Maker communities and the COVID-19 pandemic: a longitudinal analysis of Thingiverse's response to supply shortages.

The COVID-19 pandemic profoundly affected various aspects of daily life, particularly the supply and demand of essential goods, resulting in critical shortages. This included personal protective equipment for medical professionals and the general public. To address these shortages, online 'maker communities' emerged, aiming to develop and locally manufacture critical products. While some organized efforts existed, the majority of initiatives originated from individuals and groups on platforms like Thingiverse. This paper presents a longitudinal analysis of Thingiverse, one of the largest maker community websites, to examine the pandemic's effects. Our findings reveal a surge in community output during the initial lockdown periods in major contributing nations (primarily those in the Western Hemisphere), followed by a subsequent decline. Additionally, throughout 2020, pandemic-related products dominated uploads and interactions during this period. Based on these observations, we propose recommendations to expedite the community's ability to support local, national and international responses to future disasters.

Domain wall propagation and pinning induced by current pulses in cylindrical modulated nanowires.

The future developments in 3D magnetic nanotechnology require the control of domain wall dynamics by means of current pulses. While this has been extensively studied in 2D magnetic strips (planar nanowires), few reports on this exist in cylindrical geometry, where Bloch point domain walls are expected to have intriguing properties. Here, we report an investigation on cylindrical magnetic Ni nanowires with geometrical notches. An experimental work based on synchrotron X-ray magnetic circular dichroism (XMCD) combined with photoemission electron microscopy (PEEM) indicates that large current densities induce domain wall nucleation, while smaller currents move domain walls preferably antiparallel to the current direction. In the region where no pinning centers are present, we found a domain wall velocity of about 1 km s-1. Thermal modelling indicates that large current densities temporarily raise the temperature in the nanowire above the Curie temperature, leading to nucleation of domain walls during the system cooling. Micromagnetic modelling with a spin-torque effect shows that for intermediate current densities, Bloch point domain walls with chirality parallel to the Oersted field propagate antiparallel to the current direction. In other cases, domain walls can be bounced from the notches and/or get pinned outside their positions. We thus found that current is not only responsible for domain wall propagation, but also is a source of pinning due to the Oersted field action.

Ensayo clínico comparando el uso de tornillos y del sistema TighRope® Knotless en el tratamiento de las lesiones agudas de la sindesmosis / A randomized clinical trial comparing screws and the TighRope® Knotless system in the treatment of acute injuries of syndesmosis

Antecedentes y objetivo: Clásicamente el tratamiento de las lesiones agudas de la sindesmosis se ha realizado mediante tornillos. Hace unos años aparecieron implantes más flexibles que han evolucionado hasta el moderno TighRope® Knotless. El objetivo del presente estudio es comparar los resultados de ambos implantes. Material y métodos: Desde abril de 2019 hasta septiembre de 2020 reclutamos 68 pacientes diagnosticados de lesión aguda de la sindesmosis que fueron aleatorizados para tratamiento quirúrgico con tornillo o con TighRope® Knotless. Realizamos control posquirúrgico con tomografía axial computarizada, y a los 3, 6 y 12 meses se recogieron datos del rango articular, valores de escalas funcionales y se realizaron estudios de radiología simple. Resultados: Los pacientes tratados con tornillos no presentaban diferencias estadísticamente significativas en la escala AOFAS frente al grupo tratado con TighRope® Knotless a los 3 meses (83,1 vs. 81,80; p=1,03), ni a los 6 meses (88,27 vs. 88; p=0,26) ni a los 12 meses (93,03 vs. 92,10; p=0,93). Igualmente recogimos resultados similares en la escala de Olerud-Molander a los 3 meses (65 vs. 61,50; p=3,5), 6 meses (82,33 vs. 80,67; p=1,67) y 12 meses (92,67 vs. 90; p=2,67). Tampoco hubo diferencias en la tasa de malreducción posquirúrgica (ningún caso en ambos grupos), pérdida de reducción (3 en el grupo tratado con tornillo frente a 4 del grupo del TighRope® Knotless, p=0,54) o complicaciones (p=1). Conclusiones: El tratamiento de las lesiones agudas de la sindesmosis con tornillos o con TighRope® Knotless es similar tanto en resultados clínicos como radiológicos.(AU)

