CoRe study: COVID-19 and remdesivir: An insight into the current health planning and policy.

Introduction: The ongoing coronavirus disease-2019 (COVID-19) pandemic has witnessed rampant use of the repurposed drug, remdesivir, despite its conflicting evidence and rapidly changing guidelines. Methods: A cross-sectional, country-wide, questionnaire-based, electronic survey was conducted among the healthcare professionals involved in COVID-19 management from April 18 to May 18, 2021. Results: Out of 231 responses, 185 were included. Significantly, greater knowledge of trials was reported by the frontline healthcare professionals compared to those who are not involved in COVID-19 care. Medicine practitioners and pulmonologists expressed greater willingness to continue remdesivir (Odds ratio (OR) 5.329, 95% Confidence interval (CI) 2.31-12.291 and 5.063, 95% CI 1.414-18.129, respectively). The rationale attributed was personal experience, current guidelines, non-availability of any alternate antiviral drug, expert recommendations, and local hospital policy either alone (20%, 8.1%, 5.9%, 2.7%, and 2.2%, respectively) or in combination (46.5%, 39.5%, 29.2%, 21.1%, and 15.7%, respectively). Awareness of evidence and knowledge of landmark studies made no statistically significant impact on clinical decision-making. Improved clinical outcomes were reported by 10/22 (45.4%) practitioners who used remdesivir for unconventional indications. Conclusion: The study throws critical insights into the current perspectives of doctors on remdesivir in clinical management and its potential impact on current health planning strategies.

AI-CoV Study: Autoimmune Encephalitis Associated With COVID-19 and Its Vaccines-A Systematic Review.

BACKGROUND AND PURPOSE: Autoimmune encephalitis (AIE) following coronavirus disease 2019 (COVID-19) is an underexplored condition. This study aims to systematically review the clinico-investigational and pathophysiologic aspects of COVID-19 and its vaccines in association with AIE, and identify the factors predicting neurological severity and outcomes. METHODS: Relevant data sources were searched using appropriate search terms on January 15, 2022. Studies meeting the criteria for AIE having a temporal association with COVID-19 or its vaccines were included. RESULTS: Out of 1,894 citations, we included 61 articles comprising 88 cases: 71 of COVID-19-associated AIE, 3 of possible Bickerstaff encephalitis, and 14 of vaccine-associated AIE.There were 23 definite and 48 possible seronegative AIE cases. Anti-NMDAR (N-methyl-D-aspartate receptor; n=12, 16.9%) was the most common definite AIE. Males were more commonly affected (sex ratio=1.63) in the AIE subgroup. The neurological symptoms included alteredmental state (n=53, 74.6%), movement disorders (n=28, 39.4%), seizures (n=24, 33.8%), behavioural (n=25, 35.2%), and speech disturbances (n=17, 23.9%). The median latency to AIE diagnosis was 14 days (interquartile range=4-22 days). Female sex and ICU admission had higherrisks of sequelae, with odds ratio (OR) of 2.925 (95% confidence interval [CI]=1.005-8.516)and 3.515 (95% CI=1.160-10.650), respectively. Good immunotherapy response was seen in42/48 (87.5%) and 13/13 (100%) of COVID-19-associated and vaccine-associated AIE patients, respectively. Sequelae were reported in 22/60 (36.7%) COVID-19 associated and 10/13 (76.9%) vaccine-associated cases. CONCLUSIONS: The study has revealed diagnostic, therapeutic, and pathophysiological aspects of AIE associated with COVID-19 and its vaccines, and its differences from postinfectious AIE. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42021299215.

Anabolic-androgenic steroid use in a young body-builder: A case report and review of the literature.

Introduction: Anabolic-androgenic steroid (AAS) abuse is routine in athletes to enhance their overall physique. It often leads to detrimental effects, including cardiovascular diseases, hormonal imbalances, and cancer. Our case presentation emphasizes two important aspects: the first is the importance of thorough history taking in correctly diagnosing diseases with multiple etiologies. The second one relates to the reversible and preventable hazards of the increasing incidence of usage of illicit drugs, mainly androgenic anabolic steroids in young adults. Case presentation: We present a case of a 30-year-old male bodybuilder with presenting complaints of increased anxiousness, excessive anger, and dyspnea on minimal exertion. Echocardiogram showed a dilated cardiomyopathy with left ventricular ejection fraction (LVEF) of 20%. The patient was counseled for quitting AAS and symptomatically treated on heart failure management guidelines. He responded well to the management plan and now enjoying a healthy life. Conclusion: It is imperative to raise awareness regarding the substantial adverse effects of AAS abuse that might precipitate severe cardiovascular system complications leading to morbidity and eventual mortality. Most of the times, the pathological changes due to AAS abuse are reversible. This shows a good prognosis and better compliance with the management plan advised to the patients.

