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Genetic effect of MTHFR C677T, A1298C, and A1793G polymorphisms on the age at onset, plasma homocysteine, and white matter lesions in Alzheimer’s disease in the Chinese population

Aging (Albany NY). 2021 Apr 4;13. doi: 10.18632/aging.202827. Online ahead of print.

ABSTRACT

BACKGROUND: Three polymorphisms in the Methylenetetrahydrofolate reductase (MTHFR) gene (C677T, A1298C, and A1793G) were reported associated with AD. However, their genotype distributions and associations with age at onset (AAO), homocysteine, and white matter lesions (WML) were unclear in the Chinese AD population.

METHOD: We determined the presence of C677T, A1298C, and A1793G polymorphisms in the MTHFR gene using Sanger sequencing in a Chinese cohort comprising 721 AD patients (318 early-onset AD patients (EOAD) and 403 late-onset AD patients (LOAD)) and 365 elderly controls. Additionally, the homocysteine level and WML were evaluated in 121 AD patients.

RESULTS: The frequency of allele T of C677T polymorphism was significantly higher in AD patients than in controls (P = 0.040), while no statistical difference was observed in A1298C and A1793G (P > 0.05). Besides, genotype distributions of C677T and A1298C polymorphisms statistically varied between AD patients and controls (P = 0.021, P = 0.012). Moreover, the AAO was significantly lower in CT/TT (C677T) genotypes carriers (P = 0.042) and higher in AC/CC (A1298C) and AG/GG (A1793G) genotypes carriers (P = 0.034, P = 0.009) in patients with LOAD. We also found that patients with CT/TT (C677T) genotypes were prone to present an increased homocysteine level (P = 0.036) and higher Fazekas score (P = 0.024). In comparison, patients with AG/GG genotypes (A1793G) had a significantly lower Fazekas score (P = 0.013).

CONCLUSIONS: The genotype distributions of C677T and A1298C polymorphisms are associated with AD in the Chinese population. Moreover, AD patients with C677T polymorphism are prone to present an earlier onset, higher homocysteine level, and more severe WML.

PMID:33833133 | DOI:10.18632/aging.202827

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Tobacco mythbusting-tobacco is not a major driver of foot traffic in low socio-economic small retail stores

Tob Control. 2021 Apr 8:tobaccocontrol-2020-056310. doi: 10.1136/tobaccocontrol-2020-056310. Online ahead of print.

ABSTRACT

BACKGROUND: One of the opposing arguments to restricting or banning the sale of tobacco products stem from a perception that this would adversely impact on small retail stores that rely on tobacco sales for viability. It has also been argued that purchases of tobacco leads to unplanned purchasing of other items that yield income for small store owners. This study tested the veracity of these arguments in the Australian context.

METHODS: Consumer intercept surveys (n=1487) were conducted outside a comprehensive sample of small stores (n=136) selling tobacco in lower socioeconomic suburbs. Data were collected over a 2-hour period outside each store using the same methodology (36% consumer response rate). Descriptive statistics examined the proportion of tobacco and non-tobacco purchases and most common products purchased.

RESULTS: Purchasing tobacco was the primary motivation for store visits for only 3% of consumers. The vast majority of products purchased (92%) were not tobacco, with hot food, groceries and lottery tickets most frequent. Only 8% of consumers purchased tobacco. When unplanned purchasing patterns were compared, consumers’ who purchased tobacco were no more likely to buy other products.

CONCLUSION: Tobacco purchasing was rarely the reason for store visits, indicating that it is not a key driver of consumer foot traffic for small retailers. There was also no evidence that tobacco contributes to spontaneous purchases of other products that might bring retailers profit. Findings suggest that restricting the retail availability of tobacco would be unlikely to have a pronounced negative impact on small retail stores.

