Relationship of SOD-1 Activity in Metabolic Syndrome and/or Frailty in Elderly Individuals.

INTRODUCTION: Although aging is a natural phenomenon, in recent years it has accelerated. One key factor implicated in the aging process is oxidative stress. Oxidative stress also plays a role in frailty (frail) and metabolic syndrome (MetS). METHODS: A total of 66 elderly persons (65 years old and older) with no acute or severe chronic disorders were assessed for waist circumference (WC), arterial blood pressure, glycemia, glycated hemoglobin (HbA1c), plasma lipids, and activity of erythrocyte superoxide dismutase (SOD-1). Patients were classified as NonMetS-Nonfrail (n = 19), NonMetS-frail (n = 20), MetS-Nonfrail (n = 17), or MetS-frail (n = 10). RESULTS: There were no significant differences in superoxide dismutase activity among investigated elderly groups. However, the data suggest that MetS individuals, both frail and nonfrail, have higher risk factors for cardiovascular disease compared to NonMetS individuals. The correlations analyses of SOD-1 and other metabolic indices suggest that SOD-1 levels may be influenced by age, total cholesterol, HDL cholesterol, and fasting glucose levels in certain groups of seniors. CONCLUSIONS: Aging is associated with decreased antioxidant enzyme SOD-1 activity with glucose alteration in frailty syndrome as well as with lipids disturbances in metabolic syndrome. These factors provide a nuanced view of how frailty and metabolic syndrome interact with various health parameters, informing both clinical practice and future research directions.

CFTR Modulators Therapy Efficacy in Reducing Cystic Fibrosis (CF) Exacerbation and Improving Selected Spirometry Parameters: A Real-Life Study in a Single-Centre Polish Population.

Background/Objectives: Cystic fibrosis is a genetically determined disease that significantly influences and shortens life. Treatment with CFTR modulators (CFTR-T) is a new hope for patients. It can change the predictive values of a poor prognosis (e.g., exacerbation rate and FEV1 value). The aim of the study was to analyse exacerbation incidence and spirometry data before and after one year (+/- 2 weeks) of CFTR-T in 85 CF patients at the CF Centre in Poznan. To our knowledge, this is the first analysis of CFTR-T efficiency in the Central-Eastern Europe population. Methods: We retrospectively analysed the spirometry and exacerbation data of 85 CF adult patients (both men and women), who in the middle of 2022 began treatment with CFTR modulators. Results: The one-year ratio of hospitalisation caused by severe exacerbations lowered from 1.25 to 0.21 per patient per year. We also saw a 66% decline in ambulatory exacerbations. The median FEV1% increased by 9.60% in absolute values and by 460 mL. Even in the group with very severe obstruction (FEV1 < 35%), there was an increase in median FEV1% of 5.9 in absolute values. We also proved the increase in FVC% (median 17.10% in absolute value and 600 mL) in the study group. Conclusions: After one year of treatment, an impressive improvement was observed in two important predictive values of poor prognosis: exacerbation rate and FEV1 values. Further observation is needed to determine how long the improvement will be present and its influence on quality of life and life expectancy.

Genetic variants of MTHFR gene in relation to folic acid levels and bone mineral density in Polish patients with inflammatory bowel disease.

Lower bone mineral density (BMD) constitutes a common issue in inflammatory bowel disease (IBD). Studies often explore the association between BMD and folic acid level. The presented study aimed to evaluate the impact of MTHFR gene polymorphism and folic acid levels on BMD in patients with IBDs: Crohn's disease (CD) and ulcerative colitis (UC). The study group comprised IBD patients and a healthy control group. BMD, T-score, and Z-score of the lumbar spine (L1-L4) and femoral neck (FN) were assessed using dual-energy X-ray absorptiometry. Folic acid level was determined using direct chemiluminescence, and the MTHFR 677C > T (rs1801133) and 1298A > C (rs1801131) genotyping were performed by HRMA. Our study found no significant differences in the folic acid levels between the groups. Patients with CD and UC presented a lower BMD, T-score, and Z-score of the FN and L1-L4 than the CG. UC patients who were homozygotes AA in loci c.1298A>C presented lower than controls lumbar spine L1-L4 BMD and T-score values. Regarding MTHFR 677 polymorphism, we found that IBD patients carrying CC genotype demonstrated lower than controls femoral neck Z-score, lumbar spine L1-L4 BMD, T-score and Z-score. MTHFR polymorphisms were found to have no impact on folic acid concentrations. IBD patients presented a higher risk of low BMD than the healthy controls, regardless of MTHFR 677 and 1298 genotypes. However, MTHFR polymorphism may influence on bone in IBD patients. Nevertheless, it appears essential to conduct further studies.