Background and aim: Classically acute syndesmosis injuries have been treated using screws. A few years ago more flexible implants appeared evolving to current TighRope® Knotless. The primary aim of this study is to compare clinical and radiographic outcome of both implants. Material and methods: From April 2019 to September 2020 68 patients diagnosed with acute syndesmosis injury were randomized to use screws or TighRope® Knotless. Syndesmosis reduction was assessed using bilateral CT potsoperatively. Outcomes were clinically and radiologically assessed at three, six, and twelve months after surgery. Results: No significant differences were identified in the AOFAS Scale between groups at three months (83.1 vs. 81.80; P=1.03), nor at six (88.27 vs. 88; P=.26) or at twelve (93.03 vs. 92.10; P=,93). There were also no differences in Olerud-Molander scale at three (65 vs. 61.50; P=3.5), six (82.33 vs. 80.67; P=1.67) and twelve months (92.67 vs. 90; P=2.67). Likewise, there were no differences in rate of postoperative malreduction (no cases in both groups), loss of reduction (three cases in screw group vs. four in TighRope® Knotless group, P=.54) or complications (P=1). Conclusions: Treatment of acute syndesmosis injuries with screws or the TighRope® Knotless implant is similar in both clinical and radiological results.(AU)

[Translated article] A randomised clinical trial comparing screws and the TighRope® Knotless system in the treatment of acute injuries of syndesmosis / Ensayo clínico comparando el uso de tornillos y del sistema TighRope® Knotless en el tratamiento de las lesiones agudas de la sindesmosis

Antecedentes y objetivo: Clásicamente el tratamiento de las lesiones agudas de la sindesmosis se ha realizado mediante tornillos. Hace unos años aparecieron implantes más flexibles que han evolucionado hasta el moderno TighRope® Knotless. El objetivo del presente estudio es comparar los resultados de ambos implantes. Material y métodos: Desde abril de 2019 hasta septiembre de 2020 reclutamos 68 pacientes diagnosticados de lesión aguda de la sindesmosis que fueron aleatorizados para tratamiento quirúrgico con tornillo o con TighRope® Knotless. Realizamos control posquirúrgico con tomografía axial computarizada, y a los 3, 6 y 12 meses se recogieron datos del rango articular, valores de escalas funcionales y se realizaron estudios de radiología simple. Resultados: Los pacientes tratados con tornillos no presentaban diferencias estadísticamente significativas en la escala AOFAS frente al grupo tratado con TighRope® Knotless a los 3 meses (83,1 vs. 81,80; p=1,03), ni a los 6 meses (88,27 vs. 88; p=0,26) ni a los 12 meses (93,03 vs. 92,10; p=0,93). Igualmente recogimos resultados similares en la escala de Olerud-Molander a los 3 meses (65 vs. 61,50; p=3,5), 6 meses (82,33 vs. 80,67; p=1,67) y 12 meses (92,67 vs. 90; p=2,67). Tampoco hubo diferencias en la tasa de malreducción posquirúrgica (ningún caso en ambos grupos), pérdida de reducción (3 en el grupo tratado con tornillo frente a 4 del grupo del TighRope® Knotless, p=0,54) o complicaciones (p=1). Conclusiones: El tratamiento de las lesiones agudas de la sindesmosis con tornillos o con TighRope® Knotless es similar tanto en resultados clínicos como radiológicos.(AU)

