Fatty acid amide hydrolase gene inactivation induces hetero-cellular potentiation of microglial function in the 5xFAD mouse model of Alzheimer's disease.

Neuroinflammation has recently emerged as a crucial factor in Alzheimer's disease (AD) etiopathogenesis. Microglial cells play an important function in the inflammatory response; specifically, the emergence of disease-associated microglia (DAM) has offered new insights into the conflicting perspectives on the detrimental or beneficial roles of microglia. We previously showed that modulating the endocannabinoid tone by fatty acid amide hydrolase (FAAH) inactivation renders beneficial effects in an amyloidosis context, paradoxically accompanied by an exacerbated neuroinflammatory response and the enrichment of DAM population. Here, we aim to elucidate the role of microglial cells in FAAH-lacking mice in the 5xFAD mouse model of AD by using RNA-sequencing analysis, molecular determinations, and morphological studies by using in vivo multiphoton microscopy. FAAH-lacking AD mice displayed upregulated inflammatory genes and exhibited a DAM genetic profile. Conversely, genes linked to AD were downregulated. Depleting microglia using PLX5622 revealed that plaque-associated microglia in FAAH-deficient AD mice had a more stable, ramified morphology and increased Aß uptake, leading to reduced plaque growth compared to control mice. Importantly, FAAH expression was negligible in microglial cells, thus suggesting a role for FAAH in the cellular interplay in the central nervous system. Our findings show that Faah gene inactivation triggers a hetero-cellular enhancement of microglial function that was paradoxically paralleled by an exacerbated inflammatory response. Taken together, the present data highlight FAAH as a potential therapeutic target in AD.

Toolkit to Examine Lifelike Language v.2.0: Optimizing Speech Biomarkers of Neurodegeneration.

INTRODUCTION: The Toolkit to Examine Lifelike Language (TELL) is a web-based application providing speech biomarkers of neurodegeneration. After deployment of TELL v.1.0 in over 20 sites, we now introduce TELL v.2.0. METHODS: First, we describe the app's usability features, including functions for collecting and processing data onsite, offline, and via videoconference. Second, we summarize its clinical survey, tapping on relevant habits (e.g., smoking, sleep) alongside linguistic predictors of performance (language history, use, proficiency, and difficulties). Third, we detail TELL's speech-based assessments, each combining strategic tasks and features capturing diagnostically relevant domains (motor function, semantic memory, episodic memory, and emotional processing). Fourth, we specify the app's new data analysis, visualization, and download options. Finally, we list core challenges and opportunities for development. RESULTS: Overall, TELL v.2.0 offers scalable, objective, and multidimensional insights for the field. CONCLUSION: Through its technical and scientific breakthroughs, this tool can enhance disease detection, phenotyping, and monitoring.

Multivariate word properties in fluency tasks reveal markers of Alzheimer's dementia.

INTRODUCTION: Verbal fluency tasks are common in Alzheimer's disease (AD) assessments. Yet, standard valid response counts fail to reveal disease-specific semantic memory patterns. Here, we leveraged automated word-property analysis to capture neurocognitive markers of AD vis-à-vis behavioral variant frontotemporal dementia (bvFTD). METHODS: Patients and healthy controls completed two fluency tasks. We counted valid responses and computed each word's frequency, granularity, neighborhood, length, familiarity, and imageability. These features were used for group-level discrimination, patient-level identification, and correlations with executive and neural (magnetic resonanance imaging [MRI], functional MRI [fMRI], electroencephalography [EEG]) patterns. RESULTS: Valid responses revealed deficits in both disorders. Conversely, frequency, granularity, and neighborhood yielded robust group- and subject-level discrimination only in AD, also predicting executive outcomes. Disease-specific cortical thickness patterns were predicted by frequency in both disorders. Default-mode and salience network hypoconnectivity, and EEG beta hypoconnectivity, were predicted by frequency and granularity only in AD. DISCUSSION: Word-property analysis of fluency can boost AD characterization and diagnosis. HIGHLIGHTS: We report novel word-property analyses of verbal fluency in AD and bvFTD. Standard valid response counts captured deficits and brain patterns in both groups. Specific word properties (e.g., frequency, granularity) were altered only in AD. Such properties predicted cognitive and neural (MRI, fMRI, EEG) patterns in AD. Word-property analysis of fluency can boost AD characterization and diagnosis.

