A retrospective study of Cerebrolysin in patients with moderate to severe traumatic brain injury: Cognitive and functional outcomes.

In this retrospective study, we aimed to evaluate the effects of the neurotrophic compound Cerebrolysin on executive, cognitive, and functional performance in patients with traumatic brain injury (TBI) with a highly severe disability level. A total of 44 patients were included in the study, with 33 patients in the control group and 11 patients in the interventional group who received intravenous infusions of 30 mL Cerebrolysin. Both groups received standard rehabilitation therapy following the rehabilitation protocol for patients with TBI at Hospital Clínico Mutual de Seguridad. Functional and cognitive scales were evaluated at baseline, at four months, and at the endpoint of the intervention therapy at seven months (on average). The results revealed a significant improvement in the Cerebrolysin-treated group compared to the control group. Specifically, patients who received Cerebrolysin showed a moderate residual disability and a significant reduction in the need for care. Concerning the promising results and considering the limitations of the retrospective study design, we suggest that randomized controlled studies be initiated to corroborate the positive findings for Cerebrolysin in patients with moderate to severe brain trauma.

Ética en el Currículo Odontológico en 30 Facultades de Odontología de Latinoamérica y España

El objetivo de este estudio fue determinar la implementación del curso de ética dentro del currículo odontológico de las facultades pertenecientes a la Federación Internacional de Escuelas y Facultades de Odontología FIEFO, 2021. Investigación de tipo descriptivo, transversal y observacional, la población estuvo constituida por decanos y directores de la FIEFO que participaron en el seminario de Ética el 26 de febrero del 2021. A ellos se les envió, vía correo electrónico, el consentimiento informado y la encuesta. Los resultados de estudio mostraron que el 86,67 % de las universidades tienen el curso de ética de forma obligatoria; el 50 % de las universidades implementan el curso de ética de 1 a 2 horas por semana; con relación al año de dictado, se desarrolló en mayor porcentaje en el tercer año. Por último, se encontraron diferentes enfoques sobre el objetivo del curso, siendo estos los más frecuentes: "Formación del profesional para el desarrollo de una práctica ética"; "Comprensión y aplicación de la bioética" y "Formación Profesional con desarrollo de habilidades desde un enfoque ético".

The objective of this study was to determine the implementation of the ethics course within the dental curriculum of the faculties belonging to the International Federation of Schools and Faculties of Dentistry FIEFO, 2021. Descriptive, cross-sectional and observational research, the population consisted of deans and FIEFO directors who participated in the Ethics seminar on February 26, 2021. The informed consent and the survey were sent to them via email. The results of the study showed that 86.67 % of the universities have the ethics course mandatory; 50 % of the universities implement the ethics course from 1 to 2 hours per week; in relation to the year of dictation, it was developed in a higher percentage in the third year. Finally, different approaches were found on the objective of the course, these being the most frequent: "Professional training for the development of an ethical practice"; "Understanding and application of bioethics" and "Professional Training with skills development from an ethical approach".

Aß oligomers trigger necroptosis-mediated neurodegeneration via microglia activation in Alzheimer's disease.

Alzheimer's disease (AD) is a major adult-onset neurodegenerative condition with no available treatment. Compelling reports point amyloid-ß (Aß) as the main etiologic agent that triggers AD. Although there is extensive evidence of detrimental crosstalk between Aß and microglia that contributes to neuroinflammation in AD, the exact mechanism leading to neuron death remains unknown. Using postmortem human AD brain tissue, we show that Aß pathology is associated with the necroptosis effector pMLKL. Moreover, we found that the burden of Aß oligomers (Aßo) correlates with the expression of key markers of necroptosis activation. Additionally, inhibition of necroptosis by pharmacological or genetic means, reduce neurodegeneration and memory impairment triggered by Aßo in mice. Since microglial activation is emerging as a central driver for AD pathogenesis, we then tested the contribution of microglia to the mechanism of Aßo-mediated necroptosis activation in neurons. Using an in vitro model, we show that conditioned medium from Aßo-stimulated microglia elicited necroptosis in neurons through activation of TNF-α signaling, triggering extensive neurodegeneration. Notably, necroptosis inhibition provided significant neuronal protection. Together, these findings suggest that Aßo-mediated microglia stimulation in AD contributes to necroptosis activation in neurons and neurodegeneration. As necroptosis is a druggable degenerative mechanism, our findings might have important therapeutic implications to prevent the progression of AD.

Clinical and epidemiological profile of cleft lip and palate patients in Peru, 2006 - 2019.

