Digital Light Processing-3D Printing of Thermoset Materials with High Biodegradability from Amino Acid-Derived Acrylamide Monomers.

Six acrylamide resins, derived from l-phenylalanine and l-leucine, are designed for application in digital light processing (DLP) printers to obtain biodegradable thermoset polymers. The acrylamide copolymers are prepared under light irradiation at 405 nm and thermal post-curing processes. Low molecular weight poly(ethylene glycol)diacrylate (PEGDA) and N,N-dimethylacrylamide (DMAM), both liquid resins, are used as co-monomers and diluents for the amino acid-derived acrylamide solubilization. The presence of two phenylalanine units and two ester groups in the acrylamide monomer accuses a fast degradation rate in hydrolytic medium in 90 days. The residual products leached in the aqueous media prove to be non-cytotoxic, when 3D-printed samples are cultured with osteoblast cells (MG63), which represents an advantage for the safe disposal of printer waste materials. The scaled-up pieces derived from l-phenylalanine and diethylene glycol, as amino acid-derived acrylamide (named compound C), PEGDA and DMAM, present high dimensional stability after DLP printing of complex structures used as testing samples. Layers of 50 µm of thickness are well cohesive having isotropic behavior, as demonstrated with tensile-strain measurements performed in X-Y-Z (plane) directions. The compound C, which contains phenylalanine amino acid, reveals a promising potential to replace non-biodegradable acrylate polymers used in prototyping systems.

A Hardware-Based Configurable Algorithm for Eye Blink Signal Detection Using a Single-Channel BCI Headset.

Eye blink artifacts in electroencephalographic (EEG) signals have been used in multiple applications as an effective method for human-computer interaction. Hence, an effective and low-cost blinking detection method would be an invaluable aid for the development of this technology. A configurable hardware algorithm, described using hardware description language, for eye blink detection based on EEG signals from a one-channel brain-computer interface (BCI) headset was developed and implemented, showing better performance in terms of effectiveness and detection time than manufacturer-provided software.

Differential Association of Glycation Products with Bone Mineral Density and Fat Mass in Healthy and Diabetes Type 2 Subjects from Mexican Southeastern: A Cross Sectional Study.

Background: Glycation products have been linked to decreased bone mineral density (BMD) in a number of clinical settings. This study examined the correlation between early glycation products (HbA1c and glycated albumin (ALB-g)) and advanced glycation end products (pentosidine (PTD)) with BMD in two groups of participants: those with type 2 diabetes mellitus (DM2) and those without diabetes or any other comorbidities (noDM). All of the participants had resided in southeastern Mexico for a minimum of 10 years. Material and Methods: This study included 204 participants: 112 (55%) with DM2 and 92 (45%) healthy subjects. We utilized dual X-ray absorptiometry (DXA) to measure both the total and segment-specific BMD and adipose mass. In addition, the fasting blood glucose, HbA1c, PTD, and ALB-g parameters were measured. Correlation and logistic regression analyses were conducted. Results: There was an inverse correlation between PTD and BMD in all anatomical regions among postmenopausal women (PMW) in the DM2 group, whereas in non-PMW, only the waist-to-height ratio was statistically significant. A negative correlation was observed between HbA1c levels and BMD in the arms and legs of DM2 individuals. However, in the noDM group, a negative correlation was found between HbA1c levels and BMD in the pelvis, while a positive association was observed between HbA1c and indicators of adipose tissue. ALB-g, demonstrated a negative correlation with fat mass. After performing binary logistic regressions, the following odds ratios (OR) for osteopenia/osteoporosis risk were determined: PTD OR 1.1 (p = 0.047) for DM2 PMW, HbA1c OR 1.4 (p = 0.048), and fat mass content OR 1.011 (p = 0.023) for the entire sample. Conclusions: Glycation products are associated with BMD differentially depending on the analyzed anatomical segment, but PTD, HbA1c, and fat mass are significant predictors of low bone mass. In prospective studies, this association could be determined using other techniques involving three-dimensional analysis of bone architecture to evaluate bone architecture.

Bicyclic Guanidine Promoted Mechanistically Divergent Depolymerization and Recycling of a Biobased Polycarbonate.

