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Retinochoroidal vascular plexuses in patients with iron deficiency anaemia

Clin Exp Optom. 2021 May 2:1-7. doi: 10.1080/08164622.2021.1916387. Online ahead of print.

ABSTRACT

Clinical relevance: Optical coherence tomography angiography (OCT-A) may enable the identification of alteration in the retinochoroidal microvasculature in patients with iron deficiency anaemia.Background: To investigate the presence of macular microvascular alterations in females with IDA by using OCT-A.Methods: This is a cross-sectional comparative study. Forty patients with IDA and 35 age-matched healthy women underwent a complete ophthalmologic examination and OCT-A imaging. Foveal avascular zone parameters and the vessel density in the superficial (SCP) and deep capillary plexus (DCP) were calculated using automated software. All measurements were compared between groups. Correlations between the OCT-A metrics and haematological laboratory parameters were evaluated.Results: Compared to healthy subjects, IDA patients revealed significantly decreased vessel density of the SCP in all parafoveal quadrants (p < 0.05). In contrast, vessel density analysis in DCP has shown no statistically significant difference in all parafoveal quadrants (p > 0.05). Although foveal vessel density in both SCP and DCP were higher in the IDA group, only the foveal vessel density in DCP was significantly higher than controls (p = 0.001). The mean values of the foveal avascular zone area and perimeter and choriocapillaris flow area were significantly lower in the IDA group (p < 0.05). The parafoveal vessel density in SCP, foveal avascular zone area, and choriocapillaris flow area were positively correlated with haematological parameters including haemoglobin, haematocrit, mean corpuscular haemoglobin, and mean corpuscular volume (p < 0.01).Conclusion: Patients with IDA had decreased parafoveal vessel density in the SCP, but not the DCP. Foveal avascular zone metrics and choriocapillaris flow area measurements were significantly lower in IDA.

PMID:33938383 | DOI:10.1080/08164622.2021.1916387

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The role of telomerase reverse transcriptase (TERT) promoter mutations in prognosis in bladder cancer

Bioengineered. 2021 Dec;12(1):1495-1504. doi: 10.1080/21655979.2021.1915725.

ABSTRACT

Telomerase reverse transcriptase (TERT) promoter mutations have been recognized as a common genetic event in bladder cancer (BC). Many studies have found the high TERT promoter mutations’ prevalence in BC recurrence patients which may make the TERT promoter mutations become a potential prognosis prediction of BC. We performed a systematic search in Embase, PubMed, and Web of Science in January 2021. The aspects of evaluation, methods, validation, and results were used to evaluate the included studies’ quality. We reviewed two of the most common mutations in types of TC, C288T and C250T and their relationship with prognosis of BC. Eight studies contained 1382 cases were enrolled in our study. The percentage of TERT promoter mutations in these cases was 62.5%. A statistically significant association was detected between TERT promoter mutation and recurrence (HR: 2.03, 95% CI: 1.53-2.68, p < 0.001). However, TERT promoter mutation was not significant associated with overall survival (HR: 1.077, 95% CI: 0.674-1.718, p = 0.757). No significant heterogeneities were observed (I2 = 47.5%, P = 0.064; I2 = 58.7%, p = 0.120, respectively). Bladder cancer patients with TERT promoter mutations take a higher risk of recurrence. TERT promoter mutations may become a potential prediction factor for bladder cancer recurrence.

PMID:33938397 | DOI:10.1080/21655979.2021.1915725

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Impact of maternal iron deficiency anaemia on the expression of the newly discovered multi-copper ferroxidase, Zyklopen, in term placentas

J Obstet Gynaecol. 2021 May 2:1-9. doi: 10.1080/01443615.2021.1882968. Online ahead of print.