Endocannabinoid signaling in the central nervous system.

It is hard to overestimate the influence of the endocannabinoid signaling (ECS) system on central nervous system (CNS) function. In the 40 years since cannabinoids were found to trigger specific cell signaling cascades, studies of the ECS system continue to cause amazement, surprise, and confusion! CB1 cannabinoid receptors are expressed widely in the CNS and regulate cell-cell communication via effects on the release of both neurotransmitters and gliotransmitters. CB2 cannabinoid receptors are difficult to detect in the CNS but seem to "punch above their weight" as compounds targeting these receptors have significant effects on inflammatory state and behavior. Positive and negative allosteric modulators for both receptors have been identified and examined in preclinical studies. Concentrations of the endocannabinoid ligands, N-arachidonoylethanolamine and 2-arachidonoylglycerol (2-AG), are regulated by a combination of enzymatic synthesis and degradation and inhibitors of these processes are available and making their way into clinical trials. Importantly, ECS regulates many essential brain functions, including regulation of reward, anxiety, inflammation, motor control, and cellular development. While the field is on the cusp of preclinical discoveries providing impactful clinical and therapeutic insights into many CNS disorders, there is still much to be learned about this remarkable and versatile modulatory system.

Broadband and low-loss TM-pass polarizer using tilted subwavelength structures.

Photonic systems built on the Silicon-on-Insulator platform exhibit a strong birefringence, and must thus be operated with a single polarization for most applications. Hence, on-chip polarizers that can effectively suppress an undesired polarization state are key components for these systems. Polarizers that extinguish TE polarized light while letting TM polarized light pass with low losses are particularly challenging to design for the standard 220 nm Silicon-on-Insulator platform, because the modal confinement is stronger for TE polarization than for TM polarzation. Here, we propose and design a broadband, low loss and high extinction ratio TM-pass polarizer by engineering a Bragg grating that reflects the fundamental TE mode into the first order TE mode using a subwavelength metamaterial which at the same time allows the TM mode to pass. Our device achieves an extinction ratio in excess of 20 dB, insertion losses below 0.5 dB and back-reflections of the fundamental TE mode of the order of -20 dB in a bandwidth of 150 nm as demonstrated with full 3D-FDTD simulations.

Assessment of the determinants of changes and test-retest reliability in the 6-min walk test performance over a 4-month period in healthy 6-12-year-old children.

PURPOSE: The purpose of the study is to establish the determinants of change in 6-min walk test (6MWT) performance observed in children aged 6-12 years over a 4-month period, and to provide test-retest reliability (4 months) to establish the minimal detectable change (MDC). METHODS: Healthy children aged 6-12 years performed two 6MWT trials separated by a period of 4 months. Multiple linear regression analysis was performed to estimate the percentage of variance explained by the variables potentially predictive of the change in the 6MWT. We employed the intraclass correlation coefficient to assess test-retest reliability. RESULTS: Fifty-nine children (28 boys and 31 girls) were assessed. The change in distance covered during the 6MWT was significantly correlated with the growth in their height (r = 0.679; p < 0.05) and the change in their weight (r = 0.473; p < 0.05). Multiple linear regression analysis shows that the change in distance covered in the 6MWT was only explained by its growth in height (46.0% explained variance). The test-retest reliability was fair-good. After 4 months, we established a 12% change from the initial measurement (79.69 m) as the MDC for a 90% confidence level (MDC90). CONCLUSIONS: The distance covered in the 6MWT improved as the children's age, weight and height increased. The growth children's height was the most important predictor of change in distance covered in the 6MWT. An increase of at least 79.69 m (MDC90) in distance covered in the 6MWT is necessary to attribute the improvement to an intervention and not to the individual's growth.

Divergent dynamics of microbial components in two temperate shallow lakes with contrasting steady states in the Southern Hemisphere.

Factors that affect abundances of organisms in water bodies are influenced by extrinsic and intrinsic drivers that operate from outside and within a system. A high temporal coherence in the dynamics of abiotic parameters and biological communities among neighboring lakes evidences a strong extrinsic control operating similarly across lakes, and allows for prediction of ecosystems evolution in the context of global change and intensive land use. The Pampa region (Argentina) encompasses many shallow lakes submitted to different degrees of anthropic influence and showing contrasting alternative states. We studied an eutrophic clear and a hypertrophic turbid shallow lake during an annual cycle in order to evaluate whether they responded similarly to extrinsic factors or these were overridden by the effects of the steady state of each lake. Physical and chemical variables were highly coherent between both lakes, but accounted little for the large disparities among abundances and dynamics of microorganisms. While communities from the clear lake responded to a combination of extrinsic and intrinsic factors, the turbid lake showed a state less prone to be affected by climatic effects. We hypothesize that clear lakes would perform better as sentinels of climate change in the Pampa wetland.