We here report the organocatalytic and temperature-controlled depolymerization of biobased poly(limonene carbonate) providing access to its trans-configured cyclic carbonate as the major product. The base TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene) offers a unique opportunity to break down polycarbonates via end-group activation or main chain scission pathways as supported by various controls and computational analysis. These energetically competitive processes represent an unprecedented divergent approach to polycarbonate recycling. The trans limonene carbonate can be converted back to its polycarbonate via ring-opening polymerization using the same organocatalyst in the presence of an alcohol initiator, offering thus a potential circular and practical route for polycarbonate recycling.

Long-lasting brain fog is related with severity clusters of symptoms in COVID-19 patients.

BACKGROUND: COVID-19 patients may experience Long-lasting symptoms from weeks to even months. AIM: To evaluate long-term cognitive impairment based on the severity of symptoms of COVID-19 infection in a primary health system setting. MATERIAL AND METHODS: From a database of 363 patients, 83 cases aged 47 ± 15 years, (58% females) were selected from June to August 2020. In patients who survived the virus, 24 infection-related symptoms were collected to create three severity clusters (mild, moderate, and severe). The follow-up time was at least seven months. Comparing the first two clusters with the severe cluster, the existence of brain fog and risk factors (obesity, hypertension, diabetes, chronic lung disease, and hypothyroidism) were analyzed. RESULTS: Thirty-one patients (37%) had persistent symptoms lasting up to 240 days. Fifty-one patients (61%) experienced brain fog. Concentration was affected by symptom severity (odds ratio [OR] 3.63, 95% confidence interval [CI] 1.26-10.46, p = 0.02). Short- or long-term memory loss was not affected. Moreover, symptom severity was related to brain fog (OR 3.16, 95% CI 1.05-9.51, p = 0.04). Patients with persistent symptoms had a concentration impairment associated with severity patterns (OR 24.3, 95% CI 1.73-340.11, p = 0.03). CONCLUSIONS: Brain fog is associated with symptom severity in COVID-19 survivors and lasts for more than eight months.

Controlling a Mouse Pointer with a Single-Channel EEG Sensor.

(1) Goals: The purpose of this study was to analyze the feasibility of using the information obtained from a one-channel electro-encephalography (EEG) signal to control a mouse pointer. We used a low-cost headset, with one dry sensor placed at the FP1 position, to steer a mouse pointer and make selections through a combination of the user's attention level with the detection of voluntary blinks. There are two types of cursor movements: spinning and linear displacement. A sequence of blinks allows for switching between these movement types, while the attention level modulates the cursor's speed. The influence of the attention level on performance was studied. Additionally, Fitts' model and the evolution of the emotional states of participants, among other trajectory indicators, were analyzed. (2) Methods: Twenty participants distributed into two groups (Attention and No-Attention) performed three runs, on different days, in which 40 targets had to be reached and selected. Target positions and distances from the cursor's initial position were chosen, providing eight different indices of difficulty (IDs). A self-assessment manikin (SAM) test and a final survey provided information about the system's usability and the emotions of participants during the experiment. (3) Results: The performance was similar to some brain-computer interface (BCI) solutions found in the literature, with an averaged information transfer rate (ITR) of 7 bits/min. Concerning the cursor navigation, some trajectory indicators showed our proposed approach to be as good as common pointing devices, such as joysticks, trackballs, and so on. Only one of the 20 participants reported difficulty in managing the cursor and, according to the tests, most of them assessed the experience positively. Movement times and hit rates were significantly better for participants belonging to the attention group. (4) Conclusions: The proposed approach is a feasible low-cost solution to manage a mouse pointer.

Anterior cingulate and medial prefrontal cortex response to systematically controlled tonal dissonance during passive music listening.

