A computational model of current control mechanism for long-term potentiation (LTP) in human episodic memory based on gene-gene interaction.

The establishment of long-term potentiation (LTP) is a prime process for the formation of episodic memory. During the establishment of LTP, activations of various components are required in the signaling cascade of the LTP pathway. Past efforts to determine the activation of components relied extensively on the cellular or molecular level. In this paper, we have proposed a computational model based on gene-level cascading and interaction in LTP signaling for the establishment and control of current signals for achieving the desired level of activation in the formation of episodic memory. This paper also introduces a model for a generalized signaling pathway in episodic memory. A back-propagation feedback mechanism is used for updating the interaction levels in the signaling cascade starting from the last stage and ending at the start stage of the signaling cascade. Simulation of the proposed model has been performed for the LTP signaling pathway in the context of human episodic memory. We found through simulation that the qualifying genes correction factors of all stages are updated to their maximum limit. The article explains the signaling pathway for episodic memory and proves its effectiveness through simulation results.

A critical analysis of health system in Nepal; Perspective's based on COVID-19 response.

Background: Nepal moved from a unitary government to a federal system of government in 2015 under its constitution. Nepal is a federal democratic republic governed by three levels of government: a federal, provincial, and local level. The response to COVID-19 in Nepal has been majorly led and controlled by the federal government. All three levels of government are performing their responsibilities; however, they face various challenges in responding to COVID-19. This study aimed to critically analyze Nepal's health system in the context of the COVID-19 response. Methods: We conducted semi-structured in-depth interviews by telephone among the policymakers, health workers, and stakeholders at the federal, provincial, and local levels (n = 41) between January to July 2021. The interviews were audio recorded, transcribed into English, and coded using inductive-deductive approaches. Results: COVID-19 considerably impacted routine health care, mainly maternity services and immunization. Inadequate financial resources, inadequate human resources, and the lack of ventilators, ICUs, and X-ray services were the significant challenges in tackling and managing COVID-19 effectively. Conclusion: The study found that all three levels of government perform their roles and responsibilities and effectively manage the pandemic. The federal and provincial governments focused more on the plans and policy development, while the local government demonstrated greater accountability in implementing those plans and policies. Therefore, all three tiers of government need to coordinate together for preparing and communicating information in times of emergency. Besides, it is imperative to empower local governments to maintain Nepal's federal health system.

Modern-like deep water circulation in Indian Ocean caused by Central American Seaway closure.

Global overturning circulation underwent significant changes in the late Miocene, driven by tectonic forcing, and impacted the global climate. Prevailing hypotheses related to the late Miocene deep water circulation (DWC) changes driven by the closure of the Central American Seaways (CAS) and its widespread impact remains untested due to the paucity of suitable records away from the CAS region. Here, we test the hypothesis of the large-scale circulation changes by providing a high-resolution record of DWC since the late Miocene (11.3 to ~2 Ma) from the north-western Indian Ocean. Our investigation reveals a progressive shift from Pacific-dominated DWC before ~9.0 Ma to the onset of a modern-like DWC system in the Indian Ocean comprising of Antarctic bottom water and northern component water during the Miocene-Pliocene transition (~6 Ma) caused by progressive shoaling of the CAS and suggests its widespread impact.

Prevalence of precursor lesions (P53 signature, SCOUT, STIL, STIC) in fallopian tubes resected for non-neoplastic causes.

Background: High-grade pelvic serous carcinoma is a common cause of death in women worldwide and India. Recent evidence has clearly implicated the changes in the mucosa of the fimbrial end of the fallopian tube in its pathogenesis. Objective: 1) To study histopathology features of surgically resected specimens of fallopian tubes received with non-neoplastic lesions of the uterus and ovary for the presence of any precursor lesions [secretory cell outgrowth (SCOUT), serous tubal intraepithelial lesion (STIL), p53 signatures, and serous tubal intraepithelial carcinoma (STIC)]. 2) To confirm the findings with immunohistochemistry. 3) To correlate the prevalence of precursor lesions with clinical parameters and benign lesions of the uterus and ovaries. Materials and Methods: Assessment of histopathological changes in 100 specimens of distal fallopian tubes was done using the sectioning and extensive examination of the fimbrial end (SEE-FIM) protocol. H and E stain followed by immunohistochemistry for Bcl-2, p53, and Ki-67. The statistical significance of the difference in the mean values of precursor areas was evaluated by an unpaired t-test. Results: Among 100 specimens taken on H and E, precursor lesions were suspected in 49% of the cases. SCOUT, suspicious for STIC, suspicious for STIC with areas of SCOUT, and unequivocal for STIC with areas of SCOUT were seen in 8%, 4%, 33%, and 4% of the cases, respectively. However, on IHC, SCOUTS were confirmed in 45% of the cases, p53 signature in 2%, STIL in 9%, and STIC in 4% of the cases. Conclusion: Sectioning and extensive examination of the fimbrial end (SEE-FIM) should be routinely done as it provides the opportunity to detect the early malignant changes. It may help in evolving the strategies for early detection, management, and reducing mortality.