Cognition, Behavior, and Caregiver Stress in Dementia during the COVID-19 Pandemic: An Indian Perspective.

OBJECTIVES: Little is known regarding the cognitive and behavioral status of patients with dementia and their caregivers in lower middle-income countries during the COVID-19 pandemic. This study aimed to understand the impact of the pandemic on persons with dementia and their caregivers in India. METHODS: This was an observational study. A cohort of 66 persons with dementia and their caregivers were evaluated during the COVID-19 pandemic in 2 specialist hospitals in South India. Caregivers were interviewed at 2 distinct time points of the pandemic: during the national lockdown and 5 months after during later periods of the "cluster of cases" transmission phase. Participants were assessed via telephone utilizing validated instruments (Neuropsychiatric Inventory [NPI], Clinical Dementia Rating [CDR] Scale, and Depression, Anxiety and Stress Scale [DASS-21]) and a semi-structured questionnaire. The questionnaire documented sociodemographic information, clinical history, infection measures adopted, changes in caregiving routines, involvement in functional rehabilitation activities, and access to medical and long-term care support services. RESULTS: The 2-phase follow-up study found a significant worsening of behavior in dementia patients, demonstrated by a difference in the NPI sub-domain scores for anxiety (mean difference [standard deviation, SD] = -0.552 [1.993], t58 = -2.109, p = 0.039) and eating disturbances (mean difference [SD] = -1.121 [2.493], t59 = -3.424, p = 0.001). A relatively high proportion of patients developed anxiety (cumulative incidence = 24.53%) and eating disturbances (cumulative incidence = 26.92%), without having these symptoms at baseline. There was a trend toward an increase in proportion of persons with severe dementia (19.7% vs. 39.4%) on follow-up. Caregiver distress reported was significantly associated with neuropsychiatric symptoms (r = 0.712, p < 0.001) and dementia severity (ρ = 0.365, p = 0.004). In addition, difficulties in accessing medical care persisted between the 2 assessments, and there were statistically significant differences between functional rehabilitation activities such as indoor activities (p < 0.001), outdoor activities (p = 0.013), and physical exercises (p = 0.003) between baseline and follow-up. CONCLUSION: Findings suggest interruption of functional rehabilitation activities and disruption in medical care services are likely to have had an adverse impact on patients with dementia and contributed toward caregiver distress.

Systemic inflammatory syndrome in COVID-19-SISCoV study: systematic review and meta-analysis.

BACKGROUND: There has been a recent upsurge in the cases of Multisystem inflammatory syndrome in children (MIS-C) associated with Coronavirus disease (COVID-19). We performed a systematic review and meta-analysis on the demographic profile, clinical characteristics, complications, management, and prognosis of this emerging novel entity. METHODS: Using a predefined search strategy incorporating MeSH terms and keywords, all known literature databases were searched up till 10th July 2020. The review was done in accordance with PRISMA guidelines and registered in PROSPERO (CRD4202019757). RESULTS: Of the 862 identified publications, 18 studies comprising 833 patients were included for meta-analysis. The socio-demographic profile showed male predilection (p = 0.0085) with no significant racial predisposition. A higher incidence of gastrointestinal symptoms (603/715, 84.3%), myocarditis (191/309, 61.8%), left ventricular dysfunction (190/422, 45.0%), pericardial (135/436, 31.0%) and neurological symptoms (138/602, 22.9%) was reported. Serological evidence of SARS-CoV-2 had higher sensitivity compared to rtPCR (291/800, 36.4% vs 495/752, 65.8%; p < 0.001). Coronary artery anomaly (CAA) was reported in 117/681 in 9 publications (17.2%). A total of 13 (1.6%) fatalities were reported. CONCLUSION: Clinicians need to be vigilant in identifying the constellation of these symptoms in children with clinical or epidemiologic SARS-CoV-2 infection. Early diagnosis and treatment lead to a favorable outcome. IMPACT: Key message This review analyses the demographic profile, clinical spectrum, management strategies, prognosis, and pathophysiology of MIS-C among children with SARS-CoV-2 infection. The stark differences of MIS-C from Kawasaki disease with respect to demographics and clinical spectrum is addressed. Over-reliance on rtPCR for diagnosis can miss the diagnosis of MIS-C. New addition to existing literature The first systematic review and meta-analysis of published literature on MIS-C associated with COVID-19. IMPACT: The article will serve to spread awareness among the clinicians regarding this emerging novel entity, so that diagnosis can be made early and management can be initiated promptly.