Several studies have attempted to investigate how the brain codes emotional value when processing music of contrasting levels of dissonance; however, the lack of control over specific musical structural characteristics (i.e., dynamics, rhythm, melodic contour or instrumental timbre), which are known to affect perceived dissonance, rendered results difficult to interpret. To account for this, we used functional imaging with an optimized control of the musical structure to obtain a finer characterization of brain activity in response to tonal dissonance. Behavioral findings supported previous evidence for an association between increased dissonance and negative emotion. Results further demonstrated that the manipulation of tonal dissonance through systematically controlled changes in interval content elicited contrasting valence ratings but no significant effects on either arousal or potency. Neuroscientific findings showed an engagement of the left medial prefrontal cortex (mPFC) and the left rostral anterior cingulate cortex (ACC) while participants listened to dissonant compared to consonant music, converging with studies that have proposed a core role of these regions during conflict monitoring (detection and resolution), and in the appraisal of negative emotion and fear-related information. Both the left and right primary auditory cortices showed stronger functional connectivity with the ACC during the dissonant portion of the task, implying a demand for greater information integration when processing negatively valenced musical stimuli. This study demonstrated that the systematic control of musical dissonance could be applied to isolate valence from the arousal dimension, facilitating a novel access to the neural representation of negative emotion.

Scaling of adult human bone and skeletal muscle mass to height in the US population.

OBJECTIVES: The scaling of structural components to body size is well studied in mammals, although comparable human observations in a large and diverse sample are lacking. The current study aimed to fill this gap by examining the scaling relationships between total body (TB) and regional bone and skeletal muscle (SM) mass with body size, as defined by stature, in a nationally representative sample of the US population. METHODS: Subjects were 17,126 non-Hispanic (NH) white, NH black, and Mexican American men and women, aged ≥18 years, evaluated in the National Health and Nutrition Examination Survey who had TB and regional bone mineral (BMin) and lean soft tissue (LST) mass measured by dual-energy X-ray absorptiometry. BMin and appendicular LST served as surrogate bone and SM mass measures, respectively. The allometric model, BMin or LST = α(height)ß , in a logarithmic form was used to generate scaling exponents. RESULTS: The findings were similar across all gender and race groups: body mass scaled to height with powers of ~2.0 (mean ß ± SE, 1.94 ± 0.08-2.29 ± 0.09) while TB and appendicular BMin and appendicular LST scaled to height with consistently larger powers than those for body mass (eg, all P < .05 in NH white men and women); the largest BMin and LST scaling powers to height were observed in the lower extremities. CONCLUSIONS: Bone and SM mass, notably those of the lower extremities, increase as proportions of body mass with greater adult height. Metabolic and biomechanical implications emerge from these observations, the first of their kind in a representative adult US population sample.

National Clinical Practice Guidelines for the management of non-small cell lung cancer in early, locally advanced and metastatic stages. Extended version. / Guía de Práctica Clínica Nacional para el manejo del cáncer de pulmón de células no pequeñas en estadios tempranos, localmente avanzados y metastásicos.

OBJECTIVE: Lung cancer is one the leading causes of mortality worldwide. Symptomatic manifestations of the disease generally occur in the advanced-stage setting, and therefore an important number of patients have advanced or metastatic disease by the time they are diagnosed. This situation contributes to a poor prognosis in the treatment of lung cancer. Evidencebased clinical recommendations are of great value to support decision-making for daily practice, and thus improving health care quality and patient outcomes. MATERIALS AND METHODS: This document was an initiative of the Mexican Society of Oncology (SMEO) in collaboration with Mexican Center of Clinical Excellence (Cenetec) according to Interna- tional Standards. Such standards included those described by the IOM, NICE, SIGN and GI-N. An interdisciplinary Guideline Development Group (GDG) was put together which included medical oncologists, surgical oncologistsc, radiation therapists, and methodologists with expertise in critical appraisal, sys- tematic reviews and clinical practice guidelines development. RESULTS: 62 clinical questions were agreed among members of the GDG. With the evidence identified from systematic reviews, the GDG developed clinical recommendations using a Modified Delphi Panel technique. Patients' representatives validated them. CONCLUSIONS: These Clinical Practice Guideline aims to support the shared decision-making process for patients with different stages of non-small cell lung cancer. Our goal is to improve health-care quality on these patients.