Abrupt upwelling and CO2 outgassing episodes in the north-eastern Arabian Sea since mid-Holocene.

Identifying the causes and consequences of natural variations in ocean acidification and atmospheric CO2 due to complex earth processes has been a major challenge for climate scientists in the past few decades. Recent developments in the boron isotope (δ11B) based seawater pH and pCO2 (or pCO2sw) proxy have been pivotal in understanding the various oceanic processes involved in air-sea CO2 exchange. Here we present the first foraminifera-based δ11B record from the north-eastern Arabian Sea (NEAS) covering the mid-late Holocene (~ 8-1 ka). Our record suggests that the region was overall a moderate to strong CO2 sink during the last 7.7 kyr. The region behaved as a significant CO2 source during two short intervals around 5.5-4 ka and 2.8-2.5 ka. The decreased pH and increased CO2 outgassing during those abrupt episodes are associated with the increased upwelling in the area. The upwelled waters may have increased the nutrient content of the surface water through either increased supply or weaker export production. This new dataset from the coastal NEAS suggests that, as a potential result of changes in the strength of the El-Nino Southern Oscillation, the region experienced short episodes of high CO2 outgassing and pre-industrial ocean acidification comparable to or even greater than that experienced during the last ~ 200 years.

Evaluation of physicochemical and functional similarity of a new CHO derived anti-EGFR antibody P-mAb to its reference medicinal product.

Epidermal growth factor receptor (EGFR) is the primary target for the treatment of colorectal cancer, the third most diagnosed cancer worldwide. In recent years, regulatory changes have facilitated the approval of biosimilars aimed to bring more access to biologics to patients. However, it has also expended the requirements of non-clinical characterisation data using state-of-the-art and orthogonal methodologies to demonstrate similarity between proposed biologic and its reference medicinal product (RMP). The current study was aimed to develop a stable CHO-S cell line producing panitumumab biosimilar candidate, P-mAb, a fully human IgG2 anti-EGFR monoclonal antibody and assess its physicochemical and functional similarity with RMP, Vectibix. The single-cell clone from stably transfected CHO-S cell pools was used for the production of P-mAb. This was followed by purification and comparative physicochemical and biological characterisation of P-mAb and RMP using SDS-PAGE, LC/MS, MALDI, MS/MS, CD spectrometry, DSF, SAXS, ITF, MTT assay and binding affinity. SAXS and MST assays are being used for first time in biosimilarity analysis of therapeutic monoclonal antibody. The results of structural and functional analysis of anti-EGFR P-mAb, produced by stable CHO-S cell line revealed high similarity between P-mAb and RMP, vectibix, thus providing the scientific basis of its potential for therapeutic applications.

Tacrolimus induces remission in refractory and relapsing lupus nephritis by decreasing P-glycoprotein expression and function on peripheral blood lymphocytes.