Potentiation of amyloid beta phagocytosis and amelioration of synaptic dysfunction upon FAAH deletion in a mouse model of Alzheimer's disease.

BACKGROUND: The complex pathophysiology of Alzheimer's disease (AD) hampers the development of effective treatments. Attempts to prevent neurodegeneration in AD have failed so far, highlighting the need for further clarification of the underlying cellular and molecular mechanisms. Neuroinflammation seems to play a crucial role in disease progression, although its specific contribution to AD pathogenesis remains elusive. We have previously shown that the modulation of the endocannabinoid system (ECS) renders beneficial effects in a context of amyloidosis, which triggers neuroinflammation. In the 5xFAD model, the genetic inactivation of the enzyme that degrades anandamide (AEA), the fatty acid amide hydrolase (FAAH), was associated with a significant amelioration of the memory deficit. METHODS: In this work, we use electrophysiology, flow cytometry and molecular analysis to evaluate the cellular and molecular mechanisms underlying the improvement associated to the increased endocannabinoid tone in the 5xFAD mouse- model. RESULTS: We demonstrate that the chronic enhancement of the endocannabinoid tone rescues hippocampal synaptic plasticity in the 5xFAD mouse model. At the CA3-CA1 synapse, both basal synaptic transmission and long-term potentiation (LTP) of synaptic transmission are normalized upon FAAH genetic inactivation, in a CB1 receptor (CB1R)- and TRPV1 receptor-independent manner. Dendritic spine density in CA1 pyramidal neurons, which is notably decreased in 6-month-old 5xFAD animals, is also restored. Importantly, we reveal that the expression of microglial factors linked to phagocytic activity, such as TREM2 and CTSD, and other factors related to amyloid beta clearance and involved in neuron-glia crosstalk, such as complement component C3 and complement receptor C3AR, are specifically upregulated in 5xFAD/FAAH-/- animals. CONCLUSION: In summary, our findings support the therapeutic potential of modulating, rather than suppressing, neuroinflammation in Alzheimer's disease. In our model, the long-term enhancement of the endocannabinoid tone triggered augmented microglial activation and amyloid beta phagocytosis, and a consequent reversal in the neuronal phenotype associated to the disease.

Broad spectral tuning of ultra-low-loss polaritons in a van der Waals crystal by intercalation.

Phonon polaritons-light coupled to lattice vibrations-in polar van der Waals crystals are promising candidates for controlling the flow of energy on the nanoscale due to their strong field confinement, anisotropic propagation and ultra-long lifetime in the picosecond range1-5. However, the lack of tunability of their narrow and material-specific spectral range-the Reststrahlen band-severely limits their technological implementation. Here, we demonstrate that intercalation of Na atoms in the van der Waals semiconductor α-V2O5 enables a broad spectral shift of Reststrahlen bands, and that the phonon polaritons excited show ultra-low losses (lifetime of 4 ± 1 ps), similar to phonon polaritons in a non-intercalated crystal (lifetime of 6 ± 1 ps). We expect our intercalation method to be applicable to other van der Waals crystals, opening the door for the use of phonon polaritons in broad spectral bands in the mid-infrared domain.

Chikungunya and the Heart.