Background and aim: Classically acute syndesmosis injuries have been treated using screws. A few years ago more flexible implants appeared evolving to current TighRope® Knotless. The primary aim of this study is to compare clinical and radiographic outcome of both implants. Material and methods: From April 2019 to September 2020 68 patients diagnosed with acute syndesmosis injury were randomized to use screws or TighRope® Knotless. Syndesmosis reduction was assessed using bilateral CT potsoperatively. Outcomes were clinically and radiologically assessed at three, six, and twelve months after surgery. Results: No significant differences were identified in the AOFAS Scale between groups at three months (83.1 vs. 81.80; P=1.03), nor at six (88.27 vs. 88; P=.26) or at twelve (93.03 vs. 92.10; P=,93). There were also no differences in Olerud-Molander scale at three (65 vs. 61.50; P=3.5), six (82.33 vs. 80.67; P=1.67) and twelve months (92.67 vs. 90; P=2.67). Likewise, there were no differences in rate of postoperative malreduction (no cases in both groups), loss of reduction (three cases in screw group vs. four in TighRope® Knotless group, P=.54) or complications (P=1). Conclusions: Treatment of acute syndesmosis injuries with screws or the TighRope® Knotless implant is similar in both clinical and radiological results.(AU)

[Translated article] A randomised clinical trial comparing screws and the TighRope® Knotless system in the treatment of acute injuries of syndesmosis.

BACKGROUND AND AIM: Classically acute syndesmosis injuries have been treated using screws. A few years ago more flexible implants appeared evolving to current TighRope® Knotless. The primary aim of this study is to compare clinical and radiographic outcome of both implants. MATERIAL AND METHODS: From April 2019 to September 2020 68 patients diagnosed with acute syndesmosis injury were randomised to use screws or TighRope® Knotless. Syndesmosis reduction was assessed using bilateral CT potsoperatively. Outcomes were clinically and radiologically assessed at three, six, and twelve months after surgery. RESULTS: No significant differences were identified in the AOFAS Scale between groups at three months (83.1 vs. 81.80; P=1.03), nor at six (88.27 vs. 88; P=.26) or at twelve (93.03 vs. 92.10; P=.93). There were also no differences in Olerud-Molander scale at three (65 vs. 61.50; P=3.5), six (82.33 vs. 80.67; P=1.67) and twelve months (92.67 vs. 90; P=2.67). Likewise, there were no differences in rate of postoperative malreduction (no cases in both groups), loss of reduction (three cases in screw group vs. four in TighRope® Knotless group, P=.54) or complications (P=1). CONCLUSIONS: Treatment of acute syndesmosis injuries with screws or the TighRope® Knotless implant is similar in both clinical and radiological results.

A randomized clinical trial comparing screws and the TighRope® Knotless system in the treatment of acute injuries of syndesmosis. / Ensayo clínico comparando el uso de tornillos y del sistema TighRope® Knotless en el tratamiento de las lesiones agudas de la sindesmosis.

BACKGROUND AND AIM: Classically acute syndesmosis injuries have been treated using screws. A few years ago more flexible implants appeared evolving to current TighRope® Knotless. The primary aim of this study is to compare clinical and radiographic outcome of both implants. MATERIAL AND METHODS: From April 2019 to September 2020 68 patients diagnosed with acute syndesmosis injury were randomized to use screws or TighRope® Knotless. Syndesmosis reduction was assessed using bilateral CT potsoperatively. Outcomes were clinically and radiologically assessed at three, six, and twelve months after surgery. RESULTS: No significant differences were identified in the AOFAS Scale between groups at three months (83.1 vs. 81.80; P=1.03), nor at six (88.27 vs. 88; P=.26) or at twelve (93.03 vs. 92.10; P=,93). There were also no differences in Olerud-Molander scale at three (65 vs. 61.50; P=3.5), six (82.33 vs. 80.67; P=1.67) and twelve months (92.67 vs. 90; P=2.67). Likewise, there were no differences in rate of postoperative malreduction (no cases in both groups), loss of reduction (three cases in screw group vs. four in TighRope® Knotless group, P=.54) or complications (P=1). CONCLUSIONS: Treatment of acute syndesmosis injuries with screws or the TighRope® Knotless implant is similar in both clinical and radiological results.

