Trimester-specific diagnostic accuracy of ultrasound for detection of placenta accreta spectrum: systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic accuracy of ultrasound for detecting placenta accreta spectrum (PAS) during the first trimester of pregnancy and compare it with the accuracy of second- and third-trimester ultrasound examination in pregnancies at risk for PAS. METHODS: PubMed, EMBASE and Web of Science databases were searched to identify relevant studies published from inception until 10 March 2023. Inclusion criteria were cohort, case-control or cross-sectional studies that evaluated the accuracy of ultrasound examination performed at < 14 weeks of gestation (first trimester) or ≥ 14 weeks of gestation (second/third trimester) for the diagnosis of PAS in pregnancies with clinical risk factors. The primary outcome was the diagnostic accuracy of sonography in detecting PAS in the first trimester, compared with the accuracy of ultrasound examination in the second and third trimesters. The secondary outcome was the diagnostic accuracy of each sonographic marker individually across the trimesters of pregnancy. The reference standard was PAS confirmed at pathological or surgical examination. The potential of ultrasound and different ultrasound signs to detect PAS was assessed by computing summary estimates of sensitivity, specificity, diagnostic odds ratio and positive and negative likelihood ratios. RESULTS: A total of 37 studies, including 5764 pregnancies at risk of PAS, with 1348 cases of confirmed PAS, were included in our analysis. The meta-analysis demonstrated that ultrasound had a sensitivity of 86% (95% CI, 78-92%) and specificity of 63% (95% CI, 55-70%) during the first trimester, and a sensitivity of 88% (95% CI, 84-91%) and specificity of 92% (95% CI, 85-96%) during the second/third trimester. Regarding sonographic markers examined in the first trimester, lower uterine hypervascularity exhibited the highest sensitivity (97% (95% CI, 19-100%)), and uterovesical interface irregularity demonstrated the highest specificity (99% (95% CI, 96-100%)). In the second/third trimester, loss of clear zone had the highest sensitivity (80% (95% CI, 72-86%)), and uterovesical interface irregularity exhibited the highest specificity (99% (95% CI, 97-100%)). CONCLUSIONS: First-trimester ultrasound examination has similar accuracy to second- and third-trimester ultrasound examinations for the diagnosis of PAS. Routine first-trimester ultrasound screening for patients at high risk of PAS may improve detection rates and allow earlier referral to tertiary care centers for pregnancy management. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

The fasted and post-prandial physiological responses of the Patagonian blennie Eleginops maclovinus.

Eleginops maclovinus is a native species with potential for Chilean aquaculture. Understanding the variations between the post-prandial and fasted metabolic responses can contribute to improving the aquaculture of this species. This study aimed to characterize variations in intermediate metabolism during the course of the day in the liver, serum, and gills of fed and unfed fish. For this, 72 fish were assigned to two experimental groups, "fed" and "fasted". The first group was fed "ad libitum" at 8.30, while the fasted group was not fed for 24 h. Samples were taken from both groups at 9:00, and every 2 h: 11:00, 13:00, 15:00, 17:00, and 19:00. In the fed group, food spent a long time in the gastrointestinal tract, with a large increase in stomach size and without evidence of complete emptying of the stomach at 19:00 (10.5 h post-feeding). In serum, the levels of amino acids, glucose, and triglycerides presented significant differences with peak levels at different times of day in the fed group. The cortisol in the fasted group presented a diurnal pattern with high levels during the morning and very low levels after 13:00, while in the fed group, the high cortisol variability did not allow a clear pattern to be established. In the liver, the effect of time on the enzymatic activity of the intermediary metabolism was greater compared to the effect of feeding. In the liver, enzyme activity decreased at later hours of the day, while glycogen levels increased at later hours of the day in both groups: but its levels were higher in the fed group. In gills, as well as in the liver, time had a greater effect than feeding on intermediate metabolism, since feeding only had a significant effect on the levels of hexokinase, lactate, and amino acids, suggesting an effect on carbohydrate metabolism. Meanwhile, time significantly affected the levels of Na+, K+-ATPase, glutamate dehydrogenase, aspartate aminotransferase, amino acids, and proteins, suggesting an effect on amino acid metabolism. In conclusion, the intermediate metabolism of E. maclovinus presents variations according to the time of day, with an increased metabolism during the morning and decreased metabolism as the day progresses, especially at the hepatic level. The gill tissue, despite not being a metabolic organ, presents feeding-dependent variations in its metabolism. Additional studies will be required to corroborate if coordinating a feeding strategy during the first hours of the day when metabolism is greater would improve the growth of E. maclovinus.