ABSTRACT

In the present study, we investigated the effect of maternal iron deficiency anaemia (IDA) on expression of the newly discovered iron transporter, Zyklopen in term placenta, in 200 pregnant women. Placental expression of Zyklopen was studied by mRNA analysis and immunohistochemistry for the protein. In addition neonatal anthropometric parameters were also analysed. 58.8% of 200 subjects were anaemic. Both Zyklopen mRNA as well as protein expression in the placenta showed a statistically significant increase with increasing severity of anaemia. Although all the neonatal anthropometric parameters were lower in newborns of anaemic mothers, none showed any statistical significance. Zp mRNA levels did not show any significant correlation with newborn and placental parameters (except newborn skinfold thickness and head circumference). Similar to mRNA expression, Zp IHC expression correlated positively, albiet non-significantly, with newborn length and Hb levels, the correlation was however negative with birth weight, head circumference, mid-arm circumference unlike the mRNA expression, where it positively correlated with the above parameters. Our study for the first time demonstrated a definite increase in expression of Zyklopen at both mRNA and protein levels in term placenta, in maternal IDA.IMPACT STATEMENTWhat is already known on this subject? Iron deficiency anaemia (IDA) in a pregnant mother can lead to anaemia in the developing foetus; which is frequently observed to be of lesser severity than that in the mother. Recently a copper-containing oxidase called Zyklopen was discovered which was involved in iron efflux in BeWo cells. The gene encoding Zyklopen has been identified with a putative C-terminal membrane-spanning sequence and high sequence identitical to hephaestin (Heph) and ceruloplasmin (Cp), the other known vertebrate multicopper ferroxidase (MCF). Protein expression of this new MCF was observed in multiple diverse mouse tissues, including placenta and mammary gland.What do the results of this study add? Zyklopen protein immunohistochemical expression showed a statistically significant increase with increasing severity of anaemia. Similarly, placental mRNA expression of the Zyklopen gene was observed to be higher in anaemic mothers when compared to non-anaemic mothers. Our study for the first time demonstrated a definite increase in expression of Zyklopen at both protein and mRNA levels in term placenta, in maternal IDA.What are the implications of these findings for clinical practice and/or further research? This study will help us to understand better, the increased potential for influx of iron from mother to foetus in the condition of maternal iron deficiency. This study will help to determine how placental iron transport proteins can be regulated in response to maternal and neonatal iron status and will further our existing knowledge on relationships between maternal and neonatal iron status and mechanisms by which placental iron transport is modified in relation to these parameters.

PMID:33938360 | DOI:10.1080/01443615.2021.1882968

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The assessment of the relationship between the vascularity of FIGO Type 4-7 leiomyomas and abnormal uterine bleeding

J Obstet Gynaecol. 2021 May 3:1-5. doi: 10.1080/01443615.2021.1882969. Online ahead of print.

ABSTRACT

The current study aimed to analyse and compare the vascularity of FIGO Type 4-7 leiomyoma specimens obtained from women with or without abnormal uterine bleeding (AUB). The records of 31 women who underwent myomectomy for FIGO Type 4-7 leiomyomas in a university hospital setting were analysed. Group I (n = 16) was composed of women that were symptomatic for AUB and group II (n = 15) consisted of asymptomatic cases. The myomectomy material(s) of each case were processed with CD34 staining and evaluated by Image J® software (Image J 1.52a, Wayne Rasband National Institutes of Health, Bethesda, MD). There was no statistically significant difference between the rates of vascular areas in the specimens of the two groups (p>.05). Although areas with large vessels were higher in group I compared to group II, the difference did not reach statistical significance (p>.05). AUB caused by FIGO Type 4-7 leiomyomas seems to be related to factors other than vascular density.Impact StatementWhat is already known on this subject? Uterine leiomyomas are the most common benign gynaecologic neoplasms with a prevalence of approximately 40% in women of reproductive age. They are most often asymptomatic but when symptomatic, abnormal uterine bleeding (AUB) is one of the most commonly observed symptoms. Although there are some hypothetical explanations, the exact pathogenesis underlying leiomyoma-associated AUB has not yet been elucidated. Almost a century ago, the vascular abnormalities of fibroids were hypothesised as one of the etiopathological factors correlated with clinical symptoms, such as AUB, and current data suggest that the vascular map of leiomyomas consists of an avascular core surrounded by a vascularised capsule. To our knowledge, there are no studies in the literature comparing the histopathological evaluation of the vascularity scores of FIGO Type 4-7 leiomyomas in symptomatic (with AUB) and asymptomatic (without AUB) women.What the results of this study add? The study revealed that there was no statistically significant difference between the vascularity scores of FIGO Type 4-7 leiomyomas excised from the symptomatic and asymptomatic women. Large vessel densities also did not statistically significantly differ between the two groups.What the implications are of these findings for clinical practice and/or further research? This study revealed that AUB caused by FIGO Type 4-7 leiomyomas was related to factors other than vascular density.

