Comparison of the effect of two recruitment manoeuvres to conventional ventilation on lung atelectasis in paediatric laparoscopic surgery- a prospective randomised controlled trial.

BACKGROUND: There is a high incidence of pulmonary atelectasis during paediatric laparoscopic surgeries. The authors hypothesised that utilising a recruitment manoeuvre or using continuous positive airway pressure may prevent atelectasis compared to conventional ventilation. OBJECTIVE: The primary objective was to compare the degree of lung atelectasis diagnosed by lung ultrasound (LUS) using three different ventilation techniques in children undergoing laparoscopic surgeries. DESIGN: Randomised, prospective three-arm trial. SETTING: Single institute, tertiary care, teaching hospital. PATIENTS: Children of ASA PS 1 and 2 up to the age of 10 years undergoing laparoscopic surgery with pneumoperitoneum lasting for more than 30 min. INTERVENTION: Random allocation to one of the three study groups: CG group: Inspiratory pressure adjusted to achieve a TV of 5-8 ml/kg, PEEP of 5 cm H2O, respiratory rate adjusted to maintain end-tidal carbon dioxide (ETCO2) between 30-40 mm Hg with manual ventilation and no PEEP at induction. RM group: A recruitment manoeuvre of providing a constant pressure of 30 cm H2O for ten seconds following intubation was applied. A PEEP of 10 cm H2O was maintained intraoperatively. CPAP group: Intraoperative maintenance with PEEP 10 cm H2O with CPAP of 10 cm H2O at induction using mechanical ventilation was done. OUTCOME MEASURES: Lung atelectasis score at closure assessed by LUS. RESULTS: Post induction, LUS was comparable in all three groups. At the time of closure, the LUS for the RM group (8.6 ± 4.9) and the CPAP group (8.8 ± 6.8) were significantly lower (p < 0.05) than the CG group (13.3 ± 3.8). In CG and CPAP groups, the score at closure was significantly higher than post-induction. The PaO2/FiO2 ratio was significantly higher (p < 0.05) for the RM group (437.1 ± 44.9) and CPAP group (421.6 ± 57.5) than the CG group (361.3 ± 59.4) at the time of pneumoperitoneum. CONCLUSION: Application of a recruitment manoeuvre post-intubation or CPAP during induction and maintenance with a high PEEP leads to less atelectasis than conventional ventilation during laparoscopic surgery in paediatric patients. TRIAL REGISTRY: CTRI/2019/08/02058.

Role of preoperative zinc, magnesium and budesonide gargles in Postoperative Sore Throat (POST) - a randomised control trial.

BACKGROUND: Post-operative sore throat (POST) has an incidence ranging from 21 to 80%. To prevent the development of POST, several pharmacological measures have been tried. Aim of this study was to compare the efficacy of preoperative zinc, magnesium and budesonide gargles in reducing the incidence and severity of POST in patients who underwent endotracheal intubation for elective surgeries. METHODS: We conducted a prospective, randomized, double-blind, controlled equivalence trial in 180 patients admitted for elective surgical procedures under general anaesthesia. Patients were randomised into three groups; group Z received 40 mg Zinc, group M received 250 mg Magnesium Sulphate and group B received 200 µg Budesonide in the form of 30 ml tasteless and colourless gargle solutions. Sore throat assessment and haemodynamic recording was done postoperatively at immediate recovery (0 h) and 2, 4, 6, 8, 12 and 24 h post-operatively. POST was graded on a four-point scale (0-3). RESULTS: POST score was comparable at all recorded time points i.e. 0,2,4,6,8,12 and 24 h. Maximum incidence was seen at 8 h in group B (33.3%) and the minimum incidence was at 24 h in group Z (10%) (p > 0.05). It was found that the incidence of POST was more in the surgeries lasting longer than 2 h in all groups. This difference was found to be statistically significant in Groups M and B. The incidence of POST was found to be comparable between laparoscopic and open procedures. CONCLUSION: Magnesium, zinc and budesonide have an equivocal effect in the prevention of POST at different time points. The incidence of sore throat increases significantly in surgeries lasting more than two hours if magnesium or budesonide have been used as premedicant. Duration of surgery is an independent predictor for POST. TRIAL REGISTRATION: CTRI/2021/05/033741 Date-24/05/2021(Clinical Trial Registry of India).