PMID:33833091 | DOI:10.1136/tobaccocontrol-2020-056310

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Chemotherapy response score as a prognostic tool in patients with advanced stage endometrial carcinoma treated with neoadjuvant chemotherapy

Int J Gynecol Cancer. 2021 Apr 8:ijgc-2020-002202. doi: 10.1136/ijgc-2020-002202. Online ahead of print.

ABSTRACT

BACKGROUND: Chemotherapy response score (CRS) applied to interval debulking specimens quantifies histopathologic response to neoadjuvant chemotherapy in patients with advanced ovarian carcinoma and correlates with progression-free and overall survival.

OBJECTIVE: To investigate whether the chemotherapy response score could be applied to interval debulking specimens in patients with advanced endometrial carcinoma and be a prognostic indicator.

METHODS: The study included patients with clinical stage III-IV endometrial carcinoma who received neoadjuvant chemotherapy followed by interval debulking surgery. Chemotherapy response scores were assigned to omental and adnexal metastases, and categorized as no/minimal (CRS1), partial (CRS2), and complete/near-complete (CRS3) response to neoadjuvant chemotherapy. Descriptive statistics were used to evaluate baseline characteristics and feasibility of chemotherapy response score assessment. Univariate analyses were used to evaluate associations between the chemotherapy response score, complete cytoreduction, and survival.

RESULTS: This study included 40 patients. The median age was 63.5 years, and 31 patients (78%) had stage IV disease. Thirty patients had an omentectomy, 22 patients (73%) had an omental chemotherapy response score assigned. Thirty-nine patients had a bilateral salpingo-oophorectomy, 28 patients (72%) had an adnexal chemotherapy response score assigned. Omental CRS2 and CRS3 were associated with improved progression-free survival (CRS2: HR=0.18, p<0.01; CRS3: HR=0.11, p<0.01) and overall survival (CRS2: HR=0.10, p<0.01; CRS3: HR=0.16, p=0.04). Adnexal CRS2 and CRS3 were associated with improved progression-free survival (CRS2: HR=0.23, p<0.01; CRS3: HR=0.20, p=0.03). Chemotherapy response scores were also associated with an increased likelihood of having a complete cytoreduction.

CONCLUSION: Chemotherapy response score can be applied to omental and adnexal metastases in patients with advanced endometrial carcinoma and was associated with survival and complete cytoreduction. The score may be a prognostic indicator and help to guide first-line treatment of patients with endometrial carcinoma.

PMID:33833085 | DOI:10.1136/ijgc-2020-002202

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Nevin Manimala Statistics

Beyond Statistics: Uncovering the Roots of Racial Disparities in Breastfeeding

Pediatrics. 2021 Apr 8:e2020037887. doi: 10.1542/peds.2020-037887. Online ahead of print.

NO ABSTRACT

PMID:33833073 | DOI:10.1542/peds.2020-037887

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Evaluation of the impact of the voluntary safety standard for liquid laundry packets on the rate of child exposures reported to Poison Control Centers in the US

Inj Prev. 2021 Apr 8:injuryprev-2020-044115. doi: 10.1136/injuryprev-2020-044115. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the impact of the voluntary safety standard for liquid laundry packets on the rate of child exposures reported to Poison Control Centers in the US.

METHODS: The analysis was based on an interrupted time series design. The voluntary safety standard for laundry packets was published at the end of 2015. Data on reported liquid laundry packet exposures involving children under age 6 years were collected for the July 2012 through December 2017 study period. A negative binomial multiple regression model for rate data was used to quantify the impact of the voluntary standard on (1) the rate of total reported exposures and (2) the rate of reported exposures that were medically treated. The analysis controlled for laundry packet sales, time trends and seasonal variations in reported exposures.

RESULTS: The voluntary safety standard was associated with a 28.6% reduction in the rate of total reported exposures and a 36.8% reduction in the rate of medically treated exposures. The analysis also provides some evidence that these estimated reductions may underestimate overall reductions in the rate of reported exposures if pre-standard packaging improvements and possible caregiver behavioural responses to laundry packet hazard warnings are considered.

