Intravenous Dexmedetomidine-Ketamine Versus Ketamine-Propofol for Procedural Sedation in Adults Undergoing Short Surgical Procedures: A Randomized Controlled Trial.

Background and objective Moderate to deep sedation is a prerequisite during total intravenous anesthesia for short-duration surgeries, and it can be achieved by using individual drugs or in combination. Our study compared dexmedetomidine-ketamine (DK) versus ketamine-propofol (KP) in terms of sedation, procedural interference, hemodynamics, and incidence of side effects in patients undergoing short surgical procedures. Methods A total of 194 patients scheduled for short-duration elective surgeries were randomly allocated into two groups. Group DK received a loading dose of 1 µg/kg of dexmedetomidine and 1 mg/kg of ketamine followed by a maintenance infusion of dexmedetomidine at 0.3 µg/kg/h. Group KP received a loading dose of 1 mg/kg of ketamine and 1 mg/kg of propofol followed by a maintenance infusion of propofol at 25 µg/kg/h. For procedural interference, a rescue ketamine bolus was administered at 0.25 mg/kg. Patients were monitored for the requirement of rescue ketamine bolus, procedural interference, hemodynamics, sedation, recovery time, and adverse effects. Results The procedural interference was higher in group KP than in group DK and the difference was statistically significant (P=0.001). The time to the first rescue bolus was 8.72 ± 4.47 minutes in group KP and 10.82 ± 4.01 minutes in group DK, with a difference of 2.1 minutes (p=0.026). There was no statistically significant difference in the sedation scores between both groups except at time points of six minutes and 15 minutes. Conclusion For short-duration procedures, the DK combination is superior to the KP combination in terms of procedural interference and time to the first rescue bolus, while both groups were comparable with regard to safety and hemodynamics.

Molecular and epigenetic alterations in normal and malignant myelopoiesis in human leukemia 60 (HL60) promyelocytic cell line model.

In vitro cell line model systems are essential in supporting the research community due to their low cost, uniform culturing conditions, homogeneous biological resources, and easy experimental design to study the cause and effect of a gene or a molecule. Human leukemia 60 (HL60) is an in-vitro hematopoietic model system that has been used for decades to study normal myeloid differentiation and leukemia biology. Here, we show that IMDM supplemented with 20% FBS is an optimal culturing condition and induces effective myeloid differentiation compared with RPMI supplemented with 10% FBS when HL60 is induced with 1α,25-dihydroxyvitamin D3 (Vit D3) and all-trans retinoic acid (ATRA). The chromatin organization is compacted, and the repressive epigenetic mark H3K27me3 is enhanced upon HL60-mediated terminal differentiation. Differential gene expression analysis obtained from RNA sequencing in HL60 cells during myeloid differentiation showed the induction of pathways involved in epigenetic regulation, myeloid differentiation, and immune regulation. Using high-throughput transcriptomic data (GSE74246), we show the similarities (genes that did not satisfy |log2FC|>1 and FDR<0.05) and differences (FDR <0.05 and |log2FC|>1) between granulocyte-monocyte progenitor vs HL60 cells, Vit D3 induced monocytes (vMono) in HL60 cells vs primary monocytes (pMono), and HL60 cells vs leukemic blasts at the transcriptomic level. We found striking similarities in biological pathways between these comparisons, suggesting that the HL60 model system can be effectively used for studying myeloid differentiation and leukemic aberrations. The differences obtained could be attributed to the fact that the cellular programs of the leukemic cell line and primary cells are different. We validated several gene expression patterns for different comparisons with CD34+ cells derived from cord blood for myeloid differentiation and AML patients. In addition to the current knowledge, our study further reveals the significance of using HL60 cells as in vitro model system under optimal conditions to understand its potential as normal myeloid differentiation model as well as leukemic model at the molecular level.

Poorer Obstetrics Outcomes During the Second Wave of COVID-19 in India.

