Evaluation of urinary free light chains as a marker of severity of HIV disease and its correlation with CD4 count: A Pilot Study.

INTRODUCTION: Human immunodeficiency virus (HIV) infection weakens immunity. Monitoring immune status of the patient has become an important aspect of evaluating the progression of the disease and informing follow-up after treatment. Estimation of CD4 counts is quite costly and requires expertise in flow-cytometry. In certain pathologies, free light chains are secreted in serum and urine and the magnitude can be used to monitor the severity, progression and therapeutic monitoring of the disease. Urine as a specimen proves cost-effective and presents reduced risks during sample collection. The stability of light chains in urine at room temperature over extended periods simplifies the management of sample transportation as well. Hence, a pilot cross sectional study was planned to evaluate the levels of urinary immunoglobulins in HIV patients. MATERIALS AND METHODS: The study was conducted at PGIMER, Dr. Ram Manohar Lohia Hospital, N.Delhi. Sixty nine consecutive ART-naive HIV patients aged between 18-40 years and 69 age-and sex-matched healthy controls were included in the study. Urinary free Light Chains (FLC) Kappa (κ) and Lambda (λ) were measured using an immunoglobulin ELISA kit. RESULTS: Baseline urinary κ light chain levels were significantly higher in cases when compared with controls (p<0.001) and were found to be increased with increasing WHO immunological classes (p<0.001) and inversely related to CD4 cell count. However, no significant difference in mean urinary λ immunoglobulin light chain between cases and controls was found and no correlation with CD4 cell count or with stages of WHO immunological classification of HIV disease was seen. CONCLUSION: It is suggested that urinary free κ chain measurements combined with serum light chain measurements may be a useful marker in the follow-up and monitoring of response to therapies in HIV-positive patients where testing by flow cytometry is not available.

Assessment of Otoacoustic Emissions (OAE) in Birth Asphyxiated Neonates.

One of the congenital abnormalities encountered in newborns is hearing loss. Birth hypoxia, asphyxia, and ischemia have all been implicated as primary causes of early hearing loss or deafness. Prospective study was done on neonates in NICU having APGAR scoring of < 7 in 5th minute or neonates diagnosed with birth asphyxia. OAEs were measured from both ears from 3rd to 5th day in sound-proof chamber. MRI reports of these neonates were collected and analyzed. The neonates who did not clear the 1st OAE testing further underwent a second OAE testing between 10 and 14th days. Results were further plotted. 21.9% of neonates had hearing loss. 28.1% of mothers had infections amongst which 6.3% were of hypothyroidism. 56% of neonates with normal OAE result had normal MRI findings. 71.4% of neonates showing a 'REFER' in OAE had normal MRI reports. 44% of neonates with normal OAE result had abnormal MRI report. 7 neonates who failed 1st OAE underwent secondary OAE testing after 10-14 days. 28.6% of the neonates with abnormal OAE report had abnormal MRI findings. There is no statistical correlation between OAE findings with MRI findings of the birth asphyxiated neonates. (p value = 0.671). Hence, there exists no correlation between hearing loss and birth asphyxia.

BQ788 reveals glial ETB receptor modulation of neuronal cholinergic and nitrergic pathways to inhibit intestinal motility: Linked to postoperative ileus.