CONCLUSIONS: The analysis suggests that the requirements of the voluntary standard have effectively reduced the rate of injury involving liquid laundry packets.

PMID:33833071 | DOI:10.1136/injuryprev-2020-044115

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Nevin Manimala Statistics

Predictive models for cardiovascular and kidney outcomes in patients with type 2 diabetes: systematic review and meta-analyses

Heart. 2021 Apr 8:heartjnl-2021-319243. doi: 10.1136/heartjnl-2021-319243. Online ahead of print.

ABSTRACT

OBJECTIVE: To inform a clinical practice guideline (BMJ Rapid Recommendations) considering sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists for treatment of adults with type 2 diabetes, we summarised the available evidence regarding the performance of validated risk models on cardiovascular and kidney outcomes in these patients.

METHODS: We systematically searched bibliographic databases in January 2020 to identify observational studies evaluating risk models for all-cause and cardiovascular mortality, heart failure (HF) hospitalisations, end-stage kidney disease (ESKD), myocardial infarction (MI) and ischaemic stroke in ambulatory adults with type 2 diabetes. Using a random effects model, we pooled discrimination measures for each model and outcome, separately, and descriptively summarised calibration plots, when available. We used the Prediction Model Risk of Bias Assessment Tool to assess risk of bias of each included study and the Grading of Recommendations, Assessment, Development, and Evaluation approach to evaluate our certainty in the evidence.

RESULTS: Of 22 589 publications identified, 15 observational studies reporting on seven risk models proved eligible. Among the seven models with >1 validation cohort, the Risk Equations for Complications of Type 2 Diabetes (RECODe) had the best calibration in primary studies and the highest pooled discrimination measures for the following outcomes: all-cause mortality (C-statistics 0.75, 95% CI 0.70 to 0.80; high certainty), cardiovascular mortality (0.79, 95% CI 0.75 to 0.84; low certainty), ESKD (0.73, 95% CI 0.52 to 0.94; low certainty), MI (0.72, 95% CI 0.69 to 0.74; moderate certainty) and stroke (0.71, 95% CI 0.68 to 0.74; moderate certainty). This model does not, however, predict risk of HF hospitalisations.

CONCLUSION: Of available risk models, RECODe proved to have satisfactory calibration in primary validation studies and acceptable discrimination superior to other models, though with high risk of bias in most primary studies.

TRIAL REGISTRATION NUMBER: CRD42020168351.

PMID:33833070 | DOI:10.1136/heartjnl-2021-319243

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The effect of extended depth of focus contact lenses on the accommodation of presbyopic eyes

Zhonghua Yan Ke Za Zhi. 2021 Apr 11;57(4):292-296. doi: 10.3760/cma.j.cn112142-20200718-00488.

ABSTRACT

Objective: To evaluate the effect of extended depth of focus contact lenses on the accommodation of presbyopic eyes. Methods: It was a double-blind randomized controlled trial. Thirty eyes of 30 emmetropic volunteers (15 males, 15 females) who were staff or family members of Hainan Eye Hospital, aged (49.6±4.5) years, were selected. Non-dominant eyes were fitted with soft contact lenses with an extended depth of field. The subjects and examiners were double-blind. Visual acuities of the subjects were examined at 5 m, 40 cm and 60 cm distance before and after the contact lens wear. Meanwhile, the monocular accommodative amplitude, monocular accommodative facility (±1.00 D), accommodative response, binocular positive/negative relative accommodation and accommodation convergence/accommodation at 40 cm distance were measured. The data were analyzed by paired t test and Wilcoxon signed rank test before and after the contact lens wear, and a P value less than 0.05 was considered statistically significant. Results: Before and after the contact lens wear, the visual acuity at 40 cm was 4.59±0.14 and 4.69±0.10, and the difference was statistically significant (t=4.16, P<0.01). The visual acuity at 60 cm was 4.74±0.10 and 4.74±0.12, and the difference had no statistical significance (t=0.626, P>0.05). The distance visual acuity was 5.00±0.06 and 4.96±0.06, and the difference was statistically significant (t=3.89, P<0.01). The monocular accommodative amplitude was significantly improved from (3.26±0.26) D to (4.00±0.51) D (t=7.59, P<0.01). The monocular accommodative facility was also significantly improved from (2.67±1.60) cyc/min to (3.53±1.87) cyc/min (t=2.17, P<0.05). There was no statistically significant difference in the positive and negative relative accommodation (t=1.90, 0.66; P>0.05). The accommodation convergence/accommodation and adjustment lag had no statistical significance (Z=0.83, 0.11; P>0.05). Conclusion: Wearing contact lenses with an extended depth of field can improve the near vision and accommodation of presbyopes (Chin J Ophthalmol, 2021, 57:292-296).