Introduction: Outcomes of pregnancy in COVID 19-infected mothers are worse than in the general population. Due to immunological changes, antenatal women are more vulnerable to severe complications. The India has experienced two waves of the disease. We analysed whether the second wave of the disease had affected pregnancy outcomes differently by comparing pregnancy outcomes with those of the first wave. Materials and Method: The study population included all the women delivered in the same tertiary centre during both the waves. Maternal outcome parameters include maternal oxygen requirement, maternal ICU admission and maternal death. Foetal outcome parameters include APGAR scores, preterm deliveries and NICU admissions, maternal and foetal outcome parameters between the first and the second waves were compared. Results: Demographic parameters were similar in both the waves of COVID 19. No significant differences were found in pre-pregnancy comorbidities, high-risk pregnancies and mode of deliveries between the two waves. Maternal oxygen requirement increased in the second wave [first wave 6(4.7%) vs second wave 25(40.3%) (p-value < 0.001)]. There was also a significant increase in ICU admission [4(3.1%) vs 8(12.9%)], which was in positive correlation with maternal oxygen requirement during the second wave (r = 0.81, p < 0.001). However, there was no significant difference in maternal death [2(1.6%) vs 2(3.2%)]. No significant change noted in neonatal outcomes except for an increase in neonatal sepsis [0 vs 5(8.1%)]. Conclusion: Mothers had more severe diseases during the second wave. But this did not translate into significant increase in maternal mortality and poor neonatal outcomes, possibly due to better preparedness.

Tender coconut water attenuates heat stress-induced testicular damage through modulation of the NF-κB and Nrf2 pathways.

Tender coconut water (TCW), a well-known plant beverage, has been used as a stress-relieving traditional medicine since ancient times. It is also used to treat various ailments of disease, including hepatic disorders, renal disorders, gastric disorders and reproductive disorders. However, the reasons for its effectiveness as a natural antioxidant as well as its testicular protective effects against whole body heat stress (HS)-induced oxidative imbalance remain to be revealed. The present study aimed to elucidate the protective efficacy of TCW on HS-induced testicular damage in a murine system and to explore the possible mechanism of action. Standardized liquid chromatography-mass spectrometry (LC-MS) was used to detect the presence of active components in TCW. Male Wistar rats were exposed to acute HS with or without TCW treatment to evaluate the degree of testicular damage, which was monitored through histological as well as biochemical analysis. Assessment of endogenous antioxidant response and the modulation of signaling pathways associated with inflammation were also subjected to immunofluorescence and flow cytometric evaluation. Acute hyperthermia caused an elevation of excess generation of oxygen radicals following the suppression of antioxidant capacity and augmentation of lipid peroxidation in murine testicles, which was restored by treatment with TCW. The results also demonstrated marked phosphorylation of IKKα/ß and IκBα following the activation of NF-κB-guided pro-inflammation upon HS. TCW treatment reversed the HS-induced proinflammatory state through activation of the Nrf2-assisted antioxidant response, which restored the testicular damage. TCW provided competent scientific evidence to substantiate the claims for its use in the treatment of HS-induced inflammation and inflammation-mediated testicular damage.

Heat stress-induced hepatotoxicity and its prevention by resveratrol in rats.

The high ambient temperature beyond the range of comfort zone or thermoneutral zone causes environmental heat stress (HST). It causes serious physiological dysfunction that may result in heat-related diseases and even death. The underlying mechanism in the pathogenesis of hepatic dysfunction following hyperthermic challenge and the possible involvement of oxidative stress to induce oxidative deterioration of liver functions in adult rats are investigated in this study. Cellular damage was assessed in terms of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histology of liver. The effect of hyperthermia in altering the oxidative stress was evaluated on the basis of its influence on hepatic lipid peroxidation and antioxidant status-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity. The current study demonstrated that HST is associated with a complex set of integrated alterations in liver, time-dependent rise in oxidative stress followed by distinct pattern of liver injury in animals. Heat-induced hepatotoxicity was assessed by increased lipid peroxidation, depletion of antioxidant enzyme activities such as SOD, CAT, GPx and tissue damages revealed by hepatic vacuolization, and widespread necrosis. The study also revealed that pretreatment with resveratrol resulted in normalizing these parameters appreciably, emphasizing the therapeutic potentials of this polyphenol. Taken together, the results suggest that an increase in free radical formation relative to loss of the antioxidant defense system during heat stress may render liver more susceptible to oxidative damage, leading to their functional inactivation. However, resveratrol supplementation can be an effective antidote in the treatment of HST-induced malfunction.