[Inhaled levodopa: from evidence to experience]. / Levodopa inhalada: de la evidencia a la experiencia.

Most patients with Parkinson's disease experience motor fluctuations or 'off' periods, which impact on their daily activities, increase their disability and diminish their quality of life. They suffer from these fluctuations despite multiple adjustments to the schedules, doses and intake of medication. In this context, on-demand or rescue treatments are necessary to attempt to improve 'off' periods, with drugs that have the pharmacokinetic advantage of a much faster onset of action because their routes of administration are not oral. There are currently three on-demand therapies for the treatment of fluctuations: subcutaneous apomorphine, inhaled levodopa and sublingual apomorphine. Of the three alternatives, subcutaneous apomorphine generally has the fastest onset of action, sublingual apomorphine provides the longest clinical effect, and inhaled levodopa has the most favourable side effect profile. Each of these drugs has its own characteristics: the time before onset of action, the duration of action and different side effect profiles. The choice for each patient will depend on their individual needs and circumstances. To mark the first year of the introduction of inhaled levodopa, we review these therapies, focusing on the experience with this new dosage form of levodopa.

TITLE: Levodopa inhalada: de la evidencia a la experiencia.La mayoría de los pacientes con enfermedad de Parkinson sufren fluctuaciones motoras o períodos off, que impactan en sus actividades cotidianas, aumentan su discapacidad y empeoran su calidad de vida. A pesar de realizar múltiples ajustes en los horarios, en las dosis y en las tomas de medicación, no se consigue que estén libres de estas fluctuaciones. Es en este contexto en el que son necesarios los tratamientos a demanda o de rescate para tratar de mejorar los períodos off, con fármacos que tienen la ventaja farmacocinética de un inicio de acción mucho más rápido debido a que sus vías de administración no son orales. En la actualidad existen tres terapias a demanda para el tratamiento de las fluctuaciones: apomorfina subcutánea, levodopa inhalada y apomorfina sublingual. En general, la apomorfina subcutánea tiene un inicio de efecto más rápido, la apomorfina sublingual ofrece el efecto clínico más prolongado y la levodopa inhalada tiene el perfil de efectos secundarios más favorable entre las tres opciones. Cada uno de estos medicamentos tiene características únicas: tiempo de inicio, duración de acción y diferentes perfiles de efectos secundarios. La elección para cada paciente dependerá de sus necesidades y circunstancias individuales. Aprovechando el primer año de la introducción de la levodopa inhalada, revisamos estas terapias, centrándonos en la experiencia acumulada con esta nueva presentación galénica de levodopa.

The upside of cumulative conceptual interference on exemplar-level mnemonic discrimination.

Although long-term visual memory (LTVM) has a remarkable capacity, the fidelity of its episodic representations can be influenced by at least two intertwined interference mechanisms during the encoding of objects belonging to the same category: the capacity to hold similar episodic traces (e.g., different birds) and the conceptual similarity of the encoded traces (e.g., a sparrow shares more features with a robin than with a penguin). The precision of episodic traces can be tested by having participants discriminate lures (unseen objects) from targets (seen objects) representing different exemplars of the same concept (e.g., two visually similar penguins), which generates interference at retrieval that can be solved if efficient pattern separation happened during encoding. The present study examines the impact of within-category encoding interference on the fidelity of mnemonic object representations, by manipulating an index of cumulative conceptual interference that represents the concurrent impact of capacity and similarity. The precision of mnemonic discrimination was further assessed by measuring the impact of visual similarity between targets and lures in a recognition task. Our results show a significant decrement in the correct identification of targets for increasing interference. Correct rejections of lures were also negatively impacted by cumulative interference as well as by the visual similarity with the target. Most interestingly though, mnemonic discrimination for targets presented with a visually similar lure was more difficult when objects were encoded under lower, not higher, interference. These findings counter a simply additive impact of interference on the fidelity of object representations providing a finer-grained, multi-factorial, understanding of interference in LTVM.

Influence of abiotic factors on diapause termination and temperature requirements for postdiapause development in the European red mite, Panonychus ulmi (Acari: Tetranychidae).