Intestinal variation of serotonin, melatonin, and digestive enzymes activities along food passage time through GIT in Salmo salar fed with supplemented diets with tryptophan and melatonin.

In teleosts, peripheral serotonin (5-HT) and melatonin (MEL) are synthesised in the gastrointestinal tract (GIT) and regulate secretion and motility processes. Their production is regulated by diet and the passage of food through the GIT. This study aimed to evaluate how intestinal 5-HT, melatonin, and the activity of digestive enzymes varied with food passage time through GIT in Atlantic salmon (Salmo salar). We fed fish diets supplemented with tryptophan and melatonin (L-Trp 2.5% and MEL 0.01%) and measured the activity of digestive enzymes (amylase, lipase, and total protease) in the pyloric caeca, midgut, and hindgut at different times after feeding. 5-HT levels increased in all GIT portions and diets at 120 min post-intake and were highest in the pyloric caeca. Intestinal enzymatic activity was varied with diet, post-intake time and in different intestinal portions. In conclusion, food passage time directly affects GIT 5-HT secretion and digestive enzyme activity in S. salar, and diet composition regulates S. salar GIT function.

A comparison of mosquito densities, weather and infection rates of Aedes aegypti during the first epidemics of Chikungunya (2014) and Zika (2016) in areas with and without vector control in Puerto Rico.

In Puerto Rico, the first records of the transmission of Chikungunya (CHIKV) and Zika (ZIKV) viruses were confirmed in May 2014 and December 2015, respectively. Transmission of CHIKV peaked in September 2014, whereas that of ZIKV peaked in August 2016. The emergence of these mosquito-transmitted arboviruses in the context of a lack of human population immunity allowed observations of whether the outbreaks were associated with Aedes aegypti (Diptera: Culicidae) densities and weather. Mosquito density was monitored weekly in four communities using sentinel autocidal gravid ovitraps (AGO traps) during 2016 in order to provide data to be compared with the findings of a previous study carried out during the 2014 CHIKV epidemic. Findings in two communities protected against Ae. aegypti using mass AGO trapping (three traps per house in most houses) were compared with those in two nearby communities without vector control. Mosquito pools were collected to detect viral RNA of ZIKV, CHIKV and dengue virus. In areas without vector control, mosquito densities and rates of ZIKV detection in 2016 were significantly higher, similarly to those observed for CHIKV in 2014. The density of Ae. aegypti in treated sites was less than two females/trap/week, which is similar to the putative adult female threshold for CHIKV transmission. No significant differences in mosquito density or infection rates with ZIKV and CHIKV at the same sites between years were observed. Although 2016 was significantly wetter, mosquito densities were similar.

The effect of alterations in salinity and temperature on neuroendocrine responses of the Antarctic fish Harpagifer antarcticus.