OBJETIVO: El cáncer de pulmón es una de las principales causas de mortalidad alrededor del mundo. Su historia natural, con la manifestación de síntomas en etapas avanzadas y el retraso en su diagnóstico hacen que una gran proporción de pacientes se diagnostiquen en estadios tardíos de la enfermedad, lo que hace muy complicado el tratamiento exitoso de la misma. De esto deriva la importancia de dar origen a recomendaciones basadas en evidencia para soportar la toma de decisiones clínicas por parte de los grupos interdisicplinarios que se encargan del manejo de este padecimiento. MATERIAL Y MÉTODOS: Este documento se desarrolló por parte de la Sociedad Mexicana de Oncología en colaboración con el Centro Nacional de Excelencia Tec- nológica de México (Cenetec) a través de la dirección de integración de Guías de Práctica Clínica en cumplimiento a estándares internacionales como los descritos por el Ins- tituto de Medicina de EUA (IOM, por sus siglas en inglés), el Instituto de Excelencia Clínica de Gran Bretaña (NICE, por sus siglas en inglés), la Red Colegiada para el Desarrollo de Guías de Escocia (SIGN, por sus siglas en inglés), la Red Internacional de Guías (G-I-N, por sus siglas en inglés); entre otros. Se integró en representación de la Sociedad Mexicana de Oncología un Grupo de Desarrollo de la Guía (GDG) de manera interdisciplinaria, considerando oncólogos médicos, cirujanos oncólogos, cirujanos de tórax, radio-oncólogos, y metodólogos con experiencia en revisiones sistemáticas de la literatura y guías de práctica clínica. RESULTADOS: Se consensuaron 62 preguntas cllínicas que abarcaron lo establecido previamente por el GDG en el documento de alcances de la Guía. Se identificó la evidencia científica que responde a cada una de estas preguntas clínicas y se evaluó críticamente la misma, antes de ser incorporada en el cuerpo de evidencia de la Guía. El GDG acordó mediante la técnica de consenso formal de expertos Panel Delphi la redacción final de las recomendaciones clínicas. C. CONCLUSIONES: Esta Guía de Práctica Clínica pretende proveer recomendaciones clínicas para el manejo de los distintos estadios de la enfermedad y que asistan en el proceso de toma de decisiones compartida. El GDG espera que esta guía contribuya a mejorar la calidad de la atención clínica en las pacientes con cáncer de pulmón de células no pequeñas.

Low-Power Low-Cost Wireless Flood Sensor for Smart Home Systems.

This paper presents the design of a wireless flood sensor to detect the presence of water on home floors, providing early warning of water leaks. A wireless sensor network has been deployed to gather the measurements from the sensor nodes. A control central coordinates the network and processes the data. Users can remotely inquire for the presence of water, status of the batteries for a specific node, the type of liquid and information about its functionality and alarms, thanks to a proprietary software application. The alerts are also communicated to the user within the home through an audible siren. The designed device is optimized in terms of costs, ease of deployment and maintenance, thus making it widely acceptable to end users.

An Efficient Wireless Sensor Network for Industrial Monitoring and Control.

This paper presents the design of a wireless sensor network particularly designed for remote monitoring and control of industrial parameters. The article describes the network components, protocol and sensor deployment, aimed to accomplish industrial constraint and to assure reliability and low power consumption. A particular case of study is presented. The system consists of a base station, gas sensing nodes, a tree-based routing scheme for the wireless sensor nodes and a real-time monitoring application that operates from a remote computer and a mobile phone. The system assures that the industrial safety quality and the measurement and monitoring system achieves an efficient industrial monitoring operations. The robustness of the developed system and the security in the communications have been guaranteed both in hardware and software level. The system is flexible and can be adapted to different environments. The testing of the system confirms the feasibility of the proposed implementation and validates the functional requirements of the developed devices, the networking solution and the power consumption management.

A Wireless Sensor System for Real-Time Monitoring and Fault Detection of Motor Arrays.

This paper presents a wireless fault detection system for industrial motors that combines vibration, motor current and temperature analysis, thus improving the detection of mechanical faults. The design also considers the time of detection and further possible actions, which are also important for the early detection of possible malfunctions, and thus for avoiding irreversible damage to the motor. The remote motor condition monitoring is implemented through a wireless sensor network (WSN) based on the IEEE 802.15.4 standard. The deployed network uses the beacon-enabled mode to synchronize several sensor nodes with the coordinator node, and the guaranteed time slot mechanism provides data monitoring with a predetermined latency. A graphic user interface offers remote access to motor conditions and real-time monitoring of several parameters. The developed wireless sensor node exhibits very low power consumption since it has been optimized both in terms of hardware and software. The result is a low cost, highly reliable and compact design, achieving a high degree of autonomy of more than two years with just one 3.3 V/2600 mAh battery. Laboratory and field tests confirm the feasibility of the wireless system.