BACKGROUND AND PURPOSE: ET-1 signalling modulates intestinal motility and inflammation, but the role of ET-1/ETB receptor signalling is poorly understood. Enteric glia modulate normal motility and inflammation. We investigated whether glial ETB signalling regulates neural-motor pathways of intestinal motility and inflammation. EXPERIMENTAL APPROACH: We studied ETB signalling using: ETB drugs (ET-1, SaTX, BQ788), activity-dependent stimulation of neurons (high K+ -depolarization, EFS), gliotoxins, Tg (Ednrb-EGFP)EP59Gsat/Mmucd mice, cell-specific mRNA in Sox10CreERT2 ;Rpl22-HAflx or ChATCre ;Rpl22-HAflx mice, Sox10CreERT2 ::GCaMP5g-tdT, Wnt1Cre2 ::GCaMP5g-tdT mice, muscle tension recordings, fluid-induced peristalsis, ET-1 expression, qPCR, western blots, 3-D LSM-immunofluorescence co-labelling studies in LMMP-CM and a postoperative ileus (POI) model of intestinal inflammation. KEY RESULTS: In the muscularis externa ETB receptor is expressed exclusively in glia. ET-1 is expressed in RiboTag (ChAT)-neurons, isolated ganglia and intra-ganglionic varicose-nerve fibres co-labelled with peripherin or SP. ET-1 release provides activity-dependent glial ETB receptor modulation of Ca2+ waves in neural evoked glial responses. BQ788 reveals amplification of glial and neuronal Ca2+ responses and excitatory cholinergic contractions, sensitive to L-NAME. Gliotoxins disrupt SaTX-induced glial-Ca2+ waves and prevent BQ788 amplification of contractions. The ETB receptor is linked to inhibition of contractions and peristalsis. Inflammation causes glial ETB up-regulation, SaTX-hypersensitivity and glial amplification of ETB signalling. In vivo BQ788 (i.p., 1 mg·kg-1 ) attenuates intestinal inflammation in POI. CONCLUSION AND IMPLICATIONS: Enteric glial ET-1/ETB signalling provides dual modulation of neural-motor circuits to inhibit motility. It inhibits excitatory cholinergic and stimulates inhibitory nitrergic motor pathways. Amplification of glial ETB receptors is linked to muscularis externa inflammation and possibly pathogenic mechanisms of POI.

Time from Self-Detection of Symptoms to Seeking Definitive Care among Cervical Cancer Patients.

BACKGROUND: India had the burden of 97,000 new cases of cervical cancer with 60,000 deaths accounting nearly one-third of global cervical cancer deaths during the year 2018. Cervical cancer is the leading cause of cancer mortality in India. The present study aims to estimate the time interval between self-detection of cervical cancer symptoms and seeking care and different barriers for the possible time lag in seeking care. METHODS: A cross-sectional study was undertaken from April 2017 to September 2017 in a regional cancer centre in the south of India. The centre has both a population and a hospital-based cancer registry. Cervical cancer cases (N= 210) with histological confirmation were interviewed at the hospital using a pre-tested semi-structured questionnaire. RESULTS: The median time interval between the self-detection of cervical cancer symptoms and first contact with the general physician was 80 [IQR 45-150] days. The overall median time interval between the self-detection of symptoms to the initiation of primary treatment was 123[IQR 83-205] days. The major perceived reason for not seeking medical care was a lack of awareness in identifying cervical cancer symptoms in 183(92.9%) women. CONCLUSION: The median time of 80 days was observed from the self-detection of cervical cancer symptoms to the first contact with a general physician. Lack of awareness of patients pertaining to cancer symptoms was the major concern in seeking cancer care.
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Assisted breastfeeding technique to improve knowledge, attitude, and practices of mothers with cleft lip- and palate-affected infants: A randomized trial.

BACKGROUND: Cleft lip and palate is one of the most common developmental anomalies affecting the craniofacial region leading to an array of problems including the inability to feed properly. OBJECTIVES: This study aimed to compare the effectiveness of specially designed audio-visual module over traditional instructional module in improving the assisted breastfeeding habits. METHODOLOGY: Sixteen patients received training regarding the feeding practices through the traditional instructional method, and 16 subjects received training through audio-visual module. Infants in both the groups received the standard care. These infants were followed up longitudinally for 6 months. During the follow up period, the growth parameters were recorded monthly. The knowledge, attitude, and practices of the mothers regarding feeding practices were assessed using KAP questionnaire. RESULTS: There was significant improvement in the knowledge of the mothers from baseline to 6 months, however, the practices indicated that the mothers belonging to the audio-visual module group showed better understating of the condition and earlier adaptation of the breastfeeding practices. Correspondingly, the growth parameters also showed significant difference. CONCLUSION: The custom-made audio-visual module would help the mothers adapt better to the stressful situation following the birth of the infant affected with cleft lip and palate.

