Determinants of Readmission in the Intensive Care Unit: A Prospective Observational Study.

Background The antecedents of readmission among survivors of intensive care units (ICUs) are complex and comprise an array of elements that impact the rehabilitation process after leaving the ICU. The aforementioned determinants may comprise socioeconomic factors, access to follow-up healthcare, the nature and severity of the initial illness or injury, the presence of comorbidities, the sufficiency of transitional care and rehabilitation services, and patient and family support systems. Added to this, the risk of readmission may be increased by complications that develop during the ICU stay, including but not limited to infections, organ dysfunction, and psychological distress. Comprehending these determinants is of the utmost importance for healthcare providers in order to execute focused interventions that seek to diminish readmission rates, enhance patient outcomes, and elevate the standard of care for survivors of ICUs. Objective The objective of the study is to determine the factors associated with readmission among ICU survivors and the cause of readmission. Methodology This prospective observational study was conducted in a tertiary-level ICU. The duration of the study was one year and we enrolled 108 ICU survivors in our study. We have recorded patient demographic data, comorbidity, primary diagnosis, previous treatment history (vasopressor, sedation), causes of readmission, duration of previous ICU stay, and outcome of readmitted patient (discharge, death, and transfer to lower facility). Result The incidence of readmission in our ICU is 10.4%; 50-70 age groups are more prone to readmission of which the male sex is predominant (64.81%). In our study, hypertension (cardiac, 18.52%) and diabetes mellitus (11.11%) were the most common comorbidities reported in readmitted patients. The majority of patients who get readmission suffered from blunt trauma abdomen. In the majority of readmitted patients, sedation was used in the previous admission for ventilation and patient comfort (66.67%). Most of the readmitted patients (68.51%) have a previous ICU stay of more than five days. Patients were readmitted mainly because of respiratory (30.56%) and neurological (25%) complications. In this study, readmitted patients have high mortality (59.26%). Conclusion In a tertiary care ICU, the incidence rate of readmitted patients was 10.4%. Respiratory and neurological problems were the main cause of readmission. In readmitted patients, mortality was high up to 59.26%. Old age, male sex, prolonged ICU stay, comorbidities like hypertension, blunt trauma abdomen, use of sedation, and prolonged mechanical ventilation in previous ICU admission are major risk factors for ICU readmission.

Discovery of D8-03 as an Inhibitor of Intracellular Growth of Francisella tularensis.

Francisella tularensis is a Gram-negative facultative intracellular bacterial pathogen that is classified by the Centers for Disease Control and Prevention as a Tier 1 Select Agent. F. tularensis infection causes the disease tularemia, also known as rabbit fever. Treatment of tularemia is limited to few effective antibiotics which are associated with high relapse rates, toxicity, and potential emergence of antibiotic-resistant strains. Consequently, new therapeutic options for tularemia are needed. Through screening a focused chemical library and subsequent structure-activity relationship studies, we have discovered a new and potent inhibitor of intracellular growth of Francisella tularensis, D8-03. Importantly, D8-03 effectively reduces bacterial burden in mice infected with F. tularensis. Preliminary mechanistic investigations suggest that D8-03 works through a potentially novel host-dependent mechanism and serves as a promising lead compound for further development.

Prevalence and clinicopathological features of driver gene mutations profile in BCR: ABL1 negative classical myeloproliferative neoplasm-A single-center study from North India.