A mathematical framework for analysing particle flow in a network with multiple pools.

In many real-world systems, the entry rate of particles into a lane is affected by the occupancy of nearby pools. For instance, in biological networks, the concentration of molecules on the side of a membrane affects the entry of particles through the membrane. To understand the behaviour of such networks, we develop a network model of ribosome flow models (RFMs) having multiple pools where each RFM captures the dynamics of particle flow in a lane and competes for the finite resources present at the nearby pool. We study a ribosome flow model network with two pools (RFMNTP) and show that the network always admits a steady state. We then analyse the behaviour of the RFMNTP with respect to modifying the transition rate through a theoretical framework. Simulations of the RFMNTP demonstrate a counterintuitive result. For example, increasing any of the transition rates in the presence of a slow site in an RFM can increase the output rate of some RFMs and decrease the output rate of the other RFMs simultaneously. This suggests that the role of local sharing of particles incorporated is non-trivial. Finally, we illustrate how these results can provide insights into studying a network with multiple pools.

The Clinical Implications of KRAS Mutations and Variant Allele Frequencies in Pancreatic Ductal Adenocarcinoma.

The KRAS proto-oncogene is a major driver of pancreatic tumorigenesis and is nearly ubiquitously mutated in pancreatic ductal adenocarcinoma (PDAC). KRAS point mutations are detected in over 90% of PDAC cases, and these mutations have been shown to be associated with worse therapy response and overall survival. Pathogenic KRAS mutations are mostly limited to codons 12, 13 and 61, with G12D, G12V, G12R, Q61H, and G13D accounting for approximately 95% of the mutant cases. Emerging data have shown the importance of specific mutant subtypes, as well as KRAS variant allele frequency on clinical prognosis. Furthermore, novel technologies and therapies are being developed to target specific mutant subtypes, with encouraging early results. In this paper, we aim to review the recent studies regarding the relative impact of specific mutant KRAS subtypes on oncologic outcomes, the application of variant allele frequency in next generation sequencing analyses, and the ongoing research into therapies targeting specific mutant KRAS subtypes.

A Randomized, Double-Blind, Parallel-Group Phase III Trial Investigating the Glycemic Efficacy and Safety Profile of Fixed-Dose Combination Dapagliflozin and Linagliptin Over Linagliptin Monotherapy in Patients with Inadequately Controlled Type 2 Diabetes with Metformin.

INTRODUCTION: The aim of the study was to evaluate the efficacy and safety of fixed-dose combination (FDC) of dapagliflozin (10 mg) and linagliptin (5 mg) in comparison to linagliptin 5 mg (Trajenta) in patients with insufficiently controlled type 2 diabetes mellitus (T2DM) on metformin monotherapy. METHODS: The double-blind, randomized, multicentric, parallel-group phase III trial screened 287 adult patients with T2DM (age 18-65 years) from 16 sites across India. The recruited subjects were undergoing metformin monotherapy ≥ 1000 mg/day for at least 28 days. Patients with HbA1c of 7.5-10.5% (58-91 mmol/l) (n = 232) after 2 weeks of run-in period with linagliptin monotherapy and placebo dapagliflozin/linagliptin on metformin monotherapy were randomized (1:1) in parallel to once daily dapagliflozin/linagliptin 10/5 mg or linagliptin 5 mg for 16 weeks. Patients were stratified on the basis of HbA1c (≤ 9.0% and > 9.0%; ≤ 75 mmol/l and > 75 mmol/l)). A total of 225 subjects completed 16 weeks of treatment, 115 patients in the test group and 110 patients in the reference group. RESULTS: Dapagliflozin/linagliptin (p = 0.0003) exhibited a greater change in HbA1c from baseline than linagliptin (p < 0.0001) in 16 weeks (mean reduction, - 1.28% vs - 0.83%). Test group showed a significant decrease in fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and body weight compared to the reference group. The FDC was well tolerated with adverse events being more frequent in the reference group. No serious adverse events (SAEs) were reported in the study. CONCLUSION: Dapagliflozin/linagliptin combination is a novel dipeptidyl peptidase 4 (DPP4)/sodium-glucose co-transporter 2 (SGLT2) inhibitor FDC approved in India for patients with T2DM. Potential limitations of this study are a small dose of dapagliflozin (10 mg) in the FDC, a short study duration (30 weeks) and a high minimum threshold for HbA1c (≤ 7.5%; ≤ 53 mmol/l). Results indicate the FDC to be a superior therapeutic option over linagliptin for patients with T2DM on metformin monotherapy. TRIAL REGISTRATION: CTRI/2022/08/044563; 01/08/2022.