PMID:33938365 | DOI:10.1080/01443615.2021.1882969

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Exploring potential of copper and silver nano particles to establish efficient callogenesis and regeneration system for wheat (Triticum aestivum L.)

GM Crops Food. 2021 May 3:1-22. doi: 10.1080/21645698.2021.1917975. Online ahead of print.

ABSTRACT

In vitro recalcitrance of wheat to regeneration is the major bottleneck for its improvement through callus-based genetic transformation. Nanotechnology is one of the most dynamic areas of research, which can transform agriculture and biotechnology to ensure food security on sustainable basis. Present study was designed to investigate effects of CuSO4, AgNO3 and their nanoparticles on tissue culture responses of mature embryo culture of wheat genotypes (AS-2002 and Wafaq-2001). Initially, MS-based callus induction and regeneration medium were optimized for both genotypes using various concentrations of auxin (2,4-D, IAA) and cytokinins (BAP, kinetin). The genotypes differed for embryogenic callus induction and regeneration potential. Genotype AS-2002 yielded maximum embryogenic calli in response to 3.0 mg/l 2,4-D, whereas Wafaq-2001 offered the highest embryogenic calli against 3.5 mg/l 2,4-D supplemented in the induction medium. Genotype AS-2002 showed maximum regeneration (59.33%) in response to regeneration protocol comprising 0.5 mg/l IAA, 0.3 mg/l BAP and 1.0 mg/l Kin, while Wafaq-2001 performed best in response to 0.5 mg/l IAA, 0.3 mg/l BAP and 1.5 mg/l Kin with 55.33% regeneration efficiency. The same optimized basal induction and regeneration medium for both genotypes were further used to study effects of CuSO4, AgNO3 and their nano-particles employing independent experiments. The optimized induction medium fortified with various concentrations of CuSO4 or CuNPs confirmed significant effects on frequency of embryogenic callus. Addition of either 0.020 mg/l or 0.025 mg/l CuSO4, or 0.015 mg/l CNPs showed comparable results for embryogenic callus induction and were statistically at par with embryogenic callus induction of 74.00%, 75.67% and 76.83%, respectively. Significantly higher regeneration was achieved from MS-based regeneration medium supplemented with 0.015 mg/l or 0.020 mg/l CuNPs than standard 0.025 mg/l CuSO4. In another study, the basal induction and regeneration medium were fortified with AgNO3 or AgNPs ranging from 1 to 7 mg/l along with basal regeneration media devoid of AgNO3 or AgNPs (control). The maximum embryogenic calli were witnessed from medium fortified with 3.0 mg/l or 4.0 mg/l AgNPs compared with control and rest of the treatments. The standardized regeneration medium fortified with 5.0 mg/l AgNO3 or 3.0 mg/l AgNPs showed pronounced effect on regeneration of wheat genotypes and offered maximum regeneration compared with control. The individual and combined effect of Cu and Ag nanoparticles along with control (basal regeneration media of each genotype) was also tested. Surprisingly, co-application of metallic NPs showed a significant increase in embryogenic callus formation of genotypes. Induction medium supplemented with 0.015 mg/l CuNPs + 4.0 mg/l AgNPs or 0.020 mg/l CuNPs + 2.0 mg/l AgNPs showed splendid results compared to control and other combination of Cu and Ag nanoparticles. The maximum regeneration was achieved by co-application of 0.015 mg/l CuNP and 4.0 mg/l AgNPs with 21% increment of regeneration over control. It is revealed that CuNPs and AgNPs are potential candidate to augment somatic embryogenesis and regeneration of mature embryo explants of wheat.

PMID:33938377 | DOI:10.1080/21645698.2021.1917975

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Total intrapartum fetal reperfusion time (fetal resilience) and neonatal academia

J Matern Fetal Neonatal Med. 2021 May 2:1-10. doi: 10.1080/14767058.2021.1915977. Online ahead of print.

ABSTRACT

OBJECTIVE: The main objective is to study the predictive capacity of intrapartum total fetal reperfusion (fetal resilience) by itself or in combination with other parameters as a predictor of neonatal acidemia.

