Nevin Manimala

Reprod Sci. 2021 Mar 24. doi: 10.1007/s43032-021-00537-y. Online ahead of print.

ABSTRACT

Apurinic/apyrimidinic endonuclease 1/redox-factor 1 (APE1/Ref-1) gene encodes a multifunctional protein involved in the DNA base excision repair (BER) pathway, which initiates repair of apurinic/apyrimidinic (AP) sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone. APE1/Ref-1 polymorphisms are related to the occurrence of neural tube defects (NTDs), but the association between APE1/Ref-1 polymorphisms and NTDs is not reported in Chinese Han population. The aim of the present study was to evaluate the association of APE1/Ref-1 polymorphism and the risk of NTD occurrence for Han population in a high-risk area of China. APE1/Ref-1 genotypes were determined by iPLEX Gold SNP genotyping. AP sites and folate level of brain tissues were measured. The results showed that three polymorphisms (rs3136817, rs77794916, and rs1760944) of APE1/Ref-1 were statistically associated with NTD subtypes. Allele C of rs3136817, allele T of rs77794916, and allele G of rs1760944 were associated with an increased risk for encephalocele (OR = 2.52, 95% CI [1.25-5.07], P < 0.01; OR = 1.80, 95% CI [1.04-3.12], P = 0.04; and OR = 1.96, 95% CI [1.12-3.45], P = 0.02), compared with those harboring the alleles T, C, and T, respectively. The folate level in NTDs was lower than that in controls. DNA AP sites in the encephalocele were significantly higher than the control (P < 0.01). The three polymorphisms of APE1/Ref-1 were significantly related to NTD occurrence, which indicated that APE1/Ref-1 might be a potential genetic risk factor for encephalocele in a high-risk area of NTDs in China.

PMID:33761125 | DOI:10.1007/s43032-021-00537-y

J Nephrol. 2021 Mar 24. doi: 10.1007/s40620-020-00958-z. Online ahead of print.

ABSTRACT

BACKGROUND: Hemodialysis patients present a dramatic increase in cardiovascular morbidity/mortality. Circulating immune cells, activated by both uremic milieu and dialysis, play a key role in the pathogenesis of dialysis-related vascular disease. The aim of our study was to identify, through a high-throughput approach, differences in gene expression profiles in the peripheral blood mononuclear cells (PBMCs) of patients treated with on-line hemodiafiltration and bicarbonate hemodialysis.

METHODS: The transcriptomic profile was investigated in PBMCs isolated from eight patients on on-line hemodiafiltration and eight patients on bicarbonate hemodialysis by microarray analysis. The results were evaluated by statistical and functional pathway analysis and validated by real time PCR (qPCR) in an independent cohort of patients (on-line hemodiafiltration N = 20, bicarbonate hemodialysis n = 20).

RESULTS: Eight hundred and forty-seven genes were differentially expressed in patients treated with on-line hemodiafiltration and bicarbonate hemodialysis. Thirty-seven functional gene networks were identified and atherosclerosis signaling was the top canonical pathway regulated by on-line hemodiafiltration. Among the genes of this pathway, on-line hemodiafiltration was associated with a reduced expression of Platelet-derived growth factor A chain (PDGF A), Clusterin, Monoamine Oxidase A, Interleukin-6 (IL-6) and Vascular Endothelial Growth Factor C (VEGF-)C and with an increase of Apolipoprotein E. qPCR confirmed the microarray results. Platelet derived growth factor AA (PDGF-AA), IL-6 and VEGF-C serum levels were significantly lower in the on-line hemodiafiltration group. Finally, 10 patients previously on bicarbonate hemodialysis were switched to on-line hemodiafiltration and PBMCs were harvested after 6 months. The qPCR results from this perspective group confirmed the modulation of atherosclerotic genes observed in the cross-sectional analysis.

CONCLUSIONS: Our data suggest that type of dialysis (on-line hemodiafiltration versus bicarbonate hemodialysis) may modulate the expression of several genes involved in the pathogenesis of atherosclerotic disease.

PMID:33761122 | DOI:10.1007/s40620-020-00958-z

Pain Ther. 2021 Mar 24. doi: 10.1007/s40122-021-00254-z. Online ahead of print.