Metabolic Equivalent and its Associated Factors in a Rural Community of Karnataka, India.

Background Health benefits of physical activity measured in terms of metabolic equivalent minutes (MET-minutes per week) have been established. However, factors affecting physical activity, like age, gender, body mass index, waist-hip ratio, particularly in rural communities have not been documented on a large sample. Methods Baseline physical activity data of more than 4000 subjects over 30 years of age, who were enrolled in a randomised community-based study on non-communicable diseases, were analysed. Global Physical Activity Questionnaire was used and anthropometric measurements were classified according to the MONICA study manual. Three domains of physical activity were measured as MET-minutes per week - activity at work, travel to and from places and recreational activities. Association of MET-minutes with sociodemographic variables and risk factors for cardiovascular diseases was studied. Results Mean MET-minutes per week of females were found to be significantly lower than that of males and decreased with advancing age and higher BMI in both genders. Married persons, normal BMI, normal waist-hip ratio, lower leisure time activity had demonstrated higher MET values (P = 0.000). In our study, the prevalence of inactivity (<600 MET-minutes) was 3.2% which was similar in both males and females. As high as 96.2% of the subjects had MET-minutes of > 1200. Nearly 50% of the subjects had leisure time ranging from 121 to 240 minutes per day. Conclusion A large majority of adults over 30 years of age in a rural community in Karnataka (96.2%) had very high MET-minutes per week of >1200 per day. Abnormal BMI, higher waist-hip ratio and more leisure time were associated with lower MET-minutes which are modifiable. About 50% had more than 2 hours of leisure time per day. It is recommended that health promotion for active lifestyle should be encouraged.

Association of Practices Regarding Infant and Young Child Feeding with Anthropometry Measurements Among an Urban Population in Karnataka, India.

Background Mothers' knowledge of infant and young child feeding (IYCF) play a crucial role in the overall growth and development of a child, determined by their anthropometry. Malnutrition has been linked to the short- and long-term effects on child health and, ultimately, national development. This community-based cross-sectional study focuses on the nutritional parameters of infants and young children in an urban slum population. The primary objective was to study IYCF from birth up to two years of age. The secondary objective involved studying the association between feeding practices and anthropometric measurements among children of 12-23 months of age. Methods The mothers of 96 children who were between 12 and 23 months of age, living in the urban slum of B.K Nagar, Bangalore, India, were administered the United Nations Children's Fund (UNICEF) IYCF questionnaire. Breastfeeding and complementary feeding information from these children from birth to 24 months were obtained. Anthropometric measurements were measured with appropriate calibrations. Results The population consisted of 57.3% females and 42.7% males. All children had mean anthropometric measurements below the World Health Organization Multicentre Growth Reference Study (WHO-MGRS) standard (weight for age in males, P=0.009, and females P=0.005). A delay in the initiation of breastfeeding was observed in female children (54.5%), showing a significant reduction in their weight (P=0.020) as compared to those initiated early. There was also a declining trend of continuation of breastfeeding from age 12 months to 23 months. The study revealed a high consumption of gripe water (68.8%) and bottle feeding (40.4%). A significant difference was found in children who consumed nutritious food, especially meat, with height (P=0.018) and weight (P=0.011), along with other foods. Conclusion IYCF and anthropometry have a direct association, evidence of which is reflected by the mother's knowledge of feeding practices along with other socioeconomic parameters.

Erythrocytes and Platelets: A Critical Analysis of their Ontogenic Relationship through Automated Parameters.