A Smart Sensor for Defending against Clock Glitching Attacks on the I2C Protocol in Robotic Applications.

This paper presents a study about hardware attacking and clock signal vulnerability. It considers a particular type of attack on the clock signal in the I2C protocol, and proposes the design of a new sensor for detecting and defending against this type of perturbation. The analysis of the attack and the defense is validated by means of a configurable experimental platform that emulates a differential drive robot. A set of experimental results confirm the interest of the studied vulnerabilities and the efficiency of the proposed sensor in defending against this type of situation.

An adjuvanted herpes simplex virus 2 subunit vaccine elicits a T cell response in mice and is an effective therapeutic vaccine in Guinea pigs.

Immunotherapeutic herpes simplex virus 2 (HSV-2) vaccine efficacy depends upon the promotion of antigen-specific immune responses that inhibit reactivation or reactivated virus, thus controlling both recurrent lesions and viral shedding. In the present study, a candidate subunit vaccine, GEN-003/MM-2, was evaluated for its ability to induce a broad-spectrum immune response in mice and therapeutic efficacy in HSV-2-infected guinea pigs. GEN-003 is comprised of HSV-2 glycoprotein D2 (gD2ΔTMR340-363) and a truncated form of infected cell polypeptide 4 (ICP4383-766), formulated with Matrix M-2 (MM-2) adjuvant (GEN-003/MM-2). In addition to eliciting humoral immune responses, CD4(+) and CD8(+) T cells characterized by the secretion of multiple cytokines and cytolytic antigen-specific T cell responses that were able to be recalled at least 44 days after the last immunization were induced in immunized mice. Furthermore, vaccination with either GEN-003 or GEN-003/MM-2 led to significant reductions in both the prevalence and severity of lesions in HSV-2-infected guinea pigs compared to those of phosphate-buffered saline (PBS) control-vaccinated animals. While vaccination with MM-2 adjuvant alone decreased recurrent disease symptoms compared to the PBS control group, the difference was not statistically significant. Importantly, the frequency of recurrent viral shedding was considerably reduced in GEN-003/MM-2-vaccinated animals but not in GEN-003- or MM-2-vaccinated animals. These findings suggest a possible role for immunotherapeutic GEN-003/MM-2 vaccination as a viable alternative to chronic antiviral drugs in the treatment and control of genital herpes disease.

Selection, activity, and nuclease stabilization of cross-neutralizing DNA aptamers targeting HSV-1 and HSV-2.

Cross-neutralizing aptamers targeting both HSV-1 and HSV-2 were developed by selecting against the ectodomains of glycoprotein D (gD) from both viruses in parallel as well as sequentially using the SELEX method. Since gD facilitates viral invasion, sterically blocking the host-receptor interaction prevents infection. Candidate aptamers were screened, and lead aptamers were identified that exhibited exceptional neutralizing activity against both viruses in vitro. The specificity of the aptamers was confirmed by comparing their activity to scrambled versions of themselves. Modifications of the lead compounds were tested to define critical motifs to guide development. Stability of the aptamers was increased using phosphorothioate backbone linkages, and 2' methoxy substitutions of terminal and key internal bases. Aptamers were applied in a guinea pig vaginal HSV-2 infection model and found to reduce both the viral load of infected animals and the severity of the resulting disease. These results suggest that cross-neutralizing aptamers can be developed into on-demand antiviral interventions effective against both HSV-1 and HSV-2.

The Impact of Long COVID on Cognitive Performance and Sleep Quality: An Analysis of the Rancagua Chilean Study (RACHIS).

