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.

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.

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.

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.

[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.

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.

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.

Ceftriaxone-induced acute reversible encephalopathy in a patient treated for a urinary tract infection.

Encephalopathy is a rare side effect of third- and fourth-generation cephalosporins. Renal failure and previous disease of the central nervous system predispose to this neurotoxicity. We describe a case of encephalopathy with generalised triphasic waves in a patient with pre-existent cerebrovascular disease who was treated with ceftriaxone for a urinary tract infection. Early recognition of this complication is relevant given that ceftriaxone discontinuation reverted the neurological syndrome.

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.

Magnetostriction measuring device based on an optical fiber sensor with an annular photodiode.

A new simple and sensitive dilatometer to measure magnetostriction of ribbons has been developed, based on an optical fiber sensor using an annular photodiode. The optical fiber is used bidirectionally, both for emission and detection of light, simplifying the access to the ribbon under test. The working principle is based on the measurement by reflection of the longitudinal displacement of the ribbon end. For a Vitroperm amorphous ribbon of 100 mm length, 21 microm thickness, and 8.3 mm width, a displacement of 2.571 microm with a maximum uncertainty of 8 nm has been obtained.

Impaired hyperpolarization in regenerated endothelium after balloon catheter injury.

Ca(2+)-activated K(+) (K(Ca)) channels control endothelial Ca(2+) homeostasis and the formation of vasodilators. After angioplasty, dysfunction of the regenerated endothelium leads to abnormal vasoregulation. In this study, we tested the expression and function of K(Ca) channels in regenerated endothelium at 6 weeks after balloon catheter injury of rat carotid arteries (CAs) by using single-cell reverse transcription-polymerase chain reaction, patch-clamp techniques, and analysis of vasoreactivity. In single regenerated endothelial cells (ECs), the percentage of ECs expressing the K(Ca) genes, rSK3 (12+/-8%) and rIK1 (22+/-9%), was significantly lower compared with the percentage of native ECs expressing these genes (rSK3 58+/-8%, rIK1 64+/-10%). In patch-clamp experiments, K(Ca) currents and acetylcholine-induced hyperpolarization were markedly reduced in regenerated ECs (shift of membrane potential -6+/-3 mV) compared with those in native ECs (shift of membrane potential -21+/-5 mV). In pressure myograph experiments, acetylcholine-induced dilation was impaired in reendothelialized CAs compared with normal CAs. Intraluminal application of the K(Ca) blocker apamin and charybdotoxin inhibited dilation by 30% in normal CAs but was without effect in reendothelialized CAs. Intraluminal application of 1-ethyl-2-benzimidazolinone (100 micromol/L), an opener of K(Ca) channels, evoked dilation by 29% in normal CAs but had no effect in reendothelialized CAs. In conclusion, the impaired expression of K(Ca) channels in regenerated endothelium results in defective hyperpolarization and impaired dilation. Thus, the impaired K(Ca) channel function contributes to functional alterations of regenerated endothelium after angioplasty.

A new method to produce macropores in calcium phosphate cements.

A new way to create macropores in calcium phosphate cements has been developed. The method consists in adding NaHCO3 to the starting cement powder (Biocement D) and using two different liquids: first a basic liquid to form the paste and later an acid liquid to obtain CO2 bubbles. Mercury intrusion measurements showed a dramatic increase both in macropores with an average size of 100 m and in the total porosity (even higher than 50% with respect to the Biocement D). This method does not change in any significant way the final reaction products of the starting material after being soaked 3 days in Ringer solution. Only, due to the increase of the porosity. the compressive strength of the porous cement decreases significantly.

A novel bioactive and magnetic biphasic material.

A novel biphasic material has been synthetised from a sol-gel-derived glass (Si-Ca-P) and a glass-ceramic obtained from a melt-derived glass (Si-Ca-Fe). Both components of such a biphasic mixture are bioactive, but with different kinetics for the growth of an apatite-like layer on the surface of these materials, needing only one day for the sol-gel-derived glass and one month for the glass-ceramic. The glass-ceramic shows magnetic properties. The biphasic material, obtained from a mixture 1:1 of these components, is bioactive, and its surface is coated after 15 days of soaking in SBF. The biphasic material also exhibited magnetic behaviour, useful for hyperthermia.