A single amino acid substitution in MdLAZY1A dominantly impairs shoot gravitropism in Malus.

Plant architecture is 1 of the most important factors that determines crop yield potential and productivity. In apple (Malus domestica), genetic improvement of tree architecture has been challenging due to a long juvenile phase and growth as complex trees composed of a distinct scion and a rootstock. To better understand the genetic control of apple tree architecture, the dominant weeping growth phenotype was investigated. We report the identification of MdLAZY1A (MD13G1122400) as the genetic determinant underpinning the Weeping (W) locus that largely controls weeping growth in Malus. MdLAZY1A is 1 of the 4 paralogs in apple that are most closely related to AtLAZY1 involved in gravitropism in Arabidopsis (Arabidopsis thaliana). The weeping allele (MdLAZY1A-W) contains a single nucleotide mutation c.584T>C that leads to a leucine to proline (L195P) substitution within a predicted transmembrane domain that colocalizes with Region III, 1 of the 5 conserved regions in LAZY1-like proteins. Subcellular localization revealed that MdLAZY1A localizes to the plasma membrane and nucleus in plant cells. Overexpressing the weeping allele in apple cultivar Royal Gala (RG) with standard growth habit impaired its gravitropic response and altered the growth to weeping-like. Suppressing the standard allele (MdLAZY1A-S) by RNA interference (RNAi) in RG similarly changed the branch growth direction to downward. Overall, the L195P mutation in MdLAZY1A is genetically causal for weeping growth, underscoring not only the crucial roles of residue L195 and Region III in MdLAZY1A-mediated gravitropic response but also a potential DNA base editing target for tree architecture improvement in Malus and other crops.

Time Perspective as a Mediator of Depressive Symptoms in Patients with Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a chronic endocrinopathy characterized by oligo- or anovulation, clinical and/or biochemical markers of hyperandrogenism, and polycystic ovaries, and it is associated with an increased prevalence of depression. Research conducted on psychiatric patients has shown correlations between depression and decreased cognitive function. The aim of this study was to examine the possible mediation of the time perspective (TP) in the development of depressive symptoms in patients with PCOS. METHODS: A study was conducted on 83 patients with PCOS and 65 healthy women. Standardized questionnaires were used to assess depressive symptoms (Beck Depression Inventory-BDI-II) and time perspective (Zimbardo Time Perspective Inventory-ZTPI). RESULTS: Our study revealed an indirect influence of depressive symptoms on PCOS through the positive future time perspective. In the logistic regression model, which included depression and a given time perspective as predictors of PCOS, only the future TP (ß = -0.004, p < 0.003, OR = 1.004, 95% CI [1.001, 1.008]) was significantly independently related to the occurrence of PCOS. CONCLUSIONS: Our result is another argument for the role of psychoeducation and appropriate communication with a patient from the risk group in a way that builds hope and allows to regain influence on life situation.

SnRK1 kinase-mediated phosphorylation of transcription factor bZIP39 regulates sorbitol metabolism in apple.

