Can repetitive transcranial magnetic stimulation influence the visual cortex of adults with amblyopia? - systematic review.

Amblyopia is the most frequent cause of monocular vision loss. Transcranial Magnetic Stimulation (TMS) has been used to improve several vision parameters of the amblyopic eye in adulthood. This study is relevant in order to evaluate TMS effects and to raise awareness of the need for further research. Transcranial Magnetic Stimulation (TMS) is a neuromodulation technique capable of changing cortical excitability. In the last decade, it has been used to improve visual parameters in amblyopic patients. The main goal of this systematic review is to evaluate the influence of TMS in the amblyopic eye, in the visual parameters of amblyopic patients. Searches were done in PubMed and Embase databases, and a combined search strategy was performed using the following Mesh, EMBASE, and keywords: 'Amblyopia', 'Transcranial Magnetic Stimulation', and 'theta burst stimulation'. This review included randomised controlled studies, descriptive cases, and clinical case studies with adult amblyopes. All articles that had any of the following characteristics were excluded: children or animal studies, reviews, pathologies other than amblyopia, and other techniques rather than repetitive TMS (rTMS), or Theta Burst Stimulation (TBS). A total of 42 articles were found, of which only four studies (46 amblyopes) meet the criteria above. Three of the articles found significant improvement after one session of continuous TBS (cTBS) in visual parameters like visual acuity, contrast sensitivity, suppressive imbalance, and stereoacuity. One study found a significant visual improvement with 10 Hz rTMS. Only one stimulation-related dropout was reported. The few existing studies found in this review seem to show that through the usage of high-frequency rTMS and cTBS, it is possible to re-balance the eyes of an adult amblyope. However, despite the promising results, further research with larger randomised double-blind studies is needed for a better understanding of this process.

Evaluation of wakefulness electroencephalogram in OSA patients.

OBJECTIVE: Obstructive sleep apnea (OSA) has been associated with an elevated cardiovascular risk, increased daytime sleepiness, cognitive decline, and slower electroencephalographic activity (EEG). This study assesses EEG patterns during wakefulness in OSA patients compared to those without sleep-disordered breathing. MATERIALS AND METHODS: This retrospective study analyzed 30 OSA patients with an Apnea/Hypopnea Index (AHI) of 15 or higher, as well as 29 individuals without sleep-disordered breathing (AHI of 5 or lower) who underwent hospital polysomnography and met all inclusion criteria. Sociodemographic and EEG data were obtained from the sleep laboratory database. Blinded EEG analysis was conducted by two observers, assessing activity in the frontal, central, and occipital regions. RESULTS: No significant differences were observed in EEG activity between OSA and non-OSA patients. However, a weak correlation was found between decreased C3 EEG frequency and higher AHI (p = 0.033), as well as increased total sleep time and higher O2 EEG frequency (p = 0.038). Lower amplitudes in C3 (p = 0.043) and O1 (p = 0.031) were correlated with reduced average oxygen saturation. CONCLUSION: Our findings suggest that OSA-related hypoxemia may impact neuronal activity, highlighting the need to address this sleep-disordered breathing in order to potentially prevent the cognitive decline observed in OSA patients.

Evaluation of various membranes at different fluxes to enable large-volume single-use perfusion bioreactors.

The growing demand for biological therapeutics has increased interest in large-volume perfusion bioreactors, but the operation and scalability of perfusion membranes remain a challenge. This study evaluates perfusion cell culture performance and monoclonal antibody (mAb) productivity at various membrane fluxes (1.5-5 LMH), utilizing polyvinylidene difluoride (PVDF), polyethersulfone (PES), or polysulfone (PS) membranes in tangential flow filtration mode. At low flux, culture with PVDF membrane maintained higher cell culture growth, permeate titer (1.06-1.34 g/L) and sieving coefficients (≥83%) but showed lower permeate volumetric throughput and higher transmembrane pressure (TMP) (>1.50 psi) in the later part of the run compared to cultures with PES and PS membrane. However, as permeate flux increased, the total mass of product decreased by around 30% for cultures with PVDF membrane, while it remained consistent with PES and PS membrane, and at the highest flux studied, PES membrane generated 12% more product than PVDF membrane. This highlights that membrane selection for large-volume perfusion bioreactors depends on the productivity and permeate flux required. Since operating large-volume perfusion bioreactors at low flux would require several cell retention devices and a complex setup, PVDF membranes are suitable for low-volume operations at low fluxes whereas PES membranes can be a desirable alternative for large-volume higher demand products at higher fluxes.