BACKGROUND: Recurrent somatic mutations in the JAK2, CALR, and the MPL genes are noted in BCR: ABL1 negative classic myeloproliferative neoplasms (MPN) that includes polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). MATERIALS AND METHODS: Mutation profile and clinical features of MPN cases diagnosed at a tertiary care center in North India are being described. JAK2V617F mutation was screened using ARMS PCR, and CALR mutation was screened using allele-specific PCR followed by fragment analysis. MPL and JAK2 Exon 12 mutations were screened by Sanger sequencing. Some of the samples were also screened using commercial kits based on single-plex RT PCR. RESULTS: A total of 378 cases (including 124 PV, 121 ET, and 133 PMF cases) were screened over 6.5 years. JAK2V617F mutation was noted in 90.3%, 61.1%, and 69.2% of cases of PV, ET, and PMF, respectively. In PV, JAK2V617F wild-type cases were associated with a significantly lower age (44 yrs vs 54 yrs; P = 0.001), lower TLC (6.3 vs 16.9; P = 0.001), and a lower platelet count (188 × 109/L vs 435 × 109/L; P = 0.009) as compared to the JAK2V617F mutated cases. CALR and MPL mutations were noted in 17.4% and 12% and 0.8% and 5.3% of ET and PMF cases, respectively. Type 1 CALR mutations were commoner in both ET and PMF. The triple negative cases constituted 20.7% and 13.5% cases of ET and PMF, respectively. In ET, the triple negative cases were found to have a significantly lower median age of presentation (42 yrs vs 52 yrs; P = 0.001), lower median TLC (10.2 × 109/L vs 13.2 × 109/L; P = 0.024), and a higher median platelet count (1238 × 109/L vs 906 × 109/L; P = 0.001) as compared to driver genes mutated cases. In PMF, the triple negative cases were found to have a significantly lower hemoglobin level (7.9 g/dl vs 11.0 gl/dl; P = 0.001) and a significant female preponderance (P = 0.05) as compared to the mutated cases. CALR mutations were found to have a significantly lower median age (43 yrs vs 56 yrs; P = 0.001) and lower hemoglobin (9.6 g/dl vs 11.3 g/dl) as compared to the JAK2 mutations. CONCLUSION: Our data on the driver gene mutational profile of BCR: ABL1 negative MPN is one of the largest patient cohorts. The prevalence and clinicopathological features corroborate with that of other Asian studies.

Peripheral blood quantitation of CD26 positive leukemic stem cells as a predictor of tyrosine kinase inhibitor response in chronic myeloid leukemia.

INTRODUCTION: Leukemic stem cells (LSCs) are the transcriptionally low/silent cells which are resistant to the tyrosine kinase inhibitor. These have been found to play a pivotal role in disease relapse in chronic myeloid leukemia (CML) cases. The present study evaluated the correlation of absolute CML-LSC count in the peripheral blood (PB) at diagnosis and achievement of major molecular response (MMR) at 12 months in patients of CML-CP. METHODS: This was a prospective, observational, non-interventional single center study including newly diagnosed adult (>18 yrs) CML-CP patients. Absolute CD26 + CML-LSC quantification was done by multiparametric flow cytometry. Patients were treated with Imatinib treatment and subsequently monitored at 3-month intervals for BCR::ABL transcript levels. MMR was defined as a BCR::ABL1 transcript level of less than 0.1% on international scale. RESULTS: A total of 89 patients were enrolled in the study out of which 40.5% achieved MMR at 12 months. There was a significant difference in the median absolute CML-LSC count of the patients who achieved MMR at 12 months as compared to those who did not (58.5 vs 368.1 cells/µL; p value <0.001). Using a ROC analysis, a count of <165.69 CML LSC/µL was identified to have a sensitivity of 83.8% and specificity of 72.4%, in predicting the MMR at 12 months. CONCLUSION: Absolute CML-LSC count at diagnosis in the PB predicts the MMR achievement at 12 months. An absolute count of less than 165 cells/µL is highly predictive of achieving MMR at 12 months.

Mitofusin-mediated contacts between mitochondria and peroxisomes regulate mitochondrial fusion.