P-glycoprotein (P-gp)-mediated efflux of corticosteroids (CS) may contribute to treatment unresponsiveness in Lupus Nephritis (LN) patients. Tacrolimus is a P-gp inhibitor and hence, may overcome this resistance. We aimed to study the response to tacrolimus, along with the expression and function of P-gp on peripheral blood lymphocytes (PBL) in patients with refractory and relapsing proliferative Lupus Nephritis. We enrolled 12 refractory/relapsing LN patients and treated them with corticosteroids and tacrolimus for 6 months. Expression and function of P-gp on PBL was measured by flow cytometry (as relative fluorescence index, RFI and Rhodamine dye efflux assay) before and 3 months after tacrolimus therapy. Renal response was assessed according to ACR response criteria after 3 and 6 months of tacrolimus therapy. 8 out of 12 refractory/relapsing LN patients achieved renal response (5 partial response, PR and 3 complete responses, CR) as early as 3 months, and 11 patients achieved renal response (7 PR and 4 CR) at 6 months from start of tacrolimus therapy. Proteinuria decreased from median urine protein creatinine ratio (UPCR) of 2.80 (2.00-3.40) at baseline to 1.20 (0.66-1.73) at 3 months (p < 0.001) and to 0.80 (0.19-1.30) at 6 months (p < 0.01). There was significant decrease in P-gp expression [RFI, 3.33 (2.87-4.97) vs 2.03 (1.25-3.86), p < 0.05) and P-gp function (RFI, 55.7 (29.7-84.1) vs 26.8 (16.1-37.0), p < 0.01) after 3 months of tacrolimus therapy. Tacrolimus achieves renal response in refractory/relapsing proliferative LN patients which may be partly related to overcoming P-glycoprotein mediated treatment unresponsiveness.

Prevalence of sleep apnea and lung function abnormalities in patients with acromegaly.

BACKGROUND: Sleep apnea (SA) is highly prevalent in acromegaly. Ethnicity influences the prevalence of SA in the general population. We studied the prevalence of SA and other respiratory comorbidities in North Indian patients with active acromegaly. DESIGN: Prospective, observational. MATERIALS AND METHODS: Consecutive adult patients with active acromegaly (n = 35, age 39.7 ± 13.2 years) and hypersomatotropism (nonsuppression of serum growth hormone after oral glucose and elevated serum insulin-like growth factor-1 [IGF-1]) were evaluated for respiratory symptoms, scoring for SA (Epworth Sleepiness Score [ESS] and STOP-BANG), pulmonary function tests (PFT), high-resolution computerized tomography (HRCT) of the thorax, polysomnography (PSG), and transthoracic echocardiography. Age- and sex-matched healthy individuals (n = 34) served as controls. RESULTS: Acromegaly subjects had dyspnea (34%), cough (37%), excessive daytime somnolence (43%), and fatigue (49%). Clinically significant ESS (>10) and STOP-BANG score (≥3) were present in 41% and 68.6% of subjects, respectively. PFT showed restrictive and obstructive patterns in 45.7% and 11.4% of acromegalics respectively; with higher total lung capacity (TLC), thoracic gas volume (TGV), and residual volume (RV). PSG revealed significantly higher SA events in acromegalics (central [acromegaly 24.63 ± 37.82 vs. control 3.21 ± 5.5], mixed [11 ± 19.46 vs. 3.50 ± 5.96], obstructive [34.86 ± 44.37 vs. 9.71 ± 10.48], and mean apnea-hypopnea index [AHI] [16.91 ± 18.0 vs. 7.86 ± 7.84]). Acromegalics had significantly higher prevalence of obstructive SA (71.4% [mild 31.4%, moderate 20%, severe 20%]) as compared to controls (38.2%). There was no correlation of AHI with serum IGF-1 and disease duration. CONCLUSION: Acromegaly subjects have a significantly higher prevalence of respiratory symptoms, SA, and abnormalities in PFT. Screening for respiratory comorbidities should be routinely recommended in all patients with acromegaly.

Utility of neutrophil CD64 in distinguishing bacterial infection from inflammation in severe alcoholic hepatitis fulfilling SIRS criteria.

To assess utility of neutrophilCD64 (nCD64) expression in differentiating bacterial infection from inflammation in patients with severe alcoholic hepatitis (SAH) fulfilling systemic inflammatory response syndrome criteria. Patients with SAH and infection (n = 58), SAH without infection (n = 70), and healthy controls (n = 20) were included. Neutrophil CD64 expression by flowcytometry, serum Procalcitonin (ELISA) and C-reactive protein (Nephelometry) and neutrophil-lymphocyte ratio (NLR) were studied. Percentage of neutrophils with CD64 expression (nCD64%) was significantly higher in patients with SAH and infection than in those without infection and controls [76.2% (56.9-86.5) vs. 16% (12.6-23.1) vs. 7.05% (1.4-9.5), p < 0.05], as was their mean fluorescence intensity [MFI; 1431 (229-1828) vs. 853 (20-968) vs. 99.5 (54.7-140.7), p < 0.05]. Using a cut-off of 27%, the sensitivity and specificity of nCD64% to diagnose bacterial infection was 94% and 81%, respectively, with area under curve (AUC) of 0.95. At a cut-off value of 0.261 ng/ml, the sensitivity and specificity of serum procalcitonin was 83% and 72%, respectively, with AUC of 0.86. Serum CRP, total leukocyte count, NLR had AUCs of 0.78, 0.63 and 0.64, respectively. Quantitative measurement of nCD64 can better distinguish systemic bacterial infection and inflammation in SAH as compared to traditional biomarkers.