Relationship between event-related potentials and cognitive dysfunction in multiple sclerosis: A systematic review.

OBJECTIVE: This systematic review aimed to evaluate if event-related potentials (ERPs) can be a relevant tool for cognitive dysfunction diagnosis in Multiple Sclerosis (MS). METHODS: Four databases were consulted (PubMed, Embase, Scielo, and Web of Science). The included studies should include adults with clear MS diagnoses, independently of having cognitive complaints, and all should have been submitted to ERPs (P300, N400 or mismatch negativity (MMN)). The main outcomes evaluated were ERPs' amplitude and/or latency. RESULTS: 425 studies were obtained initially from all databases, with 26 studies fulfilling the eligibility criteria. P300 was the most used ERP (25 studies), showing a reduced amplitude or an increased latency in 84% of those. N400 was evaluated in one study, showing also abnormal results. MMN was addressed in two studies with inconsistent findings. Some studies further suggest that ERPs may show earlier abnormal results compared with neuropsychological tests. CONCLUSIONS: Most MS patient groups revealed ERP abnormalities, suggesting that these neurophysiological tests may be a relevant and appropriate diagnostic aid method for cognitive impairment in MS. SIGNIFICANCE: The use of ERPs in MS patients seems able to demonstrate cognitive impairment and its use should be considered as part of the regular patient evaluation.

Exploring the Insomnia-Ischemic Stroke Nexus: A Comprehensive Review.

Background: This study investigates the relationship between sleep patterns and ischemic stroke beyond the predominant focus on obstructive sleep apnea. Through a systematic review of the existing literature, we aim to elucidate the connections between insomnia, sleep duration, cardiovascular factors, and ischemic stroke onset. Methods: We searched databases, including MEDLINE, SciELO, Scopus, and Science Direct, using an adapted PICO framework. Using a search strategy with MeSH words, keywords, and expressions related to insomnia and stroke, we included clinical trials and analytical observational epidemiological studies, comprising cohort, case-control, and cross-sectional studies. Results: Following the initial search, we identified 984 records, with 779 titles and abstracts screened for eligibility after removing duplicates. From these, 63 full-text articles, including 5 in the data synthesis, were reviewed. Our findings highlight a significant correlation between poor sleep quality, extreme sleep durations, and a heightened risk of ischemic stroke, along with established cardiovascular risk factors, such as hypertension, hyperlipidemia, obesity, and diabetes. Conclusions: This systematic review offers a comprehensive analysis of ischemic stroke prevalence and its association with cardiovascular factors, such as hypertension, hyperlipidemia, obesity, and diabetes. It suggests that poor sleep quality and extreme sleep durations, particularly long ones, are linked to a heightened risk of ischemic stroke.

Pattern electroretinography response in amblyopic adults.

INTRODUCTION: Amblyopia is generally a unilateral disorder, defined by at least a difference of two lines of visual acuity between both eyes with the best-corrected visual acuity, a decrease in contrast sensitivity, and a decrease in stereopsis. Pattern electroretinogram (PERG) is a noninvasive technique that provides a retinal biopotential and is a highly sensitive indicator of changes in the macular area. Our aim was to evaluate if there are differences in the retinal response of an amblyopic eye compared with a normal eye (NE). METHODS: We evaluated twenty-four adult volunteers, twelve amblyopes (mean 43.42 ± 12.72 years old), and twelve subjects with NE (mean 35.58 ± 12.85 years old). None of the subjects in the two groups had comorbidities. A complete optometric examination was performed including parameters such as visual acuity (VA) by far and near with ETDRS chart, eye alignment with cover test, and evaluation of retinal cells response with PERG. RESULTS: The refractive error found in the NE group of subjects had a mean of - 0.95 ± 1.65D, while the amblyopic group showed a mean of - 2.03 ± 4.29D. The VA in amblyopic eyes had a mean of 0.38 ± 0.20 logMAR. Analyzing PERG data, we observed significant differences in the P50-N95 amplitudes of the amblyopic group compared with the NE group (p < 0.0001-amblyopic eye vs. NE; p = 0.039-fellow eye vs. NE). DISCUSSION: These findings suggest that amblyopic patients may also present other impairments beyond the visual cortex. PERGs seem to be an important complementary examination in the diagnosis of other impairments in amblyopia.