Sorbitol is a major photosynthate produced in leaves and transported through the phloem of apple (Malus domestica) and other tree fruits in Rosaceae. Sorbitol stimulates its own metabolism, but the underlying molecular mechanism remains unknown. Here, we show that sucrose nonfermenting 1 (SNF1)-related protein kinase 1 (SnRK1) is involved in regulating the sorbitol-responsive expression of both SORBITOL DEHYDROGENASE 1 (SDH1) and ALDOSE-6-PHOSPHATE REDUCTASE (A6PR), encoding 2 key enzymes in sorbitol metabolism. SnRK1 expression is increased by feeding of exogenous sorbitol but decreased by sucrose. SnRK1 interacts with and phosphorylates the basic leucine zipper (bZIP) transcription factor bZIP39. bZIP39 binds to the promoters of both SDH1 and A6PR and activates their expression. Overexpression of SnRK1 in 'Royal Gala' apple increases its protein level and activity, upregulating transcript levels of both SDH1 and A6PR without altering the expression of bZIP39. Of all the sugars tested, sorbitol is the only 1 that stimulates SDH1 and A6PR expression, and this stimulation is blocked by RNA interference (RNAi)-induced repression of either SnRK1 or bZIP39. These findings reveal that sorbitol acts as a signal regulating its own metabolism via SnRK1-mediated phosphorylation of bZIP39, which integrates sorbitol signaling into the SnRK1-mediated sugar signaling network to modulate plant carbohydrate metabolism.

The Effect of 75 Grams of Glucose during OGTT on Plasma Markers of Lipid and Lipoprotein Peroxidation, Oxidized LDL and Thiobarbituric Acid Reactive Substances, in People with Increased Body Mass.

Obesity, currently defined as a disease, is associated with a number of metabolic disorders, and oxidative stress is discussed as the link between them. The aim of this study was to analyze the plasma markers reflecting oxidative modification of lipids and lipoproteins, oxidized LDL (oxLDL) and thiobarbituric acid reactive substances (TBARS), under the influence of the 75 g of oral glucose during oral glucose tolerance test (OGTT), in patients with increased body mass. One hundred twenty individuals of both genders (46 women and 74 men) aged 26 to 75 years with increased body mass (BMI > 25 kg/m2) were recruited for the study. OGTT was performed in each of the qualified persons, and glycemia, insulinemia, and concentrations of oxLDL and TBARS were measured fasting and at 120 min of OGTT. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to assess the degree of insulin resistance (IR). In order to assess the changes of the investigated parameters under the influence of 75 g glucose, the index ROGTT = [120']/[0'] was calculated to obtain oxLDL-ROGTT and TBARS-ROGTT. The statistical analysis was performed in the entire study population and subsequent groups from H1 to H4, defined by HOMA-IR quartiles. In the entire study population and the subgroups, oxidative stress markers changed during OGTT. From H1 to H4 group, increasing oxLDL and TBARS were observed both in the fasting state and at 120 min of OGTT, and the oxLDL-ROGTT index decreased from the H2 to the H4 group. The intensification of IR in people with increased body mass may predispose them to enhanced oxidative modification of lipoproteins. Individual reduction in the concentration of oxLDL during OGTT, in reference to fasting value (decreased oxLDL-ROGTT), suggests increased uptake of modified lipoproteins by scavenger receptor-presenting cells or increased migration to the vascular wall.

Anthocyanin Accumulation Provides Protection against High Light Stress While Reducing Photosynthesis in Apple Leaves.

The photoprotective role of anthocyanin remains controversial. In this study, we explored the effects of anthocyanin on photosynthesis and photoprotection using transgenic 'Galaxy Gala' apple plants overexpressing MdMYB10 under high light stress. The overexpression of MdMYB10 dramatically enhanced leaf anthocyanin accumulation, allowing more visible light to be absorbed, particularly in the green region. However, through post-transcriptional regulation, anthocyanin accumulation lowered leaf photosynthesis in both photochemical reaction and CO2 fixation capacities. Anthocyanin accumulation also led to a decreased de-epoxidation state of the xanthophyll cycle and antioxidant capacities, but this is most likely a response to the light-shielding effect of anthocyanin, as indicated by a higher chlorophyll concentration and lower chlorophyll a/b ratio. Under laboratory conditions when detached leaves lost carbon fixation capacity due to the limitation of CO2 supply, the photoinhibition of detached transgenic red leaves was less severe under strong white, green, or blue light, but it became more severe in response to strong red light compared with that of the wild type. In field conditions when photosynthesis was performed normally in both green and transgenic red leaves, the degree of photoinhibition was comparable between transgenic red leaves and wild type leaves, but it was less severe in transgenic young shoot bark compared with the wild type. Taken together, these data show that anthocyanin protects plants from high light stress by absorbing excessive visible light despite reducing photosynthesis.