Translating Treg Therapy for Inflammatory Bowel Disease in Humanized Mice.

Crohn's disease and ulcerative colitis, two major forms of inflammatory bowel disease (IBD) in humans, afflicted in genetically predisposed individuals due to dysregulated immune response directed against constituents of gut flora. The defective immune responses mounted against the regulatory mechanisms amplify and maintain the IBD-induced mucosal inflammation. Therefore, restoring the balance between inflammatory and anti-inflammatory immunepathways in the gut may contribute to halting the IBD-associated tissue-damaging immune response. Phenotypic and functional characterization of various immune-suppressive T cells (regulatory T cells; Tregs) over the last decade has been used to optimize the procedures for in vitro expansion of these cells for developing therapeutic interventional strategies. In this paper, we review the mechanisms of action and functional importance of Tregs during the pathogenesis of IBD and modulating the disease induced inflammation as well as role of mouse models including humanized mice repopulated with the human immune system (HIS) to study the IBD. "Humanized" mouse models provide new tools to analyze human Treg ontogeny, immunobiology, and therapy and the role of Tregs in developing interventional strategies against IBD. Overall, humanized mouse models replicate the human conditions and prove a viable tool to study molecular functions of human Tregs to harness their therapeutic potential.

Transdermal Immunization of Elastic Liposome-Laden Recombinant Chimeric Fusion Protein of P. falciparum (PfMSP-Fu24) Mounts Protective Immune Response.

Transdermal immunization exhibits poor immunogenic responses due to poor permeability of antigens through the skin. Elastic liposomes, the ultradeformable nanoscale lipid vesicles, overcome the permeability issues and prove a versatile nanocarrier for transcutaneous delivery of protein, peptide, and nucleic acid antigens. Elastic liposome-mediated subcutaneous delivery of chimeric fusion protein (PfMSP-Fu24) of Plasmodium falciparum exhibited improved immunogenic responses. Elastic liposomes-mediated immunization of PfMSP-Fu24 conferred immunity to the asexual blood-stage infection. Present study is an attempt to compare the protective immune response mounted by the PfMSP-Fu24 upon administered through transdermal and intramuscular routes. Humoral and cell-mediated immune (CMI) response elicited by topical and intramuscularly administered PfMSP-Fu24-laden elastic liposomes (EL-PfMSP-Fu24) were compared and normalized with the vehicle control. Sizeable immune responses were seen with the transcutaneously immunized EL-PfMSP-Fu24 and compared with those elicited with intramuscularly administered antigen. Our results show significant IgG isotype subclass (IgG1and IgG3) response of specific antibody levels as well as cell-mediated immunity (CMI) activating factor (IFN-γ), a crucial player in conferring resistance to blood-stage malaria in mice receiving EL-PfMSP-Fu24 through transdermal route as compared to the intramuscularly administered formulation. Heightened immune response obtained by the vaccination of EL-PfMSP-Fu24 was complemented by the quantification of the transcript (mRNA) levels cell-mediated (IFN-γ, IL-4), and regulatory immune response (IL-10) in the lymph nodes and spleen. Collectively, elastic liposomes prove their immune-adjuvant property as they evoke sizeable and perdurable immune response against PfMSP-Fu24 and justify its potential for the improved vaccine delivery to inducing both humoral and CM immune response.

Serum CA 19-9 and CA 125 as a diagnostic marker in carcinoma of gallbladder.