STUDY DESIGN: A retrospective case-control study was carried out at the Miguel Servet University Hospital (Zaragoza, Spain) on a cohort of 5694 pregnant women between June 2017 and October 2018. Maternal, perinatal, and cardiotocographic records were collected. Two reviewers blindly described the monitors with the American College of Obstetricians and Gynecologists (ACOG) categorizations and parameters and the non-ACOG parameters. Neonatal acidemia was defined as pH <7.10. The parameters analyzed to predict acidemia were evaluated using the sensitivity for specificity 90% value, and the area under the receiver operating characteristic curve.

RESULTS: We recorded 192 infants with acidemia, corresponding to a global acidemia rate of 3.4%. Of these, 72 were excluded for lack of criteria, leaving 120 patients with arterial acidemia included in the study and 258 in the control group. The sensitivity (specificity 90%) of detection of acidemia was 42% for the ACOG III categorization (AUC, 0.524: 95% CI, 0.470-0.578), 24% for fetal reperfusion (AUC, 0.704: 95% CI, 0.649-0.759), 27% for total area of decelerations (AUC, 0.717: 95% CI, 0.664-0.771) and 50% for the multivariate model built from total reperfusion time (AUC, 0.826: 95% CI, 0.783-0.869). The total reperfusion time corresponding to a false negative rate of 10% is 23.75 min, with 28% of fetuses above this time. The AUC and sensitivity for a false negative rate of 10% are equivalent for deceleration area and time of reperfusion (p = .504).

CONCLUSION: The total reperfusion time (fetal resilience) and total deceleration area are non-ACOG parameters with a good predictive ability for neonatal acidemia, higher than the ACOG III classification and without statistical differences between them. The discrimination ability of total reperfusion time can be improved using a multivariate model. As a cutoff for its use we suggest 23.75 min in 30 min corresponding to an acidemic classification rate of 90%. New parameters in combination with other maternal, obstetrics, or fetal variables, are required for the interpretation of fetal well-being.

PMID:33938352 | DOI:10.1080/14767058.2021.1915977

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Convergence analysis of sample average approximation for a class of stochastic nonlinear complementarity problems: from two-stage to multistage

Numer Algorithms. 2021 Apr 27:1-28. doi: 10.1007/s11075-021-01110-z. Online ahead of print.

ABSTRACT

In this paper, we consider the sample average approximation (SAA) approach for a class of stochastic nonlinear complementarity problems (SNCPs) and study the corresponding convergence properties. We first investigate the convergence of the SAA counterparts of two-stage SNCPs when the first-stage problem is continuously differentiable and the second-stage problem is locally Lipschitz continuous. After that, we extend the convergence results to a class of multistage SNCPs whose decision variable of each stage is influenced only by the decision variables of adjacent stages. Finally, some preliminary numerical tests are presented to illustrate the convergence results.

PMID:33935468 | PMC:PMC8076443 | DOI:10.1007/s11075-021-01110-z

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I-Kappa-B-Zeta Regulates Interleukin-17A/Tumor Necrosis Factor-Alpha Mediated Synergistic Induction of Interleukin-19 and Interleukin-20 in Humane Keratinocytes

Ann Dermatol. 2021 Apr;33(2):122-130. doi: 10.5021/ad.2021.33.2.122. Epub 2021 Mar 8.

ABSTRACT

BACKGROUND: Interleukin (IL)-19 and IL-20 are important members of the IL-10 cytokine family, which are known to play a role in inflammatory processes. Both anti-IL-19 and -IL-20 targeting drugs have been suggested in the treatment of inflammatory diseases such as psoriasis and rheumatoid arthritis. Recently, we presented I-kappa-B-zeta (IκBζ) as a key player in psoriasis by identifying IκBζ as a regulator of IL-17/tumor necrosis factor (TNF)α-inducible psoriasis-associated genes and proteins. Some of these genes were synergistically regulated by IL-17/TNFα.

OBJECTIVE: The purpose of this study was to explore the role of IκBζ in the regulation of IL-17A/TNFα-mediated induction of IL-19 and IL-20 expression in human keratinocytes.

METHODS: In vitro experiments with cultured primary humane keratinocytes were conducted and investigated by quantitative polymerase chain reaction (qPCR), Western blotting, ELISA and EMSA. For statistics, a one- or two- way repeated-measures analysis of variance (RM ANOVA) or the Friedman test (a nonparametric equivalent to the RM ANOVA) were conducted.