BACKGROUND: The purpose of this study was to determine the clinical-epidemiological profile of patients with cleft lip and / or palate in Peru from 2006 to 2019. MATERIAL AND METHODS: This retrospective and cross-sectional study analyzed 3,923 patients with cleft lip and palate attended by surgical missions of the Operación Sonrisa Perú from January 2006 to December 2019. The clinical profile of the patients treated included: type of cleft (cleft lip CL, cleft palate CP, cleft lip and palate CLP and submucosal SM), surgery performed (cheiloplasty, palatoplasty, cleft rhinoplasty, fistula repair, pharyngeal flap), surgical time according to number of interventions. Likewise, affiliation variables such as sex, age and birthplace were recorded. Descriptive analysis was performed. Associations were determined using the Pearson's Chi-square test and Two-sample test of proportions were used for comparing the percentages during time. A p value <0.005 was considered significant. RESULTS: The most frequent diagnosis was CP (n = 1411, 35.97%). We identified a statistically significant association between the diagnosis of CL, CP and gender (p = 0.045), being more prevalent in males. A higher prevalence of CL was also observed on the left side and in males (n = 183). Cheiloplasty was the most frequent first surgical intervention performed (n = 837, 47.42%) followed by fistula repair as the second intervention (n = 428, 42.29%). CONCLUSIONS: Cleft lip and palate are more frequent in males, with CP being the most frequent. CL is more frequent on the left side and the first surgical approach in these patients is lip closure. Key words:Epidemiology, cleft lip and palate, surgical missions.

Biosafety Measures at the Dental Office After the Appearance of COVID-19: A Systematic Review.

The purpose of this research was to determine biosecurity measures at the dental office after the appearance of coronavirus disease 2019 (COVID-19). A search was conducted in the main databases of the scientific literature using the words "COVID-19, coronavirus, SARS-Cov2, biosecurity, disinfection and dentistry." We analyzed biosecurity and disinfection standards at the dental office and dental health personnel to date, and their adaptation to the needs and way of working of each. As a result, according to the information collected the following procedure was identified: a telephone appointment must be made and a questionnaire should be given before dental care; at arrival to the appointment, the temperature of the patient should be taken and proper cleaning and disinfection of the waiting room should be maintained. Panoramic radiography and CBCT are the auxiliary methods of choice. Absolute isolation and atraumatic restorative therapy techniques are a good alternative to decrease fluid exposure. The removal of protective clothing and accessories must follow a specific order and washing hands before and after is essential. In conclusion, the efficient biosecurity for dentists and patients in all dental care processes before, during, and immediately after the appointment reduces the risk of COVID-19 infection and allows healthy dental care environments.

Effectiveness and Recommendations for the Use of Dental Masks in the Prevention of COVID-19: A Literature Review.

The purpose of this investigation was to identify, synthesize, and compare all the current information on the efficacy of dental masks, emphasizing their use, types, and filters to prevent the spread and infection of COVID-19 and other infectious diseases. A bibliographic search of the main scientific databases was carried out using the words "masks, COVID-19, and dentistry." Articles without language restriction up to May 31, 2020, were obtained. The types of masks, their half-life, method to use, sterilization, and proposed alternatives for dental masks were analyzed. Most of the articles refer to the use of N95 or FFP2 respirators presented as a strategy to extend the life of the masks and limited reuse. Regarding sterilization, most of the articles presented studies using ultraviolet germicidal irradiation as the sterilization method. Regarding respirator mask half-life, we recommend prolonged use, combined with a disposable surgical mask over the respirator mask. Finally, the use of N95 or FFP2 respirators are recommended as part of personal protective equipment for dental use.

Biosafety for Dental Patients During Dentistry Care After COVID-19: A Review of the Literature.

The world is currently changing due to coronavirus disease 2019 (COVID-19), and the field of dentistry is no stranger to this. The care of patients in the dental office involves very strict biosafety protocols, and patients must be aware of the protection barriers implemented to allow satisfactory, safe dental care. The purpose of this study was to synthesize and analyze the management of the current biosafety standards for dental patients since the arrival of the COVID-19 pandemic. A bibliographic search of the main sources of information including MEDLINE (by means of PubMed), Scopus, Science Direct, SCIELO, and Google Scholar was carried out. Articles published without language restriction, systematic reviews, literature reviews, and observational studies were included. We identified the biosafety measures that must be taken before, during, and after dental practice following the arrival of COVID-19. The main measures include telephone triage, temperature taking on arrival at the office, the organization of the waiting room, washing hands before entering the office, knowing the auxiliary radiographic exams of choice and what type of treatment can be performed, albeit with restrictions. In conclusion, dental patients must comply with all the biosafety measures established by international protection standards and implemented by dentists before, during, and after dental practice to reduce the possibility of COVID-19 infection.

