Assessment of Atherosclerosis in Sle Patients by Measuring Carotid Intima Media Thickness: A Cross Sectional Study.

SLE patients have an increased burden of atherosclerosis leading to adverse cardiovascular events.Alterations in endothelial function, dysregulated immune system and increased oxidative stress are implicated in their development and progression. Carotid Artery Ultrasound has been recommended by the AHA/ACC to assess and follow progression of subclinical atherosclerosis & correlate with traditional /non traditional CV risk factors in SLE. To study the correlation between Carotid Intima Media Thickness, traditional/non traditional CV risk factors in SLE. MATERIAL: Hospital based descriptive, cross sectional study.Patients with Systemic Lupus Erythematosus, diagnosed by SLICC 2012 criteria, aged > 12 years, irrespective of therapy status, between April 2019 to August 2020, were recruited by consecutive sampling. Non consenting patients, individuals with preexisting cardiovascular disease, history of MACE, hypothyroidism (detected prior to diagnosis of SLE/disease onset), smokers, PLHIV,individuals with neck surgical, radiation, were excluded. OBSERVATION: 55 SLE patients were observed. No individuals were lost to follow up. Subgroup analysis was performed between SLE with Nephritis (36) and those without Nephritis (19) as presenting features. The mean age of the study subjects is 33 years with mean disease duration of 4.6 years.SLE nephritis patients had longer disease duration,younger age of disease onset & longer duration of steroid usage.The mean Systolic BP is 134+/-20mmHg, observed to be significantly higher in SLE nephritis patients. Framingham Risk scores were positively correlated with duration of SLE disease & SLEDAI 2K scores & duration of steroid therapy. The mean CIMT of the study population is 0.91mm with 10.9% plaque prevalence whereas Mean CIMT of Lupus nephritis patients is 1.02+/- 0.27mm; but no statistically significant difference in CIMT was observed between two subgroups. Carotid Intima Media thickness was positively correlated in bivariate analysis with anti DSDNA ab levels, Framingham Risk Scores,anaemia, SLE Disease activity scores, 24hr urine proteinuria,duration of steroid usage, Serum Creatinine & CRP. No correlation between CIMT and age of subjects,FPG,TG,serum homocysteine was observed. CONCLUSION: SLE patients have a high atherosclerosis burden and are at increased risk of adverse cardiovascular events. Carotid intima media thickness measurement by USG doppler is a reliable, non invasive, inexpensive tool which helps to detect subclinical atherosclerosis and plaques in SLE patients. In this study,Lupus Nephritis patients, Neuropsychiatric SLE and SLE with secondary APS, early age of lupus onset, longer disease duration with prolonged steroid therapy,significant proteinuria, higher antiDSDNA ab levels and hypocomplementemia are observed to have higher mean CIMT and plaque formation.

Local neuropeptide signaling modulates serotonergic transmission to shape the temporal organization of C. elegans egg-laying behavior.

Animal behaviors are often composed of distinct alternating behavioral states. Neuromodulatory signals are thought to be critical for establishing stable behavioral states and for orchestrating transitions between them. However, we have only a limited understanding of how neuromodulatory systems act in vivo to alter circuit performance and shape behavior. To address these questions, we have investigated neuromodulatory signaling in the context of Caenorhabditis elegans egg-laying. Egg-laying activity cycles between discrete states-short bursts of egg deposition (active phases) that alternate with prolonged quiescent periods (inactive phases). Here using genetic, pharmacological and optogenetic approaches for cell-specific activation and inhibition, we show that a group of neurosecretory cells (uv1) located in close spatial proximity to the egg-laying neuromusculature direct the temporal organization of egg-laying by prolonging the duration of inactive phases. We demonstrate that the modulatory effects of the uv1 cells are mediated by peptides encoded by the nlp-7 and flp-11 genes that act locally to inhibit circuit activity, primarily by inhibiting vesicular release of serotonin from HSN motor neurons. This peptidergic inhibition is achieved, at least in part, by reducing synaptic vesicle abundance in the HSN motor neurons. By linking the in vivo actions of specific neuropeptide signaling systems with the generation of stable behavioral outcomes, our study reveals how cycles of neuromodulation emanating from non-neuronal cells can fundamentally shape the organization of a behavioral program.