ABSTRACT

In a 2018 report titled, Quantifying the Epidemic of Prescription Opioid Overdose Deaths, four senior analysts of the Centers for Disease Control and Prevention (CDC), including the head of the Epidemiology and Surveillance Branch, acknowledged for the first time that the number of prescription opioid overdose deaths reported by the CDC in 2016 was erroneous. The error, they said, was caused by miscoding deaths involving illicitly manufactured fentanyl (IMF) as deaths involving prescribed fentanyl. To understand what caused this error, the authors examined the CDC’s methodology for compiling drug-related mortality data, beginning with the source data obtained from approximately 2.8 million death certificates received each year from state vital statistics registrars. Systemic problems often begin outside the CDC, with a surprisingly high rate of errors and omissions in the source data. Using the CDC’s explanation for what caused the error, the authors show why an international program used by the CDC for reporting mortality is ill-suited for compiling and reporting drug overdose deaths. Except for heroin, methadone, and opium, each of which has an individual program code, all other opioids are separated in just two program codes according to whether they are synthetic or semisynthetic/opiates. Methadone-involved deaths pose a special problem for the CDC because methadone has dual indications for treating pain and for treating opioid use disorder (OUD). In 2019, more than seven times more methadone was administered or dispensed for OUD treatment than was prescribed for pain, yet all methadone-involved deaths are coded by the CDC as involving the prescribed form of the drug. The authors conclude that the CDC was at fault for failing to recognize and correct this problem before 2016. Public policy consequences of this failure are briefly mentioned.

PMID:33761120 | DOI:10.1007/s40122-021-00254-z

Can J Public Health. 2021 Mar 24. doi: 10.17269/s41997-020-00470-8. Online ahead of print.

ABSTRACT

SETTING: The Canadian Community Health Survey (CCHS) is one of the world’s largest ongoing cross-sectional population health surveys, with over 130,000 respondents every two years or over 1.1 million respondents since its inception in 2001. While the survey remains relatively consistent over the years, there are differences between cycles that pose a challenge to analyze the survey over time.

INTERVENTION: A program package called cchsflow was developed to transform and harmonize CCHS variables to consistent formats across multiple survey cycles. An open science approach was used to maintain transparency, reproducibility and collaboration.

OUTCOMES: The cchsflow R package uses CCHS survey data between 2001 and 2014. Worksheets were created that identify variables, their names in previous cycles, their category structure, and their final variable names. These worksheets were then used to recode variables in each CCHS cycle into consistently named and labelled variables. Following, survey cycles can be combined. The package was then added as a GitHub repository to encourage collaboration with other researchers.

IMPLICATION: The cchsflow package has been added to the Comprehensive R Archive Network (CRAN) and contains support for over 160 CCHS variables, generating a combined data set of over 1 million respondents. By implementing open science practices, cchsflow aims to minimize the amount of time needed to clean and prepare data for the many CCHS users across Canada.

PMID:33761108 | DOI:10.17269/s41997-020-00470-8

Cogn Res Princ Implic. 2021 Mar 24;6(1):21. doi: 10.1186/s41235-021-00284-3.

ABSTRACT

When a visual search target frequently appears in one target-rich region of space, participants learn to search there first, resulting in faster reaction time when the target appears there than when it appears elsewhere. Most research on this location probability learning (LPL) effect uses 2-dimensional (2D) search environments that are distinct from real-world search contexts, and the few studies on LPL in 3-dimensional (3D) contexts include complex visual cues or foraging tasks and therefore may not tap into the same habit-like learning mechanism as 2D LPL. The present study aimed to establish a baseline evaluation of LPL in controlled 3D search environments using virtual reality. The use of a virtual 3D search environment allowed us to compare LPL for information within a participant’s initial field of view to LPL for information behind participants, outside of the initial field of view. Participants searched for a letter T on the ground among letter Ls in a large virtual space that was devoid of complex visual cues or landmarks. The T appeared in one target-rich quadrant of the floor space on half of the trials during the training phase. The target-rich quadrant appeared in front of half of the participants and behind the other half. LPL was considerably greater in the former condition than in the latter. This reveals an important constraint on LPL in real-world environments and indicates that consistent search patterns and consistent egocentric spatial coding are essential for this form of visual statistical learning in 3D environments.