RESULTS: We demonstrated that IL-19 and IL-20 mRNA and protein expressions were synergistically induced by IL-17A and TNFα, whereas IL-17A and TNFα alone had only a minor effect on the IL-19 and IL-20 expression. Moreover, we demonstrated IκBζ to be a regulator of this synergistic induction of IL-19 and IL-20. Finally, the IL-17A/TNFα-induced synergistic induction of IL-19 and IL-20 expression was found to be mediated by a p38 MAPK-, NF-κB- and JNK1/2-dependent mechanism.

CONCLUSION: This study demonstrates that IκBζ plays a role in the IL-17A/TNFα-mediated synergistic induction of IL-19 and IL-20 in humane keratinocytes.

PMID:33935453 | PMC:PMC8081996 | DOI:10.5021/ad.2021.33.2.122

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Predictor of Subungual Melanoma against Benign Longitudinal Melanonychia: A Retrospective Cohort Study from Korea

Ann Dermatol. 2021 Apr;33(2):147-153. doi: 10.5021/ad.2021.33.2.147. Epub 2021 Mar 8.

ABSTRACT

BACKGROUND: Longitudinal melanonychia (LM) is a common clinical finding. Most cases of LM are benign, and a wait-and-see approach is preferred in the management of this condition. Nevertheless, it is important for clinicians to distinguish subungual melanoma (SUM) from other benign LMs.

OBJECTIVE: To evaluate the demographic and clinicopathologic characteristics of LM in the Korean population and to identify the predictor of SUM against other benign conditions.

METHODS: This was a single-center retrospective cohort study including patients who underwent nail biopsy for LM from January 2000 to May 2019. To identify the predictor of SUM, receiver operating characteristic (ROC) analyses was performed.

RESULTS: A total of 68 cases of biopsy-proven LM were included in the analysis. Among the 68 cases, 8 were SUM. In univariable analysis, patients diagnosed with SUM were older (p=0.035) and had a longer disease duration (p=0.004). They also showed multicolor pigmentation of LM (p=0.022), a larger width of LM (p<0.001), and associated nail plate dystrophy (p=0.010) than patients diagnosed with benign conditions. In multivariable logistic regression, width of LM showed statistical significance (odds ratio, 1.083; 95% confidence interval, 1.018~1.153). ROC analysis suggested that an LM width >28% of the whole nail was the predictor of SUM (area under the curve=0.883; p<0.001).

CONCLUSION: SUM has distinct demographic and clinical features. The width of LM can predict SUM against other benign LMs.

PMID:33935456 | PMC:PMC8082004 | DOI:10.5021/ad.2021.33.2.147

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Combination Treatment of Intra/Perilesional Botulinum Toxin-A Injection and Ablative Fractional Laser for Better Clinical Outcomes of Hypertrophic Fibrotic Thyroidectomy Scars Following Fractional Ablative Laser Resurfacing

Ann Dermatol. 2021 Apr;33(2):170-177. doi: 10.5021/ad.2021.33.2.170. Epub 2021 Mar 8.

ABSTRACT

BACKGROUND: Recent reports have shown that intralesional botulinum toxin type-A (BTX-A) works on scar cosmesis.

OBJECTIVE: To evaluate the clinical efficacy of combination treatment of laser and BTX-A injection and compare the effects of conventional intralesional injection and intra- and perilesional BTX-A injection on fibrotic thyroidectomy scars.

METHODS: Patients with fibrotic thyroidectomy scars showing insufficient responses to previous ablative fractional laser (AFL) treatment were enrolled. Combination treatment with AFL and BTX-A injection was performed. Patients who received intra/perilesional BTX-A injections were classified into group A. Group B was patients in whom the injection was performed only intralesionally. The improvement was assessed based on the Vancouver Scar Scale (VSS).

RESULTS: A total of 24 patients was included. Statistically significant improvement in pliability and total VSS score after the combination treatment were observed in overall patient group. Subgroup analysis demonstrated that pliability, height, and total VSS improved significantly in group A. In group B, only pliability significantly improved.

CONCLUSION: BTX-A injection combined with AFL can provide better relief for the previously treated fibrotic thyroidectomy scars. Injection of BTX-A not only into the scar itself, but also into perilesional muscles that can exert tension on the scar site may provide additional benefit in flattening scar height.

PMID:33935459 | PMC:PMC8082008 | DOI:10.5021/ad.2021.33.2.170