Do SGLT2 Inhibitors Improve Cardio-Renal Outcomes in Patients With Type II Diabetes Mellitus: A Systematic Review.

Diabetes mellitus (DM) is associated with dreadful changes in the cardiovascular and renal systems, causing increased morbidity and mortality. Sodium-glucose cotransport-2 (SGLT2) inhibitors belong to the oral hypoglycemic group of drugs believed to reduce these events by various mechanisms in DM. We performed a systematic review to determine the effectiveness of SGLT2 inhibitors in reducing cardiovascular and renal complications and address safety concerns in participants with type 2 diabetes mellitus (T2DM). We explored PubMed, PubMed Central, Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane library, and ResearchGate for randomized controlled trials and observational studies done on the advantages of SGLT2 inhibitors in the prevention or reduction of worsening cardiovascular and renal changes in T2DM. Studies were screened for the quality assessment using the Cochrane risk-of-bias assessment tool and Newcastle-Ottawa scale. We screened 5615 articles, out of which 22 articles with 7,02,977 diabetes mellitus patients treated with SGLT2 inhibitors were used for the systematic review after meticulously filtering articles based on inclusion and exclusion criteria. The trials included one of the following drugs - empagliflozin, dapagliflozin, canagliflozin, and luseogliflozin. SGLT2 inhibitors significantly reduced the risk of heart failure (HF), frequency of hospitalizations due to HF, all-cause mortality, cardiovascular mortality, and nonfatal myocardial infarction. Renal outcomes showed a significant lowering of risk of acute kidney failure, progression of chronic kidney disease, renal mortality, and improvement in urinary albumin creatinine ratio. We noticed an initial worsening of the estimated glomerular filtration rate followed by stabilizing and reaching the baseline on long-term treatment, especially in end-stage renal failure patients. The review showed that SGLT2 inhibitors have adverse reactions similar to that of a placebo, with a slight increase in treatable genital mycotic and urinary tract infections but no evidence of diabetic ketoacidosis, fractures, and amputations. According to the available data, SGLT2 inhibitors can significantly prevent or reduce cardiovascular diseases and kidney abnormalities in patients with type 2 diabetes mellitus with tolerable safety outcomes.

The Outcomes of Acute Coronary Syndrome in Patients Suffering From Schizophrenia: A Systematic Review.

Acute coronary syndrome (ACS) is a principal cause of mortality and morbidity worldwide. Recent studies have suggested poorer outcomes in ACS patients who have a concurrent diagnosis of schizophrenia as compared with those without. However, the degree of interplay between schizophrenia and ACS remains poorly understood. For this reason, we conducted a systematic review on ACS outcomes in patients with schizophrenia by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We collected relevant data from PubMed, Cochrane Library, PubMed central, Jisc Library Hub Discover, and the National Library of Medicine (NLM) and performed a thorough quality appraisal. Fourteen shortlisted, relevant studies were meticulously reviewed. Mortality and major adverse cardiac events (MACE), bleeding, and stroke were more prevalent in patients with a schizophrenia diagnosis compared to those without. Additionally, schizophrenia patients received suboptimal care and follow-up when compared to patients without a psychiatric diagnosis. Clinicians need to be aware that patients with schizophrenia have worse outcomes following ACS which may relate to biological, health care, or patient-related factors.

Relationship and Effects of Vitamin D on Metabolic Syndrome: A Systematic Review.