PMID:33761042 | DOI:10.1186/s41235-021-00284-3

Environ Geochem Health. 2021 Mar 24. doi: 10.1007/s10653-021-00879-1. Online ahead of print.

ABSTRACT

The aim of this study was to determine the influence of traffic density on air pollutant levels as well as to analyse the spatial and temporal distribution of particulate pollutants and their health risk. The following species related to traffic pollution were measured: PM₁₀, elemental and organic carbon and polycyclic aromatic hydrocarbons (PAHs) in PM₁₀ and gas pollutants (SO₂, NO₂ and CO). The measurements were carried out at four crossroad sites in the city. Samples of PM₁₀ were collected over three periods (6 am to 2 pm, 2 pm to 10 pm and 10 pm to 6 am) on working days and weekends. Statistically significant differences were found between sampling sites for all pollutant concentrations, except for NO₂. The highest mass concentrations of PM₁₀, carbon and PAHs were observed in the south of the city with the highest traffic density. Concentrations of gasses (CO and NO₂) showed high values in morning and in the late afternoon and evening (west and east). At all measuring sites, the highest concentration of particle-bound pollutants was mostly recorded during morning and afternoon, except at the south, where elevated PAHs concentrations were recorded during night period, which indicated that residential heating takes up a portion of pollution sources in this area. Although for most of the pollutants the concentrations varied during the day, statistically significant differences between sampling periods were not found. The highest health risk was obtained at the south, where it was scored as significant.

PMID:33761036 | DOI:10.1007/s10653-021-00879-1

Eur J Health Econ. 2021 Mar 24. doi: 10.1007/s10198-021-01273-5. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the psychometric properties of the EQ-5D-5L and SF-6D, and to compare their performance among patients living with haemophilia in China.

METHODS: A total of 875 Chinese patients completed the EQ-5D-5L, SF-6D, and Haem-A-QoL questionnaires. Construct validity of the EQ-5D-5L and SF-6D dimensions and indices was assessed by testing hypotheses relating these measures to Haem-A-QoL and clinical measures. The Spearman correlation coefficient was used to assess convergent validity, and one-way analysis of variance (F statistic) was used to assess the known-groups validity (discriminatory power). The agreement between EQ-5D-5L and SF-6D indices was assessed using the intraclass correlation coefficient (ICC) and the Bland-Altman plot.

RESULTS: Both the EQ-5D-5L and SF-6D indices showed acceptable ceiling and floor effects. As hypothesised, both EQ-5D-5L and SF-6D were significantly correlated with Haem-A-QoL (both dimensions and overall score). EQ-5D-5L and SF-6D indices as well as EQ-VAS differentiated patients are known to differ in severity of haemophilia, bleeding status, disabling levels, and comorbidity. The F statistics in the known-groups comparisons suggested that the EQ-5D-5L was slightly more discriminative than the SF-6D. ICC (0.41) and Bland-Altman plot confirmed that the agreement between the EQ-5D-5L and SF-6D indices was poor.

CONCLUSION: Both EQ-5D-5L and SF-6D showed satisfactory construct validity in the measurement of the HRQoL among patients with haemophilia. However, the two instruments may not be used interchangeably in this patient population due to their poor agreement and differing discriminatory power.

PMID:33761029 | DOI:10.1007/s10198-021-01273-5

Eur J Clin Microbiol Infect Dis. 2021 Mar 24. doi: 10.1007/s10096-021-04211-8. Online ahead of print.