The European red mite Panonychus ulmi (Koch) is widely distributed and it can severely affect pome fruit crops, particularly apple. Pest outbreaks are related to an overuse of non-selective pesticide treatments that lead to the development of resistance and the absence of natural enemies in the orchard. A key aspect to optimize the use of pesticide treatments in the context of IPM is to increase the knowledge on the biology and ecology of the pest to better predict population dynamics and outbreaks. For the European red mite, knowledge on the conditions that lead to diapause breaking by winter eggs is essential to model population dynamics. To increase this knowledge, winter eggs were collected during field surveys in northen Spain during three years and egg hatching was monitored under controlled temperature and photoperiod conditions in the laboratory. The "number of days exposed to cold temperatures" was the most significant factor that positively affected hatching of overwintering eggs. The time required for 50% of the egg population to hatch (T50%) was also negatively modulated by the duration of exposure to cold temperature. The temperature threshold for postdiapause eggs development collected from the field was estimated between 5 and 6 ºC in 2005 and 2007, respectively. Moreover, the degree-days required for post diapause development were estimated between 263.2 and 270.3, depending on the year of collection. Collectively, we provide additional information on the diapause termination and postdiapause development of the European red mite that may effectively contribute to optimize pest population models.

Differential effects of intrinsic properties of natural scenes and interference mechanisms on recognition processes in long-term visual memory.

Humans display remarkable long-term visual memory (LTVM) processes. Even though images may be intrinsically memorable, the fidelity of their visual representations, and consequently the likelihood of successfully retrieving them, hinges on their similarity when concurrently held in LTVM. In this debate, it is still unclear whether intrinsic features of images (perceptual and semantic) may be mediated by mechanisms of interference generated at encoding, or during retrieval, and how these factors impinge on recognition processes. In the current study, participants (32) studied a stream of 120 natural scenes from 8 semantic categories, which varied in frequencies (4, 8, 16 or 32 exemplars per category) to generate different levels of category interference, in preparation for a recognition test. Then they were asked to indicate which of two images, presented side by side (i.e. two-alternative forced-choice), they remembered. The two images belonged to the same semantic category but varied in their perceptual similarity (similar or dissimilar). Participants also expressed their confidence (sure/not sure) about their recognition response, enabling us to tap into their metacognitive efficacy (meta-d'). Additionally, we extracted the activation of perceptual and semantic features in images (i.e. their informational richness) through deep neural network modelling and examined their impact on recognition processes. Corroborating previous literature, we found that category interference and perceptual similarity negatively impact recognition processes, as well as response times and metacognitive efficacy. Moreover, images semantically rich were less likely remembered, an effect that trumped a positive memorability boost coming from perceptual information. Critically, we did not observe any significant interaction between intrinsic features of images and interference generated either at encoding or during retrieval. All in all, our study calls for a more integrative understanding of the representational dynamics during encoding and recognition enabling us to form, maintain and access visual information.

Pharmacogenetic biomarkers for secukinumab response in psoriasis patients in real-life clinical practice.

BACKGROUND: Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation. OBJECTIVE: To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting. METHODS: We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed. RESULTS: A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes. CONCLUSION: We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.

Comparison between pollutants found in breast milk and infant formula in the last decade: A review.

Since ancient times, breastfeeding has been the fundamental way of nurturing the newborn. The benefits of breast milk are widely known, as it is a source of essential nutrients and provides immunological protection, as well as developmental benefits, among others. However, when breastfeeding is not possible, infant formula is the most appropriate alternative. Its composition meets the nutritional requirements of the infant, and its quality is subject to strict control by the authorities. Nonetheless, the presence of different pollutants has been detected in both matrices. Thus, the aim of the present review is to make a comparison between the findings in both breast milk and infant formula in terms of contaminants in the last decade, in order to choose the most convenient option depending on the environmental conditions. For that, the emerging pollutants including metals, chemical compounds derived from heat treatment, pharmaceutical drugs, mycotoxins, pesticides, packaging materials, and other contaminants were described. While in breast milk the most concerning contaminants found were metals and pesticides, in infant formula pollutants such as metals, mycotoxins, and packaging materials were the most outstanding. In conclusion, the convenience of using a feeding diet based on breast milk or either infant formula depends on the maternal environmental circumstances. However, it is important to take into account the immunological benefits of the breast milk compared to the infant formula, and the possibility of using breast milk in combination with infant formula when the nutritional requirements are not fulfilled only with the intake of breast milk. Therefore, more attention should be paid in terms of analyzing these conditions in each case to be able to make a proper decision, as it will vary depending on the maternal and newborn environment.

