Introduction: Cardiopulmonary resuscitation restores circulation, but with inconsistent blood-flow and pressures. Our recent approach using an extracorporeal life support system, named “controlled integrated resuscitation device” (CIRD), may lead to improved survival and neurological recovery after cardiac arrest (CA). The basic idea is to provide a reperfusion tailored to the individual patient by control of the conditions of reperfusion and the composition of the reperfusate. Hypothermia is one aspect of this concept. Here, we investigated the role of immediate short-term blood cooling after experimental CA and its influence on survival and neurological recovery. Methods: Twenty-one pigs were exposed to 20 minutes of normothermic CA. Afterwards, CIRD was immediately started for 60 minutes in all animals and the heart was converted to a sinus rhythm. The pigs either received normothermic reperfusion (37°C, n=11) or the temperature was maintained at 32°C for the first 30 minutes (n=10). Thermometric, hemodynamic and serologic data were collected during the experiment. After weaning from CIRD, neurological recovery was assessed daily by a species-specific neurological deficit score (NDS; 0: normal; 500: brain death). Results: One pig in each group could not be successfully resuscitated. Due to severe neurological deficits, only 6/11 animals in the normothermic group finished the observation time of seven days with an NDS of 37±34. In the hypothermic group, all nine surviving animals reached day seven with an NDS of 16±13. Analogous to the lower NDS, animals in the hypothermic group also showed lower neuron-specific enolase end values as a marker of brain injury. Conclusions: Within this experimental setting, immediate moderate and short-term hypothermia after CA improves survival and seems to result in statistically non-significant better neurological recovery.

Around 500 million adults in the world have diabetes mellitus, and the incidence is increasing. Over 90% of type 2 diabetes mellitus cases are associated with dysbiosis of the microbiota of the gut, chronic systemic inflammation, mitochondrial dysfunction and destruction of the β-cells of the pancreas. Paneth cells are found in the entire length of the small intestine in humans and play a key role in its innate immunity. Deficient function of Paneth cells predisposes the intestine to gastrointestinal and extra-gastrointestinal diseases, which include inflammatory bowel disease. This manuscript reviews the roles of the Paneth cells in the innate immunity of the small intestine, the link between dysbiosis and dysfunction of Paneth cells and the influence of dysbiosis in the pathogenesis of diabetes mellitus. The manuscript also reviews some strategies currently used to try to reverse dysbiosis and its consequences.

Introduction: Based on extracorporeal circulation, targeted reperfusion strategies have been developed to improve survival and neurologic recovery in refractory cardiac arrest: Controlled Automated Reperfusion of the whoLe Body (CARL). Furthermore, animal and human cadaver studies have shown beneficial effects on cerebral pressure due to head elevation during conventional cardiopulmonary resuscitation. Our aim was to evaluate the impact of head elevation on survival, neurologic recovery and histopathologic outcome in addition to CARL in an animal model. Methods: After 20 min of ventricular fibrillation, 46 domestic pigs underwent CARL, including high, pulsatile extracorporeal blood flow, pH–stat acid–base management, priming with a colloid, mannitol and citrate, targeted oxygen, carbon dioxide and blood pressure management, rapid cooling and slow rewarming. N = 25 were head-up (HUP) during CARL, and N = 21 were supine (SUP). After weaning from ECC, the pigs were extubated and followed up in the animal care facility for up to seven days. Neuronal density was evaluated in neurohistopathology. Results: More animals in the HUP group survived and achieved a favorable neurological recovery, 21/25 (84%) versus 6/21 (29%) in the SUP group. Head positioning was an independent factor in neurologically favorable survival (p < 0.00012). Neurohistopathology showed no significant structural differences between HUP and SUP. Distinct, partly transient clinical neurologic deficits were blindness and ataxia. Conclusions: Head elevation during CARL after 20 min of cardiac arrest independently improved survival and neurologic outcome in pigs. Clinical follow-up revealed transient neurologic deficits potentially attributable to functions localized in the posterior perfusion area, whereas histopathologic findings did not show corresponding differences between the groups. A possible explanation of our findings may be venous congestion and edema as modifiable contributing factors of neurologic injury following prolonged cardiac arrest.

Telomere, also known as a “molecular clock”, is a specific, unique cap-like structure of nucleoprotein with repetitive, noncoding, guanine-rich tandem of nucleotide sequences of DNA-protein located at the ends of chromosomes fashioned in a duplex “D-loop-T-loop” appearance. The dynamic and equilibrium of telomere homeostasis is a function of competing pro-telomere lengthening and pro-telomere shortening factors in determining the telomere length and telomerase activity. While many studies have been done on telomere dynamics, few have been done on telomeres and HIV with a stark gap in knowledge on the impact lifestyle modifications have on the telomeres of people living with HIV. Development of “telomere check kits” in the future will go a long way to put the “molecular clock” within our reach and be directly involved and aware of where we are in the “time or clock” of our life. Having extensively and comprehensively reviewed the healthy lifestyle and the improvement of telomere length and enhancement of telomerase activity that can result in promoting longevity and maximizing health-related quality of life, a full integration of lifestyle modifications as part of the management of HIV disease is long overdue.