ABSTRACT

This study is to determine the incidence and outcome of neonatal gram-negative bacilli (GNB) sepsis in Stockholm, Sweden, and describe bacterial characteristics. This is a retrospective cohort study. All infants with GNB-sepsis between 2006 and 2016 were included and matched with two control groups, with suspected sepsis and uninfected neonates, respectively. Outcome was death before discharge, risk of death within 5 days after sepsis onset, and morbidity. The resistance pattern from all GNB was collected, and all available isolates were subjected to genome typing. All neonates with GNB-sepsis (n = 107) were included, and the cumulative GNB-sepsis incidence was 0.35/1000 live born. The in-hospital mortality was 30/107 (28%). GNB late-onset sepsis (LOS) was associated with an increase in mortality before discharge compared to uninfected controls (OR = 3.9; CI 1.6-9.4) but not versus suspected sepsis. The suspected LOS cases did not statistically differ significantly from uninfected controls. The case fatality rate (CFR) at 5 days was 5/33 (15%) in GNB early-onset sepsis (EOS) and 25/74 (34%) in GNB-LOS. The adjusted hazard for 5 days CFR was higher in GNB-LOS versus uninfected controls (HR = 3.7; CI 1.2-11.2), but no significant difference was seen in GNB-LOS versus suspected sepsis or in suspected sepsis versus controls. ESBL production was seen in 7/107 (6.5%) of the GNB isolates. GNB-LOS was associated with a higher 5 days CFR and in-hospital mortality compared to uninfected controls but not versus suspect sepsis. The incidence of both GNB-EOS and GNB-LOS was lower than previously reported from comparable high-income settings. The occurrence of antibiotic resistance was low.

PMID:33761020 | DOI:10.1007/s10096-021-04211-8

Eur J Orthop Surg Traumatol. 2021 Mar 24. doi: 10.1007/s00590-021-02941-1. Online ahead of print.

ABSTRACT

PURPOSE: This study aims to compare the differences between direct anterior approach (DAA) and direct lateral approach (DLA) in hip hemiarthroplasty (HHA) after displaced femoral neck fracture (FNF) in early functional outcome, hospital length of stay, morbidity and mortality rates.

METHODS: This non-interventional retrospective study, carried out at a tertiary trauma centre within the Spanish National Health System, included all patients who underwent a bipolar HHA between 1st January 2018 and 31st December 2019 performed by 2 of our hip unit surgeons.

RESULTS: A total of 94 patients were included (40 in DAA group and 54 in DLA group). Median follow-up was 19.2 months (range 8-30.8 months). Postoperative degree of mobilisation showed statistically significant differences in favour of DAA group, where 35% of patients were able to walk with no assistance after surgery. DAA group had 1 day less of hospitalisation in contrast with DLA group overall (8 days vs 9 days, respectively, p < 0.05). Statistically significant differences were not detected in comparing postoperative complications, re-operations rates or 6-months mortality rate.

CONCLUSION: Our study highlights the benefits of DAA for HHA after displaced FNF in terms of postoperative mobilisation degree and hospitalisation length of stay when compared to DLA.

PMID:33760998 | DOI:10.1007/s00590-021-02941-1

Curr Pain Headache Rep. 2021 Mar 24;25(5):34. doi: 10.1007/s11916-021-00942-7.

ABSTRACT

PURPOSE OF REVIEW: Prevalence of chronic low back pain (cLBP) is increasing. Sacroiliac joint (SIJ) is a common source of cLBP, but data behind its diagnosis and treatment is controversial. There is moderate quality evidence for effectiveness of therapeutic SIJ injections. However, there are no studies comparing the two most common steroid preparations, methylprednisolone (MTP) and triamcinolone (TAC) in SIJ injections.

RECENT FINDINGS: After institutional IRB approval, a retrospective chart review was conducted to evaluate the effectiveness of SIJ injections in terms of pain relief at 1-month follow-up and compare MTP versus TAC. All injections were performed by a single pain physician with fluoroscopic guidance.

RESULTS: Sixty-five percent of patients in the MTP group and 57% patients in the TAC group had >50% pain relief at 1-month follow-up, with no statistical difference between the two groups. Patients in the TAC group had significantly greater BMI and consisted of higher proportion of smokers (72% patients in TAC group versus 39% patients in the MTP group, p-value 0.004). Other sources of pain such as facet joints were unmasked post-procedurally after SIJ injections, with this unmasking being significant for the TAC group. Opiate use decreased in the MTP group from 35% pre-procedurally to 20% post-procedurally, and this difference did not reach statistical significance. Both MTP and TAC are effective in providing pain relief for SIJ pain at 1-month follow-up, with no statistical difference between the two types of steroids. Although not statistically significant, there is a modest reduction in opiate use in the MTP group.

PMID:33760993 | DOI:10.1007/s11916-021-00942-7