Typicality in the brain during semantic and episodic memory decisions.

Concept typicality is a key semantic dimension supporting the categorical organization of items based on their features, such that typical items share more features with other members of their category than atypical items, which are more distinctive. Typicality effects manifest in better accuracy and faster response times during categorization tasks, but higher performance for atypical items in episodic memory tasks, due to their distinctiveness. At a neural level, typicality has been linked to the anterior temporal lobe (ATL) and the inferior frontal gyrus (IFG) in semantic decision tasks, but patterns of brain activity during episodic memory tasks remain to be understood. We investigated the neural correlates of typicality in semantic and episodic memory to determine the brain regions associated with semantic typicality and uncover effects arising when items are reinstated during retrieval. In an fMRI study, 26 healthy young subjects first performed a category verification task on words representing typical and atypical concepts (encoding), and then completed a recognition memory task (retrieval). In line with previous literature, we observed higher accuracy and faster response times for typical items in the category verification task, while atypical items were better recognized in the episodic memory task. During category verification, univariate analyses revealed a greater involvement of the angular gyrus for typical items and the inferior frontal gyrus for atypical items. During the correct recognition of old items, regions belonging to the core recollection network were activated. We then compared the similarity of the representations from encoding to retrieval (ERS) using Representation Similarity Analyses. Results showed that typical items were reinstated more than atypical ones in several regions including the left precuneus and left anterior temporal lobe (ATL). This suggests that the correct retrieval of typical items requires finer-grained processing, evidenced by greater item-specific reinstatement, which is needed to resolve their confusability with other members of the category due to their higher feature similarity. Our findings confirm the centrality of the ATL in the processing of typicality while extending it to memory retrieval.

Locations of objects are better remembered than their identities in naturalistic scenes: An eye-tracking experiment in mild cognitive impairment.

OBJECTIVE: Retaining the identity or location of decontextualized objects in visual short-term working memory (VWM) is impaired by healthy and pathological ageing, but research remains inconclusive on whether these two features are equally impacted by it. Moreover, it is unclear whether similar impairments would manifest in naturalistic visual contexts. METHOD: 30 people with mild cognitive impairment (MCI) and 32 age-matched control participants (CPs) were eye-tracked within a change detection paradigm. They viewed 120 naturalistic scenes, and after a retention interval (1 s) asked whether a critical object in the scene had (or not) changed on either: identity (became a different object), location (same object but changed location), or both (changed in location and identity). RESULTS: MCIs performed worse than CP but there was no interaction with the type of change. Changes in both were easiest while changes in identity alone were hardest. The latency to first fixation and first-pass duration to the critical object during successful recognition was not different between MCIs and CPs. Objects that changed in both features took longer to be fixated for the first time but required a shorter first pass compared to changes in identity alone which displayed the opposite pattern. CONCLUSIONS: Locations of objects are better remembered than their identities; memory for changes is best when involving both features. These mechanisms are spared by pathological ageing as indicated by the similarity between groups besides trivial differences in overall performance. These findings demonstrate that VWM mechanisms in the context of naturalistic scene information are preserved in people with MCI. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

[Hand hygiene and pandemic. Controversies]. / Higiene de manos y pandemia. Controversias.

During the COVID-19 pandemic, the world's healthcare systems were extremely strained. Intensive care units were stretched to capacity and healthcare facilities were forced to set up spaces to care for critically ill patients. Professionals were required to work in strenuous conditions, completely disrupting their work routines.In this scenario, hand hygiene and the use of gloves by healthcare professionals became a critical point of transmission risk.The results of the ENVIN study in 2020 and 2021, corresponding to the pandemic period, showed worrying data on the increase in infection rates, with rates rising by 250% at the worst moments of the pandemic. This suggested that excessive risk situations were occurring for the patient. Any preventive strategy must place correct hand hygiene and proper use of gloves among its priority objectives. For this reason, the Project Zero Advisory Board made a series of adaptations and recommendations based on available evidence and expert opinion related to hand hygiene and glove use during the pandemic situation to promote best practice in extreme situations. This article reviews the key aspects of hand hygiene as part of the WHO safety strategy, the main barriers to compliance and the main adaptations proposed by the Advisory Board of the Zero projects.