INTRODUCTION: Erythrocytes and platelets share an intimate development history, due to which special interest is centered on their relationship. Mature Red Blood Cells (RBCs) and platelets show a similar physiological rhythm, and are concurrently involved in numerous pathologic states. AIM: To identify subtle relationships between various RBC and platelet parameters with an objective to analyse if a linear correlation co-exists between and among them in physiological/pathological states. MATERIALS AND METHODS: A prospective analysis of 1250 EDTA blood samples was conducted. The five RBC parameters (RBC count, HCT, MCV, RDW, Hb) and four platelet parameters (platelet count, PCT, MPV, PDW) obtained from each case were statistically analysed for linear dependence. RESULTS: A statistically significant direct linear relationship was found between RDW with platelet count and PCT. A statistically significant inverse linear relationship was noticed between the following parameters: i) HCT with platelet count and PCT; ii) MCV with platelet count and PCT; iii) Haemoglobin and platelet count. CONCLUSION: A linear correlation, either direct or inverse, was seen among various parallel RBC and platelet parameters.

The birth of national mental health program for India.

The adoption of the National Mental Health Programme (NMHP) in August 1982 was a milestone in the history of Indian psychiatry. Such an ambitious program was formulated at a time where there were <1000 psychiatrists is a triumph of need for mental health care in the country. The story of the NMHP, both in terms of the technical forces and the personalities needs to be recorded for posterity. The current article recalls the community mental health initiatives of Bengaluru and Chandigarh centers providing the reason for integrating mental health care with general health care and the support of the World Health Organization, along with the role of mental health professionals and the health administrators. The lesson that come through is the value of working together with different professionals for the common good. Recording the events for posterity is especially timely in view of the formulation of a new mental health policy and the revision of the national health policy during the last few months.

Identification and pharmacological characterization of 3,6-diazabicyclo[3.1.1]heptane-3-carboxamides as novel ligands for the α4ß2 and α6/α3ß2ß3 nicotinic acetylcholine receptors (nAChRs).

We have synthesized a novel series of compounds, 3,6-diazabicyclo[3.1.1]heptane-3-carboxamides, targeting both the α4ß2 and α6/α3ß2ß3 nAChRs. Members of the obtained chemical library are partial or full agonists at both the high sensitivity (α4)2(ß2)3 and α6/α3ß2ß3 nAChRs. 3-(Cyclopropylcarbonyl)-3,6-diazabicyclo[3.1.1]heptane (TC-8831 or compound 7 herein) demonstrated a safe in vitro pharmacological profile and the potential for reducing or preventing L-dopa-induced dyskinesias (LID) in several in vivo animal models [1-4]. In vivo metabolism studies in rat and in vitro metabolism studies in liver microsomes from human, rat, dog and monkey showed TC-8831 to be relatively stable. In vivo pharmacokinetic analysis in the rat confirmed brain penetration, with an average brain:plasma ratio of approximately 0.3 across time points from 0.5 to 4 h. Docking into homology models predicted alternative binding modes for TC-8831 and highlighted the importance of the cationic center, hydrogen-bond acceptor, and hydrophobic aliphatic features in promoting binding affinity to both nAChRs. Pharmacophore elucidation confirmed the importance of these key interactions. QSAR modeling suggested that binding affinity is primarily driven by ligand shape, relative positive charge distribution onto the molecular surface, and molecular flexibility. Of the two subtypes, ligand binding to α6ß2ß3 appears to be more sensitive to bulkiness and flexibility.

Novel nicotinic acetylcholine receptor agonists containing carbonyl moiety as a hydrogen bond acceptor.

A novel series of α4ß2 nAChR agonists lacking common pyridine or its bioisosteric heterocycle have been disclosed. Essential pharmacophoric elements of the series are exocyclic carbonyl moiety as a hydrogen bond acceptor and secondary amino group within diaza- or azabicyclic scaffold. Computer modeling studies suggested that molecular shape of the ligand also contributes to promotion of agonism. Proof of concept for improving working memory performance in a novel object recognition task has been demonstrated on a representative of the series, 3-propionyl-3,7-diazabicyclo[3.3.0]octane (34).

Discovery of 3-(5-chloro-2-furoyl)-3,7-diazabicyclo[3.3.0]octane (TC-6683, AZD1446), a novel highly selective α4ß2 nicotinic acetylcholine receptor agonist for the treatment of cognitive disorders.