Essential Role of Anisotropy in Bioengineered Cardiac Tissue Models.

As regulatory bodies encourage alternatives to animal testing, there is renewed interest in engineering disease models, particularly for cardiac tissues. The aligned organization of cells in the mammalian heart controls the electrical and ionic currents and its ability to efficiently circulate blood to the body. Although the development of engineered cardiac systems is rising, insights into the topographical aspects, in particular, the necessity to design in vitro cardiac models incorporating cues for unidirectional cell growth, is lacking. This review first summarizes the widely used methods to organize cardiomyocytes (CMs) unidirectionally and the ways to quantify the resulting cellular alignment. The behavior of CMs in response to alignment is described, with emphasis on their functions and underlying mechanisms. Lastly, the limitations of state-of-the-art techniques to modulate CM alignment in vitro and opportunities for further development in the future to improve the cardiac tissue models that more faithfully mimic the pathophysiological hallmarks are outlined. This review serves as a call to action for bioengineers to delve deeper into the in vivo role of cellular organization in cardiac muscle tissue and draw inspiration to effectively mimic in vitro for engineering reliable disease models.

MIR159 regulates multiple aspects of stamen and carpel development and requires dissection and delimitation of differential downstream regulatory network for manipulating fertility traits.

Unravelling genetic networks regulating developmental programs are key to devising and implementing genomics assisted trait modification strategies. It is crucial to understand the role of small RNAs, and the basis of their ability to modify traits. MIR159 has been previously reported to cause defects in anther development in Arabidopsis; however, the complete spectrum and basis of the defects remained unclear. The present study was therefore undertaken to comprehensively investigate the role of miR159 from Brassica juncea in modulating vegetative and reproductive traits. Owing to the polyploid nature of Brassica, paralogous and homeologous copies of MIR159A, MIR159B, and, MIR159C were identified and analysis of the precursor uncovered extensive structural and sequence variation. The MIR159 locus with mature miR159 with perfect target complimentarily with MYB65, was cloned from Brassica juncea var. Varuna for functional characterization by generating constitutively over-expressing lines in Arabidopsis thaliana Col-0. Apart from statistically significant difference in multiple vegetative traits, drastic differences were observed in stamen and pistil. Over-expression of miR159a led to shortening of filament length and loss of tetradynamous condition. Anthers were apiculate, with improper lobe formation, and unsynchronized cellular growth between connective tissue and another lobe development. Analysis revealed arrested meiosis/cytokinesis in microspores, and altered lignin deposition pattern in endothecial walls thus affecting anther dehiscence. In the gynoecium, flaccid, dry stigmatic papillae, and large embryo sac in the female gametophyte was observed. Over-expression of miR159a thus severely affected pollination and seed-set. Analysis of the transcriptome data revealed components of regulatory networks of anther and carpel developmental pathway, and lignin metabolism that are affected. Expression analysis allowed us to position the miR159a-MYB65 module in the genetic network of stamen development, involved in pollen-grain maturation; in GA-mediated regulation of stamen development, and in lignin metabolism. The study, on one hand indicates role of miR159a-MYB65 in regulating multiple aspects of reproductive organ development that can be manipulated for trait modification, but also raises several unaddressed questions such as relationship between miR159a and male-meiosis, miR159a and filament elongation for future investigations. Accession numbers: KC204951-KC204960. Project number PRJNA1035268. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01377-7.