Is it time to change the goals of lipid management in type 1 diabetes mellitus? Changes in apolipoprotein levels during the first year of type 1 diabetes mellitus. Prospective InLipoDiab1 study.

Introduction: Apolipoprotein complement is a critical determinant of lipoprotein function and metabolism. The relation between exogenous insulin and apolipoproteins (apos) in newly diagnosed type 1 diabetes mellitus (T1DM) has not yet been studied extensively. The aim of this study was to prospectively observe the changes in serum apos AI (apo AI) and AII (apo AII) in patients with newly diagnosed T1DM and their association with the daily insulin requirement. Material and methods: Thirty-four participants of the InLipoDiab1 study aged 26 (IQR: 22-32) were enrolled in this analysis. Apolipoprotein AI and AII concentrations were assessed at diagnosis and at follow-up after 3 weeks, 6 months, and 1 year of insulin treatment. The daily dose of insulin (DDI) was calculated as the amount of short- and long-acting insulin at discharge from the hospital and at follow-up visits. Results: The changes in apo AI concentration were observed after 3 weeks of insulin treatment (p = 0.04), with the largest increase between 3 weeks and 6 months of observation (p < 0.001). Apolipoprotein AII level did not change significantly after 3 weeks, while a significant increase was observed between 3 weeks and 6 months of treatment (p < 0.001). The correlations between DDI and apo concentration were not statistically significant. Conclusions: In the first year of T1DM, there is a significant increase in apos concentration. Due to the significant deviation of apos concentration from accepted norms, changes in the recommendations of lipid control criteria in T1DM may be considered.

An Assessment of Selected Molecular and Biochemical Markers of the Folate Pathway as Potential Risk Factors for Fetal Trisomy 21 during the First Trimester of Pregnancy in the Polish Population.

Are the maternal gene variants MTHFR: c.665C>T, MTHFR: c.1286A>C, MTR: c.2756A>G, MTRR: c.66A>G, RFC1: c.80C>T and TCN2: c.776G>C and blood markers of the folate pathway important factors in assessing the risk of fetal trisomy 21 (fetal-T21)? Twenty pregnant women with a high risk and twenty with a low risk of fetal-T21 underwent prenatal examination. Selected gene variants and folate pathway markers and pregnancy-associated plasma protein A (PAPP-A) and free ß-subunit of human chorionic gonadotropin ß (free-ß-hCG) multiple of the medians (MoMs) were determined. The distributions of the alternative alleles and genotypes of the gene variants did not differ between the studied groups. There was no relationship between PAPP-A and ß-hCG MoM values and the presence of allele alternative genotype variants. The occurrence of alternative variants of the selected genes and concentrations of most of the studied folate pathway markers may not play a crucial role in the risk of fetal-T21 in pregnant women. However, the relationships between erythrocyte folate concentrations and the occurrence of alternative variants: c.665C>T MTHFR and c.776G>C TCN2, as well as the methylmalonic acid concentration and the occurrence of alternative variant c.776G>C TCN2 in pregnant women with fetal-T21, encourage further research. So far, of the biochemical markers, maternal PAPP-A and ß-hCG MoM values remain independent risk factors for fetal-T21.

Clinical significance of basic laboratory parameters in predicting the use of various methods of oxygen supplementation in COVID-19.