BACKGROUND: Gall bladder carcinoma is endemic in North India along the Ganges belt. Most of the cases usually present in late stage when prognosis is poor. That mandates a necessity for proper screening in these areas for gall bladder lesions. Tumor markers CA 19-9 and CA 125 have been studied in various GI cancers and may also help in the screening, diagnosis and evaluation of gall bladder carcinoma. Aims: To assess serum CA19-9 and serum CA125 in patients with gall bladder lesions and find out a cut off value for diagnosis of carcinoma gallbladder. METHODS AND MATERIAL: Study included 118 cases, with female: male ratio of 4:1.Out of it, 91 (77 %) cases were benign and 27 (23 %) were malignant. Patients' sera was collected and analyzed for CA19-9 and CA 125 by CMIA method. RESULTS: The Mean (SD) value of CA19-9 for benign and malignant cases was found to be 12.86 (17.54) and 625.35(186.52) U/ml. For CA 125 it was found to be 17.98(13.69) and 239.63(73.72) U/ml respectively. The difference was statistically significant (P< 0.001). When Mean - 2SD value of malignant lesions were taken as cut off a value of CA 19-9 and CA 125 were found be 252.31 U/ml & 92.19U/ml respectively, found to be significant to suggest /diagnose a case of carcinoma gall bladder along with clinicoradiological findings. Taking these value as cut off Sensitivity & Specificity for CA 19-9 and CA 125 in detecting malignant cases were found to be 100% & 98.90% and 100% & 94.50% respectively. CONCLUSIONS: It is concluded that both serum CA 19-9 and serum CA 125 may act as a good adjunct for diagnosis of cases of carcinoma gallbladder along with imaging studies. However, changes in CA19-9 are more significant than CA 125.

Role of P-gp and HDAC2 and their Reciprocal Relationship in Uncontrolled Asthma.

INTRODUCTION: Resistance to corticosteroid is an essential mechanism in uncontrolled asthma as the corticosteroid is the mainstay of therapy. There are recent reports that epigenetic factors play a crucial role in the regulation of steroid action. Overexpression of P glycoprotein (P-gp) and reduced expression of Histone Deacetylase 2 (HDAC2) have been linked to regulating the steroid action in other diseases like Nephrotic Syndrome (NS). However, their role in uncontrolled asthma is still not clear and warrants further investigation. We evaluated the expression and activity of P-gp and HDAC2 in patients with Controlled Asthma (CA) and Uncontrolled Asthma (UA). METHODS: A total of 60 CA (mean age 51.72±17.02 years, male=38), and 38 of UA (mean age=53.55±11.90 years, male=17) were recruited. The level of control was defined according to (Global Initiative for Asthma) GINA 2016 criteria. The mRNA expression of HDAC2 and P-gp was studied by quantitative real-time Polymerase Chain Reaction (PCR), the functional activity of P-gp was evaluated by a commercially available kit via flow cytometry, and HDAC2 enzymatic activity was measured by commercially available kit by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: P-gp expression and the functionality were significantly higher in the UA group of patients as compared to the CA group of patients (p<0.005), moreover HDAC2 expression was significantly reduced in UA patients as compared to CA patients, (p<0.005). The enzymatic activity of HDAC2 was also significantly reduced in UA patients as compared to CA patients (p<0.005). CONCLUSION: P-gp overexpression and HDAC2 under expression play an essential role in uncontrolled asthma by impairing the response to corticosteroid.

Identification and management of young infants with possible serious bacterial infection where referral was not feasible in rural Lucknow district of Uttar Pradesh, India: An implementation research.