Lymphogranuloma venereum: a retrospective analysis of an emerging sexually transmitted disease in a Lisbon Tertiary Center.

BACKGROUND: Lymphogranuloma venereum (LGV) is a sexual transmitted infection (STI), currently endemic within the population of men who have sex with men (MSM) of Western Countries. L2B variant has been reported as the predominant strain in the current LGV epidemics, although a shift towards L2-434 has been observed in some European countries. OBJECTIVES: To evaluate and characterize the population with LGV infection diagnosed in Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal. METHODS: A retrospective analysis of all LGV diagnoses between 2016 and 2019 was performed. The diagnosis was established through ompA-genotyping of samples yielding a positive result to Chlamydia trachomatis (CT). All considered samples were retrieved from the clinician activity, through swabbing and urine analysis and CT infection diagnosis was obtained using real-time PCR. RESULTS: During the period studied 16 279 CT diagnostics tests were employed, with a striking increase from 2016 (n = 467) to 2019 (n = 9362). A total of 1602 diagnoses of CT were established, from which 168 (10.5%) corresponded to LGV, with both infections showing a rising evolution, between 2016 and 2019, of 2.9 and 2.7 times, respectively. The majority of the LGV strains were genotyped as L2/434 (67.3%; n = 113). LGV predominantly affected MSM and men who have sex with men and women (97.0%; n = 163). Anorectal infection was the most prevalent one (90.5%; n = 152), being proctitis the main clinical presentation (76.2%; n = 128). Absence of symptoms was reported in almost 15% of the cases (n = 24). The presence of concomitant infection with human immunodeficiency virus was dominant (73.2%; n = 123) and the prevalence of one or more STI co-infections was about 60.1% (n = 99). CONCLUSIONS: An increasing evolution of CT and LGV testing and diagnosing was observable throughout the studied period. Characteristics of the population are similar with those described within LGV epidemics. In accordance with recent European studies, predominance towards L2 genotype was identified.

Micromagnetism of permalloy antidot arrays prepared from alumina templates.

Magnetic hysteresis processes of hexagonal arrays of permalloy antidots have been studied by means of micromagnetic simulations as a function of geometrical parameters. The ideal system shows a maximum of the coercive field as a function of the antidot diameter. The simulated magnetic behavior has been compared with experimental values for antidot arrays of permalloy prepared from alumina templates with thicknesses between 2 and 60 nm, showing a monotonic increase of the coercive field as a function of the antidot diameter. We show that the introduction into simulations of the combination of variable antidot diameters from bottom to top due to the fabrication process and, more importantly, large geometrical domains, which break the sample symmetry, solves the discrepancy between the simulations and the experiment.

Novel in vitro systems for prediction of veterinary drug residues in ovine milk and dairy products.

A new in vitro tool was developed for the identification of veterinary substrates of the main drug transporter in the mammary gland. These drugs have a much higher chance of being concentrated into ovine milk and thus should be detectable in dairy products. Complementarily, a cell model for the identification of compounds that can inhibit the secretion of drugs into ovine milk, and thus reduce milk residues, was also generated. The ATP-binding cassette transporter G2 (ABCG2) is responsible for the concentration of its substrates into milk. The need to predict potential drug residues in ruminant milk has prompted the development of in vitro cell models over-expressing ABCG2 for these species to detect veterinary drugs that interact with this transporter. Using these models, several substrates for bovine and caprine ABCG2 have been found, and differences in activity between species have been reported. However, despite being of great toxicological relevance, no suitable in vitro model to predict substrates of ovine ABCG2 was available. New MDCKII and MEF3.8 cell models over-expressing ovine ABCG2 were generated for the identification of substrates and inhibitors of ovine ABCG2. Five widely used veterinary antibiotics (marbofloxacin, orbifloxacin, sarafloxacin, danofloxacin and difloxacin) were discovered as new substrates of ovine ABCG2. These results were confirmed for the bovine transporter and its Y581S variant using previously generated cell models. In addition, the avermectin doramectin was described as a new inhibitor of ruminant ABCG2. This new rapid assay to identify veterinary drugs that can be concentrated into ovine milk will potentially improve detection and monitoring of veterinary drug residues in ovine milk and dairy products.