Increased levels of tissue monoaminergic neurotransmitters, as well as circulating catecholamines, appear to play a role in the regulation of the physiological responses of teleost fish. Harpagifer antarcticus is a stenothermic, Antarctic notothenioid fish. The aim of this study was to determine the effect of increased seawater temperature and decreased salinity on the levels of 5-HT, 5-HIAA, DA, and Noradrenaline in the brain, stomach, and gut of H. antarcticus. Wild-gathered fish were acclimatized to habitat conditions (2 °C, 33 PSU) prior to placement in aquaria with 4 temperatures (2, 5, 8 and 11 °C) and 3 salinities (23, 28 and 33 PSU) for 10 days. Fish exposed to 11 °C had higher levels of the brain neurotransmitters than those at 2 °C. Concomitant exposure to low salinity exacerbated the effect of exposure to 11 °C. At lower temperatures, concomitant alterations in salinity induced differential effects on brain neurotransmitters. When fish were exposed to 28 PSU, 5-HIAA, DA, and Noradrenaline levels at 5 and 8 °C presented no significant differences with those at 2 °C. In contrast, only 5HT and 5-HIAA levels in fish at 33 PSU were elevated at 5 and 8 °C respectively. Fish at 28 and 33 PSU had lower Gut 5HT levels at the 3 elevated temperatures, meanwhile fish at 23 PSU showed a biphasic effect when exposed to elevated temperatures. 5-HIAA levels decreased at 5 and 8 °C at 33 PSU. Stomach 5HT levels also showed a differential response at the 3 salinity levels when exposed to increased temperatures. At 11 °C, 5HT levels were markedly higher than those at 2 °C for fish at 33 PSU, moderately elevated for fish at 28 PSU, and lower for fish at 23 PSU, meanwhile 5-HIAA levels only increased with temperature at 33 PSU. These findings indicate that rapid exposure to alterations in temperate with or without concomitant changes in salinity is associated with differential responses in tissue monoaminergic neurotransmitter levels. The relatively high changes in neurotransmitter levels in fish exposed to moderate salinity and high temperature changes may indicate the physiological plasticity of H. antarcticus to possible changes in ocean temperature and salinity.

Effect of ration level on growth performance, body composition, intermediary metabolism and serum parameters in juvenile Patagonian blennie Eleginops maclovinus.

Eleginops maclovinus is an endemic species of the southern cone with beneficial physiological characteristics for aquaculture. However, this species has a low growth rate under captive conditions, and the optimal feed ration together with the metabolic process is unknown. This study aimed to determine the optimum feed ration during 90 days based on growth performance, body composition, intermediary metabolism, and serum parameters. For this, fish were randomly assigned to rations of 0.5, 1, 2 and 4% of body weight. No fish mortality was registered, but all fish, developed fatty liver. The results of weight, length, growth performance (WGR, SGR), and body parameters (HSI, VSI and K) followed a similar pattern, with the lowest values observed in the 0.5% and no significant differences between rations of 1, 2 and 4%. The feed intake and feces increased with the feed ration. However, the percentage of food consumed by the fish decreased with the ration size and the feed conversion ratio was lowest in the 1% ration. Total serum proteins and calcium were lowest in the 0.5% ration and presented no differences in the rations 1, 2 and 4%, while triglyceride content was significantly different only between the rations of 0.5 and 4%. Blood cortisol levels were significantly higher in the rations of 0.5 and 1%, and decreased in rations of 2 and 4%. The lipids, fiber, and energy of the total body mass increased with the feed ration, while dry matter, proteins, and ash of the body decreased to higher feed ration. In liver, triglyceride and protein levels decreased with a larger feed ration, amino acids increased in the rations of 0.5 and 4%, while glucose levels increased in rations of 2 and 4%. Liver enzymes Glucose-6-phosphate dehydrogenase and Glutamate dehydrogenase increased their activity at a higher feed ration, while Glycogen Phosphorylase, Aspartate aminotransferase and 3-Hydroxyacyl-CoA dehydrogenase presented their highest enzymatic activity only in the 4% ration. Fructose-1,6-bisphosphate showed low enzymatic activity in rations of 2 and 4% and Glycerol-3-phosphate dehydrogenase was significantly different only between the ration of 0.5 and 1%. Finally, our results suggests that optimal feed rations for E. maclovinus corresponds to 1% since this ration size produces the highest growth and metabolism with a minimum loss of food and feces present in the environment. Additionally, we recommend to reduce the percentage of fat in the diet to avoid the development of fatty liver.