Metabolic syndrome (MetS) is a persistent public health problem in the United States (U.S.) due to its increasing prevalence and its positive correlation with type-2 diabetes (T2DM) and cardiovascular disease (CVD). According to National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) criteria, MetS has six main components, which are obesity, dyslipidemia, raised blood pressure (BP), insulin resistance (IR) or glucose intolerance, pro-inflammatory state, and prothrombotic state. Vitamin D (Vit D) regulates the absorption of calcium and phosphorus and thus, is universally accepted as an essential vitamin for bone strength as well as a facilitator of immune system function. Vit D was also shown to reduce the risks of CVD, multiple sclerosis, and developing seasonal flu. We conducted a systematic review to identify the general association between Vit D level and MetS, to highlight specific associations between Vit D level and individual components of MetS, and finally, to explore the effects of Vit D supplementation on each component of MetS. In this paper, we reviewed 14 recent studies investigating the relationships between Vit D, MetS, and components of MetS. From the review of seven studies, we confirmed a significant association between Vit D and MetS as a whole. Four out of the five observational studies we reviewed support that Vit D level is significantly associated with the following components of MetS: obesity and BMI, dyslipidemia, BP, and insulin and glucose metabolism. We did not discover any significant relationship between Vit D level and other MetS components. The review of seven additional randomized clinical trials (RCT)-based studies suggest that Vit D supplementation has significant effects on BP, abdominal obesity, and insulin and glucose metabolism.

Parvovirus Infection and Thrombotic Thrombocytopenic Purpura in an Adult Patient With Sickle Cell Beta-Thalassemia.

Parvovirus infection and thrombotic thrombocytopenic purpura (TTP) are rare manifestations in adults with sickle cell beta-thalassemia. Due to the lack of a clear demarcation between the complications related to sickle cell disease (SCD) and TTP, the diagnosis is often challenging. The treatment requirements for both these entities are divergent and complicated, thus necessitating a careful plan of action during atypical presentations. Here we present a case of a 22-year-old woman during the peripartum period with fever, generalized body aches, and large joint pains that soon evolved into labor. The patient's history was suggestive of an undiagnosed and inherited blood disorder. The presentation of aplastic crisis-splenic sequestration during early adulthood is atypical for the SCD course in general populations. Moreover, as the patient's clinical status deteriorated with blood transfusion, the diagnosis and management of a sickle cell crisis event and TTP added to the dilemma in the presence of non-classic parvovirus infection. Though the causation of TTP due to SCD-parvovirus infection is questionable, the treatment of the baseline sickle cell crisis with the novel supportive measures resolved the underlying complications in our patient, suggesting the causal effect. As a result of this, we emphasize the importance of being vigilant about such atypical presentations to avoid delays in diagnosis and treatment of such life-threatening emergencies like TTP.

A Spectrum of Pulmonary Complications Occurring in End-Stage Renal Disease Patients on Maintenance Hemodialysis.

Objective To investigate the trends of end-stage renal disease (ESRD) in patients undergoing maintenance hemodialysis (MHD) and find the correlation with effects on the pulmonary system in such patients. Methodology A multicentric prospective study was conducted in the city of Solapur, India. Data were collected from 250 patients through interpersonal interrogation using a questionnaire to capture basic demographic details, the history of ESRD, and relevant respiratory symptoms like breathlessness, cough, fever, etc. related to their disease. Symptoms that are likely associated with the pulmonary system were analyzed and referred to the pulmonology department. Appropriate diagnoses were made using relevant diagnostic tools like X-rays and sputum studies. The association between various disease attributes and pulmonary diagnoses was analyzed using the chi-square (χ2) test, with a p-value of value less than or equal to 0.05 considered statistically significant. Various socio-demographic variables, existing comorbidities, occupation-related risk factors, smoking history, past or current history of any respiratory conditions, the association between the causes of ESRD, time since the first dialysis and sociodemographic factors, and frequency of pulmonary complications were the other covariates in the study. Results Our study reports that 31.6% of our patients had significant impairment in their functioning due to respiratory complaints. The prevalence of respiratory complications was 27.2%. Major contributors were pleural effusion (33.8), pneumonia (25), pulmonary edema (20.58), pleuritis (11.76), collapse (8.8), tuberculosis (5.8), fibrosis (4.4), pericardial effusion (4.4), calcification (2.9), and hydrothorax (1.47). We report one case of Urinothorax as a rare cause of hydrothorax in such patients. Overall, our analysis found a significant association between non-reporting of respiratory complaints and acute admissions to the intensive care unit (ICU) with a respiratory cause at p-value 0.0076 with a greater predilection toward the rural populations. Conclusion Our study results highlight the prevalence of pulmonary complications in ESRD patients. The occurrence of pulmonary complications, irrespective of the presence of symptoms and a greater association between non-reporting of respiratory symptoms and acute admissions to the ICU, is a hallmark to consider the importance of history and clinical vigilance during patient visits.