PMID:33832054 | DOI:10.3760/cma.j.cn112142-20200718-00488

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Regulation of bFGF and TGF-β2 in human scleral fibroblasts by the lumican gene mutation associated with myopia

Zhonghua Yan Ke Za Zhi. 2021 Apr 11;57(4):277-283. doi: 10.3760/cma.j.cn112142-20200825-00553.

ABSTRACT

Objective: To investigate the regulation of basic fibroblast growth factor (bFGF) and transforming growth factor (TGF)-β2 in human scleral fibroblasts (HSFs) by the adenovirus-mediated Lumican gene mutation, and to illustrate the effect of this mutation on myopia. Methods: Experimental study. The HSFs were isolated and cultured from human scleral tissues. The 3rd to 5th generation HSFs were transduced with Lumican mutant (c.596T>C) adenovirus, Lumican wild-type adenovirus, and defective adenovirus as the mutant group, wild group, and negative control group, respectively. Untransduced HSFs were defined as control group. The operation was conducted three times in each group. The expression levels of Lumican, bFGF and TGF-β2 were detected by qPCR. Statistical analysis of gene expression differences between groups was performed by fold changes. The differences were analyzed by one way ANOVA combined with LSD-t test. Results: The expressions of Lumican in the mutant group and the wild group were 103.146-fold and 398.646-fold increased compared to the control group with significant difference (t=-16.641, -21.729; P<0.05). There was no statistical difference between the negative control group and the control group (t=1.689, P>0.05). The expressions of bFGF and TGF-β2 in the mutant group were 2.812-fold and 2.346-fold increased compared to the control group with significant difference, and higher than the other groups (t=-3.921, -4.851; P<0.05). There was no significant difference among the wild group, negative control group and control group (P>0.05). Conclusions: The Lumican mutation (c.596T>C) increased the expressions of bFGF and TGF-β2 in HSFs. It indicates that the Lumican mutation (c.596T>C) may change the metabolism of extracellular matrix in the sclera by regulating bFGF and TGF-β2 to participate in scleral remodeling during the process of myopia. (Chin J Ophthalmol, 2021, 57:277-283).

PMID:33832052 | DOI:10.3760/cma.j.cn112142-20200825-00553

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Clinical value of emergency endovascular embolization in the interventional treatment for oral hemorrhage caused by carcinoma

Zhonghua Kou Qiang Yi Xue Za Zhi. 2021 Apr 9;56(4):370-373. doi: 10.3760/cma.j.cn112144-20200603-00312.