INTRODUCTION: The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection resulted in significant worldwide morbidity and mortality. The aim of our study was to evaluate the results of laboratory tests performed on patients on admission to the hospital between groups of patients requiring and not requiring oxygen supplementation, and to find predictive laboratory indicators for the use of high-flow nasal oxygen therapy (HFNOT)/continuous positive airway pressure (CPAP)/bilevel positive airway pressure (BPAP). MATERIALS AND METHODS: We retrospectively analysed the data of consecutive patients hospitalised in the Pulmonology Department of the Temporary COVID Hospital in Poznan from February to May 2021. On admission to the department, the patients had a panel of laboratory blood tests. RESULTS: The study group consisted of 207 patients with a mean age of 59.2 ± 15.0 years of whom 179 (72%) were male. During hospitalisation, oxygen supplementation was required by 87% of patients. Patients requiring oxygen supplementation and/or the use of HFNOT/CPAP/BPAP had lower lymphocyte counts and higher levels of urea, C-reactive protein, D-dimer, troponin, glucose, lactate dehydrogenase (LDH) as well as higher white blood cell and neutrophil counts, The parameter that obtained the highest area under curve value in the receiver operator curve analysis for the necessary use of HFNOT/CPAP/BPAP or CPAP/BPAP was LDH activity. CONCLUSIONS: Among the basic parameters assessed on admission to the temporary hospital, LDH activity turned out to be the most useful for assessing the need for CPAP/BPAP active oxygen therapy. Other parameters that may be helpful for predicting the need for HFNOT/CPAP/BPAP are serum levels of urea, D-dimer and troponin.

Cyberbullying and its protective and risk factors among Polish adolescents.

BACKGROUND: Cyberbullying has recently attracted attention because of its increasing occurrence and serious consequences for victims. The purpose of the study was to examine the prevalence rates of cyberbullying and the association between cyberbullying and protective/risk factors (cognitive empathy, assertiveness, cooperation, pro-social behaviour, and social support) among Polish adolescents. PARTICIPANTS AND PROCEDURE: Participants (822 students, 448 girls and 374 boys, M = 12.97, SD = 1.02) completed a computer-based online questionnaire. RESULTS: The majority of respondents did not experience cyberbul-lying in the last six months, while a significant group still experienced cyberbullying regularly (28.1%). Engaging in cyberbullying appeared to be even less common: it was reported by 12.3% of respondents. Family and peer social support appeared to be the strongest protective factor against experiencing cyberbullying while assertiveness was a characteristic that makes a person more likely to engage in cyberbullying. CONCLUSIONS: The results of our study can serve as guidance for preventive interventions against cyberbullying.

The role of oxidant-antioxidant markers and resistin in metabolic syndrome elderly individuals.

In elderly, hormones and oxidant-antioxidant interplay are suggested to mediate biochemical balance between adipose tissue to other tissues. Thus the study attempts to explore metabolic traits, plasma resistin, and oxidant-antioxidant markers in metabolic syndrome (MetS) in comparison to non-metabolic syndrome (non-MetS) elderly individuals. A total of 541 healthy elderly Caucasians, with no acute and/or chronic disorders were invited. After taking into account inclusion/exclusion criteria's the MetS was defined as the presence of three out of five abnormal findings and allowed to divided groups into: non-metabolic syndrome, non-MetS (n = 25, median age 69.0 years), and newly diagnosed MetS (n = 29; median age 70.5 years) individuals. Glucose, plasma lipids, resistin (Res), thiobarbituric acid-reacting substances (TBARS), total antioxidant status (TAS), and Cu,Zn-superoxide dismutase (SOD-1) were measured. The MetS had higher resistin than non-MetS (p < 0.04). The linear correlation (all at p < 0.05) showed correlation for Res&triacylglycerols (R = 0.44), and for Res&diastolic blood pressure (R = -0.58) and for SOD-1&fasting glucose (R = -0.34) in MetS, while in the non-MetS group fasting glucose correlates with Res (R = 0.58) and with TAS (R = -0.43). The multiple regression analysis (alone and in combination) showed that independently from other factors resistin correlated positively with fasting glucose (ß = 0.37; R = 0.58; R2 = 0.23; p < 0.01) in all investigated elderly participants. In the MetS resistin correlated negatively with diastolic blood pressure (ß = -0.68; R = 0.80; R2 = 0.53; p = 0.0004) moreover in that group TAS correlated negatively with HDL-C (ß = -0.71; R = 0.72; R2 = 0.37; p = 0.01). While age correlated negatively with systolic blood pressure (ß = -0.60; R = 0.62; R2 = 0.14; p = 0.03) independently from other factors in the non-MetS group. Various metabolic factors contribute to maintain serum resistin and oxidant-antioxidant balance in the elderly people in the presence or absence of MetS. Resistin may serve as a predictor of MetS in the elderly, while strong antioxidant defense interactions in older individuals may indicate good health.