EEG Observations in Probable Sporadic CJD.

INTRODUCTION: Sporadic Creutzfeldt Jakob Disease, the most common reported prion disease, is a fatal neurodegenerative disease caused by the misfolding of protein PrPC to PrPSC. EEG is the first in vivo test to support the clinical diagnosis of sporadic CJD (sCJD). This study is carried out to describe the comprehensive electroencephalography changes in a cohort of patients with probable sCJD from south India. METHODOLOGY: This retrospective observational study is conducted by reviewing case records from 2013-2020. Demographic, clinical, imaging details were noted. Electroencephalogram (EEG) recordings were retrieved and reviewed independently by two qualified epileptologists and the findings were visually analyzed and correlated with clinical and imaging abnormalities. RESULTS: Fifty patients with probable sCJD with the availability of artefact-free EEG were included in the study. The mean age was 59.76 ± 8.17 years and M: F was 31:19. Magnetic resonance imaging (MRI) brain showed abnormality defining CJD in 48/50, i.e., 96%patients. EEG showed specific and or nonspecific abnormalities in 88%. The specific abnormalities, i.e., periodic sharp wave complexes (PSWC), were noted 66%. PSWC were mostly asymmetric (90%) and more frequently seen in the right hemisphere (57.6%). Amplitude maximum in the occipital region was noted in 42.4% and in frontal region in 36.4%. The sensitivity of EEG specific abnormalities to diagnose probable sCJD according to CDC 2018 criteria with positive MRI findings was 68.75%. CONCLUSION: This study showed that EEG is a relatively inexpensive and sensitive tool and assists in the diagnosis of sCJD. However, it can be normal or show nonspecific abnormalities in the early stages of the disease.

MOG antibody seropositive aseptic meningitis: A new clinical phenotype.

The spectrum of myelin oligodendrocyte glycoprotein antibody (MOG-Ab) associated demyelination is evolving. Our case report describes a unique clinical presentation of aseptic meningitis with demyelinating lesions of the brain resembling acute disseminated encephalomyelitis and MOG-Ab seropositivity. A 22-year-old lady presented with history of fever of one week duration followed by headache, vomiting and neck stiffness. She had bilateral papilledema and signs of meningeal irritation. Neuroimaging revealed T2 and FLAIR hyperintense lesions in the right caudate, temporal lobe and left insula with enhancement on gadolinium contrast along with leptomeningeal enhancement. An extensive search for infectious and inflammatory etiology was negative while serum was positive for MOG-Abs tested twice at an interval of 12 days. She showed remarkable clinical-radiological resolution with steroids and has remained symptom free on follow up.

Monoclonal antibody therapeutics with up to five specificities: functional enhancement through fusion of target-specific peptides.

The recognition that few human diseases are thoroughly addressed by mono-specific, monoclonal antibodies (mAbs) continues to drive the development of antibody therapeutics with additional specificities and enhanced activity. Historically, efforts to engineer additional antigen recognition into molecules have relied predominantly on the reformatting of immunoglobulin domains. In this report we describe a series of fully functional mAbs to which additional specificities have been imparted through the recombinant fusion of relatively short polypeptides sequences. The sequences are selected for binding to a particular target from combinatorial libraries that express linear, disulfide-constrained, or domain-based structures. The potential for fusion of peptides to the N- and C- termini of both the heavy and light chains affords the bivalent expression of up to four different peptides. The resulting molecules, called zybodies, can gain up to four additional specificities, while retaining the original functionality and specificity of the scaffold antibody. We explore the use of two clinically significant oncology antibodies, trastuzumab and cetuximab, as zybody scaffolds and demonstrate functional enhancements in each case. The affect of fusion position on both peptide and scaffold function is explored, and penta-specific zybodies are demonstrated to simultaneously engage five targets (ErbB2, EGFR, IGF-1R, Ang2 and integrin αvß3). Bispecific, trastuzumab-based zybodies targeting ErbB2 and Ang2 are shown to exhibit superior efficacy to trastuzumab in an angiogenesis-dependent xenograft tumor model. A cetuximab-based bispecific zybody that targeting EGFR and ErbB3 simultaneously disrupted multiple intracellular signaling pathways; inhibited tumor cell proliferation; and showed efficacy superior to that of cetuximab in a xenograft tumor model.

