Intake of folic acid by Polish women with higher education — a survey research: can we do more?

Objectives: The objective of the study is to determine efficacy of the Primary Prevention Program of Neural Tube Defects in Polish women with higher education in 5-year interval. Material and methods: Survey research was conducted twice (in 2008 and 2013) in 630 female students of universities: 305 female medical students and 325 female non-medical students. The survey was also done among women aged 27– 35 who graduated from medical or non-medical universities and have at least one child. Questions concerned knowledge about prophylaxis and periconceptional folic acid intake. Chi square test was used to assess the significance. Results: Knowledge concerning prophylaxis was significantly higher in female medical students comparing to non-medical ones, both in 2008 (p < 0,001), and in 2013 (p < 0,001). 92.9% in 2008 and 93.9% in 2013 of medical students knew about the necessity of periconceptional folic acid intake. Awareness of female non-medical students was lower (2008 — 35.3% and 2013 — 41.1%) and did not change in the 5-year long period (p = 0.3). There was no significant difference in preconceptional folic acid intake among mothers with medical and non-medical education (53.3% vs. 45% p = 0.4). However, the highest folic acid intake was among mothers –medical doctors who treat children with neural tube defect. Conclusions: Difference between medical and non-medical students shows that better educational programs may improve knowledge about prophylaxis. Aside from knowledge, compliance with recommendations of Primary Prevention Program of Neural Tube Defects is unsatisfactory

Treatment of twin to twin transfusion syndrome – comparison of two therapeutic methods – amnioreduction and lasertherapy

Background: Twin to twin transfusion syndrome occurs in 15% of monochorionic twin pregnancies. Untreated, TTTS has been reported to have a mortality of nearly 100%. Two main therapies include serial amnioreduction and fetoscopic laser coagulation for the vascular anastomoses. Objectives: The aim of the project was to investigate the optimal diagnostic and therapeutic procedure in pregnancies complicated by TTTS. Additionally, the study was supposed to compare non – invasive and invasive methods of treatment and to show antenatal and postnatal follow – up to 4 months of age. Methods: 42 pregnant women with twin-to-twin transfusion syndrome were assigned to laser therapy using diode laser and 33 pregnant women underwent only several amnioreductions. Selected parameters characterizing the pregnancy were compared in both groups. Results: In the amnioreduction group, the perinatal survival rate seven days after the delivery was 31.8%. The survival rate of at least one twin was 39.4%. As compared to the amnioreduction group, in the laser group the survival rate of at least one twin was observed in 31 cases (31/42) and it was equal to 74%. Neurological complications in the amninoreduction group were obsereved in 19% (4/21) of cases, in the laser group and in 5% (2/40) of neonates at 4 months of age. Conclusions: Currently, the preferred and only method that addresses the cause of the disease is the endoscopic laser coagulation of anastomoses. Comparison of the two treatments shows better outcomes with higher survival rates and minor neurological defects in cases treated with laser coagulation

Terapia płodu – ocena zastosowania shuntu komorowo-owodniowego w leczeniu wodogłowia