Longstanding effects of continuous theta burst stimulation in adult amblyopes.

CLINICAL RELEVANCE: Continuous theta burst stimulation may be an important tool in the therapeutic management of amblyopia, when trying to correct the established neuronal imbalance. It is important to understand whether two sessions of continuous theta burst stimulation produce greater and longstanding changes in visual acuity and suppressive imbalance than one session of continuous theta burst stimulation. BACKGROUND: We hypothesise that through the usage of continuous theta burst stimulation (cTBS) it is possible to change cortical excitability in a situation where visual impairment is present. METHODS: We selected 22 adult amblyopes, 18 females and 4 males, with an age range of 20-59 years. They were randomised into two groups: group A with 10 amblyopes was submitted to one session of cTBS and group B with 12 amblyopes submitted to two sessions of cTBS. Visual acuity (VA) and suppressive imbalance (SI) were evaluated immediately before and after stimulation in both groups A and B. A follow-up was done in both groups. RESULTS: For both group A and B, the VA improvements were significant after cTBS (p = 0.005 and p = 0.003, respectively). Regarding SI, both group A and B had significant improvements after cTBS (p = 0.03 and p = 0.005, respectively). Comparing groups, A and B no significant differences were found with regard to the results obtained both for VA (p = 0.72) and SI (p = 0.24). However, significant differences were found between group A and B with regard to the duration of stimulation effect for VA (p = 0.049) and SI (p = 0.03). CONCLUSION: We conclude that two sessions of cTBS do not produce better results than one session of stimulation. However, it seems that two sessions of cTBS produce longstanding effects in VA and SI.

Body posture as a factor determining sleep quality in patients using non-invasive ventilation.

OBJECTIVE: Sleep quality is influenced by multiple factors. Slow-wave sleep and REM sleep play a key role in homeostasis and are useful indicators of sleep quality. Studies indicate that obstructive sleep apnea (OSA) in the supine position correlates with anatomical changes that exacerbate respiratory events and influence the effectiveness of ventilation therapy. This study aimed to evaluate the correlation of body posture with polysomnographic data and adherence of patients using continuous positive airway pressure (CPAP). MATERIAL AND METHODS: This was a retrospective study of patients with OSA who had polysomnography in Rainha Santa Isabel Hospital's sleep laboratory in Torres Novas, Portugal, and met all the inclusion and exclusion criteria. Sociodemographic, polysomnographic, and ventilation therapy variables were collected from that sleep laboratory database between 2015 and 2019. RESULTS: In 30 patients with OSA, residual apnea-hypopnea index (AHIr) and arousal index were lower in the non-supine position compared to the supine position (p value 0.005 and 0.009 respectively). As measures of sleep quality, total sleep time in SWS and REM sleep were greater in the non-supine position compared to the supine position (p value of 0.002 and 0.010 respectively). CONCLUSION: The findings suggest that a supine position significantly impairs sleep quality mainly by increasing the number of respiratory events and associated sleep fragmentation. The findings also suggest that the difference in AHIr between supine and non-supine positions may contribute to non-adherence with CPAP in patients with OSA.

High-frequency repetitive magnetic stimulation rescues ischemia-injured neurons through modulation of glial-derived neurotrophic factor present in the astrocyte's secretome.