Suppression of serum lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism by intensive insulin therapy in the first year of type 1 diabetes mellitus: Prospective InLipoDiab1 study.

BACKGROUND AND AIMS: Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are crucial proteins in reverse cholesterol transport. There are insufficient data on regulating these proteins by insulin therapy in type 1 diabetes mellitus (T1DM). We aimed to assess prospectively the impact of insulin therapy initiation on transfer proteins serum levels in adults with newly diagnosed T1DM. METHODS AND RESULTS: 57 adults with newly diagnosed T1DM were enrolled in the InLipoDiab1 Study. All participants were treated with subcutaneous insulin in the model of intensive insulin therapy since the diagnosis of diabetes. Serum PLTP and CETP concentrations were measured at diagnosis, after three weeks, six months, and after one year of insulin treatment, using the immunoenzymatic method ELISA. A significant decrease in PLTP and CETP concentrations were demonstrated during twelve months of insulin therapy in newly diagnosed T1DM. The dynamics of changes in the level of these proteins varied depending on the occurrence of remission after a year of the disease. In the group without remission, a significant decrease in PLTP and CETP levels appeared after six months of follow-up. The remission group was characterized by a decrease in proteins concentration only after one year of treatment. In the non-remission group, significant negative correlations were found between the daily dose of insulin and levels of PLTP and CETP. CONCLUSION: Exogenous insulin is an inhibitor of lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism in the first year of treatment.

A comparison of the oxidative stress response in single-incision laparoscopic versus multi-trocar laparoscopic totally extraperitoneal inguinal hernia repair.

INTRODUCTION: Surgical treatment is always associated with tissue damage and the subsequent development of oxidative stress. AIM: To compare the oxidative stress response in patients treated operatively for inguinal hernia with multi-trocar laparoscopic totally extraperitoneal technique (TEP) or single-incision laparoscopic totally extraperitoneal technique (TEP-SI). MATERIAL AND METHODS: A randomized group of 34 patients with one-sided inguinal hernia was enrolled in the study. Seventeen patients were treated with a standard TEP method (group 1) and the other 17 patients were treated with the TEP-SI technique (group 2). Thiobarbituric acid reactive substances (TBARS) and total antioxidant status (TAS) as the oxidative stress markers were measured before surgery (0), 1 day (1) and 4 days (2) after surgery. RESULTS: A decrease in TAS on the first day after surgery was observed in both groups. Sustained reduction on the fourth day after surgery was observed in group 1, whereas in group 2 an increase followed. A statistically significant difference was observed in TAS (2 : 0) ratio with a meaningful decrease in group 1. TBARS concentration was elevated 1 day after surgery in both groups. It remained at an elevated level on the fourth day after surgery in group 1, while it decreased in group 2. The duration of surgery was higher in group 2 (mean: 57.5 min) than in group 1 (mean: 50.0 min) (p = 0.0286). CONCLUSIONS: Oxidative stress levels are lower in patients treated operatively by TEP-SI technique than by TEP. TEP-SI may be considered as a less invasive technique associated with less tissue injury.