A conserved dopamine-cholecystokinin signaling pathway shapes context-dependent Caenorhabditis elegans behavior.

An organism's ability to thrive in changing environmental conditions requires the capacity for making flexible behavioral responses. Here we show that, in the nematode Caenorhabditis elegans, foraging responses to changes in food availability require nlp-12, a homolog of the mammalian neuropeptide cholecystokinin (CCK). nlp-12 expression is limited to a single interneuron (DVA) that is postsynaptic to dopaminergic neurons involved in food-sensing, and presynaptic to locomotory control neurons. NLP-12 release from DVA is regulated through the D1-like dopamine receptor DOP-1, and both nlp-12 and dop-1 are required for normal local food searching responses. nlp-12/CCK overexpression recapitulates characteristics of local food searching, and DVA ablation or mutations disrupting muscle acetylcholine receptor function attenuate these effects. Conversely, nlp-12 deletion reverses behavioral and functional changes associated with genetically enhanced muscle acetylcholine receptor activity. Thus, our data suggest that dopamine-mediated sensory information about food availability shapes foraging in a context-dependent manner through peptide modulation of locomotory output.

The impaired synthesis of insulin and its inability to inhibit platelet aggregation in cerebrovascular accident.

Both ischemic stroke (IS) and hemorrhagic stroke (HS) are reported to occur due to thrombosis on the arteries of the brain. As diabetes mellitus is a risk factor for strokes and insulin is reported to prevent thrombosis, the role of insulin in IS and HS was investigated. Forty eight stroke victims (IS = 22, HS = 26) and equal number of aged and sex matched normal volunteers participated in the study. Nitric oxide was determined by methemoglobin method. Insulin and Dermcidin isoform-2 (DCN2) level was determined by ELISA by using insulin and dermcidin antibody. Insulin binding to the platelet membrane was analyzed by scat chard plot. Treatment of normal platelet rich plasma (10(8)platelets/ml) with 15µUnits insulin/ml produced 1.41 nmol NO. The PRP from the IS and HS victims produced 0.38 nmol NO and 0.08 nmol NO respectively. Pretreatment of PRP from IS or HS subjects with 15 µM aspirin followed by 15µUnits of insulin/ml resensitized the platelets to the inhibitory effect of insulin. Mice hepatocytes treated with 0.14 µM DCN2 abolished the glucose induced insulin synthesis by NO that can be reversed by using 15 µM aspirin. It can be concluded that presence of DCN2 in stroke causes a condition similar to type I diabetes and nullified the effect of insulin in the inhibition of platelet aggregation in both IS and HS. The effect was reversed by 15 µM aspirin.

The PAPS transporter PST-1 is required for heparan sulfation and is essential for viability and neural development in C. elegans.

Sulfations of sugars, such as heparan sulfates (HS), or tyrosines require the universal sulfate donor 3'-phospho-adenosine-5'-phosphosulfate (PAPS) to be transported from the cytosol into the Golgi. Metazoan genomes encode two putative PAPS transporters (PAPST1 and PAPST2), which have been shown in vitro to preferentially transport PAPS across membranes. We have identified the C. elegans orthologs of PAPST1 and PAPST2 and named them pst-1 and pst-2, respectively. We show that pst-1 is essential for viability in C. elegans, functions non-redundantly with pst-2, and can act non-autonomously to mediate essential functions. Additionally, pst-1 is required for specific aspects of nervous system development rather than for formation of the major neuronal ganglia or fascicles. Neuronal defects correlate with reduced complexity of HS modification patterns, as measured by direct biochemical analysis. Our results suggest that pst-1 functions in metazoans to establish the complex HS modification patterns that are required for the development of neuronal connectivity.