Due to its ability to improve the most frequent clinical sequelae left by ischemia, repetitive transcranial magnetic stimulation has been considered a promising therapeutic strategy for stroke. Those improvements are associated with changes in neurons and their synaptic liaisons. However, the hypothesis that this technique modulates astrocytes, potentiating their neuroprotective capabilities, was also raised. This study aims to identify the effects triggered by high-frequency repetitive magnetic stimulation (HF-rMS) on astrocytes that contribute to its neuroprotective effects. Neuron-glia and astrocyte cortical cultures subject to oxygen and glucose deprivation were used as an in vitro model of ischemia. Neuroprotection promoted by HF-rMS was evaluated by analysis of markers of neuronal activity and morphometric analysis of neurons. Glial reactivity was determined by immunocytochemistry. The levels of growth factors in the astrocyte-conditioned medium (CM) were assessed through a Growth Factor Array and glial-derived neurotrophic factor (GDNF) expression was analyzed by RT-PCR and Western blot. Our results show that neurons injured by ischemia can be rescued through the modulation of astrocytes by HF-rMS. This modulation helps to maintain the number and length of neurites and increases the number of neurons expressing ERK1/2 and c-Fos. Analysis of the astrocyte-CM showed that HF-rMS stimulated the release of several trophic factors by astrocytes. Moreover, GDNF was one of the released factors that contributed to the recovery mechanisms triggered by HF-rMS. Our results show that modulation of astrocytes by HF-rMS effectively rescues neurons injured by ischemia and suggest that by targeting astrocytes this approach can also be used to promote neuroprotection in other brain lesions.

Perfil de stress dos enfermeiros de urgência/ emergência em contexto COVID-19: determinantes profissionais / Stress profile of emergency nurses in a COVID-19 context: professional determinants

As evidências revelam que os enfermeiros de urgência/emergência desenvolveram problemas de saúde relacionados com o Stress em contexto de pandemia por COVID-19. Foram identificados riscos para estes profissionais de saúde, emergindo, assim, a necessidade major de prevenir níveis elevados de Stress que podem resultar em Burnout. Objetivos: Estudar a relação entre o perfil de Stress dos enfermeiros de urgência/emergência em contexto COVID-19 e as variáveis de caracterização profissional. Metodologia: Estudo transversal, quantitativo, descritivo-correlacional, através da aplicação da Escala de Perceção de Stress (EPS) de Cohen, Kamarck & Mermelstein (1983), adaptada para a população portuguesa por Pais Ribeiro & Marques (2009), a uma amostra de 355 enfermeiros de urgência/emergência em contexto COVID-19 a nível nacional, maioritariamente (51,3%) com idades entre 36 e 50 anos, em funções no setor público (85,9%), com experiência profissional entre 11-20 anos (40,8%). Resultados: O estudo da relação entre o perfil de Stress numa amostra de 355 enfermeiros portugueses de urgência/emergência em contexto COVID-19, com uma média de idades de 39,25±8,89 anos e as variáveis de caracterização profissional, veio revelar que o título profissional, o serviço/unidade onde exercem funções e a localização geográfica do local de trabalho, apresentam efeito significativo no perfil de Stress percecionado (p < 0,005). Neste âmbito considerativo, os enfermeiros especialistas (p = 0,005) a exercerem funções nos SUP e BO (p = 0,002) da Região de Lisboa e Vale do Tejo (p = 0,001), foram aqueles onde a perceção de Stress é mais alta. Por outro lado, os enfermeiros generalistas (p = 0,005) a exercerem funções no INEM (p = 0,002) e que exercem na Região Autónoma da Madeira (p = 0,001), demonstraram um perfil de Stress mais baixo. Conclusão: Os resultados devem ser analisados no sentido de ter este tipo de amostras laborais sob análise e atenção. Num primeiro momento recomendam-se consultas na Medicina de Trabalho anti-Stress, e num segundo momento, consideram-se essenciais a aplicação de formações para Treino de Gestão de Stress, no sentido de reduzir o Stress, promovendo estratégias adaptativas para o efeito. A avaliação do Stress no local de trabalho entre enfermeiros, em contexto de doente crítico, deve ser o foco de intervenção dos gestores e líderes institucionais.

