Rejected

The integration between physiologically-based pharmacokinetics (PBPK) models and pharmacodynamics (PD) models makes it possible to describe the absorption, distribution, metabolism and excretion processes of drugs, together with the concentration-response relationship, being a fundamental framework with wide applications in pharmacology. Nevertheless, the enormous complexity of PBPK models and the large number of parameters that define them leads to the need to study and understand how the uncertainty of the parameters affects the variability of the models output. To study this issue, this paper proposes a global sensitivity analysis (GSA) to identify the parameters that have the greatest influence on the response of the model. It has been selected as study cases the PBPK models of an inhaled anesthetic and an analgesic, along with two PD interaction models that describe two relevant clinical effects, hypnosis and analgesia during general anesthesia. The subset of the most relevant parameters found adequately with the GSA method has been optimized for the generation of a virtual population that represents the theoretical output variability of various model responses. The generated virtual population has the potential to be used for the design, development and evaluation of physiological closed-loop control systems.

Mass vaccination is the most effective strategy against the spread of the COVID-19 pandemic. However, concerns about the vaccine's safety and effectiveness remain a huge obstacle to vaccine acceptance. The aim of the present study was to explore different COVID-19 vaccine outcomes, including the development of adverse events and/or COVID-19 infection following COVID-19 vaccination. A cross-sectional study was conducted by distributing an online survey targeting staff and students at the British university in Egypt. A total of 637 participants fully completed the survey. Of these, 609 (95.6%) participants received the COVID-19 vaccine. Only 12.6% of the total vaccinated participants reported COVID-19 infection after vaccination. Of these, only 2.8% reported having severe symptoms while 9.9% reported having no or mild symptoms. The most common side effects reported after the first vs. second dose were headache (36.3% vs. 14.6%), tiredness and fatigue (26.9% vs. 10.7), and fever (25.6% vs. 6.7%). In conclusion, the present study explored different COVID-19 vaccine outcomes where the overall incidence of side effects is higher after the first dose than after the second dose. There is a relationship between COVID-19 vaccines' side effects and gastrointestinal disorders, gender, and the type of COVID-19 vaccine. Post-vaccination symptoms were more frequently reported in women compared to men and more frequent with viral vector vaccines compared to other types. The effectiveness of different types of COVID-19 vaccines was confirmed by the lower incidence rate of post-vaccination COVID-19 infection.

To describe an alternative method of measuring the Epidural Waveform Analysis (EWA), a technique through which anesthesiologists can confirm the position of a needle and/or catheter tip in the epidural space. EWA consists of epidural catheter transduction with a pressure system typically used for invasive arterial blood pressure monitoring which generates a characteristic oscillatory waveform (provided the catheter tip is within the epidural space) in synchrony with the pulsatile epidural circulation. The technique requires a double-male connector, a 3-way stopcock and an arterial pressure extension tubing along with the patient's existing arterial line setup while ensuring a meticulously sterile technique to mitigate the risks of neuraxial infection. The technique described herein has been successfully and routinely applied within our institution to measure EWA with the advantage of being potentially less wasteful. EWA allows anesthesiologists to confirm the correct position of an epidural needle/catheter. We describe a method of successfully measuring EWA while reducing wastefulness.

Diclofenac belongs to the class of nonsteroidal anti-inflammatory drugs (NSAIDs), which are amongst the most frequently prescribed drugs to treat fever, pain and inflammation. Despite the presence of NSAIDs on the pharmaceutical market for several decades, epidemiological studies have shown new clinical applications of NSAIDs, and new mechanisms of their action were discovered. The unfolded protein response (UPR) activated under endoplasmic reticulum (ER) stress is involved in the pathophysiology of many diseases and may become a drug target, therefore, the study evaluated the effects of diclofenac on the tunicamycin-induced UPR pathways in endothelial cells. RT PCR analysis showed that diclofenac significantly inhibited activation of ER stress-responsive genes, i.e., CHOP/DITT3, GRP78/HSPA5 and DNAJB9. Additionally, the drug diminished the significant upregulation and release of the GRP78 protein, as evaluated using the ELISA assay, which was likely to be involved in the mechanism of the UPR activation resulting in apoptosis induction in endothelial cells. These results suggest the value of diclofenac as a factor capable of restoring the ER homeostasis in endothelial cells by diminishing the UPR.

The use of esthetic products by millennials is increasing, yet published clinical trial data in this population are limited.

Gastrointestinal pathologies associated with abdominal pain, such as irritable bowel syndrome or inflammatory bowel disease, lack sufficiently effective treatments. In our study we have used a rat model of visceral pain (72 animals; = 8-13 per experimental group) to analyze the consequences of intracolonic administration of the irritant acetic acid on visceral sensitivity, histology of the colonic wall, and inflammatory response. Moreover, we have studied the possible beneficial effects of a pretreatment with a commercial probiotic (Actimel). Contrary to expectations, acetic acid application (7 cm proximal to the anus) decreased the nociceptive response to intracolonic mechanical stimulation, with a slight increase in the histological damage of colonic mucosa. The intensity of these changes depended on the concentration (4% or 0.6%) and the time of application (30 or 60 min). Pretreatment with probiotics (by daily gavage, for 1 week) normalized the values obtained in the visceral sensitivity test but revealed an increase in the number of macrophages. These results suggest a possible activation of inhibitory mechanisms early after colonic irritation, not previously described (which need further experimental confirmation), and the ability of probiotics to normalize the effects of acetic acid. In addition, pretreatment with probiotics has a direct effect on immune functions, stimulating macrophagic activity.

Repetitive task practice reduces mean upper extremity motor impairment in of patients with chronic stroke, but response is highly variable. A method to predict meaningful reduction in impairment in response to training based on biomarkers and other data collected prior to an intervention is needed to establish realistic rehabilitation goals and to effectively allocate resources.

Although the number of farmers in Korea is declining, the proportion of older farmers aged ≥60 increases.

We describe a unique case of intrathecal baclofen overdose mimicking brainstem death, during bilateral anterior cingulate cortex deep brain stimulation (DBS) for pain. A 37-year-old man with chronic regional pain syndrome requiring an intrathecal baclofen pump underwent DBS under general anaesthesia and experienced an intraoperative generalised tonic-clonic seizure on dural opening. Once the operation was completed, the patient was noted to have fixed, dilated pupils bilaterally and was transferred for an emergency computed tomography scan of the head, which did not reveal any acute intracranial pathology. The patient was transferred to the intensive care unit for management of concurrent hypotension, bradycardia and supportive management of his low Glasgow Coma Scale (GCS) score. A trial of atropine to counter the bradycardia was unsuccessful. Intrathecal baclofen toxicity was suspected as a diagnosis of exclusion, necessitating urgent aspiration of the baclofen pump. The patient's GCS score improved after pump aspiration and he was discharged home several days later. It was noted that the intrathecal baclofen pump had been refilled several days previously and the patient had reported intermittent episodes of somnolence. In perioperative patients with intrathecal baclofen pumps in situ, baclofen toxicity should always be considered as a differential in perioperative complications, even if it is considered a rare event.

To investigate whether a cocktail therapy of dexamethasone, ropivacaine, dexmedetomidine, and vitamin B12 can achieve satisfactory pain relief and promote early functional recovery after PPECD.