Diversification of essential nicotinic cholinergic pharmacophoric elements, i.e., cationic center and hydrogen bond acceptor, resulted in the discovery of novel potent α4ß2 nAChR selective agonists comprising a series of N-acyldiazabicycles. Core characteristics of the series are an exocyclic carbonyl moiety as a hydrogen bond acceptor and endocyclic secondary amino group. These features are positioned at optimal distance and with optimal relative spatial orientation to provide near optimal interactions with the receptor. A novel potent and highly selective α4ß2 nAChR agonist 3-(5-chloro-2-furoyl)-3,7-diazabicyclo[3.3.0]octane (56, TC-6683, AZD1446) with favorable pharmaceutical properties and in vivo efficacy in animal models has been identified as a potential treatment for cognitive deficits associated with psychiatric or neurological conditions and is currently being progressed to phase 2 clinical trials as a treatment for Alzheimer's disease.

Chitosan and chitosan chlorhydrate based various approaches for enhancement of dissolution rate of carvedilol.

BACKGROUND AND THE PURPOSE OF THE STUDY: Carvedilol nonselective ß-adrenoreceptor blocker, chemically (±)-1-(Carbazol-4-yloxy)-3-[[2-(o-methoxypHenoxy) ethyl] amino]-2-propanol, slightly soluble in ethyl ether; and practically insoluble in water, gastric fluid (simulated, TS, pH 1.1), and intestinal fluid (simulated, TS without pancreatin, pH 7.5) Compounds with aqueous solubility less than 1% W/V often represents dissolution rate limited absorption. There is need to enhance the dissolution rate of carvedilol. The objective of our present investigation was to compare chitosan and chitosan chlorhydrate based various approaches for enhancement of dissolution rate of carvedilol. METHODS: The different formulations were prepared by different methods like solvent change approach to prepare hydrosols, solvent evaporation technique to form solid dispersions and cogrind mixtures. The prepared formulations were characterized in terms of saturation solubility, drug content, infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), electron microscopy, in vitro dissolution studies and stability studies. RESULTS: The practical yield in case of hydrosols was ranged from 59.76 to 92.32%. The drug content was found to uniform among the different batches of hydrosols, cogrind mixture and solid dispersions ranged from 98.24 to 99.89%. There was significant improvement in dissolution rate of carvedilol with chitosan chlorhdyrate as compare to chitosan and explanation to this behavior was found in the differences in the wetting, solubilities and swelling capacity of the chitosan and chitosan salts, chitosan chlorhydrate rapidly wet and dissolve upon its incorporation into the dissolution medium, whereas the chitosan base, less water soluble, would take more time to dissolve. CONCLUSION: This technique is scalable and valuable in manufacturing process in future for enhancement of dissolution of poorly water soluble drugs.

Fine-needle aspiration diagnosis of extranodal non-Hodgkin's lymphoma of the tongue.

Primary non-Hodgkin's lymphoma (NHL) of the oral region is rare. Oral manifestation is present in 3-5% of cases of NHL and oral lesions are rarely the initial manifestations. We describe primary NHL, diffuse, mixed, small and large cell type in a 50-year-old female, who presented with mass lesion primarily involving the base of the tongue; initially diagnosed by fine needle aspiration cytology and later confirmed by histopathology and immunohistochemistry. Pertinent literature is being reviewed.

De-novo histoid leprosy.

Histoid leprosy is a rare form of multibacillary leprosy with distinct clinical and histopathological features. It is a variant of lepromatous leprosy. It occurs in lepromatous patients, who relapse after dapsone monotherapy, in the presence of dapsone resistance or at times 'de-novo'. We describe here a case of histoid leprosy, clinically mimicking neurofibromatosis.

The prevalence and correlates of DSM-IV disorders in the Iraq Mental Health Survey (IMHS).