Mitofusins are large GTPases that trigger fusion of mitochondrial outer membranes. Similarly to the human mitofusin Mfn2, which also tethers mitochondria to the endoplasmic reticulum (ER), the yeast mitofusin Fzo1 stimulates contacts between Peroxisomes and Mitochondria when overexpressed. Yet, the physiological significance and function of these "PerMit" contacts remain unknown. Here, we demonstrate that Fzo1 naturally localizes to peroxisomes and promotes PerMit contacts in physiological conditions. These contacts are regulated through co-modulation of Fzo1 levels by the ubiquitin-proteasome system (UPS) and by the desaturation status of fatty acids (FAs). Contacts decrease under low FA desaturation but reach a maximum during high FA desaturation. High-throughput genetic screening combined with high-resolution cellular imaging reveal that Fzo1-mediated PerMit contacts favor the transit of peroxisomal citrate into mitochondria. In turn, citrate enters the TCA cycle to stimulate the mitochondrial membrane potential and maintain efficient mitochondrial fusion upon high FA desaturation. These findings thus unravel a mechanism by which inter-organelle contacts safeguard mitochondrial fusion.

Efficacy of ShotBlocker device versus vapocoolant spray for spinal needle pain relief during spinal anaesthesia in elective caesarean section - A randomised controlled trial.

Background and Aims: Apprehension of pain due to a spinal needle is often a cause of anxiety and refusal. ShotBlocker provides non-painful physical stimulation, inhibiting pain perception. The vapocoolant spray contains ethyl chloride vapours, rapidly raising the skin temperature and hampering the transmission of noxious stimuli. The present study compared the effectiveness of the ShotBlocker device and the vapocoolant spray in reducing spinal needle-associated pain in primigravida women undergoing elective lower-segment caesarean section (LSCS). Methods: We enroled 144 primigravida women undergoing elective LSCS and were randomised to Group SB (the ShotBlocker device was firmly pressed over the skin, and the spinal needle was inserted through its slit), Group V (the vapocoolant spray was applied at the puncture site before spinal needle insertion), and Group C (received local infiltration before spinal anaesthesia (SA)). The groups were compared for needle-associated pain and patient satisfaction using a 10-point visual analogue scale (VAS) and a 3-point Likert scale. Results: The mean (standard deviation) [95% confidence interval (CI)] VAS scores of Group SB 3.85 (0.74) [3.64, 4.07] and Group V 3.04 (0.74) [2.83, 3.26] were significantly lower than that of Group C 5.19 (0.92) [3.28, 3.62]). On the Likert scale, the maximum number of patients in the vapocoolant group (64.6%) responded satisfactorily, while in the control group, the majority (62.5%) of participants responded dissatisfied (P < 0.001). Conclusion: Both the ShotBlocker and vapocoolant spray reduce needle puncture-associated pain before SA in primigravida patients undergoing elective LSCS. However, the vapocoolant spray is more beneficial in reducing spinal needle-associated pain than the ShotBlocker device.

Efficacy of Infraclavicular Brachial Plexus Block Alone Versus Combination With Suprascapular Nerve Block in Patients Undergoing Shoulder Surgeries: A Single-Blind, Randomized Trial.

Background and aim The regional anesthesia technique is commonly used for upper extremity surgery as an alternative to general anesthesia. The study aimed to compare the efficacy of infraclavicular brachial plexus block (BPB) and a combination of infraclavicular brachial plexus block with suprascapular nerve block for postoperative analgesia in patients undergoing shoulder surgeries. Method A total of 62 patients of both sexes with the American Society of Anaesthesiologists (ASA) physical status I/II/III, aged between 18 and 65 years, and undergoing shoulder surgery, were included in this prospective, single-blinded, randomized controlled trial. Patients were equally allocated into two groups: 31 in group A and 31 in group B. After pre-anesthetic evaluation, the purpose and protocol of the study were explained to patients, and informed consent was obtained. Thirty-one patients in group A were given infraclavicular brachial plexus block using 30 ml 0.375% bupivacaine while 31 patients in group B were given a combination of infraclavicular brachial plexus block using 30 ml 0.375% bupivacaine and suprascapular nerve block using 5 ml 0.375% bupivacaine. Blocks were given using ultrasound guidance and a peripheral nerve stimulator; the suprascapular block was given in the sitting position while the infraclavicular block was provided in the supine position. General anesthesia was administered in the operation theatre in the supine position after the administration of blocks. The pain was assessed using the visual analog scale (VAS) and the satisfaction score was assessed by the numeric rating scale (NRS). The Mann-Whitney U test was applied for comparison of pain between the two groups. The chi-square test was utilized for comparing the categorical variables. Result The postoperative pain was significantly lower (p<0.001) in group B as compared to group A at all the periods of observation, i.e., 0h (2.77±0.72 vs. 5.42±0.77), 6h (3.89±0.70 vs. 5.94±0.73), 12h (5.66±0.93 vs. 6.58±0.88), and 24h (6.16±0.80 vs. 6.74±0.90). These findings illustrate that group B patients who received a combination of infraclavicular brachial plexus block and suprascapular nerve block for shoulder surgeries had better pain relief than group A patients who received only the infraclavicular approach. The mean NRS score of patient satisfaction in group B (7.26±0.58) was significantly higher (p<0.001) in comparison to group A (6.16±0.64). Diaphragmatic palsy was observed in only one case in group A and none in group B. No other complication was observed in any of the patients during the study period. Conclusion The combination of infraclavicular brachial plexus block and suprascapular nerve block displays a positive postoperative analgesic profile with less usage of rescue analgesic doses and better patient satisfaction after shoulder surgery.