[Translated article] Randomized, placebo-controlled, double-blind clinical trial to evaluate efficacy and safety of topical tranexamic acid in saving blood loss in patients undergoing prosthetic knee surgery.

BACKGROUND AND OBJECTIVE: Knee arthroplasty is a major surgery with potential significant blood loss. Assess the efficacy and safety of topical administration of 3g of tranexamic acid (TXA) in terms of reducing blood loss in knee arthroplasty. MATERIAL AND METHOD: A randomized, phase III, double-blind, placebo-controlled clinical trial has been conducted. We included 150 patients in 2 parallel treatment groups (75 per arm). The solution was administered topically intra-articular after cementation and prior to capsular closure. Analytical determinations were made before and after surgery to quantify blood loss. RESULTS: Total blood loss for the placebo group was 831.5ml and 662.3ml for the TXA group. The difference between the 2 groups was 169.2ml; which means a save of 20.4%; this difference being statistically significant (p<.001). There were no differences in terms of the onset of ambulation, days of admission or visual analogue scale at one month of surgery. Ten patients were rejected for presurgical urinary tract infection, metal allergy, selection failure, patellar weakening, prosthetic instability, intrasurgical tibial fracture, change of indication to unicompartimental prosthesis and a loss of follow-up. There was only one complication unrelated to the investigational drug (bladder balloon). CONCLUSION: The administration of TXA topically after cementation of the prosthetic components in total knee arthroplasty in a single dose has demonstrated being safe and effective.

Similar mechanisms of temporary bindings for identity and location of objects in healthy ageing: an eye-tracking study with naturalistic scenes.

The ability to maintain visual working memory (VWM) associations about the identity and location of objects has at times been found to decrease with age. To date, however, this age-related difficulty was mostly observed in artificial visual contexts (e.g., object arrays), and so it is unclear whether it may manifest in naturalistic contexts, and in which ways. In this eye-tracking study, 26 younger and 24 healthy older adults were asked to detect changes in a critical object situated in a photographic scene (192 in total), about its identity (the object becomes a different object but maintains the same position), location (the object only changes position) or both (the object changes in location and identity). Aging was associated with a lower change detection performance. A change in identity was harder to detect than a location change, and performance was best when both features changed, especially in younger adults. Eye movements displayed minor differences between age groups (e.g., shorter saccades in older adults) but were similarly modulated by the type of change. Latencies to the first fixation were longer and the amplitude of incoming saccades was larger when the critical object changed in location. Once fixated, the target object was inspected for longer when it only changed in identity compared to location. Visually salient objects were fixated earlier, but saliency did not affect any other eye movement measures considered, nor did it interact with the type of change. Our findings suggest that even though aging results in lower performance, it does not selectively disrupt temporary bindings of object identity, location, or their association in VWM, and highlight the importance of using naturalistic contexts to discriminate the cognitive processes that undergo detriment from those that are instead spared by aging.

Radiology volunteers to support a breast cancer screening program in Peru: Description of the project, preliminary results, and impressions.

Breast cancer is the second most common cancer in Peruvian women. Due to limitations in national breast cancer screening programs, especially in rural areas, more than 50% of cases of breast cancer in Peru are diagnosed in advanced stages. In collaboration with a local clinic registered as a nongovernmental organization (CerviCusco), RAD-AID International aims to create a sustainable diagnostic structure to improve breast cancer screening in Cuzco. With the support of local, national, and international partners that have collaborated in analyzing radiological resources, raising awareness in the population, acquiring equipment, training clinical staff, and building referral networks, our teams of radiologists, included in the RAD-AID team, have participated in training CerviCusco staff in breast ultrasound, thus enabling additional training for radiology residents through a regulated international collaboration.

Can physiological stimulation prior to ileostomy closure reduce postoperative ileus? A prospective multicenter pilot study.