Data on the prevalence and correlates of anxiety, mood, behavioral, and substance disorders are presented from a 2007-8 national survey of the Iraq population, the Iraq Mental Health Survey (IMHS). The IMHS was carried out by the Iraq Ministry of Health in collaboration with the Iraq Ministry of Planning and the World Health Organization (WHO) World Mental Health (WMH) Survey Initiative. Interviews were administered to a probability sample of Iraqi household residents by trained lay interviewers. The WHO Composite International Diagnostic interview (CIDI) was used to assess DSM-IV disorders. The response rate was 95.2%. The estimated lifetime prevalence of any disorder was 18.8%. Cohort analysis documented significantly increasing lifetime prevalence of most disorders across generations. This was most pronounced for panic disorder and post-traumatic stress disorder, with lifetime-to-date prevalence 5.4-5.3 times as high at comparable ages in the youngest (ages 18-34) as oldest (ages 65+) cohorts. Anxiety disorders were the most common class of disorders (13.8%) and major depressive disorder (MDD) the most common disorder (7.2%). Twelve-month prevalence of any disorder was 13.6%, with 42.1% of cases classified mild, 36.0% moderate, and 21.9% serious. The disorders most often classified serious were bipolar disorder (76.9%) and substance-related disorders (54.9%). Socio-demographic correlates were generally consistent with international epidemiological surveys, with the two exceptions of no significant gender differences in mood disorders and positive correlations of anxiety and mood disorders with education. Only 2.2% of IMHS respondents reported receiving treatment for emotional problems in the 12 months before interview, including 23.7% of those with serious, 9.2% with moderate, and 5.3% with mild disorders and 0.9% of other respondents. Most healthcare treatment, which was roughly equally distributed between the general medical and specialty sectors, was of low intensity. Further analyses of barriers to seeking treatment are needed to inform government efforts to expand the detection and treatment of mental disorders.

Donovanosis with auto-amputation of penis in a HIV-2 infected person.

Donovanosis is a slowly progressive, granulomatous ulcerative disease , caused by Klebsiella (Calymmatobacterium) granulomatis. The disease is known to persist for years together, leading to complications. A male patient aged 30 years with underlying HIV-2 infection presented to the department of STD with painful ulceration over the genital region of 5 months duration, with absence of penis. Tissue smear from the ulcer and histopathological examination revealed large histiocytes with intracellular Donovan bodies (Pund cell). A final diagnosis of donovanosis with auto-amputation of penis with HIV-2 infection was made. The old conventional medicines, viz. streptomycin, doxycycline and amoxycillin, were effective. Though HIV-2 infections are milder than HIV-1 infections in all aspects, donovanosis in this HIV-2 infected case presented with complications. However, since the CD4 count was 748 cells/cmm, the severity is attributed to the long standing nature and negligence by the patient, and not to possible immunodeficiency.

Experiences of stigma and discrimination endured by people suffering from schizophrenia.

OBJECTIVE: It is important to understand stigma in India, given its varied culture and mixture of rural and urban populations. Information from western literature cannot be applied without considering the sociocultural differences. AIMS: The research aimed to study the subjective experiences of stigma and discrimination undergone by people suffering from schizophrenia in rural and urban environments in India. SETTINGS AND DESIGN: Patients were selected from the outpatient services of six adult psychiatric units of the National Institute of Mental Health and Neurosciences (NIMHANS), India, and from the six outreach centers located in rural areas. MATERIALS AND METHOD: Two hundred patients diagnosed with schizophrenia were selected from rural and urban areas. The experiences of stigma and discrimination were assessed using a semi-structured instrument. STATISTICAL TECHNIQUES: Both quantitative and qualitative analyses were done. RESULTS: Significant differences were seen between rural and urban respondents. Urban respondents felt the need to hide their illness and avoided illness histories in job applications, whereas rural respondents experienced more ridicule, shame, and discrimination. The narratives provide direct views of patients, supporting the key findings. CONCLUSION: Mental health programs and policies need to be sensitive to the consumers' needs and to organize services and to effectively decrease stigma and discrimination.