A Streptococcus pneumoniae lineage usually associated with pneumococcal conjugate vaccine (PCV) serotypes is the most common cause of serotype 35B invasive disease in South Africa, following routine use of PCV.

Pneumococcal serotype 35B is an important non-conjugate vaccine (non-PCV) serotype. Its continued emergence, post-PCV7 in the USA, was associated with expansion of a pre-existing 35B clone (clonal complex [CC] 558) along with post-PCV13 emergence of a non-35B clone previously associated with PCV serotypes (CC156). This study describes lineages circulating among 35B isolates in South Africa before and after PCV introduction. We also compared 35B isolates belonging to a predominant 35B lineage in South Africa (GPSC5), with isolates belonging to the same lineage in other parts of the world. Serotype 35B isolates that caused invasive pneumococcal disease in South Africa in 2005-2014 were characterized by whole-genome sequencing (WGS). Multi-locus sequence types and global pneumococcal sequence clusters (GPSCs) were derived from WGS data of 63 35B isolates obtained in 2005-2014. A total of 262 isolates that belong to GPSC5 (115 isolates from South Africa and 147 from other countries) that were sequenced as part of the global pneumococcal sequencing (GPS) project were included for comparison. Serotype 35B isolates from South Africa were differentiated into seven GPSCs and GPSC5 was most common (49 %, 31/63). While 35B was the most common serotype among GPSC5/CC172 isolates in South Africa during the PCV13 period (66 %, 29/44), 23F was the most common serotype during both the pre-PCV (80 %, 37/46) and PCV7 period (32 %, 8/25). Serotype 35B represented 15 % (40/262) of GPSC5 isolates within the global GPS database and 75 % (31/40) were from South Africa. The predominance of the GPSC5 lineage within non-vaccine serotype 35B, is possibly unique to South Africa and warrants further molecular surveillance of pneumococci.

Impact of Hajj on the S. pneumoniae carriage among Indian pilgrims during 2016- a longitudinal molecular surveillance study.

BACKGROUND: The population flow dynamics of Hajj increases the probability of pneumococcal acquisition and amplification among Hajis. This multi-site longitudinal molecular surveillance study was designed to assess the impact and potential variations of pneumococcal carriage in a single cohort of pre and post-Hajj pilgrims from India. METHOD: A total of 3228 pre and post-Hajj, nasopharyngeal and oropharyngeal swabs were collected from 807 pilgrims with an interval of 40 ±â€¯5 days. The carriage was detected by culture and qmPCR. Quellung test, mPCR-FAF, PCRseqTyping, and MLST was used for typing. Antibiogram was performed by MIC method. RESULTS: An increased incidence of pneumococcal carriage was detected in post Hajj cohort by qmPCR (19% vs 21.8%) (p-value = 0.0487) and culture (6.5% vs 8.2%) (p-value = 0.0645). Fragment analysis could identify multiple serotype carriage in 76 pilgrims. Increase in drug resistance was also observed in post-hajj cohort for Tetracycline (29% vs 51%), Erythromycin (26% vs 46%) and Levofloxacin (6% vs 17%). Multidrug resistant strains in post Hajj group was 32% compared to 11% in pre Hajj group (p-value = 0.0002). CONCLUSION: Our results confirm high acquisition rate of multidrug-resistant S. pneumoniae in Hajj pilgrims and highlight its potential spread to home countries upon their return. Surveillance studies are needed to evaluate modifiable factors associated with carriage.

Consensus Recommendation for India and Bangladesh for the Use of Pneumococcal Vaccine in Mass Gatherings with Special Reference to Hajj Pilgrims.

Respiratory tract infections are prevalent among Hajj pilgrims with pneumonia being a leading cause of hospitalization. Streptococcus pneumoniae is a common pathogen isolated from patients with pneumonia and respiratory tract infections during Hajj. There is a significant burden of pneumococcal disease in India, which can be prevented. Guidelines for preventive measures and adult immunization have been published in India, but the implementation of the guidelines is low. Data from Bangladesh are available about significant mortality due to respiratory infections; however, literature regarding guidelines for adult immunization is limited. There is a need for extensive awareness programs across India and Bangladesh. Hence, there was a general consensus about the necessity for a rapid and urgent implementation of measures to prevent respiratory infections in pilgrims traveling to Hajj. About ten countries have developed recommendations for pneumococcal vaccination in Hajj pilgrims: France, the USA, Kuwait, Qatar, Bahrain, the UAE (Dubai Health Authority), Singapore, Malaysia, Egypt, and Indonesia. At any given point whether it is Hajj or Umrah, more than a million people are present in the holy places of Mecca and Madina. Therefore, the preventive measures taken for Hajj apply for Umrah as well. This document puts forward the consensus recommendations by a group of twenty doctors following a closed-door discussion based on the scientific evidence available for India and Bangladesh regarding the prevention of respiratory tract infections in Hajj pilgrims.

Knockout of Atg5 delays the maturation and reduces the survival of adult-generated neurons in the hippocampus.