Recent advances and future directions in etiopathogenesis and mechanisms of reactive oxygen species in cancer treatment.

A class of exceptionally bioactive molecules known as reactive oxygen species (ROS) have been widely studied in the context of cancer. They play a significant role in the etiopathogenesis for cancer. Implication of ROS in cancer biology is an evolving area, considering the recent advances; insights into their generation, role of genomic and epigenetic regulators for ROS, earlier thought to be a chemical process, with interrelations with cell death pathways- Apoptosis, ferroptosis, necroptosis and autophagy has been explored for newer targets that shift the balance of ROS towards cancer cell death. ROS are signal transducers that induce angiogenesis, invasion, cell migration, and proliferation at low to moderate concentrations and are considered normal by-products of a range of biological activities. Although ROS is known to exist in the oncology domain since time immemorial, its excessive quantities are known to damage organelles, membranes, lipids, proteins, and nucleic acids, resulting in cell death. In the last two decades, numerous studies have demonstrated immunotherapies and other anticancer treatments that modulate ROS levels have promising in vitro and in vivo effects. This review also explores recent targets for therapeutic interventions in cancer that are based on ROS generation or inhibition to disrupt the cell oxidative stress balance. Examples include-metabolic targets, targeted therapy with biomarkers, natural extracts and nutraceuticals and targets developed in the area of nano medicine. In this review, we present the molecular pathways which can be used to create therapy plans that target cancer by regulating ROS levels, particularly current developments and potential prospects for the effective implementation of ROS-mediated therapies in clinical settings. The recent advances in complex interaction with apoptosis especially ferroptosis and its role in epigenomics and modifications are a new paradigm, to just mechanical action of ROS, as highlighted in this review. Their inhibition by nutraceuticals and natural extracts has been a scientific challenging avenue that is explored. Also, the inhibition of generation of ROS by inhibitors, immune modulators and inhibitors of apoptosis and ferroptosis is explored in this review.

How Not To Fix a Tibial Fracture: A Case Report on Treatment By a Quack.

Quackery in the orthopaedic profession has existed for quite a long time. Due to the shortage of orthopaedic healthcare staff in public hospitals and the high costs in private facilities, members of disadvantaged communities turn to unlicensed and unskilled practitioners (quacks). The main factors responsible for the increased number of quacks performing orthopaedic treatment are illiteracy, high treatment cost, mismatch in the orthopaedic surgeon-to-population ratio, especially in rural areas, and the absence of any form of health insurance. Moreover, their easy availability and offer of low-cost treatment draw innocent and illiterate patients to them, even though these quacks perform orthopaedic treatment in the most unhygienic, unsterilized, and unconventional manner. The government should intervene and take measures to make orthopaedic treatment more affordable and accessible, especially to the rural population.

Deletion of the mRNA stability factor ELAVL1 (HuR) in pancreatic cancer cells disrupts the tumor microenvironment integrity.

Stromal cells promote extensive fibrosis in pancreatic ductal adenocarcinoma (PDAC), which is associated with poor prognosis and therapeutic resistance. We report here for the first time that loss of the RNA-binding protein human antigen R (HuR, ELAVL1) in PDAC cells leads to reprogramming of the tumor microenvironment. In multiple in vivo models, CRISPR deletion of ELAVL1 in PDAC cells resulted in a decrease of collagen deposition, accompanied by a decrease of stromal markers (i.e. podoplanin, α-smooth muscle actin, desmin). RNA-sequencing data showed that HuR plays a role in cell-cell communication. Accordingly, cytokine arrays identified that HuR regulates the secretion of signaling molecules involved in stromal activation and extracellular matrix organization [i.e. platelet-derived growth factor AA (PDGFAA) and pentraxin 3]. Ribonucleoprotein immunoprecipitation analysis and transcription inhibition studies validated PDGFA mRNA as a novel HuR target. These data suggest that tumor-intrinsic HuR supports extrinsic activation of the stroma to produce collagen and desmoplasia through regulating signaling molecules (e.g. PDGFAA). HuR-deficient PDAC in vivo tumors with an altered tumor microenvironment are more sensitive to the standard of care gemcitabine, as compared to HuR-proficient tumors. Taken together, we identified a novel role of tumor-intrinsic HuR in its ability to modify the surrounding tumor microenvironment and regulate PDGFAA.