The evidence shows that emergency nurses developed stress-related health problems in the context of the COVID-19 pandemic. Risks were identified for these health professionals, thus emerging the major need to prevent high levels of Stress that may result in Burnout. Objectives: To study the relationship between the Stress Profile of emergency nurses in the context of COVID-19 and the variables of professional characterisation. Methodology: Cross-sectional, quantitative, descriptive and correlational study, through the application of Cohen, Kamarck & Mermelstein's Stress Perception Scale (SPS) (1983), adapted for the Portuguese population by Pais Ribeiro & Marques (2009), to a sample of 355 nurses in an emergency room in a COVID-19 context at national level, mostly (51.3%) aged between 36 and 50 years, working in the public sector (85.9%), with professional experience between 11-20 years (40.8%). Results: The study on the relationship between the Stress Profile in a sample of 355 Portuguese emergency nurses in COVID-19 context, with a mean age of 39.25±8.89 years and the variables of professional characterisation revealed that the professional title, the service/unit where they work and the geographical location of their workplace had a significant effect on the perceived Stress Profile (p < 0.005). Within this scope, the specialist nurses (p = 0.005) working in the SUP and OR (p = 0.002) of the Lisbon and Tagus Valley Region (p = 0.001) were those with the highest perception of Stress. On the other hand, the generalist nurses (p = 0.005) working at the INEM (p = 0.002) and working in the Autonomous Region of Madeira (p = 0.001) showed a lower stress profile. Conclusion: The results should be analysed in order to have this kind of work samples under analysis and attention. In a first stage, anti-stress consultations with Occupational Medicine are recommended, and in a second stage, the application of Stress Management Training is considered essential to reduce Stress, promoting adaptive strategies for this purpose. The assessment of Stress at the workplace among nurses in the context of critically ill patients should be the focus of intervention by managers and institutional leaders.

Comparison of process mass intensity (PMI) of continuous and batch manufacturing processes for biologics.

Biologics encompasses a wide variety of therapeutics including monoclonal antibodies, fusion proteins, and enzymes, among others. The biologics market is growing at a rapid pace and different manufacturing processes, including continuous manufacturing processes, are being increasingly adopted. There is a strong drive to assess the sustainability of such processes. Here, we calculated the process mass intensity (PMI) of a continuous manufacturing process and compared it to the PMI of batch processes for monoclonal antibodies (mAbs). Results show that the PMI of continuous manufacturing process is comparable to that of batch processes. Sensitivity analysis was performed to assess the impact of different process strategies on the material usage efficiency of continuous processes. Although PMI is a useful benchmarking metric of sustainability, it does not account for factors such as energy consumption which is a key driver of sustainability for biologics manufacturing. Comparison of a higher PMI continuous process with a lower PMI batch process operating at the same bioreactor scale shows that since the productivity (in g of drug substance, DS) per unit time is multifold higher for the continuous process, the overall energy consumption per unit of DS produced might be lower leading to a more environmentally sustainable process. This study highlights some of these key aspects that would require additional metrics and models to be developed to assess the overall sustainability of biologics processes.

KPC-3-, GES-5-, and VIM-1-Producing Enterobacterales Isolated from Urban Ponds.

Carbapenems are antibiotics of pivotal importance in human medicine, the efficacy of which is threatened by the increasing prevalence of carbapenem-resistant Enterobacterales (CRE). Urban ponds may be reservoirs of CRE, although this hypothesis has been poorly explored. We assessed the proportion of CRE in urban ponds over a one-year period and retrieved 23 isolates. These were submitted to BOX-PCR, PFGE, 16S rDNA sequencing, antibiotic susceptibility tests, detection of carbapenemase-encoding genes, and conjugation assays. Isolates were affiliated with Klebsiella (n = 1), Raoultella (n = 11), Citrobacter (n = 8), and Enterobacter (n = 3). Carbapenemase-encoding genes were detected in 21 isolates: blaKPC (n = 20), blaGES-5 (n = 6), and blaVIM (n = 1), with 7 isolates carrying two carbapenemase genes. Clonal isolates were collected from different ponds and in different campaigns. Citrobacter F6, Raoultella N9, and Enterobacter N10 were predicted as pathogens from whole-genome sequence analysis, which also revealed the presence of several resistance genes and mobile genetic elements. We found that blaKPC-3 was located on Tn4401b (Citrobacter F6 and Enterobacter N10) or Tn4401d (Raoultella N9). The former was part of an IncFIA-FII pBK30683-like plasmid. In addition, blaGES-5 was in a class 3 integron, either chromosomal (Raoultella N9) or plasmidic (Enterobacter N10). Our findings confirmed the role of urban ponds as reservoirs and dispersal sites for CRE.

Can pattern electroretinography be a relevant diagnostic aid in amblyopia? - A systematic review.