ABSTRACT

To evaluate the clinical value of emergency endovascular embolization in the interventional treatment for oral hemorrhage caused by carcinoma, 32 patients with oral hemorrhage caused by carcinoma, who received emergency endovascular embolization due to unsatisfactory hemostatic effect of conventional conservative treatment in the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2019, were included in this study and their clinical data, laboratory data and imaging information were retrospectively analyzed. There were 16 males and 16 females, aged (60.6±13.6) years (34-88 years). Technical successful rate of emergency endovascular embolization, immediate successful rate of controlling hemorrhage, blood pressure before and after operation, hemoglobin before and after operation, postoperative complications and recurrence rate of oral hemorrhage were statistically analyzed. Results showed that technical successful rate of operation and immediate successful rate of controlling oral hemorrhage are both 100% (32/32). Recurrent oral hemorrhage occurred in 4 patients (13%). The hemorrhagic shock symptoms of all patients were significantly improved after interventional therapy. After operation, local swelling happened in 34% (11/32) patients and intermittent local pain happened in 22% (7/32) within 24 hours; the swelling and the pain gradually disappeared from 2nd to 5th days. Mild complications of transient fever happened in 9% (3/32) patients and disappeared spontaneously in the short term. No serious complications such as blindness, cerebrovascular accident or central nervous system disturbance occurred in all patients after operations. During the whole follow-up period (1 to 12 months), a total of 8 patients died. The causes of death were progression and metastasis of carcinoma (n=4), heart failure (n=2), severe pneumonia (n=1) and respiratory failure caused by recurrent oral hemorrhage (n=1). Owing to the remarkable short-term curative effect, repeatable operation, low recurrence rate of oral hemorrhage and low incidence of complications, emergency endovascular embolization can be used in the clinical therapy and application of oral hemorrhage caused by carcinoma.

PMID:33832039 | DOI:10.3760/cma.j.cn112144-20200603-00312

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Effect of subpressure on the bonding strength of resin to polycrystalline particulates modified zirconia ceramic

Zhonghua Kou Qiang Yi Xue Za Zhi. 2021 Apr 9;56(4):342-348. doi: 10.3760/cma.j.cn112144-20200929-00518.

ABSTRACT

Objective: To explore the effect of subpressure on the bonding strength of resin to polycrystalline particulates modified zirconia ceramic. Methods: One hundred and twenty pre-sintered zirconia discs were prepared and divided into the control group, the sandblasting group and the 30, 50, 70 s acid etching group (24 per group) by the random number table method. There was no additional treatment in the control group and sandblasting group before sinering. The 30, 50, and 70 s acid etching groups were immersed in HF for 30, 50, 70 s, respectively, and then they were placed into CaCl2 solution for 90 s and dipped in NaOH solution at 80 ℃ for 2 h. After sintering, the sandblasting group was subjected to sandblasting. The surface tomography and roughness were tested. According to whether subpressure was applied or not after the adhesives were applied, each group was randomly divided into two subgroups with a random number table: a subpressure subgroup and a normal pressure subgroup (12 per subgroup). Resin columns were bonded to these specimens. Shear bonding strength (SBS) test was conducted and the bonding interface, fracture surface and failure mode were analyzed. Results: The surface of control group was smooth, and its roughness was (0.24±0.11) μm. The rough surface was formed after sandblasting in the sandblasting group, and its roughness was (0.95±0.12) μm. The surface roughness of 30, 50, 70 s acid etching groups [(0.60±0.15), (1.04±0.11), (1.57±0.16) μm] increased as the HF immersion time prolonged, and the difference in surface roughness of zirconia specimens among each group was statistically significant (P<0.05). The SBS values between zirconia and resin of all the subpressure subgroups, namely: the control group, the sandblasting group, and the 30, 50, 70 s acid etching group [(13.56±1.19), (20.98±2.11), (17.37±2.44), (24.19±2.97), (21.36±2.16) MPa] were significantly stronger than those in the normal pressure subgroups, namely: the control group, sandblasting group, 30, 50, 70 s acid etching group [(10.74±0.93), (18.47±2.14), (14.81±1.54), (20.74±2.56), (17.75±2.54) MPa] (P<0.05). No obvious gaps and bubbles were observed in the bonding interfaces in subpressure subgroups. The proportion of mixed failure was significantly increased after applying subpressure (P<0.05). Conclusions: The subpressure can effectively enhance the bonding strength between the resin and polycrystalline particulates modified zirconia ceramic and improve the bonding effect.

PMID:33832035 | DOI:10.3760/cma.j.cn112144-20200929-00518