Are insulin-resistance and oxidative stress cause or consequence of aging.

IMPACT STATEMENT: Insulin resistance is associated with oxidative stress leading to cardiovascular diseases. However, little research has been performed examining elderly individuals with or without insulin-resistance. We demonstrate that antioxidant defense systems alone is not able to abrogate insulin action in elderly individuals at high risk for atherosclerosis, whereas the combined oxidant-antioxidant markers (thiobarbituric acid-reacting substances (TBARS), Cu,Zn-superoxide dismutase (SOD-1), and total antioxidant status (TAS)) might be more efficient and perhaps produce better clinical outcome. In fact, a decrease in oxidative stress and strong interaction between antioxidant defense can be seen only among insulin-resistant elderly individuals. This is, in our opinion, valuable information for clinicians, since insulin-resistance is considered strong cardiovascular risk factor.

Apple ALMT9 Requires a Conserved C-Terminal Domain for Malate Transport Underlying Fruit Acidity.

Malate accumulation in the vacuole largely determines apple (Malus domestica) fruit acidity, and low fruit acidity is strongly associated with truncation of Ma1, an ortholog of ALUMINUM-ACTIVATED MALATE TRANSPORTER9 (ALMT9) in Arabidopsis (Arabidopsis thaliana). A mutation at base 1,455 in the open reading frame of Ma1 leads to a premature stop codon that truncates the protein by 84 amino acids at its C-terminal end. Here, we report that both the full-length protein, Ma1, and its naturally occurring truncated protein, ma1, localize to the tonoplast; when expressed in Xenopus laevis oocytes and Nicotiana benthamiana cells, Ma1 mediates a malate-dependent inward-rectifying current, whereas the ma1-mediated transmembrane current is much weaker, indicating that ma1 has significantly lower malate transport activity than Ma1. RNA interference suppression of Ma1 expression in 'McIntosh' apple leaves, 'Empire' apple fruit, and 'Orin' apple calli results in a significant decrease in malate level. Genotyping and phenotyping of 186 apple accessions from a diverse genetic background of 17 Malus species combined with the functional analyses described above indicate that Ma1 plays a key role in determining fruit acidity and that the truncation of Ma1 to ma1 is genetically responsible for low fruit acidity in apple. Furthermore, we identified a C-terminal domain conserved in all tonoplast-localized ALMTs essential for Ma1 function; protein truncations into this conserved domain significantly lower Ma1 transport activity. We conclude that the truncation of Ma1 to ma1 reduces its malate transport function by removing a conserved C-terminal domain, leading to low fruit acidity in apple.

The significance of maternal blood pregnancy-associated plasma protein A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (ß-hCG) levels for the risk assessment of fetal trisomy 18 during the first prenatal testing between 11 and 13+6 weeks of pregnancy.

OBJECTIVE: The aim of the study was to evaluate the significance of the maternal blood level of pregnancy-associated plasma protein A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (ß-hCG), to estimate the risk of fetal trisomy 18 and their correlation with the assessment of nuchal translucency (NT) during the first prenatal testing. MATERIAL AND METHODS: Examinations of 93 pregnant women between 11 and 13+6 weeks of pregnancy were conducted, which included determination of ß-hCG and PAPP-A concentrations in the maternal serum and ultrasound assessment of fetal nuchal translucency. Concentrations of biochemical parameters were expressed as multiples of median (MoM) for the appropriate gestational age. The risk assessment of trisomy 18 was analyzed using Astraia software. Pregnant women with a high (≥ 1:300) risk of trisomy 18 were offered a genetic amniocentesis with an examination of fetal karyotype. Twenty cases were healthy and 23 with trisomy 18. RESULTS: PAPP-A and ß-hCG MoM values < 0.3 were found in 61% cases of fetal trisomy 18. In 26% of cases, PAPP-A and ß-hCG MoM values < 0.2 were NT-independent risk factors for trisomy 18. There were no significant differences between groups with normal fetal karyotype (40%) and trisomy 18 (35%) in PAPP-A and ß-hCG MoM 0.2-0.5 range. CONCLUSIONS: Maternal free ß-hCG MoM was found to change parallelly to fetal NT widening in case of trisomy 18 diagnosis. Maternal ß-hCG and PAPP-A MoM results presented less then 0.2 might be used independently of NT widening in fetus for trisomy 18 risk evaluation. Above 0.2 for PAPP-A and ß-hCG MoMs, fetal NT measurement was an requirment.