Psychophysiological correlates of coping and quality of life in patients with ALS.

OBJECTIVE: Self-regulation models of coping suggest that patients with chronic diseases reporting low quality of life (QoL), an indicator of failed coping efforts, should show facilitated access to disease related words. Here we investigated whether a reduced N400 amplitude within an incongruent, i.e. unpredictable disease-related context would be a correlate of this facilitated access. METHODS: ERPs were recorded in N=18 patients with amyotrophic lateral sclerosis (ALS) and N=20 age-matched healthy controls during reading of sentences, ending either with congruent or incongruent words. Incongruent and congruent words were disease related or disease unrelated. Mean N400 amplitudes were analyzed with mixed models. RESULTS: Generally, incongruent words elicited a more negative N400 amplitude than congruent words in all groups and conditions, i.e. an N400 effect. In patients with high QoL this N400 effect did not differ between disease related and unrelated words. In patients with low QoL, however, the N400 effect was significantly smaller for disease related than for disease unrelated words. In healthy controls N400 amplitudes showed no such interaction between congruence, disease relatedness and QoL. Results remained stable when controlling for disease severity, duration and depression. CONCLUSION: The N400 indicates increased accessibility to disease related information in ALS patients with low QoL. The increased access may imply a constantly activated disease related context which is linked to low QoL. SIGNIFICANCE: N400 modulation by disease related information may serve as a psychophysiological correlate of coping and the patient's QoL.

Application of synthetic photostable retinoids induces novel limb and facial phenotypes during chick embryogenesis in vivo.

We have recently developed a range of synthetic retinoid analogues which include the compounds EC23 and EC19. They are stable on exposure to light and are predicted to be resistant to the normal metabolic processes involved in the inactivation of retinoids in vivo. Based on the position of the terminal carboxylic acid groups in the compounds we suggest that EC23 is a structural analogue of all-trans retinoic acid (ATRA), and EC19 is an analogue of 13-cis retinoic acid. Their effects on the differentiation of pluripotent stem cells has been previously described in vitro and are consistent with this hypothesis. We present herein the first description of the effects of these molecules in vivo. Retinoids were applied to the anterior limb buds of chicken embryos in ovo via ion-exchange beads. We found that retinoid EC23 produces effects on the wing digits similar to ATRA, but does so at two orders of magnitude lower concentration. When larger quantities of EC23 are applied, a novel phenotype is obtained involving production of multiple digit 1s on the anterior limb. This corresponds to differential effects of ATRA and EC23 on sonic hedgehog (shh) expression in the developing limb bud. With EC23 application we also find digit 1 phenotypes similar to thumb duplications described in the clinical literature. EC23 and ATRA are shown to have effects on the entire proximal-distal axis of the limb, including hitherto undescribed effects on the scapula. This includes suppression of expression of the scapula marker Pax1. EC23 also produces effects similar to those of ATRA on the developing face, producing reductions of the upper beak at concentrations two orders of magnitude lower than ATRA. In contrast, EC19, which is structurally very similar to EC23, has novel, less severe effects on the face and rarely alters limb development. EC19 and ATRA are effective at similar concentrations. These results further demonstrate the ability of retinoids to influence embryonic development. Moreover, EC23 represents a useful new tool to investigate developmental processes and probe the mechanisms underlying congenital abnormalities in vertebrates including man.