INTRODUCTION: Pattern Electroretinography (PERG) is a highly sensitive electrophysiological technique used as an indicator of changes in retinal macular area. Amblyopia seems to result from a cortical visual imbalance but changes at the retinal level may also be present. The purpose of this systematic review was to evaluate if there are any consistent changes described in the scientific literature in PERG responses of amblyopic eyes. MATERIALS AND METHODS: Searches were conducted in PubMed and Embase databases, using the keywords "Electroretinography" and "Amblyopia", combined with MeSH or Emtree terms "Pattern Electroretinography", "amblyopia", "PERG" and "amblyopia". PERG P50-N95 amplitude and P50 latency were analysed as well as the methodology used. RESULTS: A total of 234 articles were found and 6 articles were included for review. One of the articles reported results in adults and five of them in children. One of the articles in children reported no changes in either P50-N95 amplitude or P50 latency. All articles that described differences between the amblyopic eye and the normal eye found a decrease in P50-N95 amplitude and/or a delay in P50 latency. CONCLUSIONS: This review shows promising findings for the use of PERG in amblyopia as an aid in the diagnostic protocol, since this technique may be able to detect an apparent functional impairment of the amblyopic eye.

Eugenol ß-Amino/ß-Alkoxy Alcohols with Selective Anticancer Activity.

Eugenol, 4-allyl-2-methoxyphenol, is the main constituent of clove essential oil and has demonstrated relevant biological activity, namely anticancer activity. Aiming to increase this activity, we synthesized a series of eugenol ß-amino alcohol and ß-alkoxy alcohol derivatives, which were then tested against two human cancer cell lines, namely gastric adenocarcinoma cells (AGS) and lung adenocarcinoma cells (A549). An initial screening was performed to identify the most cytotoxic compounds. The results demonstrated that three ß-amino alcohol derivatives had anticancer activity that justified subsequent studies, having been shown to trigger apoptosis. Importantly, the most potent molecules displayed no appreciable toxicity towards human noncancer cells. Structure-activity relationships show that changes in eugenol structure led to enhanced cytotoxic activity and can contribute to the future design of more potent and selective drugs.

Theta burst stimulation in adults with symmetric and asymmetric visual acuity.

PURPOSE: Theta Burst Stimulation can influence adult neuro-visual response in imbalanced visual pathways, possibly by influencing cortical excitability. Our objective was to compare suppressive imbalance (SI) and visual acuity (VA) after applying repetitive Transcranial Magnetic Stimulation between groups of subjects with normal binocular vision, visual asymmetry, and amblyopia. METHODS: Thirty-five volunteers between 19 and 51 years of age were split into three groups: 6 volunteers with asymmetric VA (group A); 19 amblyopes (group B); and 10 subjects with normal binocular vision (group C). VA and SI of all groups were evaluated before and after a single session of continuous Theta Burst Stimulation (cTBS) or placebo stimulation over the right occipital cortex. RESULTS: In both groups A and B, we found a significant VA improvement in the non-dominant eye after cTBS (p = 0.04 and p = 0.01, respectively). In SI evaluation, group A and group B also revealed a significant improvement after the cTBS session (p = 0.03 and p = 0.01, respectively). Finally, in the group of volunteers with normal binocular vision and for placebo groups A and B, there were no significant differences in VA and SI after cTBS. CONCLUSIONS: Amblyopic and visually asymmetric individuals improved VA and SI of the non-dominant eye after cTBS when compared to baseline and to placebo stimulation. These enhancements were not found in the group of volunteers with normal binocular vision. We can therefore reasonably assume that cTBS may interfere with the visual system of subjects that present some kind of asymmetry, possibly by improving neuronal imbalances.

Amino Alcohols from Eugenol as Potential Semisynthetic Insecticides: Chemical, Biological, and Computational Insights.

A series of ß-amino alcohols were prepared by the reaction of eugenol epoxide with aliphatic and aromatic amine nucleophiles. The synthesized compounds were fully characterized and evaluated as potential insecticides through the assessment of their biological activity against Sf9 insect cells, compared with a commercial synthetic pesticide (chlorpyrifos, CHPY). Three derivatives bearing a terminal benzene ring, either substituted or unsubstituted, were identified as the most potent molecules, two of them displaying higher toxicity to insect cells than CHPY. In addition, the most promising molecules were able to increase the activity of serine proteases (caspases) pivotal to apoptosis and were more toxic to insect cells than human cells. Structure-based inverted virtual screening and molecular dynamics simulations demonstrate that these molecules likely target acetylcholinesterase and/or the insect odorant-binding proteins and are able to form stable complexes with these proteins. Encapsulation assays in liposomes of DMPG and DPPC/DMPG (1:1) were performed for the most active compound, and high encapsulation efficiencies were obtained. A thermosensitive formulation was achieved with the compound release being more efficient at higher temperatures.