BACKGROUND: Based on World Health Organization guidelines, Government of India recommended management of possible serious bacterial infection (PSBI) in young infants up to two months of age on an outpatient basis where referral is not feasible. We implemented the guideline in program setting to increase access to treatment with high treatment success and low resultant mortality. METHODS: Implementation research was conducted in four rural blocks of Lucknow district in Uttar Pradesh, India. It included policy dialogues with the central and state government and district level officials. A Technical Support Unit was established. Thereafter, capacity building across all cadres of health workers in the implementation area was done for strengthening of home based newborn care (HBNC) program, skills enhancement for identification and management of PSBI, logistics management to ensure availability of necessary supplies, monitoring and evaluation as well as providing feedback. Data was collected by the research team. RESULTS: From June 2017 to February 2019 there were 24,448 live births in a population of 856106. We identified 1302 infants, aged 0-59 days, with any sign of PSBI leading to a coverage of 53% (1302/2445), assuming an incidence of 10%. However, in the establishment phase the coverage was 33%, while it was 85% in the implementation phase. Accredited social health activists (ASHAs) identified 81.2% (1058/1302) cases while rest were identified by families. ASHAs increased home visits within first 7 days of life in home based newborn care program from 74.3% (2781/3738) to 89.0% (3128/3513) and detection of cases of PSBI from 1.6% (45/2781) to 8.7% (275/3128) in the first and last quarter of the project, respectively. Of these 18.7% (244/1302) refused referral to government health system and 6.7% (88/1302) were treated in a hospital. Among cases of PSBI, there were 13.3% (173/1302) cases of fast breathing in young infant aged 7-59 days in whom referral was not needed. Of these 147 were treated by oral amoxicillin and 95.2% (140/147) were cured. Among those who needed referral, simplified treatment was given when referral was refused. There were 2.9% (37/1302) cases of fast breathing at ages of 0-6 days of which 34 were treated by simplified treatment with100% (34/34) cured;66.5% (866/1302) were cases of clinical severe infection of which 685 treated by simplified treatment with94.2% (645/685)cured and 09 died;17.3% (226/1302) cases of critical illness of which 93 were treated by simplified treatment, as a last resort, 72% (67/93) cured and 16 died. Among 255 cases who either did not seek formal treatment or sought it at private facilities, 96 died. CONCLUSION: Simplified treatment for PSBI is feasible in public program settings in northern India with good cure rates. It required system strengthening and supportive supervision.

Steroid Responsiveness in Duchenne Muscular Dystrophy - Predictive Value of Epigenetic Regulator Histone Deacetylase 2.

OBJECTIVE: To find the role of an epigenetic regulator histone deacetylase (HDAC-2) in predicting steroid responsiveness in patients with Duchenne muscular dystrophy (DMD). METHODS: Peripheral blood mononuclear cells were isolated from three milliliters of venous blood sample of patients with DMD for estimation of HDAC-2 levels. The patients were then given prednisolone at 0.75 mg/kg/d and followed up for response. Improvement in muscle power and timed function tests were evaluated 2 monthly for 6 mo. Side- effects of steroids were also noted. RESULTS: HDAC-2 values showed a linear correlation with improvement in muscle power at 6 mo as reflected in direct assessment and in various functional tests. When ≥3 point change from baseline was considered in power of various muscle groups at 6 mo as cut off to distinguish good responders (GR) from poor responders (PR) of steroid, a HDAC-2 value of ≥4.40 seemed to be 92.6% sensitive and 100% specific to distinguish GRs. CONCLUSIONS: The degree of improvement in power and various timed function tests at 6 mo could be predicted from the HDAC-2 value of the individual patient recorded at baseline. HDAC-2 levels at baseline might be a good biomarker for predicting steroid response in patients with DMD.

An evaluation of liposome-based diagnostics of pulmonary and extrapulmonary tuberculosis.

Introduction: Tuberculosis (TB) is still one of the major global health threats and delayed diagnosis or misdiagnosis continues to fuel the global epidemic. The conventional diagnostic approaches have shortcomings that might hinder the process of diagnosis of the disease and ultimately affect the prognosis.Area covered: We emphasize on the process of the synthesis of liposomes, its physicochemical properties affecting the formulation and their utilization in the field of molecular diagnostics for TB. The review also sheds a light on other nanoparticle-based molecular diagnostic approaches for TB. Despite the advent of science, we are yet to have a diagnostic tool that is simple, rapid, sensitive, and specific, and most importantly, one that enables us to demarcate patients with active tuberculosis from those with quiescent lesions, prior vaccination, or other diseases.Expert opinion: The utility of liposomes for diagnostic purposes has been attempted so as to overcome the challenges posed by conventional diagnostic tools for TB. Through this review, we present insights into liposome formulation and selection processes, various studies that report the use of liposome-based diagnostic tools for TB, as well as the limitations associated with the same that can be improvised to make the technology more efficient.

Diagnosis of obstructive sleep apnea in women: Is there any difference?- Experience from a tertiary care hospital of North India.