A Novel 3DNA® Nanocarrier effectively delivers payloads to pancreatic tumors.

INTRODUCTION: Standard-of-care systemic chemotherapies for pancreatic ductal adenocarcinoma (PDAC) currently have limited clinical benefits, in addition to causing adverse side effects in many patients. One factor known to contribute to the poor chemotherapy response is the poor drug diffusion into PDAC tumors. Novel treatment methods are therefore drastically needed to improve targeted delivery of treatments. Here, we evaluated the efficacy of the 3DNA® Nanocarrier (3DNA) platform to direct delivery of therapeutics to PDAC tumors in vivo. MATERIALS AND METHODS: A panel of PDAC cell lines and a patient tissue microarray were screened for established tumor-specific proteins to identify targeting moieties for active targeting of the 3DNA. NRG mice with or without orthotopic MIA PaCa-2-luciferase PDAC tumors were treated intraperitoneally with 100 µl of fluorescently labeled 3DNA. RESULTS: Folic acid and transferrin receptors were significantly elevated in PDAC compared to normal pancreas. Accordingly, both folic acid- and transferrin-conjugated 3DNA treatments significantly increased delivery of 3DNA specifically to tumors in comparison to unconjugated 3DNA treatment. In the absence of tumors, there was an increased clearance of both folic acid-conjugated 3DNA and unconjugated 3DNA, compared to the clearance rate in tumor-bearing mice. Lastly, delivery of siLuciferase by folic acid-conjugated 3DNA in an orthotopic model of luciferase-expressing PDAC showed significant and prolonged suppression of luciferase protein expression and activity. CONCLUSION: Our study progresses the 3DNA technology as a reliable and effective treatment delivery platform for targeted therapeutic approaches in PDAC.

Mitochondrial calcium uniporter b deletion inhibits platelet function and reduces susceptibility to arterial thrombosis.

BACKGROUND: Mitochondrial calcium uniporter b (MCUb) is a negative regulator of the mitochondrial calcium uniporter (MCU) and is known to limit mitochondrial calcium ion (Ca2+) uptake. The role of MCUb in platelet function remains unclear. OBJECTIVES: Utilizing MCUb-/- mice, we examined the role of MCUb in regulating platelet function and thrombosis. METHODS: Platelet activation was evaluated in agonist-induced standardized in vitro assays. Susceptibility to arterial thrombosis was evaluated in FeCl3 injury-induced carotid artery and laser injury-induced mesenteric artery thrombosis models. The glycolytic proton efflux rate and oxygen consumption rate were measured to evaluate aerobic glycolysis. RESULTS: Upon stimulation, MCUb-/- platelets exhibited reduced cytoplasmic Ca2+ responses concomitant with increased mitochondrial Ca2+ uptake. MCUb-/- platelets displayed reduced agonist-induced platelet aggregation and spreading on fibrinogen and decreased α and dense-granule secretion and clot retraction. MCUb-/- mice were less susceptible to arterial thrombosis in FeCl3 injury-induced carotid and laser injury-induced mesenteric thrombosis models with unaltered tail bleeding time. In adoptive transfer experiments, thrombocytopenic hIL-4Rα/GPIbα-transgenic mice transfused with MCUb-/- platelets were less susceptible to FeCl3 injury-induced carotid thrombosis compared with hIL-4Rα/GPIbα-Tg mice transfused with wild type platelets, suggesting a platelet-specific role of MCUb in thrombosis. MCUb-/- stimulated platelets exhibited reduced glucose uptake, decreased glycolytic rate, and lowered pyruvate dehydrogenase phosphorylation, suggesting that mitochondrial Ca2+ mediates bioenergetic changes in platelets. CONCLUSION: Our findings suggest that mitochondrial Ca2+ signaling and glucose oxidation are functionally linked in activated platelets and reveal a novel role of MCUb in platelet activation and arterial thrombosis.