Role of miRNAs in T-cell activation and Th17/Treg-cell imbalance in acquired aplastic anemia.

BACKGROUND: Altered T-cell repertoire with an aberrant T-cell activation and imbalance of the Th17/Treg cells has been reported in acquired aplastic anemia (aAA). miRNAs are well known to orchestrate T-cell activation and differentiation, however, their role in aAA is poorly characterized. The study aimed at identifying the profile of miRNAs likely to be involved in T-cell activation and the Th17/Treg-cell imbalance in aAA, to explore newer therapeutic targets. METHODS: Five milliliters peripheral blood samples from 30 patients of aAA and 15 healthy controls were subjected to flow cytometry for evaluating Th17- and Treg-cell subsets. The differential expression of 7 selected miRNAs viz; hsa-miR-126-3p, miR-146b-5p, miR-155-5p, miR-16, miR-17, miR-326, and miR-181c was evaluated in the PB-MNCs. Expression analysis of the miRNAs was performed using qRT-PCR and fold change was calculated by 2-ΔΔCt method. The alterations in the target genes of deregulated miRNAs were assessed by qRT-PCR. The targets studied included various transcription factors, cytokines, and downstream proteins. RESULTS: The absolute CD3+ lymphocytes were significantly elevated in the PB of aAA patients when compared with healthy controls (p < 0.0035), however, the CD4:CD8 ratio was unperturbed. Th17: Treg-cell ratio was altered in aAA patients (9.1 vs. 3.7%, p value <0.05), which correlated positively with disease severity and the PNH positive aAA. Across all severities of aAA, altered expression of the 07 miRNAs was noted in comparison to controls; upregulation of miR-155 (FC-2.174, p-value-0.0001), miR-146 (FC-2.006, p-value-0.0001), and miR-17 (FC-3.1, p-value-0.0001), and downregulation of miR-126 (FC-0.329, p-value-0.0001), miR-181c (FC-0.317, p-value-0.0001), miR-16 (FC-0.348, p-value-0.0001), and miR-326 (FC-0.334, p-value-0.0001). Target study for these miRNAs revealed an increased expression of transcription factors responsible for Th1 and Th17 differentiation (T-bet, RORϒt, IL-17, IL-6, and IFN-ϒ), T-cell activation (NFκB, MYC, and PIK3R2), downregulation of FOX-P3, and other regulatory downstream molecules like SHIP-1, ETS-1, IRAK-1, TRAF-6, and PTEN. CONCLUSION: The study for the first time highlights the plausible role of different miRNAs in deregulating the Th17/Treg-cell imbalance in aAA, and comprehensively suggest the role of altered NF-kB and mTOR pathways in aAA. The axis may be actively explored for development of newer therapeutic targets in aAA.

Relationship Between Pre- and Post-Operative C-Reactive Protein (CRP), Neutrophil-to-Lymphocyte Ratio (NLR), and Platelet-to-Lymphocyte Ratio (PLR) With Post-Operative Pain After Total Hip and Knee Arthroplasty: An Observational Study.