CONTEXT: Obstructive sleep apnea (OSA) considered classically to be a male-dominant disease, may have significant gender-based differences in clinical presentation and diagnosis. AIMS: To evaluate gender-based differences in the clinical profile and polysomnographic features of Indian patients with OSA. SETTINGS AND DESIGN: A prospective observational study was conducted over a period of 12 months involving adult ambulatory patients, referred for evaluation of OSA. METHODS AND MATERIALS: Enrolled patients underwent detailed clinical evaluation followed by supervised polysomnography. Sleep studies were manually validated and analyzed. STATISTICAL ANALYSIS USED: Continuous variables were compared using two-tailed independent- sample t-test. For the univariate analysis, the Chi-square test was used. RESULTS: Out of 150 enrolled patients, 94 (62.7%) were males (male-to-female: 1.7:1; age: 51.85 ± 12.60 years; BMI: 32.09 ± 5.53 kg/m2). Most common presenting features were excessive daytime somnolence, snoring, and easy fatiguability. Women with OSA were older than men. Insomnia and anxiety were significantly higher among females. Parameters defining sleep architecture were similar in both groups. Although obstructive apneas and hypopneas were similar, mean apnea hypopnea index was significantly higher (P < 0.05) in males compared to females with higher titratable continuous positive airway pressure. CONCLUSIONS: There are gender-specific differences in the clinical presentation of OSA due to various anatomical, physiological, and psychosocial factors. Their potential influence on the clinical features, natural history, and implications on treatment need further evaluation on a larger scale.

Utility of neutrophil CD64 and serum TREM-1 in distinguishing bacterial infection from disease flare in SLE and ANCA-associated vasculitis.

Bacterial and opportunistic infections are a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis owing to treatment with immunosuppressants. Commonly used laboratory tests are unreliable in differentiating infection from active disease patients. Fc receptor (FcγR1 or CD64) expression on neutrophils and soluble TREM-1 (triggering receptor expressed on monocytes) are potential biomarkers of bacterial infections. Our aim was to measure the clinical usefulness of quantitative CD64 measurement on neutrophils and soluble TREM-1 measurements in differentiating bacterial infection from active disease in patients with SLE and ANCA vasculitis. Patients with bacterial infection (n = 25), active disease (n = 51), and healthy controls (n = 20) were included. Neutrophil CD64 expression using flow cytometry and sTREM-1 and procalcitonin levels by ELISA were studied. The percentage of neutrophils with CD64 expression and their mean fluorescence intensity in patients with infection (68.8 (56.9-86.5)%, 1037 (229-1828)) were significantly (p < 0.05) higher as compared to those without infection (7.7 (2.6-13.1)%, 456 (20-968)) and controls (7.05 (1.4-9.5)%, 99.5 (54.7-140.7)). The sensitivity and specificity of CD64 expression on neutrophils to diagnose bacterial infection (using a cutoff value of 30%) was 85% and 84%, respectively, whereas the sensitivity and specificity of procalcitonin was 75% and 85%, respectively. There was no significant difference in soluble TREM-1 levels between the two groups. Quantitative measurement of CD64 on neutrophils can distinguish between systemic infection and the flare of autoimmune diseases.

Correlation of Neutrophil CD64 with Clinical Profile and Outcome of Sepsis Patients during Intensive Care Unit Stay.

INTRODUCTION: Neutrophil CD64 (nCD64) has been found to identify sepsis from nonseptic patients. It is also reported to be a predictor of survival and severity of sepsis. The goal of this study was to correlate serial nCD64 with Intensive Care Unit (ICU) outcome and severity of sepsis. MATERIALS AND METHODS: A prospective observational study was conducted in 12-bedded critical care unit of a tertiary care center. Adult patients with sepsis were included in this study. Demographics, illness severity scores, clinical parameters, laboratory data, and 28-day outcome were recorded. Serial nCD64 analysis was done (on days 0, 4, and 8) in consecutive patients. RESULTS: Fifty-one consecutive patients were included in the study. Median Acute Physiology and Chronic Health Evaluation II was 16 (12-20) and mean Sequential Organ Failure Assessment was 9 (8-10). Compared to survivors, nonsurvivors had higher nCD64 on day 8 (P = 0.001). nCD64 was higher in the septic shock group compared to sepsis group on days 0 and 8 (P < 0.05). Survivors showed improving trend of nCD64 over time while nonsurvivors did not. This trend was similar in the presence or absence of septic shock. nCD64 count was a good predictor of the septic shock on day 0 (area under the curve [AUC] = 0.747, P = 0.010) and moderate predictor at day 8 (AUC = 0.679, P = 0.028). CONCLUSION: Monitoring serial nCD64 during ICU stay may be helpful in determining the clinical course of septic patients.