Assessment of residual gastric volume using point-of-care ultrasonography in adult patients who underwent elective surgery.

BACKGROUND: Aspiration pneumonitis remains a dreaded complication that may lead to almost 9% of anaesthesia-related deaths. The presence of gastric contents has always been a contributing factor to an increased risk of aspiration. Preoperative gastric ultrasound has been suggested as a modality for determining residual volume in special populations and conditions. We conducted an observational study to determine the gastric residual volume in preoperative patients of elective surgery with gastric ultrasound and to study its correlation with patient factors. METHODS: We enrolled 411 patients in the age group of 18-80 with ASA-PS I and II having BMI less than 35 kg/m2. Patients with prior gastrointestinal surgery and parturients were excluded from the present study. Gastric antrum in both supine and right lateral decubitus positions was measured using USG in the immediate preoperative period, and gastric residual volume was calculated, which was subsequently correlated with various patient factors. RESULTS: On qualitative assessment, 97 and 118 patients were observed to have distended stomachs in the supine and right lateral decubitus positions, respectively. On quantitative assessment, 336 had safe GRV, 60 patients were classified as having a low risk of aspiration (GRV < 1.5 ml/kg) while 13 had a high risk of aspiration (> 1.5 ml/kg). Eight patients with a fasting duration of more than ten hours and five who fasted between 6 and 10 h had a gastric residual volume of more than 1.5 ml/h. Patients who were premedicated with histamine blockers had a statistically significant higher antral cross-sectional area (p-value - 0.022*) and GRV (p-value - 0.018*) in the right lateral decubitus position compared to patients who had taken proton pump inhibitors (PPIs). As BMI increased, there was a statistically significant (p-value < 0.001) increase in mean antral CSA in both supine and right lateral decubitus positions. There was a statistically significant association found between type 2 diabetes (p-value 0.045*) with antral grade. DISCUSSION: Patients can have significant residual volume (> 1.5 ml/kg) despite adequate fasting, and preoperative gastric ultrasound can help in assessing the same and guiding perioperative airway management. PPIs are more effective in reducing gastric residual volume as compared to histamine blockers. Patients with a BMI of more than 30 and type 2 diabetes mellitus have significant correlation with increased gastric residual volume mandating preoperative gastric ultrasound assessment for effective management. CONCLUSIONS: Patients with BMI over 30 and type 2 diabetes may benefit from POCGUS to guide perioperative airway management by stratifying GRV. Trial registration Name of registry-Clinical Trial Registry of India. Trial registration number-2020/03/024083. Date of registration-19.3.2020. URL- http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=39961&EncHid=&userName=.

Cross-cultural Adaptation and Validation of Hindi Version of Roland Morris Disability Questionnaire for Chronic Low Back Pain in Indian Population.

STUDY DESIGN: A cross-cultural adaptation, validation, and psychometric analysis. OBJECTIVE: The main aim was to assess the validity and reliability of the Hindi version of the Roland Morris Disability Questionnaire (Hi-RMDQ) for chronic low back pain. SUMMARY OF BACKGROUND DATA: Roland Morris Disability Questionnaire is a standardized, self-administered tool for disability assessment in patients with chronic low back pain. However, its Hindi version has not been validated. MATERIALS AND METHODS: Cognitive debriefing was carried out with 10 patients to ensure the comprehensibility of the Hi-RMDQ. Following this, 120 patients were asked to complete the finalized questionnaire along with the modified Oswestry Disability Index Questionnaire, Quebec Back Pain Disability Score, and the Verbal Numeric Rating Scale. The patients were then asked to again fill out the finalized questionnaire after 72 hours. The internal consistency and retest reliability of the Hindi translated version of the questionnaire was tested. Its correlation with the other scores was also analyzed. RESULTS: The translated questionnaire showed excellent internal consistency (Cronbach α=0.989) and excellent retest reliability (intraclass correlation coefficient=0.978). There was a positive and statistically significant association between the Hi-RMDQ, modified Oswestry Disability Index Questionnaire ( r =0.807; P <0.01), Quebec Back Pain Disability Score ( r =0.839; P <0.01), and Verbal Numeric Rating Scale ( r =0.713; P <0.01). CONCLUSION: The Hi-RMDQ version is an easy-to-use, acceptable, reliable, and valid tool to measure disability in the Indian population with nonspecific back pain with or without leg pain. LEVEL OF EVIDENCE: 3.