Human trichinellosis in Sourthern Spain: serologic and epidemiologic study.

An outbreak of trichinellosis caused by wild boar meat occurred in the Iruela (Jaen) in southern Spain in February 1996. Thirty-five people were diagnosed on the basis of epidemiologic data, but only 24 patients agreed to participate in this study. Twenty-three (96%) had symptoms suggestive of trichinellosis. Immunofluorescent and Western blot test results for trichinellosis were positive in 18 persons, and 15 had circulating Trichinella spiralis antigens. These findings suggest that results of tests for circulating antigens in conjunction with clinical presentation are useful for the diagnosis of trichinellosis.

In vitro release of gentamicin from OHAp/PEMA/PMMA samples.

The influence of hydroxyapatite (OHAp) and gentamicin sulphate (GEN) contents on the release kinetics of GEN, in samples composed of OHAp, poly(methyl methacrylate) (PMMA) and poly(ethyl methacrylate) (PEMA) has been studied. For this purpose, samples with 30 and 40% of OHAp and 5 and 9% of GEN were prepared. The in vitro release study was carried out soaking the samples in simulated body fluid (SBF) at 37 degrees C for 70 days. The release profiles showed a faster release during the first 10 h, diminishing progressively until the end of the study. It was noticed that the percentage of released GEN increased with the OHAp content. For samples with 40% of OHAp, GEN release is nearly independent of the initial amount of such drug (in the range 5-9%), whereas for samples with 30% of OHAp, the release process is favoured by higher contents of GEN, which would favour a higher SBF uptake. GEN release is related to SBF uptake, which is in turn related, on the one hand, to the OHAp content (increase of the porosity and the hydrophilic character of the samples) and on the other hand, to content of GEN.

Biphasic materials for bone grafting and hyperthermia treatment of cancer.

Three biphasic materials have been synthesized from a magnetic glass-ceramic (Si-Ca-Fe) and a bioactive sol-gel glass (Si-P-Ca). The ratios of glass-ceramic:sol-gel glass used in this work were 1:1, 2:1, and 5:1. These materials show bioactive and magnetic properties and can be used as thermoseeds for hyperthermia treatment of bone tumors. The sol-gel glass content affects the textural properties of the glass-ceramic, giving rise to porosity, which plays a fundamental role in the formation of an apatite-like layer on the surface. On the other hand, as the sol-gel glass content increases, the magnetic properties change due to the diffusion of Fe ions to the glassy phases of the biphasic materials. The biphasic nature of these materials allows the changing of both properties, depending on the requirements of the patient.

In vivo bone response to porous calcium phosphate cement.

We conducted an in vivo experiment to evaluate the resorption rate of a calcium phosphate cement (CPC) with macropores larger than 100 microm, using the CPC called Biocement D (Merck Biomaterial, Darmstadt, Germany), which after setting only shows pores smaller than 1 microm. The gas bubble method used during the setting process created macroporosity. Preset nonporous and porous cement implants were inserted into the trabecular bone of the tibial metaphysis of goats. The size of the preset implants was 6 mm and the diameter of the drill hole was 6.3 mm, leaving a gap of 0.3 mm between implant surface and drill wall. After 2 and 10 weeks, the animals were euthanized and cement implants with surrounding bone were retrieved for histologic evaluation. Light microscopy at 2 weeks revealed that the nonporous implants were surrounded by connective tissue. On the cement surface, we observed a monolayer of multinucleated cells. Ten weeks after implantation, the nonporous implants were still surrounded by connective tissue. However, a thin layer of bone now covered the implant surface. No sign of cement resorption was observed. In contrast, the porous cement evoked a completely different bone response. At 2 weeks, bone formation had already occurred inside the implant porosity. Bone formation even appeared to occur as a result of osteoinduction. Also, at their outer surface, the porous implants were completely surrounded by bone. At 2 weeks, about 31% of the initial cement was resorbed. After 10 weeks, 81% of the initial phosphate cement was resorbed and new bone was deposited. On the basis of these observations, we conclude that the creation of macropores can significantly improve the resorption rate of CPC. This increased degradation is associated with almost complete bone replacement.