Effect of Flavobacterium psychrophilum on the neuroendocrine response of rainbow trout (Oncorhynchus mykiss) in a time course experiment.

The aim of this study was to examine the effects of Flavobacterium psychrophilum, a pathogen that is economically important in the aquaculture sector, on the neuroendocrine response of Oncorhynchus mykiss during a time course experiment with sampling at 0.5, 1, 2, 6, 10, and 30 days post injection (dpi). In the brain, serotonin (5HT) content increased in the infected group at all the measured time points, a similar pattern was observed for 5-hydroxyindole-3-acetic acid (5HIAA). Infected fish presented an increase in brain dopamine levels on day 0.5 and 1 dpi. A non-significant variation in noradrenaline levels was observed on all treatment days. Foregut 5-HT and 5-HIAA content in the infected group presented the highest 5-HT concentrations with 248.6 and 983.5 ng/g tissue at 0.5 dpi respectively. Midgut 5-HT and 5-HIAA levels presented the highest 5-HT concentrations, 486.9 ng/g tissue and 1006.4 ng/g tissue respectively, at the beginning of the experiment (0.5 dpi). 5-HT levels in the hindgut presented the highest concentrations with 233.9 ng/g tissue at 0.5 dpi, while 5-HIAA presented the highest concentrations, 690.5 ng/g tissue, at the same time point. After injection with F. psychrophilum the neuroendocrine response in rainbow trout was tissue dependent. Brain levels of 5HT and 5HIIA indicate that the neuroendocrine response increased together with dopamine following intramuscular infection. These increases are in line with reports from other authors, indicating an early response of catecholamines as neurotransmitters to stressful stimulus. In addition the intestinal response was also increased, implying that there could be a possible relationship between the serotonergic system at the intestinal level and the immune system.

Multifractal analysis to study break points in temperature data sets.

Since the last century, the air surface temperature has increased at a global scale, showing trends and inhomogeneities that vary from place to place. Many statistical methods can be used to analyze whether or not an inhomogeneity or break point exists in a meteorological data series, and even to detect the time of the break. Sometimes, there is no agreement in the year at which the inhomogeneity occurs detected by different tests. The scale invariance of a process can be studied through its multifractal properties that can be related to the existence of break points in it. In this work, the multifractal properties of monthly temperature data series are used to test what is the right break point year in those situations at which different dates are found by two different tests: the Pettitt and the Standard Normal Homogeneity tests. The comparison of the fractal dimension function Dq and the multifractal spectrum obtained by the box counting method for both the original data sets and for those obtained by splitting the original into two considering the break point years was made. When different multifractal functions and parameters were obtained, a break point was confirmed. Whereas, if equal values appeared, the break point year was discarded. These results let to select the most suitable test to be applied to detect inhomogeneities in a certain data set that will be very useful for climate change studies.

Immunological response of the Sub-Antarctic Notothenioid fish Eleginops maclovinus injected with two strains of Piscirickettsia salmonis.

Eleginops maclovinus is an endemic fish to Chile that lives in proximity to salmonid culture centers, feeding off of uneaten pellet and salmonid feces. Occurring in the natural environment, this interaction between native and farmed fish could result in the horizontal transmission of pathogens affecting the aquaculture industry. The aim of this study was to evaluate the innate and adaptive immune responses of E. maclovinus challenged with P. salmonis. Treatment injections (in duplicate) were as follows: control (100 µL of culture medium), wild type LF-89 strain (100 µL, 1 × 108 live bacteria), and antibiotic resistant strain Austral-005 (100 µL, 1 × 108 live bacteria). The fish were sampled at various time-points during the 35-day experimental period. The gene expression of TLRs (1, 5, and 8), NLRCs (3 and 5), C3, IL-1ß, MHCII, and IgMs were significantly modulated during the experimental period in both the spleen and gut (excepting TLR1 and TLR8 spleen expressions), with tissue-specific expression profiles and punctual differences between the injected strains. Anti-P. salmonis antibodies increased in E. maclovinus serum from day 14-28 for the LF-89 strain and from day 14-35 for the Austral-005 strain. These results suggest temporal activation of the innate and adaptive immune responses in E. maclovinus tissues when injected by distinct P. salmonis strains. The Austral-005 strain did not always cause the greatest increases/decreases in the number of transcripts, so the magnitude of the observed immune response (mRNA) may not be related to antibiotic resistance. This is the first immunological study to relate a pathogen widely studied in salmonids with a native fish.