Background Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to prolonged symptoms post-recovery, commonly known as long-term coronavirus disease 2019 (COVID-19) or "long COVID." Neuropsychiatric consequences of long COVID include cognitive dysfunction and sleep disturbances, which significantly impair daily living. This study aimed to explore the impact of long COVID on cognitive performance and sleep quality in patients receiving outpatient care. Material and methods This study involved a random sample of 138 of 363 patients, corresponding to 38% of the cohort, who tested positive for SARS-CoV-2 via polymerase chain reaction (PCR) between May 2020 and April 2021. These unvaccinated, non-hospitalized individuals, predominantly exhibiting mild disease symptoms, were prospectively assessed 11 months post-positive PCR test. After informed consent, demographic data, memory, and concentration impairment levels were collected through interviews. Participants reporting cognitive symptoms underwent the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MOCA), and the Pittsburgh Sleep Quality Index. Statistical analyses were conducted, including Student's t-test, Chi-square, Fisher's test, Kruskal-Wallis test, and Pearson correlation coefficient, with a significance threshold set at p<0.05. Results Of the 138 participants, 76 (55.1%) were female and 62 (44.9%) were male. The mean age was 45.9 years (± 13.0), with an average educational attainment of 10.4 years (± 3.7). Roughly 50% of the patients reported significant memory and concentration issues (p<0.001). Thirty-three participants underwent detailed cognitive assessments, revealing a 2:1 female-to-male ratio and a significantly higher prevalence of depression in female participants. Cognitive deficits were diagnosed in five (15.2%) participants via the MMSE and in 26 (78.8%) via the MOCA test, with notable deficits in visuospatial/executive functions, language repeat, and deferred recall (p<0.001). A lower educational level was correlated with higher cognitive deficits (p=0.03). Conclusion The study findings reveal that cognitive impairments, as a consequence of COVID-19, can persist up to 11 months post-infection. The MOCA test proved more effective in diagnosing these deficits and requires adjustments based on educational background. Sleep parameters remained largely unaffected in this cohort, likely attributed to the mild nature of the initial symptoms and the outpatient management of the disease.

[Intermittent fasting: effects in diverse clinical settings]. / Ayuno intermitente: efectos en diversos escenarios clínicos.

Introduction: Introduction: intermittent fasting plans propose to limit food intake during specific periods as nutritional therapeutic strategies to treat different metabolic conditions in various clinical entities. However, the heterogeneity between each context of intermittent fasting could generate different results in metabolic parameters. Objective: to evaluate the clinical application of intermittent fasting and to discern whether it offers advantages over other traditional strategies. Methods: structured questions were formulated (PICO), and the methodology followed the guidelines established by the PRISMA 2020 statement. The search was conducted in different databases (PubMed, Cochrane Library and Google Scholar). Results: we found 3,962 articles, of which 56 were finally included; 3,906 articles that did not directly or indirectly answer the structured questions were excluded. Conclusions: compared to conventional diets, the various AI schemes do not generate advantages or disadvantages in terms of weight loss and lipid profile, although in the alternate-day variant there are greater insulin reductions than those observed in the continuous energy restriction. The heterogeneity of the interventions, the populations studied, the comparators, the results, and the type of design make it impossible to extrapolate the effects found in all clinical scenarios and generalize the recommendations.

Introducción: Introducción: los esquemas de ayuno intermitente (AI) proponen limitar la ingestión de alimentos durante periodos específicos. Se han propuesto como estrategia dietoterapéutica para tratar distintas condiciones metabólicas en diversos padecimientos, sin embargo, la heterogeneidad entre cada contexto de ayuno intermitente pudiera generar diferentes resultados en parámetros metabólicos. Objetivo: evaluar la aplicación clínica del ayuno intermitente y discernir si ofrece ventajas sobre otras estrategias tradicionales. Métodos: se formularon preguntas estructuradas (PICO) y la metodología se apegó a las guías establecidas por la declaración PRISMA 2020. Se realizó una búsqueda de literatura científica en las plataformas de PubMed, Cochrane Library y Google Scholar. Resultados: se encontraron 3.962 artículos, de los cuales se incluyeron finalmente 56, eliminando 3.906 trabajos que no contestaban directa o indirectamente las preguntas estructuradas. Conclusiones: frente a las dietas convencionales, los diversos esquemas de AI no generan ventajas ni desventajas en cuanto a pérdida de peso o perfil lipídico, aunque en la variante a días alternos se producen mayores reducciones de insulina a las observadas en la restricción energética continua. La heterogeneidad de las intervenciones y poblaciones estudiadas, así como los comparadores, los desenlaces y el tipo de diseño imposibilitan extrapolar los efectos a todos los escenarios clínicos y generalizar las recomendaciones.