BACKGROUND: Anesthetic technique and postoperative pain management are crucial for total joint arthroplasty (TJA) patients. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) are new, simple, and cost-effective predictors for prognosis. The predictive value of NLR as an inflammatory marker can predict post-operative pain caused by inflammatory pathways secondary to surgical trauma. CRP is also the most sensitive and specific biomarker of inflammation whereas PLR was also recently considered a possible marker for inflammation which may further contribute to pain and sequelae. Thus, anesthetists can make decisions about the amount, time, and type of analgesic to use based on preoperative values of these parameters to provide maximum postoperative pain control and facilitate early rehabilitation. Thus, the current study was conducted to determine the relationship between CRP, NLR, and PLR levels and the intensity of pain in patients following total hip arthroplasty (THA) and total knee arthroplasty (TKA). MATERIALS AND METHODS: A total of 105 patients scheduled for THA and TKA fulfilling the study's inclusion criteria were enrolled. Inclusion criteria of the study were all the patients giving written consent, ASA Grade I-III, patients between 18 and 90 years who were scheduled for elective lower extremity TJA, and all the patients who remained admitted until stitches were removed. Patients were given intrathecal 15 mg hyperbaric bupivacaine via 25G atraumatic spinal needle in the L3-L4 interspace. The recorded data were demographic characteristics, preexisting comorbidities, number of blood transfusions, and operation time, postoperative analgesics given, duration of hospital stay, time of mobility, pain scoring as per visual analog scale (VAS) scoring system with an aim to establish a relationship between pre- and post-operative (Days 3 & 5) CRP, NLR, and PLR with post-operative pain after THA and TKA. RESULT: The present study demonstrated a significant correlation (p < 0.002) between preoperative and postoperative NLR with pain after TJA whereas PLR and CRP did not show any significant relationship with post-operative pain after THA and TKA. A significantly higher NLR ratio was observed for patients on all the periods of observation (pre-op., Day 3, and Day 5). Pre-op. and Day 5 NLR of patients who required transfusion were significantly higher than those who did not require transfusion and patients with higher NLR values could be mobilized significantly later and had significantly higher duration of hospital stay. The correlation of CRP levels and PLR levels at different time intervals did not show a significant correlation with Day 3 and Day 5 pain scores. CONCLUSION: The present study demonstrated a significant correlation between preoperative and postoperative NLR with pain after TJA.

Value of new advanced hematological parameters in early prediction of severity of COVID-19.

INTRODUCTION: COVID-19 usually presents with upper respiratory tract infection in varying severity which can lead to sepsis. Early prediction of sepsis may reduce mortality by timely interventions. The intended purpose of this study was to determine whether the advanced parameters like the extended inflammation parameters (EIPs) can predict prognosis and early progression to sepsis as a sequel of COVID-19 infection and can be used as a screening profile. Also, to evaluate the Intensive Care Infection Score (ICIS) and the COVID-19 prognostic score and validate the scores for our population. METHODS: Prospective observational study of 50 reverse transcription- polymerase chain reaction (RT-PCR) proven admitted COVID-19 patients. The data assessed included complete blood counts (CBC) with EIP measurements, from Day 1 of admission to Day 10. The following groups were studied: noncritical (NC) and critical illness (CI) in COVID-19 positive cases, COVID negative sepsis and nonsepsis cases, and healthy volunteers for reference range. RESULTS: The parameters that showed statistically significant higher mean in CI group compared to the NC group are reactive lymphocyte number and percentage (RE-LYMPH#, RE-LYMPH%), antibody synthesizing lymphocyte number and percentage (AS-LYMPH#, AS-LYMPH%), Reactive monocyte count and percentage (RE-MONO#, RE-MONO%/M), ICIS, COVID-19 prognostic score (p-value <0.05). The AUC confirmed the diagnostic accuracy of all these parameters. From the multivariate logistic regression, the significant risk factor was RE-LYMPH# with cut-off >0.10 (p value: 0.011). CONCLUSION: The new EIP parameters, RE-MONO#, RE-MONO%/M, ICIS score and COVID-19 prognostic score are useful for early prediction of critical illness. AS-LYMPH is the most useful predictor of critical illness on multivariate analysis. RE-MONO# and RE-MONO%/M parameter are useful in distinguishing critical and noncritical non-COVID and COVID-19 patients.