Determination of protein concentration in downstream biomanufacturing processes by in-line index of refraction.

Protein concentration determination is a necessary in-process control for the downstream operations within biomanufacturing. As production transitions from batch mode to an integrated continuous bioprocess paradigm, there is a growing need to move protein concentration quantitation from off-line to in-line analysis. One solution to fulfill this process analytical technology need is an in-line index of refraction (IoR) sensor to measure protein concentration in real time. Here the performance of an IoR sensor is evaluated through a series of experiments to assess linear response, buffer matrix effects, dynamic range, sensor-to-sensor variability, and the limits of detection and quantitation. The performance of the sensor was also tested in two bioprocessing scenarios, ultrafiltration and capture chromatography. The implementation of this in-line IoR sensor for real-time protein concentration analysis and monitoring has the potential to improve continuous bioprocess manufacturing.

Theta burst stimulation over the prefrontal cortex: Effects on cerebral oximetry and cardiovascular measures in healthy humans.

Theta Burst Stimulation (TBS) is a non-invasive neurophysiological technique, able to induce changes in synaptic activity. Research suggests that TBS may induce changes in cerebral oxygenation, cerebral blood flow, blood pressure and heart rate but there are conflicting results across studies. Thus, the objective of our sham-controlled study is to evaluate if TBS applied to the dorsolateral prefrontal cortex (DLPFC) of healthy volunteers produces changes in cerebral oximetry, heart rate and blood pressure. Forty-nine volunteers of both sexes were randomly allocated to one of five stimulation groups. Before and after real TBS or sham stimulation, blood pressure, heart rate, and cerebral oxygenation of the volunteers were measured. Cerebral oxygenation values were obtained with a near infra-red spectroscopy system. We found a significant reduction in left cortex oximetry after continuous TBS (cTBS) over the left DLPFC (p = 0.039) and a non-significant reduction in right cortex oximetry (p = 0.052). Right hemisphere inhibition (using cTBS) seemed to originate a significant reduction of 8 mmHg in systolic arterial pressure. No other changes were seen in oximetry, cardiac frequency and diastolic arterial pressure. In our group of normal subjects, cTBS applied to the left DLPFC was able to reduce oxygenation in the left cortex. Right hemisphere inhibition was associated with a significant reduction in systolic pressure.

Astrocytes contribute to the neuronal recovery promoted by high-frequency repetitive magnetic stimulation in in vitro models of ischemia.

After decades of effort, there are no effective clinical treatments to induce the recovery of ischemia-injured tissues, and among the several strategies that have been explored, repetitive transcranial magnetic stimulation has proven to be one of the most promising, with beneficial effects in limb motor function, aphasia, hemispatial neglect, or dysphagia. Despite the clinical evidences, little is known about the mechanisms underlying those effects. The present study aimed to explore the cellular and molecular effects of high-frequency repetitive magnetic stimulation (HF-rMS) on an in vitro model of ischemia. Using primary cortical cultures exposed to oxygen and glucose deprivation followed by reperfusion, we observed that HF-rMS treatment prevents the ischemia-induced neuronal death by 21.2%, and the neurite degeneration triggered by ischemia. Our results also demonstrate that with this treatment there is an increase of 89.2% on the number cells expressing ERK1/2, of 20.1% on the number of cells expressing c-Fos, and a synaptogenic effect, through an increase of 62.9% in the number of synaptic puncta as well as of 49.4% in their intensity. Interestingly, our results indicate that astrocytes are crucial to the beneficial effects triggered by HF-rMS after ischemia, thus suggesting a direct effect of HF-rMS on these cells. The modulation of astrocytes with this non-invasive brain stimulation technique is a promising approach to promote the recovery of ischemia-induced injured tissues; however, it is essential to understand how these effects can be modulated in order to optimize the protocols and enhance the beneficial outcomes.