Simultaneous targeting of TNF and Ang2 with a novel bispecific antibody enhances efficacy in an in vivo model of arthritis.

Despite the clinical success of anti-tumor necrosis factor (TNF) therapies in the treatment of inflammatory conditions such as rheumatoid arthritis, Crohn disease and psoriasis, full control of the diseases only occurs in a subset of patients and there is a need for new therapeutics with improved efficacy against broader patient populations. One possible approach is to combine biological therapeutics, but both the cost of the therapeutics and the potential for additional toxicities needs to be considered. In addition to the various mediators of immune and inflammatory pathways, angiogenesis is reported to contribute substantially to the overall pathogenesis of inflammatory diseases. The combination of an anti-angiogenic agent with anti-TNF into one molecule could be more efficacious without the risk of severe immunosuppression. To evaluate this approach with our Zybody technology, we generated bispecific antibodies that contain an Ang2 targeting peptide genetically fused to the anti-TNF antibody adalimumab (Humira®). The bispecific molecules retain the binding and functional characteristics of the anti-TNF antibody, but with additional activity that neutralizes Ang2. In a TNF transgenic mouse model of arthritis, the bispecific anti-TNF-Ang2 molecules showed a dose-dependent reduction in both clinical symptoms and histological scores that were significantly better than that achieved by adalimumab alone.

An albumin-butyrylcholinesterase for cocaine toxicity and addiction: catalytic and pharmacokinetic properties.

Butyrylcholinesterase (BChE, EC 3.1.1.8) is important in human cocaine metabolism despite its limited ability to hydrolyze this drug. Efforts to improve the catalytic efficiency of this enzyme have led to a quadruple mutant cocaine hydrolase, "CocH", that in animal models of addiction appears promising for treatment of overdose and relapse. We incorporated the CocH mutations into a BChE-albumin fusion protein, "Albu-CocH", and evaluated the pharmacokinetics of the enzyme after i.v. injection in rats. As assessed from the time course of cocaine hydrolyzing activity in plasma, Albu-CocH redistributed into extracellular fluid (16% of estimated total body water) with a t(1/2) of 0.66h and it underwent elimination with a t(1/2) of 8h. These results indicate that the enzyme has ample stability for short-term applications and may be suitable for longer-term treatment as well. Present data also confirm the markedly enhanced power of Albu-CocH for cocaine hydrolysis and they support the view that Albu-CocH might prove valuable in treating phenomena associated with cocaine abuse.

Structural and functional characterization of CC chemokine CCL14.

CC chemokine ligand 14, CCL14, is a human CC chemokine that is of recent interest because of its natural ability, upon proteolytic processing of the first eight NH2-terminal residues, to bind to and signal through the human immunodeficiency virus type-1 (HIV-1) co-receptor, CC chemokine receptor 5 (CCR5). We report X-ray crystallographic structures of both full-length CCL14 and signaling-active, truncated CCL14 [9-74] determined at 2.23 and 1.8 A, respectively. Although CCL14 and CCL14 [9-74] differ in their ability to bind CCR5 for biological signaling, we find that the NH2-terminal eight amino acids (residues 1 through 8) are completely disordered in CCL14 and both show the identical mode of the dimeric assembly characteristic of the CC type chemokine structures. However, analytical ultracentrifugation studies reveal that the CCL14 is stable as a dimer at a concentration as low as 100 nM, whereas CCL14 [9-74] is fully monomeric at the same concentration. By the same method, the equilibrium between monomers of CCL14 [9-74] and higher order oligomers is estimated to be of EC1,4 = 4.98 microM for monomer-tetramer conversion. The relative instability of CCL14 [9-74] oligomers as compared to CCL14 is also reflected in the Kd's that are estimated by the surface plasmon resonance method to be approximately 9.84 and 667 nM for CCL14 and CCL14 [9-74], respectively. This approximately 60-fold difference in stability at a physiologically relevant concentration can potentially account for their different signaling ability. Functional data from the activity assays by intracellular calcium flux and inhibition of CCR5-mediated HIV-1 entry show that only CCL14 [9-74] is fully active at these near-physiological concentrations where CCL14 [9-74] is monomeric and CCL14 is dimeric. These results together suggest that the ability of CCL14 [9-74] to monomerize can play a role for cellular activation.