Towards a more precise neurophysiological assessment of cognitive functions in patients with disorders of consciousness.

PURPOSE: To analyze the principles that guide inference of covert cognitive functions and consciousness in patients with extremely severe brain damage on the basis of neurophysiological test results. METHODS: (1) A quantitative analysis of a range of possible inferences based on neurophysiological findings in low- and non-responsive patients; (2) a logical analysis of the various possible orders of application of neurophysiological tests in such patients. RESULTS: Surprisingly, improvement of neurophysiological test qualities contributes to the improvement of diagnostic results less than some other factors, such as the structure of the patient population, the quality of the previous clinical diagnosis, and the variability of the methods used. CONCLUSIONS: A sequential decision procedure is suggested. Different test paradigms should be combined most effectively to arrive at a reliable evaluation of cognitive functions in this patient population.

Carotid cavernous fistula after surgically assisted rapid maxillary expansion with a bone anchored appliance.

Surgically assisted rapid maxillary expansion (SARME) is an effective and stable method for treating severe maxillary transverse discrepancies in skeletally mature individuals, but it has potential complications. The authors report the case of a 34-year-old woman who developed carotid cavernous fistula after undergoing SARME with a bone anchored appliance and discuss the possible etiological basis of this condition.

The auditory p300-based SSBCI: a door to minimally conscious patients?

In this study we report on the evaluation of a novel auditory single-switch BCI in nine patients diagnosed with MCS. The task included a simple and a complex oddball paradigm, the latter uses the tone stream segregation phenomenon. In all patients a significant difference between deviant and frequent tones could be observed in EEG. However, in some cases the deviant tones produce a significant negative peak and in some a very late positive peak. These preliminary findings are relevant in order to address future customization of this auditory ssBCI-based paradigm for unresponsive patients.

Nanomagnets with high shape anisotropy and strong crystalline anisotropy: perspectives on magnetic force microscopy.

We report on a new approach for magnetic imaging, highly sensitive even in the presence of external, strong magnetic fields. Based on FIB-assisted fabricated high-aspect-ratio rare-earth nanomagnets, we produce groundbreaking magnetic force tips with hard magnetic character where we combine a high aspect ratio (shape anisotropy) together with strong crystalline anisotropy (rare-earth-based alloys). Rare-earth hard nanomagnets are then FIB-integrated to silicon microcantilevers as highly sharpened tips for high-field magnetic imaging applications. Force resolution and domain reversing and recovery capabilities are at least one order of magnitude better than for conventional magnetic tips. This work opens new, pioneering research fields on the surface magnetization process of nanostructures based either on relatively hard magnetic materials-used in magnetic storage media-or on materials like superparamagnetic particles, ferro/antiferromagnetic structures or paramagnetic materials.

Analysis of the effect of the bovine adenosine triphosphate-binding cassette transporter G2 single nucleotide polymorphism Y581S on transcellular transport of veterinary drugs using new cell culture models.