INTRODUCTION: Neglected tropical diseases are a group of communicable diseases that occur in tropical and subtropical conditions and are closely related to poverty and inadequate sanitation conditions. Among these entities, chikungunya remains one of the most widely spread diseases. Although the main symptoms are related to a febrile syndrome, cardiovascular (CV) involvement has been reported, with short- and long-term implications. As part of the "Neglected Tropical Diseases and other Infectious Diseases involving the Heart" (NET-Heart) Project, the aim of this review is to compile all the information available regarding CV involvement of this disease, to help healthcare providers gain knowledge in this field, and contribute to improving early diagnosis, treatment, and prevention strategies. METHODS: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement in conducting and reporting this systematic review. The search was conducted using MEDLINE/PubMed, SciELO, and LILACS databases to identify any relevant studies or reviews detailing an association between chikungunya and cardiac involvement published from January 1972 to May 31, 2020. RESULTS: Despite its mechanism not being fully understood, CV involvement has been described as the most frequent atypical presentation of chikungunya (54.2%). Myocarditis is the most prevalent CV complication. Different rhythm disturbances have been reported in 52% of cases, whereas heart failure was reported in 15% of cases, pericarditis in 5%, and acute myocardial infarction in 2%. Overall estimated CV mortality is 10%, although in patients with other comorbidities, it may increase up to 20%. In the proper clinical setting, the presence of fever, polyarthralgia, and new-onset arrhythmia suggests chikungunya virus-related myocarditis. CONCLUSION: Although most cases are rarely fatal, CV involvement in chikungunya infection remains the most frequent atypical presentation of this disease and may have severe manifestations. Timely diagnosis and appropriate management are necessary to improve patient outcomes.

Twisted Nano-Optics: Manipulating Light at the Nanoscale with Twisted Phonon Polaritonic Slabs.

Recent discoveries have shown that, when two layers of van der Waals (vdW) materials are superimposed with a relative twist angle between them, the electronic properties of the coupled system can be dramatically altered. Here, we demonstrate that a similar concept can be extended to the optics realm, particularly to propagating phonon polaritons-hybrid light-matter interactions. To do this, we fabricate stacks composed of two twisted slabs of a vdW crystal (α-MoO3) supporting anisotropic phonon polaritons (PhPs), and image the propagation of the latter when launched by localized sources. Our images reveal that, under a critical angle, the PhPs isofrequency curve undergoes a topological transition, in which the propagation of PhPs is strongly guided (canalization regime) along predetermined directions without geometric spreading. These results demonstrate a new degree of freedom (twist angle) for controlling the propagation of polaritons at the nanoscale with potential for nanoimaging, (bio)-sensing, or heat management.

Perfectly vertical surface grating couplers using subwavelength engineering for increased feature sizes.

We present perfectly vertical grating couplers for the 220 nm silicon-on-insulator platform incorporating subwavelength metamaterials to increase the minimum feature sizes and achieve broadband low back-reflection. Our study reveals that devices with high coupling efficiencies are distributed over a wide region of the design space with varied back-reflections, while still maintaining minimum feature sizes larger than 100 nm and even 130 nm. Using 3D-finite-difference time-domain simulations, we demonstrate devices with broadband low back-reflection of less than -20dB over more than 100 nm bandwidth centered around the C-band. Coupling efficiencies of 72% and 67% are achieved for minimum feature sizes of 106 nm and 130 nm, respectively. These gratings are also more fabrication tolerant compared to similar designs not using metamaterials.

[Protocolized referral to endoscopy and Helicobacter pylori detected in stools aimed to decrease endoscopy waiting lists]. / La derivación protocolizada a endoscopía asociada a la detección de Helicobacter pylori mediante antígeno en deposiciones disminuye lista de espera para endoscopía y optimiza la detección de lesiones pre-malignas y cáncer gástrico incipiente.

Background Chile has one of the highest mortality rates by gastric cancer (GC) worldwide. Primary prevention of GC and detection of pre-neoplastic and early neoplastic lesions should be a national priority. Aim To assess the impact of the protocolization of endoscopy referral and the use of H. pylori stool antigen test (HPSA) in the management of dyspepsia to decrease the waiting list for endoscopy and increase the detection of gastric pre-neoplastic and early neoplastic lesions. Material and Methods We included all patients referred to the Endoscopy Unit of a regional hospital, from January 2015 to December 2017. We also included patients with known pre-neoplastic lesions and all those with first degree relatives with GC. We implemented protocols for referral of patients with dyspepsia considering the use of HPSA test, prioritizing to endoscopy those with a higher risk of GC. Results A total of 4,641 endoscopies and 2,631 HPSA tests were carried out. After the adoption of these protocols, we observed a 52% decrease in the waiting time for endoscopy. The GC detection rate in this period was 1.8 to 3.1 cases per 100 endoscopies. After the adoption of the protocols, we observed a significant increase in early GC detection rate (from none in 2015 to 13% in 2017, p = 0.03). Conclusions The protocolization of the referral for endoscopy associated with widespread use of HPSA test in the management of patients with dyspepsia, are successful strategies to decrease waiting lists for endoscopy and optimize the detection rate of pre-neoplastic lesions and early GC.