Can photobiomodulation therapy (PBMT) control blood glucose levels and alter muscle glycogen synthesis?

Photobiomodulation therapy (PBMT) has many effects on the energy metabolism of musculoskeletal tissue, such as increased glycogen and adenosine triphosphate synthesis. In addition, these effects may be due to a systemic blood glucose control. Twenty-four Wistar rats were randomly and equally allocated into four groups: sham, PBMT 10 J/cm2, PBMT 30 J/cm2 and PBMT 60 J/cm2. The animals were fasting for 6 h for blood glucose evaluations during pre-irradiation period, 1 h, 3 h and 6 h after PBMT. Muscle glycogen synthesis was measured 24 h after PBMT. This PBMT used a cluster of 69 LEDs (light-emitting diodes) with 35 red (630 ± 10 nm) and 34 infrared (850 ± 20 nm); 114 mW/cm2 for 90s (10 J/cm2), 270 s (30 J/cm2), 540 s (60 J/cm2) applied on large muscle areas (back and hind legs) of the animals. The 10 J/cm2 group showed lower blood glucose levels and glucose variability over 6 h (5.92 mg/dL) compared to the sham (13.03 mg/dL), 30 J/cm2 (7.77 mg/dL) and 60 J/cm2 (9.07 mg/dL) groups. The PBMT groups had the greatest increase in muscle glycogen (10 J/cm2 > 60 J/cm2 > 30 J/cm2 > sham), characterizing a triphasic dose-response of PBMT. There was a strong negative correlation between blood glucose variability over 6 h and muscle glycogen concentration for 10 J/cm2 group (r = -0.94; p < .001) followed by 30 J/cm2 group (r = -0.84; p < .001) and 60 J/cm2 group(r = -0.73; p < .006). These results suggest that PBMT can play a very important role in the control of blood glucose levels, and its possible mechanism of action is the induction of greater muscle glycogen synthesis independently of physical exercise.

Correction: The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease.

Parkinson's disease (PD) is the second most common neurodegenerative condition, characterized by motor impairment due to the progressive degeneration of dopaminergic neurons in the substantia nigra and depletion of dopamine release in the striatum. Accumulating evidence suggest that degeneration of axons is an early event in the disease, involving destruction programs that are independent of the survival of the cell soma. Necroptosis, a programmed cell death process, is emerging as a mediator of neuronal loss in models of neurodegenerative diseases. Here, we demonstrate activation of necroptosis in postmortem brain tissue from PD patients and in a toxin-based mouse model of the disease. Inhibition of key components of the necroptotic pathway resulted in a significant delay of 6-hydroxydopamine-dependent axonal degeneration of dopaminergic and cortical neurons in vitro. Genetic ablation of necroptosis mediators MLKL and RIPK3, as well as pharmacological inhibition of RIPK1 in preclinical models of PD, decreased dopaminergic neuron degeneration, improving motor performance. Together, these findings suggest that axonal degeneration in PD is mediated by the necroptosis machinery, a process here referred to as necroaxoptosis, a druggable pathway to target dopaminergic neuronal loss.

Effects of Polarized Training on Cardiometabolic Risk Factors in Young Overweight and Obese Women: A Randomized-Controlled Trial.

Introduction: Volume and intensity are major variables governing exercise training-mediated beneficial effects in both athletes and patients. Although polarized endurance training optimizes and maximizes physiological gains in highly trained individuals, its cardiometabolic protective-effects have not been established. The purpose of the present single site, randomized-controlled trial was to compare the effects of 12-weeks of high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and polarized volume training (POL) programs on cardiometabolic risk factors in young overweight and obese women. Materials and Methods: A total of 64 overweight/obese young women (age 23.3 ± 3.8 years, body mass index 33.8 ± 3.8 kg/m2) were randomly assigned to four groups: control group (CTRL), polarized volume training group, moderate-intensity endurance training group, and HIIT group. The cardiorespiratory capacity, glycemic and lipid profiles, whole-body substrate utilization, and body composition were assessed before and after the intervention. Results: After the intervention, VO2peak and power output at VO2peak increased in all exercised-groups (time effect: p < 0.0001). Power output at VT1 was increased only in the POL group compared to the CTRL group (p = 0.019). Relative fold changes in fasting plasma glucose concentrations decreased only in POL group (p = 0.002). Training induced a significant increase in relative fat oxidation in all the groups (time effect: p < 0.001). Relative fat oxidation increased only in the POL group compared to the CTRL group (training effect: p = 0.032). Conclusion: Twelve-weeks of polarized volume training showed overall superior effects on cardiorespiratory fitness, basal glycemic control, and substrate oxidation in comparison to MICT and HIIT training modalities. These data suggest that polarized volume training is an effective non-pharmacological treatment strategy for reducing cardiovascular disease risk factors in young overweight and obese women. The trial is registered at ISRCTN, number ISRCTN34421723.