Mycosynthesis of Zinc Oxide Nanoparticles Exhibits Fungal Species Dependent Morphological Preference.

Filamentous fungi can synthesize a variety of nanoparticles (NPs), a process referred to as mycosynthesis that requires little energy input, do not require the use of harsh chemicals, occurs at near neutral pH, and do not produce toxic byproducts. While NP synthesis involves reactions between metal ions and exudates produced by the fungi, the chemical and biochemical parameters underlying this process remain poorly understood. Here, the role of fungal species and precursor salt on the mycosynthesis of zinc oxide (ZnO) NPs is investigated. This data demonstrates that all five fungal species tested are able to produce ZnO structures that can be morphologically classified into i) well-defined NPs, ii) coalesced/dissolving NPs, and iii) micron-sized square plates. Further, species-dependent preferences for these morphologies are observed, suggesting potential differences in the profile or concentration of the biochemical constituents in their individual exudates. This data also demonstrates that mycosynthesis of ZnO NPs is independent of the anion species, with nitrate, sulfate, and chloride showing no effect on NP production. These results enhance the understanding of factors controlling the mycosynthesis of ceramic NPs, supporting future studies that can enable control over the physical and chemical properties of NPs formed through this "green" synthesis method.

Therapeutic spectrum of piperine for clinical practice: a scoping review.

Translation of traditional knowledge of herbs into a viable product for clinical use is still an uphill task. Piperine, a pungent alkaloid molecule derived from Piper nigrum and Piper longum possesses diverse pharmacological effects. Traditionally, pepper is used for arthritis, bronchitis, gastritis, diarrhea, snake bite, menstrual pain, fever, and bacterial infections, etc. The anti-inflammatory, antioxidant and immunomodulatory actions of piperine are the possible mechanisms behind its therapeutic potential. Various in-silico and experimental studies have shown piperine as a possible promising molecule in coronavirus disease (COVID-19), ebola, and dengue due to its immunomodulatory and antiviral activities. The other important clinical applications of piperine are due to its bio enhancing effect on drugs, by modulating, absorption in the gastrointestinal tract, altering activities of transporters like p-glycoprotein substrates, and modulating drug metabolism by altering the expression of cytochrome P450 or UDP-glucuronosyltransferase enzymes. Piperine attracted clinicians in treating patients with arthritis, metabolic syndrome, diabetes, skin infections, gastric and liver disorders. This review focused on systematic, evidence-based insight into the use of piperine in clinical settings and mechanistic details behind its therapeutic actions. Also, highlights a number of clinical trials of piperine at various stages exploring its clinical application in cancer, neurological, respiratory, and viral disease, etc.

An Analysis of M-protein in Plasma cell Dyscrasia Patients Identifies that IgG Lambda Subtype is More Commonly Associated with Normal Serum Free Light Chain (SFLC) Ratio.

The determination of monoclonal protein (M-protein) by SPE, IFE and SFLC assay is fundamental in the diagnosis of Plasma cell proliferative disorder (PCPD). In the present study, we seek to assess the diagnostic performance and concordance of these three techniques in un-treated PCPD patients. All new patients with dysproteinemia and/or suspected PCPD were included in this retrospective observational study. The baseline parameters were retrieved from electronic medical records. SPE was performed on gel electrophoresis system; monoclonal component was identified by IFE. SFLC assays were performed by nephelometry using a latex-enhanced immunoassay. Total 402 patients of PCPD were included (10.9% of MGUS/SMM and 89.1% of multiple myeloma). The combination of SPE + rSFLC (ratio of kappa/lambda light chain) and SPE + IFE + rSFLC was able to detect M-protein across all subgroups of patients. In 61 patients, rSFLC values were within normal range (54.5% of MGUS/SMM and 10.3% of MM) and was more commonly seen with IgG lambda M-protein (57.4% vs. all-others). The median dFLC value, among these patients, was higher for MM than MGUS/SMM patients (23.8 vs. 14.4 mg/L, respectively). The combination of SPE and rSFLC can be reliably used to detect M-protein in PCPD patients. In a small subgroup of MM patients, despite the presence of an intact immunoglobulin (M-protein), the rSFLC is not abnormal. Historically, these patients should respond better to treatment. However, a further follow-up analysis with more number of such patients would be advantageous for better understanding.