BACKGROUND: The aim of this study was to assess the impact of ileostomy closure following preoperative physiological stimulation (PPS) on postoperative ileus (POI) in patients with loop ileostomy after low anterior resection for rectal cancer. METHODS: Patients who underwent ileostomy closure between January 2017 and February 2020 in two tertiary referral centers were prospectively included. PPS stimulation was compared to standard treatment. Stimulation was carried out daily during the 15 days prior to ileostomy closure by the patient's self-instillation of 200 ml of fecal contents from the ileostomy bag via the efferent loop, using a rectal catheter. Standard treatment (ST) consisted of observation. Outcomes measures were POI, morbidity, stimulation feasibility, and predictors to ileus. RESULTS: A total of 58 patients were included [42 males and 16 females, median age 67 (43-85) years]. PPS was used in 24 patients, who completed the entire stimulation process, and ST in 34 patients. No differences in preoperative factors were found between the two groups. POI was significantly lower in the PPS group (4.2%) vs the ST group (32.4%); p < 0.01, OR: 0.05 (CI 95% 0.01-0.65). The PPS group had a shorter time to restoration of bowel function (1 day vs 3 days) p = 0.02 and a shorter time to tolerance of liquids (1 day vs 2 days), p = 0.04. Age (p = 0.01), open approach at index surgery, p = 0.03, adjuvant capecitabine (p = 0.01). and previous abdominal surgeries (p = 0.02) were associated with POI in the multivariate analysis. C-reactive-protein values on the 3rd (p = 0.02) and 5th (p < 0.01) postoperative day were also associated with POI. CONCLUSIONS: PPS for patients who underwent ileostomy closure after low anterior resection for rectal cancer is feasible and might reduce POI.

Randomized, placebo-controlled, double-blind clinical trial to evaluate efficacy and safety of topical tranexamic acid in saving blood loss in patients undergoing prosthetic knee surgery. / Ensayo clínico aleatorizado, controlado con placebo y doble ciego para evaluar la eficacia y la seguridad del ácido tranexámico tópico en el ahorro de pérdidas sanguíneas en pacientes tratados mediante cirugía protésica de rodilla.

BACKGROUND AND OBJECTIVE: Knee arthroplasty is a major surgery with potential significant blood loss. Assess the efficacy and safety of topical administration of 3g of tranexamic acid (TXA) in terms of reducing blood loss in knee arthroplasty. MATERIAL AND METHOD: A randomized, phase III, double-blind, placebo-controlled clinical trial has been conducted. We included 150 patients in 2parallel treatment groups (75 per arm). The solution was administered topically intra-articular after cementation and prior to capsular closure. Analytical determinations were made before and after surgery to quantify blood loss. RESULTS: Total blood loss for the placebo group was 831.5ml and 662.3ml for the TXA group. The difference between the 2groups was 169.2ml; which means a save of 20.4 per cent; this difference being statistically significant (P<.001). There were no differences in terms of the onset of ambulation, days of admission or Visual Analogue Scale at one month of surgery. Ten patients were rejected for presurgical urinary tract infection, metal allergy, selection failure, patellar weakening, prosthetic instability, intrasurgical tibial fracture, change of indication to unicompartimental prosthesis and a loss of follow-up. There was only one complication unrelated to the investigational drug (bladder balloon). CONCLUSION: The administration of TXA topically after cementation of the prosthetic components in total knee arthroplasty in a single dose has demonstrated being safe and effective.

Factors affecting the performance of P22 ELISA for the diagnosis of caprine tuberculosis in milk samples.

Caprine tuberculosis (TB) is a zoonosis caused by members of the Mycobacterium tuberculosis complex (MTBC). Caprine TB eradication programmes are based mainly on intradermal tuberculin tests and slaughterhouse surveillance. However, the use of serological test has been extended as a potential diagnostic tool in goats through the use of serum, plasma, or even milk samples. Milk production and the antibodies (Ab) present in milk can vary depending on several circumstances. In the present study, different factors that may affect the performance of humoral TB diagnosis were analysed using goat milk samples: 1) lactation stage, 2) a recent previous skin test (booster effect) and 3) the effect of freeze-thaw cycles on milk samples preserved with azidiol. TB-infected animals (n = 44) were selected to evaluate the evolution of the Ab levels during the 6-month lactation period, along with its potential effect on the P22 ELISA results. In general, no significant changes (p = 0.079) were observed throughout the study as regards Ab levels in milk samples between consecutive analysis although the reactivity to P22 ELISA decreased when samplings were performed at the last two months of the lactation. Regarding the booster effect, the quantitative results showed a significant variation (p < 0.001) for both milk and serum samples when serological tests were carried out 15 days after the skin test. Finally, there were no significant differences (p = 0.99) in the P22 ELISA results when using milk samples preserved with azidiol that had undergone freeze-thaw cycles.