Cannabinoid CB2 receptors in the mouse brain: relevance for Alzheimer's disease.

BACKGROUND: Because of their low levels of expression and the inadequacy of current research tools, CB2 cannabinoid receptors (CB2R) have been difficult to study, particularly in the brain. This receptor is especially relevant in the context of neuroinflammation, so novel tools are needed to unveil its pathophysiological role(s). METHODS: We have generated a transgenic mouse model in which the expression of enhanced green fluorescent protein (EGFP) is under the control of the cnr2 gene promoter through the insertion of an Internal Ribosomal Entry Site followed by the EGFP coding region immediately 3' of the cnr2 gene and crossed these mice with mice expressing five familial Alzheimer's disease (AD) mutations (5xFAD). RESULTS: Expression of EGFP in control mice was below the level of detection in all regions of the central nervous system (CNS) that we examined. CB2R-dependent-EGFP expression was detected in the CNS of 3-month-old AD mice in areas of intense inflammation and amyloid deposition; expression was coincident with the appearance of plaques in the cortex, hippocampus, brain stem, and thalamus. The expression of EGFP increased as a function of plaque formation and subsequent microgliosis and was restricted to microglial cells located in close proximity to neuritic plaques. AD mice with CB2R deletion exhibited decreased neuritic plaques with no changes in IL1ß expression. CONCLUSIONS: Using a novel reporter mouse line, we found no evidence for CB2R expression in the healthy CNS but clear up-regulation in the context of amyloid-triggered neuroinflammation. Data from CB2R null mice indicate that they play a complex role in the response to plaque formation.

Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of Real-world Experience.

Prophylactic human papillomavirus (HPV) vaccination programs constitute major public health initiatives worldwide. We assessed the global effect of quadrivalent HPV (4vHPV) vaccination on HPV infection and disease. PubMed and Embase were systematically searched for peer-reviewed articles from January 2007 through February 2016 to identify observational studies reporting the impact or effectiveness of 4vHPV vaccination on infection, anogenital warts, and cervical cancer or precancerous lesions. Over the last decade, the impact of HPV vaccination in real-world settings has become increasingly evident, especially among girls vaccinated before HPV exposure in countries with high vaccine uptake. Maximal reductions of approximately 90% for HPV 6/11/16/18 infection, approximately 90% for genital warts, approximately 45% for low-grade cytological cervical abnormalities, and approximately 85% for high-grade histologically proven cervical abnormalities have been reported. The full public health potential of HPV vaccination is not yet realized. HPV-related disease remains a significant source of morbidity and mortality in developing and developed nations, underscoring the need for HPV vaccination programs with high population coverage.

Fiber-chip edge coupler with large mode size for silicon photonic wire waveguides.

Fiber-chip edge couplers are extensively used in integrated optics for coupling of light between planar waveguide circuits and optical fibers. In this work, we report on a new fiber-chip edge coupler concept with large mode size for silicon photonic wire waveguides. The coupler allows direct coupling with conventional cleaved optical fibers with large mode size while circumventing the need for lensed fibers. The coupler is designed for 220 nm silicon-on-insulator (SOI) platform. It exhibits an overall coupling efficiency exceeding 90%, as independently confirmed by 3D Finite-Difference Time-Domain (FDTD) and fully vectorial 3D Eigenmode Expansion (EME) calculations. We present two specific coupler designs, namely for a high numerical aperture single mode optical fiber with 6 µm mode field diameter (MFD) and a standard SMF-28 fiber with 10.4 µm MFD. An important advantage of our coupler concept is the ability to expand the mode at the chip edge without leading to high substrate leakage losses through buried oxide (BOX), which in our design is set to 3 µm. This remarkable feature is achieved by implementing in the SiO2 upper cladding thin high-index Si3N4 layers. The Si3N4 layers increase the effective refractive index of the upper cladding near the facet. The index is controlled along the taper by subwavelength refractive index engineering to facilitate adiabatic mode transformation to the silicon wire waveguide while the Si-wire waveguide is inversely tapered along the coupler. The mode overlap optimization at the chip facet is carried out with a full vectorial mode solver. The mode transformation along the coupler is studied using 3D-FDTD simulations and with fully-vectorial 3D-EME calculations. The couplers are optimized for operating with transverse electric (TE) polarization and the operating wavelength is centered at 1.55 µm.