Objective: The aim of the study was to establish optimal diagnostic and therapeutic scheme and to assess the efficacy of intrauterine therapy of hydrocephalus. Material and methods: The study was carried out between 1992-2012 on the total of 222 fetuses with hydrocephalus, using Orbis-Sigma and ACCU-Flow valves (168 cases) and Cook’s shunts, according to a strictly defined diagnostic and therapeutic scheme. Results: In the first stage of the study (between 1992-2001), a total of 168 fetuses with prenatally diagnosed hydrocephalus received intrauterine therapy. In 91.6% of the cases the therapy resulted in a decreased size of cerebral ventricles. The valve dislocated in 23 cases (13.6%). Preterm delivery occurred in 44% of the affected neonates. Severe mental impairment occurred in 17.76%, average in 36.8%, and slight in 32.9% of the infants. Normal mental development at the age of 3 was observed in 12.5% of the children. A total of 11.2% of children did not require further neurosurgical reatment. In the second stage of the study (between 2006-2012) after therapy, the size of the right lateral cerebral ventricle decreased by 54.76% (average of 27.54 mm to 12.46 mm) and the left lateral cerebral ventricle decreased by 53.12% (average of 26.41 mm to 12.38 mm ) (p=0.0018). The maximum and minimum width of the cerebral cortex increased by 23.06% and 27% (average of 9.04 mm to 11.75 mm vs. 3.65 mm to 5mm), respectively. Early complications were observed in 22% of the cases: PROM (6), intrauterine fetal death (4), intrauterine infection (1), and premature detachment of the placenta (1). Average gestational age at delivery was 34 weeks, and 24% of the patients delivered at term. Conclusions: • Implantation of ventriculo- amniotic shunts proved to be an effective form of therapy, resulting in normalization of intracranial pressure. • In both stages of therapy, reduction of ventricular size in patients with hydrocephalus and good neurological outcome (45.4% in I stage, 60% in II stage) were observed • In the second stage of therapy, the size of lateral brain ventricles after fetal therapy was significantly lower (54%). A total of 18% of the neonates did not require neurosurgical treatment.Cel pracy: Opracowanie optymalnego sposobu postępowania diagnostyczno-terapeutycznego oraz ocena skuteczności terapii wewnątrzmacicznej wodogłowia u płodu. Materiał i metody: Leczenie wewnątrzmaciczne w przypadkach wodogłowia u płodu prowadzono w dwóch etapach u 222 ciężarnych, początkowo z użyciem zastawek Orbis-Sigma i ACCU-Flow (168 przypadków), a następnie shuntów Cook’a, wg ściśle przyjętego schematu postępowania diagnostyczno-terapeutycznego. Wyniki: W pierwszym etapie (w latach 1992-2001) zabiegi wewnątrzmaciczne wykonano na 168 płodach z rozpoznanym prenatalnie wodogłowiem. W 91,6 % uzyskano zmniejszenie układu komorowego mózgu. W 23 przypadkach (13,6 %) zestaw odbarczający uległ dyslokacji. W 44 % przypadków wystąpił poród przedwczesny. Upośledzenie w stopniu ciężkim wystąpiło u 17,76 % dzieci, w stopniu średnim u 36,8 %, w stopniu lekkim u 32,9%. Prawidłowy rozwój w 3 roku życia wykazywało 12,5 % dzieci, leczenia nie wymagało 11,2 % dzieci. W drugim etapie (2006-2012) wielkość prawej komory bocznej mózgu zmniejszyła się o 54,76% ( średnio z 27,54 mm do 12,46 mm), zaś komory bocznej lewej o 53,12% (średnio z 26,41 mm do 12,38 mm) (p=0,0018). Maksymalna szerokość kory mózgu wzrosła o 23,06% (średnio z 9,04 mm do 11,75mm), natomiast minimalna szerokość o 27% ( średnio z 3,65mm do 5mm). Powikłania wczesne terapii (do 7 dni od zabiegu) zaobserwowano u 22% pacjentek, w tym: PROM u 6 pacjentek, zgon wewnątrzmaciczny płodu u 4 pacjentek, infekcja wewnątrzmaciczna u 1 pacjentki, przedwczesne oddzielenie łożyska u 1 pacjentki. Średni czas trwania ciąży wyniósł 34 tyg. 24% pacjentek urodziło w terminie porodu. Wnioski: • Zakładanie shuntów komorowo-owodniowych okazało się skuteczną formą terapii powodującą normalizację ciśnienia wewnątrzczaszkowego. • W obu etapach obserwowano zmniejszenie wodogłowia po terapii oraz dobre efekty neurologiczne w I etapie – u 45,4% a w II etapie u ponad 60% dzieci. • W drugim etapie terapii szerokość komór bocznych mózgu mierzona po zabiegu była istotnie mniejsza (54%). 18% noworodków nie wymagało leczenia neurochirurgicznego

An association between polymorphism of the heme oxygenase-1 and -2 genes and age-related macular degeneration