Purcell Enhancement of Erbium Ions in TiO2 on Silicon Nanocavities.

Isolated solid-state atomic defects with telecom optical transitions are ideal quantum photon emitters and spin qubits for applications in long-distance quantum communication networks. Prototypical telecom defects, such as erbium, suffer from poor photon emission rates, requiring photonic enhancement using resonant optical cavities. Moreover, many of the traditional hosts for erbium ions are not amenable to direct incorporation with existing integrated photonics platforms, limiting scalable fabrication of qubit-based devices. Here, we present a scalable approach toward CMOS-compatible telecom qubits by using erbium-doped titanium dioxide thin films grown atop silicon-on-insulator substrates. From this heterostructure, we have fabricated one-dimensional photonic crystal cavities demonstrating quality factors in excess of 5 × 104 and corresponding Purcell-enhanced optical emission rates of the erbium ensembles in excess of 200. This easily fabricated materials platform represents an important step toward realizing telecom quantum memories in a scalable qubit architecture compatible with mature silicon technologies.

Diagnostic Accuracy and Optimal Cut-off of Controlled Attenuation Parameter for the Detection of Hepatic Steatosis in Indian Population.

Background and aims: Ultrasound of the liver is not good to pick up mild steatosis. Controlled attenuation parameter (CAP) evaluated in transient elastography (FibroScan) is widely available in India. However, data regarding the diagnostic accuracy and optimal cut-off values of CAP for diagnosing hepatic steatosis are scarce in Indian population. MRI-PDFF is an accurate technique for quantifying hepatic steatosis. Thus, this study examined the diagnostic accuracy and optimal cut-off values of CAP for diagnosing steatosis with MRI-PDFF as reference standard. Methods: A total of 137 adults underwent CAP and MRI-PDFF measurements prospectively. A subset of participants (n = 23) underwent liver biopsy as part of liver transplantation evaluation. The optimal cut-off values, area under the receiver operating characteristic (AUROC) curves, sensitivity, and specificity for CAP in detecting MRI-PDFF ≥5% and ≥10% were assessed. Results: The mean age and body mass index (BMI) were 44.2 ±10.4 years and 28.3 ±3.9 kg/m2, respectively. The mean hepatic steatosis was 13.0 ±7.7% by MRI-PDFF and 303 ±54 dB/m by CAP. The AUROC of CAP for detecting hepatic steatosis (MRI-PDFF ≥5%) was 0.93 (95% CI, 0.88-0.98) at the cut-off of 262 dB/m, and of MRI-PDFF ≥10% was 0.89 (95% CI, 0.84-0.94) at the cut-off of 295 dB/m. The CAP of 262 dB/m had 90% sensitivity and 91% specificity for detecting MRI-PDFF ≥5%, while the CAP of 295 dB/m had 86% sensitivity and 77% specificity for detecting MRI-PDFF ≥10%. Conclusions: The optimal cut-off of CAP for the presence of liver steatosis (MRI-PDFF ≥5%) was 262 dB/m in Indian individuals. This CAP cut-off was associated with good sensitivity and specificity to pick up mild steatosis.

Discovery and Functional Characterization of Two Regulatory Variants Underlying Lupus Susceptibility at 2p13.1.

