seems to be a promising intervention for improving cardiometabolic and oxidative stress parameters in patients with CKD.

Probiotic, prebiotic, and synbiotic supplementation seems to be a promising intervention for improving cardiometabolic and oxidative stress parameters in patients with CKD.The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing over the years and is now as high in Asia as in the Western world, so much so that it should no longer be considered a Western disease. In fact, China is expected to have the largest increase in the number of NAFLD cases in the coming years. The increase in prevalence of NAFLD in Asia lags behind that of the Western world; thus, there will be a lag in more severe liver disease in Asia despite a similar prevalence of the disease. NAFLD is more prevalent among patients with diabetes mellitus, which is also an important risk factor for more severe liver disease. Patients with diabetes mellitus thus represent an important target for screening for NAFLD and more severe liver disease. Although the PNPLA3 gene polymorphism is the most studied in NAFLD, it is increasingly clear that the cumulative effect of multiple genes likely predisposes to NAFLD and more severe liver disease in the different ethnic groups, and polygenic risk scores are emerging. Lean NAFLD has been largely reported in Asia but is increasingly recognized worldwide. Multiple risk factors have been identified for the disease that manifests in metabolically unhealthy normal weight individuals; however, it responds to lifestyle intervention, similar to the disease in obese individuals. Lastly, the newer term “metabolic dysfunction-associated fatty liver disease” provides a more accurate reflection of the disease, giving more focus to clinicians and researchers in tackling this increasingly common and challenging disease.Breastfeeding plays a major role in the health and wellbeing of mother and infant. However, information on the safety of maternal medication during breastfeeding is lacking for most medications. This leads to discontinuation of either breastfeeding or maternal therapy, although many medications are likely to be safe. Since human lactation studies are costly and challenging, validated non-clinical methods would offer an attractive alternative. This review gives an extensive overview of the non-clinical methods (in vitro, in vivo and in silico) to study the transfer of maternal medication into the human breast milk, and subsequent neonatal systemic exposure. Several in vitro models are available, but model characterization, including quantitative medication transport data across the in vitro blood-milk barrier, remains rather limited. Furthermore, animal in vivo models have been used successfully in the past. However, these models don’t always mimic human physiology due to species-specific differences. Several ts. Such a non-clinical platform will be developed and thoroughly evaluated by the Innovative Medicines Initiative ConcePTION.

To investigate motor and cardiovascular responses to dexmedetomidine or fentanyl in isoflurane-anaesthetized pigs.

Experimental, balanced, block randomized, two-group design.

A group of 16 crossbred pigs, 55 ± 8 days (mean ± standard deviation) old.

Deltoid electromyography (EMG) was recorded during isoflurane anaesthesia. Electrical stimulation using 5, 10, 20 and 40 mA of the distal right thoracic limb elicited a nociceptive withdrawal reflex (NWR), quantified by the area under the curve (AUC) for the simulation intensity versus EMG amplitude response curve. Latency to movement evoked by clamping a claw for maximum 60 seconds was noted. Arterial blood pressure and pulse rate were recorded. Data were sampled at baseline and during dexmedetomidine 0.25, 0.5, 1.0, 2.0, 4.0 and 8.0 μg kg

hour

or fentanyl 5, 10, 20, 40, 80 and 160 μg kg

hour

infusions. The influence of infusion rate on NWR AUC and spontaneous EMG was analysed using a mixed model, with p < 5%.

NWR AUC increased at fentanyl 5 μg kg

hour

but decreased at fentanyl 40, 80 and 160 μg kg

hour

and dexmedetomidine 4.0 and 8.0 μg kg

hour

. All pigs at fentanyl 80 μg kg

hour

, and three pigs at dexmedetomidine 8.0 μg kg

hour

had mechanical latencies greater than 60 seconds. Spontaneous EMG activity increased accompanied by visually evident ‘shivering’ at fentanyl 5, 10 and 20 μg kg

hour

but decreased at dexmedetomidine 2, 4 and 8 μg kg

hour

. Clinically relevant effects of increasing infusion rates on blood pressure or pulse rate were not observed.

If anaesthetic plane or antinociception is evaluated in pigs, response to claw clamping and NWR will not necessarily give uniform results when comparing drugs. If only one method is used, results should be interpreted cautiously.

If anaesthetic plane or antinociception is evaluated in pigs, response to claw clamping and NWR will not necessarily give uniform results when comparing drugs. If only one method is used, results should be interpreted cautiously.

While emergency physicians are familiar with the management of hypoxemic respiratory failure, management of mechanical ventilation and advanced therapies for oxygenation in the emergency department have become essential during the coronavirus disease 2019 (COVID-19) pandemic.

We review the current evidence on hypoxemia in COVID-19 and place it in the context of known evidence-based management of hypoxemic respiratory failure in the emergency department.

COVID-19 causes mortality primarily through the development of acute respiratory distress syndrome (ARDS), with hypoxemia arising from shunt, a mismatch of ventilation and perfusion. Management of patients developing ARDS should focus on mitigating derecruitment and avoiding volutrauma or barotrauma.

High flow nasal cannula and noninvasive positive pressure ventilation have a more limited role in COVID-19 because of the risk of aerosolization and minimal benefit in severe cases, but can be considered. Stable patients who can tolerate repositioning shoule patients who can tolerate repositioning should be placed in a prone position while awake. Once intubated, patients should be managed with ventilation strategies appropriate for ARDS, including targeting lung-protective volumes and low pressures. Increasing positive end-expiratory pressure can be beneficial. Inhaled pulmonary vasodilators do not decrease mortality but may be given to improve refractory hypoxemia. Prone positioning of intubated patients is associated with a mortality reduction in ARDS and can be considered for patients with persistent hypoxemia. Disufenton clinical trial Neuromuscular blockade should also be administered in patients who remain dyssynchronous with the ventilator despite adequate sedation. Finally, patients with refractory severe hypoxemic respiratory failure in COVID-19 should be considered for venovenous extracorporeal membrane oxygenation.