Iron may be implicated in the generation of oxidative stress by the catalyzing the Haber–Weiss or Fenton reaction. On the other hand, oxidative stress has been implicated in the pathogenesis of age-related macular degeneration (AMD) and heme oxygenase-1 (HO-1), encoded by the HMOX1 gene and heme oxygenase-2 (HO-2), encoded by the HMOX2 gene are important markers of iron-related oxidative stress and its consequences. Therefore, variability of the HMOX1 and HMOX2 genes might be implicated in the pathogenesis of AMD through the modulation of the cellular reaction to oxidative stress. In the present work, we investigated the association between AMD and a G → C transversion at the 19 position in the HMOX1 gene (the 19G>C-HMOX1 polymorphism, rs2071747) and a A → G transition at the −42 + 1444 position in the HMOX2 gene (the −42 + 1444A>G-HMOX2 polymorphism, rs2270363) and its modulation by some environmental factors. 279 patients with AMD and 105 controls were recruited in this study and the polymorphisms were typed by restriction fragment length polymorphism and allele-specific polymerase chain reaction (PCR). We observed an association between the occurrence of dry AMD and the G/A genotype of the −42 + 1444A>G-HMOX2 polymorphism (odds ratio (OR) 2.72), whereas the G/G genotype reduced the risk of dry AMD (OR 0.41). The G/C genotype and the C allele of the 19 G>C-HMOX1 polymorphism and the G/G genotype and the G allele of the −42 + 1444A>G-HMOX2 polymorphism were associated with progression of AMD from dry to wet form (OR 4.83, 5.20, 2.55, 1.69, respectively). On the other hand, the G/G genotype and the G allele of the 19 G>C-HMOX1 polymorphism and the A/G genotype and the A allele of the −42 + 1444A>G-HMOX2 polymorphism protected against AMD progression (OR 0.19, 0.19, 0.34, 0.59, respectively). Therefore, the 19G>C-HMOX1 and the −42 + 1444A>G-HMOX2 polymorphisms may be associated with the occurrence and progression of AMD

Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open -label, international, multicenter, natural history -controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy and safety of idebenone treatment (900 mg/day) in patients with LHON up to 5 years after symptom onset (N = 199) and over a treatment period of 24 months, compared to an external natural history control cohort (N = 372), matched by time since symptom onset. LEROS meets its primary endpoint and confirms the long-term efficacy of idebenone in the subacute/dynamic and chronic phases;the treatment effect varies depending on disease phase and the causative mtDNA mutation. The findings of the LEROS study will help guide the clinical management of patients with LHON

Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy and safety of idebenone treatment (900 mg/day) in patients with LHON up to 5 years after symptom onset (N = 199) and over a treatment period of 24 months, compared to an external natural history control cohort (N = 372), matched by time since symptom onset. LEROS meets its primary endpoint and confirms the long-term efficacy of idebenone in the subacute/dynamic and chronic phases; the treatment effect varies depending on disease phase and the causative mtDNA mutation. The findings of the LEROS study will help guide the clinical management of patients with LHON

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

Transferrin receptor levels and polymorphism of its gene in age-related macular degeneration

The aim of the present study was to investigate the association of age related macular degeneration (AMD) risk with some aspects of iron homeostasis: iron concentration in serum, level of soluble transferrin receptor (sTfR), and transferrin receptor (TFRC) genetic variability. Four hundred and ninety one AMD patients and 171 controls were enrolled in the study. Restriction fragment length polymorphism PCR was employed to genotype polymorphisms of the TFRC gene, and colorimetric assays were used to determine the level of iron and sTfR. Multiple logistic regression was applied for all genotype/allele-related analyses and the ANOVA test for iron and sTfR serum level comparison. We found that the genotypes and alleles of the c.-253G > A polymorphism of the TFRC gene were associated with AMD risk and this association was modulated by smoking status, AMD family history, living environment (rural/urban), body mass index and age. The levels of sTfR was higher in AMD patients than controls, whereas concentrations of iron did not differ in these two groups. No association was found between AMD occurrence and the p.Gly142Ser polymorphism of the TRFC gene. The results obtained suggest that transferrin receptor and variability of its gene may influence AMD risk

Variability of the Transferrin Receptor 2 Gene in AMD

Oxidative stress is a major factor in the pathogenesis of age-related macular degeneration (AMD). Iron may catalyze the Fenton reaction resulting in overproduction of reactive oxygen species. Transferrin receptor 2 plays a critical role in iron homeostasis and variability in its gene may influence oxidative stress and AMD occurrence. To verify this hypothesis we assessed the association between polymorphisms of the TFR2 gene and AMD. A total of 493 AMD patients and 171 matched controls were genotyped for the two polymorphisms of the TFR2 gene: c.1892C>T (rs2075674) and c.−258+123T>C (rs4434553). We also assessed the modulation of some AMD risk factors by these polymorphisms. The CC and TT genotypes of the c.1892C>T were associated with AMD occurrence but the latter only in obese patients. The other polymorphism was not associated with AMD occurrence, but the CC genotype was correlated with an increasing AMD frequency in subjects with BMI < 26. The TT genotype and the T allele of this polymorphism decreased AMD occurrence in subjects above 72 years, whereas the TC genotype and the C allele increased occurrence of AMD in this group. The c.1892C>T and c.−258+123T>C polymorphisms of the TRF2 gene may be associated with AMD occurrence, either directly or by modulation of risk factors