[The IRCCS San Raffaele Hospital organizational model to assess the clinical documentation completeness and the appropriateness of hospitalization: the SVAD experience and the results of the three-year period 2018-2020.] / Modello di organizzazione dei controlli interni di completezza della documentazione clinica e di appropriatezza dei ricoveri all'IRCCS Ospedale San Raffaele: il Servizio Valutazione Appropriatezza della Documentazione clinica (SVAD) e i risultati del triennio 2018-2020.

According to the progressive increase in the number of medical records checked by the Agenzia di Tutela della Salute (ATS) of the Metropolitan City of Milan, the San Raffaele Hospital established a Unit supporting healthcare personnel in clinical documentation management. Therefore, in 2003 the Servizio Valutazione Appropriatezza della Documentazione clinica (SVAD), consisting of a nursing staff highly qualified in checking the appropriateness of clinical pathways, completeness and correctness of the clinical documentation and appropriate coding in the hospital discharge cards, was set up in the Health Directorate. Since 2018, the Service has seen an increase in resources, a re-organization and integration with the Operating Units. The aim of the article is to describe the introduction of a new organizational model and the results obtained, with reference to the quality self-control carried out for the ATS. In order to conduct a descriptive analysis of the trend, the sample data, required by the ATS in the three-year period 2018-2020, stratified by outcome and consequent percentage of reduction on the reimbursement of hospitalization, were considered. We observe an overall percentage increase in medical records without any reduction from 2018 to 2020, going from 84% to 94% (+ 10%); at the same time, there is a constant trend of medical records with complete curtailment between 2018 and 2019, while there is a reduction between 2019 and 2020, going from 4% to 2% (-2%). The positive results demonstrate the essential role of SVAD and consolidate an alternative career for nursing staff.

The relationship between plasma lipids, oxidant-antioxidant status, and glycated proteins in individuals at risk for atherosclerosis.

Objective: Ageing is one of the major risks for atherosclerosis. The age-related changes of interactions between plasma lipids, oxidative stress, antioxidant defense, and glycation processes are still not established while we age. Thus, the aim of the study was to analyze such relationships in individuals at risk for atherosclerosis due to their age. Methods: Elderly and middle-aged persons with no acute disease or severe chronic disorder were assessed. Fasting plasma lipids (total cholesterol (T-C), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol, and triacylglycerols), thiobarbituric acid reacting substances (TBARS), plasma total antioxidant status (TAS), and glucose and glycated proteins (fructosamine (FA) and glycated hemoglobin (HbA1c)) were determined. An oral glucose tolerance test allowed exclusion of persons with type 2 diabetes. Results: Lipid profiles were significantly profitable, increased HDL-C especially (p<0.0001), in the elderly versus middle-aged group. Decreased TBARS and TAS were found in the elderly versus middle-aged group (p=0.0001 and p=0.00002, respectively). Increased fructosamine was found in the elderly (255±30 µmol/L) versus middle-aged (236±33 µmol/L) group (p=0.006). Multiple regression analysis showed that in the middle-aged group TBARS correlated with T-C and HDL-C, and in the elderly group with HbA1c and FA independently of other factors. Conclusion: The factors which have an impact on oxidant-antioxidant status are crucial to understanding the pathomechanisms of senescence as well as the development of chronic diseases. Healthy aging may be maintained throughout proper lipid control. Moreover, data support the premise that the balance between lipid metabolism and oxidative stress may play a role in the initial phases of glycation plasma proteins particularly among elderly persons.