Design and implementation of a new real-time frequency sensor used as hardware countermeasure.

A new digital countermeasure against attacks related to the clock frequency is presented. This countermeasure, known as frequency sensor, consists of a local oscillator, a transition detector, a measurement element and an output block. The countermeasure has been designed using a full-custom technique implemented in an Application-Specific Integrated Circuit (ASIC), and the implementation has been verified and characterized with an integrated design using a 0.35 mm standard Complementary Metal Oxide Semiconductor (CMOS) technology (Very Large Scale Implementation-VLSI implementation). The proposed solution is configurable in resolution time and allowed range of period, achieving a minimum resolution time of only 1.91 ns and an initialization time of 5.84 ns. The proposed VLSI implementation shows better results than other solutions, such as digital ones based on semi-custom techniques and analog ones based on band pass filters, all design parameters considered. Finally, a counter has been used to verify the good performance of the countermeasure in avoiding the success of an attack.

Intermittent therapy with helicase-primase inhibitor IM-250 efficiently controls recurrent herpes disease and reduces reactivation of latent HSV.

Herpes is a contagious life-long infection with persistently high incidence and prevalence, causing significant disease worldwide. Current therapies have efficacy against active HSV infections but no impact on the latent viral reservoir in neurons. Thus, despite treatment, disease recurs from latency and the infectious potential remains unaffected within patients. Here, efficacy of the helicase-primase inhibitor (HPI) IM-250 against chronic neuronal HSV infections utilizing two classic herpes in vivo latency/reactivation animal models (intravaginal guinea pig HSV-2 infection model and ocular mouse HSV-1 infection model) is presented. Intermittent therapy of infected animals with 4-7 cycles of IM-250 during latency silences subsequent recurrences analyzed up to 6 months. In contrast to common experience, our studies show that the latent reservoir is indeed accessible to antiviral therapy altering the latent viral reservoir such that reactivation frequency can be reduced significantly by prior IM-250 treatment. We provide evidence that antiviral treatment during HSV latency can reduce future reactivation from the latent reservoir, supporting a conceptual shift in the antiviral field, and reframing what is achievable with respect to therapy of latent neuronal HSV infections.

Design and evaluation of a digital health intervention with proactive follow-up by nurses to improve healthcare and outcomes for patients with breast cancer in Mexico: protocol for a randomised clinical trial.

INTRODUCTION: Nearly 30 000 Mexican women develop breast cancer annually, frequently presenting unmet supportive care needs. In high-income countries, incorporating electronic patient-reported outcomes (ePROs) into cancer care has demonstrated potential for increasing patient-centred care and reducing unmet needs. No such ePRO interventions have been implemented in Mexico. This paper presents the study protocol for designing and evaluating an ePRO digital health application combined with proactive follow-up by nurses. METHODS AND ANALYSIS: We designed a two-component intervention for women receiving breast cancer treatment: a responsive web application for monitoring ePROs and clinical algorithms guiding proactive follow-up by nurses. We will conduct a pilot test of the intervention with 50 patients with breast cancer for 6 weeks to assess feasibility and adjust the application. We will conduct a parallel arm randomised controlled trial assigning 205 patients each to intervention and control in one of Mexico's largest public oncology hospitals. The intervention will be provided for 6 months, with additional 3 months of post-intervention observation. The control group will receive usual healthcare and a list of breast cancer information sources. Women diagnosed with stages I, II or III breast cancer who initiate chemotherapy and/or radiotherapy will be invited to participate. The primary study outcome will be supportive care needs; secondary outcomes include global quality of life and breast symptoms. Information on the outcomes will be obtained through web-based self-administered questionnaires collected at baseline, 1, 3, 6 and 9 months. ETHICS AND DISSEMINATION: The National Research and Ethics Committees of the Mexican Institute of Social Security approved the study (R-2021-785-059). Participants will sign an informed consent form prior to their inclusion. Findings will be disseminated through a policy brief to the local authorities, a webinar for patients, publications in peer-reviewed journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05925257.