialists [48 clinicians (42.9%), 38 statisticians (34.0%), 17 trial managers (15.2%)], 7 regulators (6.3%), 2 funders (1.8%)]. Most trialists had no experience designing (73, 70.9%), conducting (52, 50.5%), or reporting (88, 85.4%) PROs in DFOT. Most agreed that PROs could identify new toxicities (75, 67.0%) and provide data on the frequency (86, 76.8%) and duration (81, 72.3%) of toxicities. The top 3 barriers were lack of guidance regarding PRO selection (73/103, 70.9%), missing PRO data (71/103, 68.9%), and overburdening staff (68/103, 66.0%). NCRI survey: 57 responses on 21 March 2021. A total of 28 (49.1%) were willing to spend <15 min/day completing PROs. Most (55, 96.5%) preferred to complete PROs online. 61 (54.5%) trialists and 57 (100%) consumers agreed that patient-reported adverse events should be used to inform dose-escalation decisions.

CONCLUSION: Stakeholders reported minimal experience using PROs in DFOT but broadly supported their use. Guidelines are needed to standardize PRO selection, analysis, and reporting in DFOT.

PMID:35762393 | DOI:10.1093/oncolo/oyac117

Oral Health Prev Dent. 2022 Jun 28;20(1):279-294. doi: 10.3290/j.ohpd.b3170043.

ABSTRACT

PURPOSE: To summarise the available data on the effects of chlorhexidine (CHX) mouthwash in treating gingivitis during treatment with fixed orthodontic appliances.

MATERIALS AND METHODS: Multiple electronic databases were searched up to December 7th, 2021. Only randomised controlled trials (RCTs) were eligible for inclusion. The quality of the included RCTs was assessed with the Cochrane risk of bias tool for randomised trials (RoB 2.0). After data extraction and risk of bias assessment, differences were recorded in several oral hygiene indices in time and mean percentage change in those indices using different antimicrobial solutions.

RESULTS: Fourteen studies were deemed eligible for inclusion, reporting on a total of 602 patients with an age range of 11-35 years. The experimental solution was a 0.06%, 0.12%, or 0.2% CHX mouthwash with the control either a placebo mouthwash or a selection from a variety of mouthwashes. Treatment duration varied from 1 day to almost 5 months and the follow-up period varied from 1 min to 5 months. Chlorhexidine mouthrinses led to reduced plaque accumulation and gingival inflammation during orthodontic treatment, while at the same time, some of the control group mouthrinses were deemed equally effective. No statistically significant difference was detected in the meta-analysis between CHX and mouthwashes with propolis/probiotics/herbs in terms of the gingival index at 3 to 4 weeks (mean difference 0.07, 95% CI: -0.18, 0.31, p = 0.59).

CONCLUSION: Chlorhexidine mouthwash in orthodontic patients successfully controls gingival inflammation and bleeding when compared to untreated controls, but is equally effective as other mouthrinses where various oral health indices are concerned.

PMID:35762364 | DOI:10.3290/j.ohpd.b3170043