A study of platelet aggregation in patients with acute myocardial infarction at presentation and after 48 hrs of initiating standard anti platelet therapy.

AIMS & OBJECTIVES: Platelet aggregation is a key factor behind coronary artery disease. Various complications after an attack of acute coronary syndrome are often related to the platelet hyperactivity in the early hours following the event. There is a growing concern regarding aspirin & clopidogrel resistance, which has put the time-tested therapies under scrutiny. Time has come to address the issue of platelet hyperactivity in the early hours & whether to individualize therapy and drug doses in different patients. MATERIALS & METHODS: We prospectively enrolled 41 patients with a diagnosis of acute myocardial infarction (AMI) between July 2009 and July 2010 admitted to the cardiology ward and ICCU of Medical College, Kolkata, after fulfillment of inclusion & exclusion criteria. The study was reviewed and approved by the Institutional Ethical Committee. Platelet Aggregation (PA) with 10 microM epinephrine, 2 microg/ml collagen and 10 microM ADP was performed with light transmittance aggregometry in all patients according to the standard protocol. Tests were done within 3 hours of sampling with platelet-rich plasma (PRP) by the turbidometric method in a 2-channel aggregometer (Chrono-Log 490 Model, Chrono-Log Corp, Havertown, Pa). Aspirin & clopidogrel resistance were defined as per ACC/AHA guidelines. Platelet aggregation studies were done at presentation (zero hour) and 48 hours after instituting dual antiplatelet therapy in standard doses. RESULTS: Patients with first attack of AMI showed a high mean platelet aggregation at 0 hours of 77.4% +/- 18.8% with ADP, 77.5% +/- 26% with Epinephrine & 73.5% +/- 24.9% with Collagen. With all three agonists, the initial hyperactivity of platelets at 0 hours was significantly higher among diabetics & obese. Though reduced, significant platelet hyperactivity remained at 48 hours after initiating standard antiplatelet therapy; 50.3% +/- 14.3% with ADP, 56.5% +/- 21.6% with epinephrine & 38.4% +/- 22% with collagen. CONCLUSION: In the early hours after AMI there is a fairly high degree of platelet aggregation. Even after 48 hours of standard antiplatelet therapy the platelet aggregation though reduced, still remains significantly high. Since recurrent ischemic episodes frequently occur in this vulnerable period, time has come to assess platelet aggregation status in high risk groups, if not in all patients of acute coronary syndrome during this period so that therapy may be individualized. Further researches are required in this area.

A conserved neuropeptide system links head and body motor circuits to enable adaptive behavior.

Neuromodulators promote adaptive behaviors that are often complex and involve concerted activity changes across circuits that are often not physically connected. It is not well understood how neuromodulatory systems accomplish these tasks. Here, we show that the Caenorhabditis elegans NLP-12 neuropeptide system shapes responses to food availability by modulating the activity of head and body wall motor neurons through alternate G-protein coupled receptor (GPCR) targets, CKR-1 and CKR-2. We show ckr-2 deletion reduces body bend depth during movement under basal conditions. We demonstrate CKR-1 is a functional NLP-12 receptor and define its expression in the nervous system. In contrast to basal locomotion, biased CKR-1 GPCR stimulation of head motor neurons promotes turning during local searching. Deletion of ckr-1 reduces head neuron activity and diminishes turning while specific ckr-1 overexpression or head neuron activation promote turning. Thus, our studies suggest locomotor responses to changing food availability are regulated through conditional NLP-12 stimulation of head or body wall motor circuits.

Left atrial extension of lung malignancy with ECG changes resembling STEMI.

Lung malignancy extending into left atrium is seen very infrequently. We had a patient with a fast growing symptomatic lung mass and electrocardiogram showing persistent coving ST elevation without any biomarker change. Transthoracic echocardiography showed a large left atrial mass which was fixed to the free walls and extended into the appendage. There was also a large lung mass that was compressing the heart from its lateral aspect. CT-scan of chest corroborated the lung mass & CT-guided FNAC showed small cell carcinoma.