Understanding the meaning of lactate threshold in resistance exercises.

This study compares acute cardiorespiratory, metabolic, mechanical and rating of perceived effort (RPE) responses to 2 different prolonged constant-load exercises, half-squat (HS) and cycle ergometry, performed at a workload corresponding to the lactate threshold (LT). A total of 18 healthy subjects completed 5 exercise tests separated by 48 h rest periods: an incremental cycle ergometer test, a constant-load cycle ergometer test at LT intensity, a one-repetition maximum (1RM) HS test, an incremental HS test and a constant-load HS test at LT intensity. In both constant-load tests, cardiorespiratory, metabolic and RPE data were recorded. Mechanical responses before and after each test were assessed in terms of jump height and mean power measured in a counter movement jump (CMJ) test. In both exercises, cardiorespiratory and metabolic responses stabilized, though cardiorespiratory responses were significantly greater for cycle ergometry (P<0.001), with the exception of respiratory exchange ratio (RER), which was higher for HS (P=0.028). Mechanical fatigue was observed in only HS (P<0.001). In conclusion, different exercise modalities induced different yet stable acute cardiorespiratory and metabolic responses. Although such responses were significantly reduced in HS, greater mechanical fatigue was produced, most likely because of the particular muscle actions involved in this form of exercise.

Multifractal analysis of validated wind speed time series.

Multifractal properties of 30 min wind data series recorded at six locations in Cadiz (Southern Spain) have been studied in this work with the aim of obtaining detailed information for a range of time scales. Wind speed records have been validated, applying various quality control tests as a pre-requisite before their use, improving the reliability of the results due to the identification of incorrect values which have been discarded in the analysis. The scaling of the wind speed moments has been analysed and empirical moments scaling exponent functions K(q) have been obtained. Although the same critical moment (qcrit) has been obtained for all the places, some differences appear in other multifractal parameters like γmax and the value of K(0). These differences have been related to the presence of extreme events and zero data values in the data series analysed, respectively.

Spatial distribution and contamination assessment of heavy metals in urban topsoils from Las Tunas City, Cuba.

Concentrations of Cr, Co, Ni, Cu, Zn, Pb and Fe in the topsoils (0-10 cm) from Las Tunas city were measured by X-ray fluorescence analysis. The mean Cr, Co, Ni, Cu, Zn and Pb contents in the urban topsoil samples (97 ± 30, 14 ± 2, 35 ± 36, 94 ± 26, 199 ± 87 and 42 ± 29 mg kg⁻¹ dry weight, respectively) were compared with mean concentrations for other cities around the world with similar population. Cr content in school grounds, parks and residential areas exceed in 20 % the average Cr background level. Highest content for Ni was determined in residential areas, for Zn in market gardens soils and as for Pb, the highest topsoil-background content ratios were observed for market gardens (2.7) and residential areas (2.3). Spatial distribution maps indicated the same behaviour for Cr-Co-Ni and Pb-Zn, respectively, whereas the spatial distribution of Cu differs from other heavy metals. On the other hand, the metal-to-iron normalisation, using (10-20 cm) bottom soil contents as background, showed that topsoils in Las Tunas city are severely enriched with lead and not enriched with the rest of the determined metals. The average values of integrated pollution index (IPI) indicated that soils are moderately contaminated by heavy metals (1.17 ≤ IPI(ave) ≤ 1.39), but enrichment index values shows that metal concentrations on the studied locations are not above the permissible levels for urban agriculture.