Genome-wide association studies have identified 2p13.1 as a prominent susceptibility locus for systemic lupus erythematosus (SLE)­a complex, multisystem autoimmune disease. However, the identity of underlying causal variant (s) and molecular mechanisms for increasing disease susceptibility are poorly understood. Using meta-analysis (cases = 10,252, controls = 21,604) followed by conditional analysis, bioinformatic annotation, and eQTL and 3D-chromatin interaction analyses, we computationally prioritized potential functional variants and subsequently experimentally validated their effects. Ethnicity-specific meta-analysis revealed striking allele frequency differences between Asian and European ancestries, but with similar odds ratios. We identified 20 genome-wide significant (p < 5 × 10−8) variants, and conditional analysis pinpointed two potential functional variants, rs6705628 and rs2272165, likely to explain the association. The two SNPs are near DGUOK, mitochondrial deoxyguanosine kinase, and its associated antisense RNA DGUOK-AS1. Using luciferase reporter gene assays, we found significant cell type- and allele-specific promoter activity at rs6705628 and enhancer activity at rs2272165. This is supported by ChIP-qPCR showing allele-specific binding with three histone marks (H3K27ac, H3K4me3, and H3K4me1), RNA polymerase II (Pol II), transcriptional coactivator p300, CCCTC-binding factor (CTCF), and transcription factor ARID3A. Transcriptome data across 28 immune cell types from Asians showed both SNPs are cell-type-specific but only in B-cells. Splicing QTLs showed strong regulation of DGUOK-AS1. Genotype-specific DGOUK protein levels are supported by Western blots. Promoter capture Hi-C data revealed long-range chromatin interactions between rs2272165 and several nearby promoters, including DGUOK. Taken together, we provide mechanistic insights into how two noncoding variants underlie SLE risk at the 2p13.1 locus.

Recent developments in the utility of saturated azaheterocycles in peptidomimetics.

To a large extent, the physical and chemical properties of peptidomimetic molecules are dictated by the integrated heterocyclic scaffolds they contain. Heterocyclic moieties are introduced into a majority of peptide-mimicking molecules to modulate conformational flexibility, improve bioavailability, and fine-tune electronics, and in order to achieve potency similar to or better than that of the natural peptide ligand. This mini-review delineates recent developments, limited to the past five years, in the utility of selected saturated 3- to 6-membered heterocyclic moieties in peptidomimetic design. Also discussed is the chemistry involved in the synthesis of the azaheterocyclic scaffolds and the structural implications of the introduction of these azaheterocycles in peptide backbones as well as side chains of the peptide mimics.

Geo-Mapping of Early Childhood Caries Risk: A Community Oriented Preventive Oral Health Promotional Approach.

CONTEXT: Given the uneven distribution of dental caries, there is an exigent need for a database of dental caries and its spatial distribution for better planning and efficient delivery of health promotional and preventive programs. Geo-mapping is a helpful tool for policy makers/administrators for efficient allocation of limited resources. AIMS: To geo-map spatial distribution of caries risk in preschoolers of Lucknow and to identify associated predisposing factors. SETTINGS AND DESIGN: A cross-sectional study was done among 1000 preschool children (3-5 years of age) attending pediatrics, outpatient department at a medical college in Lucknow, Uttar Pradesh. METHODS AND MATERIAL: Children were enrolled using the systematic random sampling. Each child was geo-coded with respect to his/her residence, clinically examined for dental caries and given a Decayed Missing Filled Tooth (DMFT) index score. A pre-tested questionnaire was used to collect socio-demographic data. Caries prevalence was geo-mapped using color codes. STATISTICAL ANALYSIS USED: Median DMFT scores were compared using Mann-Whitney and Kruskal-Wallis test. QQ plot/Shapiro-Wilk's test was used to check the normality of data. RESULTS: Prevalence of caries was found to be 76%. 10% children had DMFT score of 4 and more. A significant difference in distribution of DMFT score was observed for gender, income levels and between wards. Wards closer to the center of Lucknow district had a higher prevalence of caries. CONCLUSIONS: Geo-mapping of caries prevalence gives a quick visual glance of specific areas vulnerable to caries and help deliver specific tailor-made services.