Echocardiographic profile of ART naïve human immunodeficiency virus (HIV) infected patients in a tertiary care hospital in Kolkata.

AIMS AND OBJECTIVE: Cardiac affection in human iummunodeficiency virus (HIV) infection is a recognized entity. Some form of heart disease is demonstrable at autopsy in approximately 40 percent of cases and by echocardiography in approximately 25 percent of patients with HIV. the studies indicate that cardiac involvements associated with HIV are mainly characterized by cardiomyopathy and pericardial disease. HIV infection is a global pandemic which is also rapidly spreading in india. We conducted the study to have some insight into the profile oflndian patients. MATERIAL & METHODS: In this cross sectional hospital based study, we evaluated immunological (CD4 count) and echocardiographic status of 45 asymptomatic HIV seropositive patients who did not receive anti-retroviral therapy. The results were compared with age and sex matched controls. Statistical analysis was done using appropriate statistical methods. RESULTS: Most common cardiovascular abnormalities were diastolic dysfunction (18%) followed by pericardial effusion (13%) and systolic dysfunction (7%). When compared with controls the study population had statistically higher number of diastolic dysfunction (p value = 0.035) but not systolic dysfunction (p value = 0.61); none of the control population was having pericardial effusion. Low CD4 count was significantly associated with pericardial effusion (p value 0.048) but the association with diastolic dysfunction (p value = 0.46) or systolic dysfunction (p value = 0.84) was not statistically significant. CONCLUSION: Cardiovascular complications are common among HIV infected patients in india, most common being diastolic dysfunction and pericardial effusion. Low CD4 counts are associated significantly with pericardial effusion. These abnormalities are likely to be found with greater frequency in clinical practice as management of opportunistic infections continues to improve.

Gorham's disease of mandible--a rare case presentation in pediatric patient.

Gorham's disease or vanishing bone disease is a rare, progressive musculoskeletal disorder characterized by resorption of bone matrix, and later replaced by fibrous connective tissue. The disease has no specific predilection for age, gender, or race. The most common sites of involvement are the shoulder and pelvic bones. To date, nearly 50 cases of Gorham's disease with maxillofacial involvement have been reported in the literature. The etiology of Gorham's disease is not known, clinical features are variable, and prognosis is generally good unless vital structures are involved. Due to the rarity of the condition, no definite treatment protocol exists for this disorder. Here, we described a pediatric case of Gorham's disease with mandibular involvement.

In the proper context: Neuropeptide regulation of behavioral transitions during food searching.

Neuromodulation enables transient restructuring of anatomically fixed neural circuits, generating alternate outputs and distinct states that allow for flexible organismal responses to changing conditions. We recently identified a requirement for the neuropeptide-like protein NLP-12, a Caenorhabditis elegans homolog of mammalian Cholecystokinin (CCK), in the control of behavioral responses to altered food availability. We showed that deletion of nlp-12 impairs turning during local food searching while nlp-12 overexpression is sufficient to induce deep body bends and enhance turning. nlp-12 is solely expressed in the DVA interneuron that is located postsynaptic to the dopaminergic PDE neurons and presynaptic to premotor and motor neurons, well-positioned for modulating sensorimotor tasks. Interestingly, DVA was previously implicated in a NLP-12 mediated proprioceptive feedback loop during C. elegans locomotion. Here, we discuss the modulatory effects of NLP-12 with an emphasis on the potential for circuit level integration with olfactory information about food availability. In addition, we propose potential mechanisms by which DVA may integrate distinct forms of sensory information to regulate NLP-12 signaling and mediate context-dependent modulation of the motor circuit.

Paraneoplastic optic neuritis as the first manifestation of periampullary carcinoma.