In commercial dairy production, the risk of drug residues and environmental pollutants in milk from ruminants has become an outstanding problem. One of the main determinants of active drug secretion into milk is the ATP-binding cassette transporter G2/breast cancer resistance protein (ABCG2/BCRP). It is located in several organs associated with drug absorption, metabolism, and excretion, and its expression is highly induced during lactation in the mammary gland of ruminants, mice, and humans. As a consequence, potential contamination of milk could expose suckling infants to xenotoxins. In cows, a SNP for this protein affecting quality and quantity of milk production has been described previously (Y581S). In this study, our main purpose was to determine whether this polymorphism has an effect on transcellular transport of veterinary drugs because this could alter substrate pharmacokinetics and milk residues. We stably expressed the wild-type bovine ABCG2 and the Y581S variant in Madin-Darby canine kidney epithelial cells (MDCKII) and MEF3.8 cell lines generating cell models in which the functionality of the bovine transporter could be addressed. Functional studies confirmed the greater functional activity in mitoxantrone accumulation assays for the Y581S variant with a greater relative V(MAX) value (P = 0.040) and showed for the first time that the Y581S variant presents greater transcellular transport of the model ABCG2 substrate nitrofurantoin (P = 0.024) and of 3 veterinary antibiotics, the fluoroquinolone agents enrofloxacin (P = 0.035), danofloxacin (P = 0.001), and difloxacin (P = 0.008), identified as new substrates of the bovine ABCG2. In addition, the inhibitory effect of the macrocyclic lactone ivermectin on the activity of wild-type bovine ABCG2 and the Y581S variant was also confirmed, showing a greater inhibitory potency on the wild-type protein at all the concentrations tested (5 µM, P = 0.017; 10 µM, P = 0.001; 25 µM, P = 0.008; and 50 µM, P = 0.003). Differential transport activity depending on the genotype together with the differential inhibition pattern might have clinical consequences, including changes in substrate pharmacokinetics (and subsequently pharmacodynamics) and more specifically, changes in secretion of ABCG2 substrates into milk, potentially implying important consequences to veterinary therapeutics.

Involvement of breast cancer resistance protein (BCRP/ABCG2) in the secretion of danofloxacin into milk: interaction with ivermectin.

Danofloxacin, a veterinary fluoroquinolone antimicrobial drug, is actively secreted into milk by an as yet unknown mechanism. One of the main determinants of active drug secretion into milk is the transporter (BCRP/ABCG2). The main purpose was to determine whether danofloxacin is an in vitro substrate for Bcrp1/BCRP and to assess its involvement in danofloxacin secretion into milk. In addition, the role of potential drug-drug interactions in this process was assessed using ivermectin. Danofloxacin was transported in vitro by Bcrp1/BCRP, and ivermectin efficiently blocked this transport. Experiments with Bcrp1(-/-) mice showed no evidence of the involvement of Bcrp1 in plasma pharmacokinetics of danofloxacin. However, the milk concentration and milk-to-plasma ratio of danofloxacin were almost twofold higher in wild-type compared with Bcrp1(-/-) mice. The in vivo interaction with ivermectin was studied in sheep after co-administration of danofloxacin (1.25 mg/kg, i.m.) and ivermectin (0.2 mg/kg, s.c.). Ivermectin had no significant effect on the plasma levels of danofloxacin but significantly decreased danofloxacin concentrations in milk by almost 40%. Concomitant administration of multiple drugs, often used in veterinary therapy, may not only affect their pharmacological activity but also their secretion into milk, because of potential drug-drug interactions mediated by BCRP.

Milk secretion of nitrofurantoin, as a specific BCRP/ABCG2 substrate, in assaf sheep: modulation by isoflavones.

Studies on residues in milk used for human consumption have increased due to health concerns and priority interest in the control of potentially risky drugs. The protein BCRP/ABCG2, present in the mammary epithelia, actively extrudes drugs into milk and can be modulated by isoflavones. Nitrofurantoin is a specific BCRP substrate which is actively excreted into milk by this transporter. In this research, we studied nitrofurantoin transport into milk in four experimental groups: G1-calves fed forage with isoflavones; G2-calves fed forage with isoflavones and administered exogenous genistein and daidzein; G3-calves fed forage without isoflavones; G4-calves fed forage without isoflavones and administered exogenous genistein and daidzein. Results show increased levels of nitrofurantoin in milk from calves without isoflavones (G3) and decreased nitrofurantoin residues in milk when isoflavones were present, either by forage (G1 and G2) or by exogenous administration (G4). The values of C(max) in milk were significantly lower in those groups with isoflavones in forage (G1, G2). Plasma levels were low and unmodified among the groups. Inter-individual variation was high. All these results seem to point to a feasible control of drug secretion into milk through isoflavones in the diet when the drug is a good BCRP/ABCG2 substrate.