In vivo study of dermal collagen of striae distensae by confocal Raman spectroscopy.

This research work mainly deals with studying qualitatively the changes in the dermal collagen of two forms of striae distensae (SD) namely striae rubrae (SR) and striae albae (SA) when compared to normal skin (NS) using confocal Raman spectroscopy. The methodology includes an in vivo human skin study for the comparison of confocal Raman spectra of dermis region of SR, SA, and NS by supervised multivariate analysis using partial least squares discriminant analysis (PLS-DA) to determine qualitatively the changes in dermal collagen. These groups are further analyzed for the extent of hydration of dermal collagen by studying the changes in the water content bound to it. PLS-DA score plot showed good separation of the confocal Raman spectra of dermis region into SR, SA, and NS data groups. Further analysis using loading plot and S-plot indicated the participation of various components of dermal collagen in the separation of these groups. Bound water content analysis showed that the extent of hydration of collagen is more in SD when compared to NS. Based on the results obtained, this study confirms the active involvement of dermal collagen in the formation of SD. It also emphasizes the need to study quantitatively the role of these various biochemical changes in the dermal collagen responsible for the variance between SR, SA, and NS.

An FT-Raman, FT-IR, and Quantum Chemical Investigation of Stanozolol and Oxandrolone.

We have studied the Fourier Transform Infrared (FT-IR) and the Fourier transform Raman (FT-Raman) spectra of stanozolol and oxandrolone, and we have performed quantum chemical calculations based on the density functional theory (DFT) with a B3LYP/6-31G (d, p) level of theory. The FT-IR and FT-Raman spectra were collected in a solid phase. The consistency between the calculated and experimental FT-IR and FT-Raman data indicates that the B3LYP/6-31G (d, p) can generate reliable geometry and related properties of the title compounds. Selected experimental bands were assigned and characterized on the basis of the scaled theoretical wavenumbers by their total energy distribution. The good agreement between the experimental and theoretical spectra allowed positive assignment of the observed vibrational absorption bands. Finally, the calculation results were applied to simulate the Raman and IR spectra of the title compounds, which show agreement with the observed spectra.

IRE1 signaling exacerbates Alzheimer's disease pathogenesis.

Altered proteostasis is a salient feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress and abnormal protein aggregation. ER stress triggers the activation of the unfolded protein response (UPR), a signaling pathway that enforces adaptive programs to sustain proteostasis or eliminate terminally damaged cells. IRE1 is an ER-located kinase and endoribonuclease that operates as a major stress transducer, mediating both adaptive and proapoptotic programs under ER stress. IRE1 signaling controls the expression of the transcription factor XBP1, in addition to degrade several RNAs. Importantly, a polymorphism in the XBP1 promoter was suggested as a risk factor to develop AD. Here, we demonstrate a positive correlation between the progression of AD histopathology and the activation of IRE1 in human brain tissue. To define the significance of the UPR to AD, we targeted IRE1 expression in a transgenic mouse model of AD. Despite initial expectations that IRE1 signaling may protect against AD, genetic ablation of the RNase domain of IRE1 in the nervous system significantly reduced amyloid deposition, the content of amyloid ß oligomers, and astrocyte activation. IRE1 deficiency fully restored the learning and memory capacity of AD mice, associated with improved synaptic function and improved long-term potentiation (LTP). At the molecular level, IRE1 deletion reduced the expression of amyloid precursor protein (APP) in cortical and hippocampal areas of AD mice. In vitro experiments demonstrated that inhibition of IRE1 downstream signaling reduces APP steady-state levels, associated with its retention at the ER followed by proteasome-mediated degradation. Our findings uncovered an unanticipated role of IRE1 in the pathogenesis of AD, offering a novel target for disease intervention.