Paraneoplastic optic neuritis is a rare phenomenon that often presents as a diagnostic challenge. It has been mostly reported with small cell cancers or thymoma. Prompt treatment of the malignancy is the only effective therapy for the condition. Visual loss, once established usually becomes irreversible. We here report a case of paraneoplastic optic neuritis in a 40-year-old female with periampullary carcinoma. This is probably the first report of this association in the medical literature.

γ-Benzene hexachloride poisoning leading to acute hepatorenal decompensation.

γ-Benzene hexachloride is a commonly used insecticide of organochlorine group. Notable toxic effects include seizures, ataxia, confusion and other central nervous system dysfunction. A 30-year-old male farmer with suicidal ingestion of γ-benzene hexachloride poison developed acute intrinsic renal failure with azotaemia and diminished urine output along with features of acute fulminate liver failure. Renal function recovered with haemodialysis and liver parameters gradually normalised with time. As per our knowledge simultaneous acute hepatic and kidney injury associated with γ-benzene hexachloride poison is never reported in humans. The exact pathophysiology of this life-threatening complication is an enigma. However, oxidative stress has been postulated as a contributory factor as suggested in animal studies. Conservative management with successful outcome in our case stresses on the impact of watchful observation and aggressive management. He was discharged after 3 weeks at stable condition and was healthy at 3 months follow-up.

Study of C reactive protein as a prognostic marker in malaria from Eastern India.

BACKGROUND: C-reactive protein (CRP) is useful as marker of severity in malaria. African studies have shown that serum CRP levels correlate with parasite burden and complications in malaria, especially falciparum. However, there are very few data on CRP levels in Indian malaria patients. MATERIALS AND METHODS: We assessed CRP levels in malaria patients at presentation and studied for any relation of CRP levels with subsequent prognosis. Statistical tests included student's t-test, Mann Whitney U test, and chi square test, all with 2-tailed analyzes. RESULTS: Of 71 patients in our study, 42 (59.1%) were infected with P. falciparum. 23 (32.4%) patients needed admission and 10 (14.1%) died. Average CRP levels were quite high in malaria patients (31.29 ± 20.4 mg/L). There was no significant difference in CRP between vivax and falciparum cases. Admitted patients had significantly higher CRP levels compared to those treated on outdoor basis (47.11 ± 19.13 vs. 23.71 ± 16.35 mg/L; P < 0.0001). 8 patients were admitted with multiple complications. They had significantly high CRP level compared to those with 1 complication (P = 0.015). Also, patients who died had higher CRP levels compared to survivors (P = 0.000346). CRP levels at presentation showed positive correlation with duration of hospital stay (r = 0.59; P < 0.05). CRP levels >35 mg/L was highly sensitive in predicting mortality. CONCLUSION: Our study in Indian population corroborates the findings in African studies regarding prognostic role of CRP in malaria. CRP is an effective biomarker in assessing malaria severity and also for follow-up.

Elucidation of functional domains of Chandipura virus Nucleocapsid protein involved in oligomerization and RNA binding: implication in viral genome encapsidation.

Chandipura virus, a member of the vesiculovirus genera, has been recently recognized as an emerging human pathogen. Previously, we have shown that Chandipura virus Nucleocapsid protein N is capable of binding to both specific viral leader RNA as well as non-viral RNA sequences, albeit in distinct monomeric and oligomeric states, respectively. Here, we distinguish the regions of N involved in oligomerization and RNA binding using a panel of deletion mutants. We demonstrate that deletion in the N-terminal arm completely abrogates self-association of N protein. Monomer N specifically recognizes viral leader RNA using its C-terminal 102 residues, while oligomerization generates an additional RNA binding surface involving the N-terminal 320 amino acids of N overlapping with a protease resistant core that is capable of forming nucleocapsid like structure and also binding heterogeneous RNA sequences. Finally, we propose a model to explain the mechanism of genome encapsidation of this important human pathogen.

Case report of two sisters suffering from Weill-Marchesani syndrome with pulmonary stenosis.