CDOM Sources and Photobleaching Control Quantum Yields for Oceanic DMS Photolysis.

Photolysis is a major removal pathway for the biogenic gas dimethylsulfide (DMS) in the surface ocean. Here we tested the hypothesis that apparent quantum yields (AQY) for DMS photolysis varied according to the quantity and quality of its photosensitizers, chiefly chromophoric dissolved organic matter (CDOM) and nitrate. AQY compiled from the literature and unpublished studies ranged across 3 orders of magnitude at the 330 nm reference wavelength. The smallest AQY(330) were observed in coastal waters receiving major riverine inputs of terrestrial CDOM (0.06-0.5 m3 (mol quanta)-1). In open-ocean waters, AQY(330) generally ranged between 1 and 10 m3 (mol quanta)-1. The largest AQY(330), up to 34 m3 (mol quanta)-1), were seen in the Southern Ocean potentially associated with upwelling. Despite the large AQY variability, daily photolysis rate constants at the sea surface spanned a smaller range (0.04-3.7 d-1), mainly because of the inverse relationship between CDOM absorption and AQY. Comparison of AQY(330) with CDOM spectral signatures suggests there is an interplay between CDOM origin (terrestrial versus marine) and photobleaching that controls variations in AQYs, with a secondary role for nitrate. Our results can be used for regional or large-scale assessment of DMS photolysis rates in future studies.

Measurement of Serum 17α-Hydroxyprogesterone in Infants by Radioimmunoassay.

UNLABELLED: Determination of 17α-nyaroxyprogesterone (17OHP) is used for the diagnosis and monitoring of Congenital Adrenal Hyperplasia (CAH). Problems associated with the specificity of antibodies used in direct immunoassays can yield high false results. OBJECTIVES: To analyze serum levels of direct 17OHP (17OHPd) and previous extraction (17OHPe) in the neonatal period, in order to establish reference values. To relate levels of 17OHPd and 17OHPe with other androgens in CAH patients. SUBJECTS AND METHODS: Serum 17OHPd and 17OHPe were measured via RIA-DPC in 400 healthy newborns and infants (aged 2-365 days), and 100 treated CAH patients (aged 1-18 years). The extraction was performed with 3% isopropanol/heptane. The influence of age and gender was assessed by ANOVA. RESULTS: The serum levels of 17OHP were significantly correlated with chronological age, but not with gestational age, sex or birth weight. The difference between 17OHPd and 17OHPe decreased with age. The correlation index between 17OHPd and 17OHPe in CAH patients was 0.93 (p < 0.01). CONCLUSION: The present results provide 17OHP reference values for infants from birth up to one year of life. The extraction method is necessary in the neonatal period up to 6 months of life. Our data might be useful to make an early CAH diagnosis and follow-up newborns with high 17OHP levels without adrenal pathology.

[Assessment for learning: experience in an undergraduate medical theoretical course]. / Evaluación para el aprendizaje: experiencia en un curso teórico de pregrado en medicina.

BACKGROUND: Assessment for learning is a paradigm that is taking shape in the field of medical education. This approach aims to embed the assessment process within the educational and learning process. AIM: To evaluate the impact of curricular changes, from a focus of assessment of learning to one of assessment for learning, in the perception of undergraduate students of medicine and their final grades obtained in a theoretical course (TCG). MATERIAL AND METHODS: In the year 2011 lectures were reduced and intermediate assessments followed by a feedback session were introduced. The activities of each program course, surveys about student perceptions of the course and the final grades of students (assessments with multiple choice questions) were compared between the periods prior and after curricular changes (2005-2010 and 2011-2013). RESULTS: As a consequence of curricular changes, time for lectures was reduced by 19.5%, time for summative assessments was increased by 8.5%, and feedback activity, occupying 7.3% of the course time was added. There were significant improvements in student is perceptions in all areas assessed by surveys, emphasizing feedback and assessments. The overall grade assigned to the course dictated after implementing the changes increased from 6.18 to 6.59 (p < 0.001, 1-7 scale). The grades of students also improved from an average of 5.78 to 6.43 (p < 0.001, 1-7 scale). CONCLUSIONS: Assessment for learning achieved the desired educational impact without increasing the assigned curricular time. Programmatic assessment is favorably perceived by students.