Ghrelin stimulates myogenic differentiation in a mouse muscle satellite cell line and in primary cultures of bovine myoblasts.

Ghrelin is an acylated hormone that influences food intake, energy metabolism and reproduction, among others. Ghrelin may also stimulate proliferating myoblast cell differentiation and multinucleated myotube fusion. The aim of this work was to assess the effect of human ghrelin (hGHRL) and human ghrelin fragment 1-18 (hGHRL1-18) on myoblast differentiation by means of mRNA expression and protein level. Two types of cells were tested, the cell line i28 obtained from mouse skeletal muscle and primary cultures of bovine myoblasts. Both ghrelin and its N-terminal fragment hGHRL1-18 were used at concentrations of 0, 0.01, 0.1, 1, 10 and 100 nm. Treatments were applied to pre-confluent cultures and were maintained for 4 days. We determined that between 0.1 and 100 nm, hGHRL and hGRHL1-18 had similar effects on myogenic differentiation of i28 cells (p < 0.01). On the other hand, only the higher concentrations (10 and 100 nm) of hGHRL stimulated bovine myoblast differentiation. These results could be attributed to the presence, in both i28 cells and in bovine myoblasts, of the mRNA for GHS-R1a and CD36 receptors. The use of ghrelin in livestock production is still questionable because of the limited effects shown in this study, and additional research is needed in this field.

Comparison of different field tests to assess the physical capacity of post-COVID-19 patients.

BACKGROUND: In coronavirus disease (COVID-19), physical capacity is one of the most impaired sequelae. Due to their simplicity and low cost, field tests such as the six-minute walk test (6MWT) are widely used However, in many places it is difficult to perform them and alternatives can be used such as the 1 min sit-to-stand test (1min-STST) or the Chester step test (CST). Therefore, our objective was to compare the 6MWT, 1min-STST and the CST in post-COVID-19 patients. METHODS: We conducted a cross-sectional analysis in post-COVID-19 patients, compared with matched controls (CG). Demographic characteristics and comorbidities were collected. We analysed oxygen saturation (SpO2), heart rate (HR), and the modified Borg scale in the 6MWT, 1min-STST, and CST. Additionally, the correlations between tests were analysed. RESULTS: We recruited 27 post-COVID-19 patients and 27 matched controls. The median age was 48 (IQR 43-59) years old (44% female). The median distance walked in 6MWT was 461 (IQR 415-506) m in post-COVID-patients and 517 (IQR 461-560) m in CG (p = 0.001). In 1min-STST, the repetitions were 21.9 ± 6.7 and 28.3 ± 7.1 in the post-COVID-19 group and CG, respectively (p = 0.001). In the CST, the post-COVID-19 group performed 150 (86-204) steps vs the CG with 250 (250-250) steps (p < 0.001). We found correlations between the 6MWT with the 1min-STST in COVID-19 patients (r = 0.681, p < 0.001) and CG (r = 0.668, p < 0.001), and between the 6MWT and the CST in COVID-19 patients (r = 0.692, p < 0.001). CONCLUSION: The 1min-STST and the CST correlated significantly with the 6MWT in patients post-COVID-19 being alternatives if the 6MWT cannot be performed.

Tyrosinase inactivation in its action on dopa.

Under aerobic or anaerobic conditions, tyrosinase undergoes a process of irreversible inactivation induced by its physiological substrate L-dopa. Under aerobic conditions, this inactivation occurs through a process of suicide inactivation involving the form oxy-tyrosinase. Under anaerobic conditions, both the met- and deoxy-tyrosinase forms undergo irreversible inactivation. Suicide inactivation in aerobic conditions is slower than the irreversible inactivation under anaerobic conditions. The enzyme has less affinity for the isomer D-dopa than for L-dopa but the velocity of inactivation is the same. We propose mechanisms to explain these processes.

Antipsychotics as environmental pollutants: An underrated threat?