Modeling mRNA Translation With Ribosome Abortions.

We derive a deterministic mathematical model for the flow of ribosomes along a mRNA called the ribosome flow model with extended objects and abortions (RFMEOA). This model incorporates important cellular features such as every ribosome covers several codons and they may detach from various regions along the track due to more realistic biological situations including phenomena of ribosome-ribosome collisions. We prove that the ribosome density profile along the mRNA in the RFMEOA and in particular, the protein production rate converge to a unique steady-state. Simulations of the RFMEOA demonstrate a surprising result that an increase in the initiation rate may sometimes lead to a decrease in the production rate. We believe that this model could be helpful to provide insight into the effects of premature termination on the protein expression and be useful for understanding and re-engineering the translation process.

Early prognosis prediction in acute myeloid and acute lymphoid leukemia patients using cell-free DNA concentration ratios.

Background: Cell-free DNA (cfDNA) is a promising biomarker for disease prediction in many cancers, including acute leukemia (acute myeloid leukemia [AML] and acute lymphoblastic leukemia [ALL]). This study investigated the role of cfDNA in predicting relapse or unfavorable outcomes in acute leukemia patients upon initial diagnosis. Methods: Paired peripheral blood samples of 25 patients with ALL and AML were compared at baseline and induction/follow-up and clinically correlated with clinicopathological and outcome variables according to the risk category. cfDNA was isolated using commercial cfDNA extraction kits. The probability of poor outcomes in high-risk groups and a cut-off value for risk stratification minimal residual disease (MRD) positivity and outcome prediction were derived. Results: Twenty-five patients diagnosed with AML and ALL were risk-stratified based on NCI risk stratification, and of these 25 patients, 4 patients were of standard risk (SR) and 1 patient was of intermediate risk (IR), while a majority of patients (80%) were of high risk (HR). Of these, four HR patients passed away. The ratio of cfDNA reduction at baseline and the end of induction was a strong predictor of poor outcomes in high-risk patients, regardless of the MRD status. A cfDNA ratio score of 2.6 or higher at diagnosis/remission predicted poor outcomes, with higher accuracy than conventional MRD detection by flow cytometry. Conclusion: A higher cfDNA ratio at diagnosis/remission or at baseline predicts poor outcomes in acute leukemia patients. This pilot study suggests that cfDNA ratio scoring may be a useful tool for predicting prognosis in acute leukemia patients, regardless of the MRD status.

Correlates of loneliness and dissatisfaction following SARS pandemic lockdown: Child and parent perspective.

Background Studying loneliness among children is important because it causes much social pain and is considered to be a risk factor for many mental and physical problems. Methods We did an online survey between July and September 2020 among students and their parents from a cluster of government and private schools chosen from north, south, east and west of Chandigarh. The survey consisted of child and parent versions of the Loneliness and Social Dissatisfaction Questionnaire, Parent-Child Relationship (PCR) Questionnaire and Conflict Behaviour Questionnaire SF. Parental distress was assessed using the Depression, Anxiety and Stress Scale-21. Results The majority of children and parent participants reported high loneliness and dissatisfaction among children. A significant positive association was found between children and parent reported loneliness and dissatisfaction, and between child reported PCR and parent perception of PCR. A child's appraisal of her loneliness had a significant negative association with depression among parents. Parent's perception of child loneliness and dissatisfaction was negatively associated with PCR and parental anxiety. High loner boys reported poor quality of relationship and more conflicts with their parents than girls. Children who share cordial relations with their parents had fewer conflicts and also scored low on loneliness. Conclusion These results suggest that the issue of loneliness and dissatisfaction among children has attained epidemic proportions in the Covid-19 era, and active interventions are needed to safeguard the mental health of children. Our study emphasizes the need to plan guidance strategies with a joint effort of schools and families to strengthen within family relations of children.