We report two sisters having a rare congenital anomaly-Weill-Marchesani syndrome having disproportionate short height, restriction of joint movements, brachydactyly, dislocation of lens, bilateral glaucomatous optic atrophy, and pulmonary stenosis.

Cryptogenic cirrhosis: metabolic liver disease due to insulin resistance.

OBJECTIVE: Etiopathogenesis of cryptogenic cirrhosis (CC) is not yet well established. Up to 20% of non-alcoholic fatty liver disease (NAFLD) may progress to cirrhosis, mostly termed as cryptogenic. Insulin resistance and altered metabolic parameters form a major pathogenic link between NAFLD and CC. CC may thus be actually a metabolic liver disease. MATERIALS AND METHODS: Thirty-four patients of CC and 32 patients having cirrhosis due to chronic hepatitis B (Hep B) were assessed in a cross-sectional study in a tertiary hospital for insulin resistance, % ß-cell activity, obesity indices, plasma glucose, lipid profiles, and many other parameters. RESULTS: CC patients had higher homeostasis model assessment (HOMA)-IR compared to Hep B group (P = 0.000016). A positive correlation between IR values and Child-Pugh score among CC patients was found ("r" = 0.87; P < 0.00001). Out of 34 CC patients, 15 (44.1%) had obesity contrary to 6 (18.8%) in the control group (P = 0.0022). Differences were observed in subcutaneous fat (P = 0.0022), intra-abdominal fat (P = 0.0055), waist circumference (P = 0.014), and percentage body fat (P = 0.047) between the two groups. Significant differences were observed in the levels of triglyceride, total cholesterol, and very low density lipoprotein (VLDL). CONCLUSION: Most of the CC patients showed significantly higher prevalence of HOMA-IR, obesity indices, and various parameters of "lipotoxicity" and metabolic syndrome, suggesting that CC may be the long-term consequence of a type of "metabolic liver disease." Further studies are required to evaluate the role of therapeutic interventions to enhance insulin sensitivity in such patients.

Initiation of encapsidation as evidenced by deoxycholate-treated Nucleocapsid protein in the Chandipura virus life cycle.

Encapsidation of nascent genome RNA into an RNase-resistant form by nucleocapsid protein, N is a necessary step in the rhabdoviral life cycle. However, the precise mechanism for viral RNA specific yet processive encapsidation remains elusive. Using Chandipura virus as a model system, we examined RNA binding specificity of N protein and dissected the biochemical steps involved in the rhabdoviral encapsidation process. Our analysis suggested that N protein in its monomeric form specifically binds to the first half of the leader RNA in a 1:1 complex, whereas, oligomerization imparts a broad RNA binding specificity. We also observed that viral P protein and dissociating detergent deoxycholate, both were able to maintain N in a monomeric form and thus promote specific RNA recognition. Finally, use of a minigenome length RNA in an in vitro encapsidation assay revealed the monomeric N and not its oligomeric counterpart, to be the true encapsidating unit. Based on our observations, we propose a model to explain encapsidation that involves two discrete biochemically separable steps, initiation and elongation.

P-protein of Chandipura virus is an N-protein-specific chaperone that acts at the nucleation stage.

The nucleocapsid protein N of Chandipura virus is prone to aggregation in vitro. We have shown that this aggregation occurs in two phases in a nucleation-dependent manner. Electron microscopy suggests that the aggregated state may have a ring-like structure. Using a GFP fusion, we have shown that the N-protein also aggregates in vivo. The P-protein suppresses the N-protein aggregation efficiently, both in vitro and in vivo. Increased lag phase in the presence of the P-protein suggests that chaperone-like action of the P-protein occurs before the nucleation event. The P-protein, however, does not exert any chaperone-like action against other proteins, suggesting that it binds to the N-protein specifically. Surface plasmon resonance and fluorescence enhancement indeed suggest that the P-protein binds tightly to the native N-protein. The P-protein is thus an N-protein-specific chaperone which inhibits the nucleation phase of N-protein aggregation, thus keeping a pool of encapsidation-competent N-protein for viral maturation.