Estudo de linfonodos por espectroscopia Raman confocal / Lymph node study by confocal Raman spectroscopy

Dentre os órgãos linfoides encontram-se os linfonodos. Também conhecidos como nódulos linfáticos, os quais são considerados como filtros da linfa por serem ricos em linfócitos e outras células de defesa. Entre os fatores que contribuem para o seu comprometimento temos a invasão de sua estrutura por células neoplásicas. A citologia constitui o exame padrão ouro no diagnóstico sendo, a PAAF a técnica mais utilizada para a obtenção do material a ser analisado. Entretanto, alguns estudos questionam a sua utilização, devido à perda da arquitetura celular. A espectroscopia Raman confocal por meio da sua capacidade em utilizar as diferenças bioquímicas de tecidos e células vem se destacando cada vez mais neste tipo de diagnóstico. O estudo teve por objetivo identificar as principais características bioquímicas em linfonodos normais, comprometidos e lesão cervical utilizando a espectroscopia Raman confocal. Foram analisadas 12 amostras de linfonodos normais e alterados de pacientes com indicação cirúrgica para linfadenectomia pela espectroscopia seguida pela análise estatística de componentes principais (PCA) e análise de discriminante linear (LDA). Após as análises observou-se que a técnica utilizada conseguiu discriminar os tecidos com valores de especificidade, sensibilidade e acurácia de 83%. Portanto, a espectroscopia Raman confocal se mostrou uma importante ferramenta na caracterização de linfonodos podendo futuramente auxiliar no diagnóstico de lesões linfonodais.

Among the lymphoid organs there are lymph nodes,, which are considered as lymph filters because they are rich in lymphocytes and other defense cells. Among the factors that contribute to their impairment we note the invasion of its structure by neoplastic cells. Cytology is the gold-standard diagnostic test, and FNA is the technique most used to obtain the material to be analyzed. However, some studies question its use, due to the loss of cellular architecture. Confocal Raman spectroscopy, through its ability to utilize biochemical differences in tissues and cells, has been increasingly prominent in this type of diagnosis. The study aimed to identify the main biochemical characteristics in normal and compromised lymph nodes and cervical lesion using confocal Raman spectroscopy. We analyzed 12 normal and altered lymph node samples from patients with medical indications for a lymphadenectomy by spectroscopy, followed by statistical analysis of the main components (PCA) and linear discriminant analysis (LDA). After the analysis, it was observed that this technique was able to discriminate the tissues with values of specificity, sensitivity and accuracy of up to 83%. Therefore, confocal Raman spectroscopy has been shown to be an important tool in the characterization of lymph nodes, and may help in the diagnosis of lymph node lesions in the future.

Micro-Raman spectroscopic study of thyroid tissues.

Thyroid carcinomas are the most common endocrine malignancy. Inconclusive results for the analysis of malignancies are an issue in the diagnosis of thyroid carcinomas; 20% of thyroid cancer diagnoses are indeterminate or suspicious, resulting in a surgical procedure without immediate need. The use of Raman spectroscopy may help improve the diagnosis of thyroid carcinoma. In this study, 30 thyroid samples, including normal thyroid, goiter and thyroid cancer, were analyzed by confocal Raman spectroscopy. Principal component analysis (PCA), linear discriminant analysis (LDA) with cross validation and binary logistic regression (BLR) analysis were applied to discriminate among tissues. Significant discrimination was observed, with a consistent rate of concordant pairs of 89.2% for normal thyroid versus cancer, 85.7% for goiter versus cancer and 80.6% for normal thyroid versus goiter using just the amide III region. Raman spectroscopy was thus proven to be an important and fast tool for the diagnosis of thyroid tissues. The spectral region of 1200-1400cm-1 discriminated normal versus goiter tissues despite the great similarity of these tissues.

Increased susceptibility to Aß toxicity in neuronal cultures derived from familial Alzheimer's disease (PSEN1-A246E) induced pluripotent stem cells.

Alzheimer's disease (AD) is the most common cause of late-life dementia and represents one of the leading causes of death worldwide. The generation of induced pluripotent stem cells (iPSC) has facilitated the production and differentiation of stem cells from patients somatic cells, offering new opportunities to model AD and other diseases in vitro. In this study, we generated iPSCs from skin fibroblasts obtained from a healthy individual, as well as sporadic (sAD) and familial AD (fAD, PSEN1-A246E mutation) patients. iPSC lines were differentiated into neuronal precursors (iPSC-NPCs) and neurons that were subjected to amyloid beta (Aß) toxicity assays. We found that neurons derived from the fAD patient have a higher susceptibility to Aß1-42 oligomers compared with neurons coming from healthy and sAD individuals. Our findings suggest that neurons from patients with PSEN1-A246E mutation have intrinsic properties that make them more susceptible to the toxic effects of Aß1-42 oligomers in the AD brain.