The heterogeneous class of what we nowadays call antipsychotics was born almost 70 years ago with the serendipitous discovery of chlorpromazine. Their utilization is constantly growing because they are used to treat a diverse group of diseases and patients across all age groups: schizophrenia, bipolar disease, depression, autism, attention deficit hyperactivity disorder, behavioural and psychological symptoms in dementia, among others. They possess a complex pharmacological profile, acting on multiple receptors: dopaminergic, serotoninergic, histaminergic, adrenergic, and cholinergic, leading scientists to call them "agents with rich pharmacology" or "dirty drugs". Serotonin, dopamine, acetylcholine, noradrenaline, histamine and their respective receptors are evolutionary ancient compounds, and as such, are found in many different living beings in the environment. Antipsychotics do not disappear once excreted by patient's urine or faeces and are transported to wastewater treatment plants. But as these plant's technology is not designed to eliminate drugs and their metabolites, a variable proportion of the administered dose ends up in the environment, where they have been found in almost every matrix: municipal wastewater, hospital sewage, rivers, lakes, sea and even drinking water. We believe that reported concentrations found in the environment might be high enough to exert significant effect to aquatic wildlife. Besides, recent studies suggest antipsychotics, among others, are very likely bioaccumulating through the web food. Crucially, psychotropics may provoke behavioural changes affecting populations' dynamics at lower concentrations. We believe that so far, antipsychotics have not received the attention they deserve with regards to drug pollution, and that their role as environmental pollutants has been underrated.

Multidisciplinary consensus on cancer management during pregnancy.

Cancer during pregnancy is a challenge for multi- and interdisciplinary collaboration due to the diagnostic, prognostic and therapeutic implications, the need for an integrated harmonization of medical action for the pregnant patient and the embryo or foetus and the characteristics of each gestational period, which will determine the protocol to be proposed and its limitations. For this reason, a group of experts appointed by participating scientific societies, which includes the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica-SEOM), the Spanish Association of Surgeons (Asociación Española de Cirujanos-AEC), the Spanish Society of Gynaecology and Obstetrics (Sociedad Española de Ginecología y Obstetricia-SEGO), the Spanish Society of Nuclear Medicine and Molecular Imaging (Sociedad Española de Medicina Nuclear e Imagen Molecular-SEMNIM), the Spanish Society of Oncological Radiotherapy (Sociedad Española de Oncología Radioterápica-SEOR) and the Spanish Society of Medical Radiology (Sociedad Española de Radiología Médica-SERAM), have worked together to establish consensus recommendations that allow the harmonization of management and ultimately the optimization of the healthcare of pregnant patients with cancer. When cancer is detected in a pregnant woman, the week of gestation in which the diagnosis is made must be considered, as well as the characteristics of the tumour. It is strongly recommended that a multidisciplinary team assesses the situation and guides the patient and her family during the informing, diagnosis and treatment process. Likewise, the foetus should be monitored and managed by specialized obstetricians who are part of a multidisciplinary cancer committee.

Melanogenesis inhibition by tetrahydropterines.

There is controversy in the literature concerning the action of tetrahydropterines on the enzyme tyrosinase and on melanogenesis in general. In this study, we demonstrate that tetrahydropterines can inhibit melanogenesis in several ways: i) by non-enzymatic inhibition involving purely chemical reactions reducing o-dopaquinone to L-dopa, ii) by acting as substrates which compete with L-tyr and L-dopa, since they are substrates of tyrosinase; and iii) by irreversibly inhibiting the enzymatic forms met-tyrosinase and deoxy-tyrosinase in anaerobic conditions. Three tetrahydropterines have been kinetically characterised as tyrosinase substrates: 6-R-L-erythro-5,6,7,8-tetrahydrobiopterin, 6-methyl-5,6,7,8-tetrahydropterine and 6,7-(R,S)-dimethyl-5,6,7,8-tetrahydropterine. A kinetic reaction mechanism is proposed to explain the oxidation of these compounds by tyrosinase.