Autophagy is an evolutionarily conserved lysosomal degradation pathway that plays important roles in cell maintenance, expansion and differentiation. Removal of genes essential for autophagy from embryonic neural stem and precursor cells reduces the survival and inhibits neuronal differentiation of adult-generated neurons. No study has modified autophagy within the adult precursor cells, leaving the cell-autonomous role of autophagy in adult neurogenesis unknown. Here we demonstrate that autophagic flux exists in the adult dividing progenitor cells and their progeny in the dentate gyrus. To investigate the role of autophagy in adult hippocampal neurogenesis, we genetically deleted Autophagy-related gene 5 (Atg5) that reduced autophagic flux and the survival of the progeny of dividing progenitor cells. This significant reduction in survival of adult-generated neurons is accompanied by a delay in neuronal maturation, including a transient reduction in spine density in the absence of a change in differentiation. The delay in cell maturation and loss of progeny of the Atg5-null cells was not present in mice that lacked the essential pro-apoptotic protein Bax (Bcl-2-associated X protein), suggesting that Atg5-deficient cells die through a Bax-dependent mechanism. In addition, there was a loss of Atg5-null cells following exposure to running, suggesting that Atg5 is required for running-induced increases in neurogenesis. These findings highlight the cell-autonomous requirement of Atg5 in the survival of adult-generated neurons.

Value addition to rice straw through pyrolysis in hydrogen and nitrogen environments.

Pyrolysis of rice straw has been carried out under hydrogen atmosphere at 300, 350, 400 and 450 °C and pressures of 1, 10, 20, 30 and 40 bar and in nitrogen atmosphere, experiments have been carried out at the same temperatures. It has been observed that the optimum process conditions for hydropyrolysis are 400 °C and 30 bar pressure and for slow pyrolysis, the optimum temperature is 400 °C. The bio-oil has been characterised using GC-MS, (1)H NMR and FT-IR and bio-char using FT-IR, SEM and XRD. The bio-oil yield under hydrogen pressure was observed to be 12.8 wt.% (400 °C and 30 bar) and yield under nitrogen atmosphere was found to be 31 wt.% (400 °C). From the product characterisation, it was found that the distribution of products is different for hydrogen and nitrogen environments due to differences in the decomposition reaction mechanism.

Standardisation and evaluation of a quantitative multiplex real-time PCR assay for the rapid identification of Streptococcus pneumoniae.

Rapid diagnosis of Streptococcus pneumoniae can play a significant role in decreasing morbidity and mortality of infection. The accurate diagnosis of pneumococcal disease is hampered by the difficulties in growing the isolates from clinical specimens and also by misidentification. Molecular methods have gained popularity as they offer improvement in the detection of causative pathogens with speed and ease. The present study aims at validating and standardising the use of 4 oligonucleotide primer-probe sets (pneumolysin [ply], autolysin [lytA], pneumococcal surface adhesion A [psaA] and Spn9802 [DNA fragment]) in a single-reaction mixture for the detection and discrimination of S. pneumoniae. Here, we validate a quantitative multiplex real-time PCR (qmPCR) assay with a panel consisting of 43 S. pneumoniae and 29 non-pneumococcal isolates, 20 culture positive, 26 culture negative and 30 spiked serum samples. A standard curve was obtained using S. pneumoniae ATCC 49619 strain and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene was used as an endogenous internal control. The experiment showed high sensitivity with lower limit of detection equivalent to 4 genome copies/µl. The efficiency of the reaction was 100% for ply, lytA, Spn9802 and 97% for psaA. The test showed sensitivity and specificity of 100% with culture isolates and serum specimens. This study demonstrates that qmPCR analysis of sera using 4 oligonucleotide primers appears to be an appropriate method for the genotypic identification of S. pneumoniae infection.

Investigation on antidiarrhoeal activity of Aristolochia indica Linn. Root extracts in mice.

BACKGROUND: The present study aimed at investigating the effect of ethanolic extract (EtAI), and aqueous extract (AqAI) of Aristolochia indica Linn roots on castor oil-induced diarrhoea and study on small intestinal transit. Phytochemical analysis of extracts was performed as per standard procedure. MATERIALS AND METHODS: The oral toxicity study using Swiss albino mice was performed in accordance with OECD guidelines. The EtAI and AqAI extracts of Aristolochia indica Linn were studied for antidiarrhoeal property using castor oil-induced diarrhoeal model and charcoal-induced gastrointestinal motility test in Swiss albino mice. RESULTS: Among the tested doses of 200 and 400 mg/kg body weight, the extracts reduced the frequency and severity of diarrhoea in test animals throughout the study period. At the same doses, the extract delayed the intestinal transit of charcoal meal in test animals as compared to the control and the results were statistically significant. CONCLUSION: Experimental findings showed that ethanol extract of Aristolochia indica Linn root possess significant antidiarrheal activity and may be a potent source of anti-diarrhoeal drug in future.

Nasopharyngeal carriage, antibiogram & serotype distribution of Streptococcus pneumoniae among healthy under five children.

BACKGROUND & OBJECTIVES: Information related to nasopharyngeal carriage of Streptococcus pneumoniae among healthy children is scanty in India. This prospective study was undertaken to determine the presence of asymptomatic nasopharyngeal colonization, assess serogroups/types (SGT) and drug resistance of S. pneumoniae in children below five years of age. METHODS: A total of 109 male and 81 female children in the age group of three months to five years belonging to different socio-economic classes were enrolled. They were recruited across all age groups from those attending paediatric OPD of a tertiary care and research centre for immunization program. Fifty three isolates identified as pneumococci were tested for their antimicrobial susceptibility pattern by Kirby-Bauer's disc diffusion and E-Test methods. Serotyping was performed by detection of the quelling reaction with specific antiserum. RESULT: The pneumococcal carriage rate in the study population was 27.9 per cent. The isolation rate was associated with age being higher (49.2%) in smaller children (3-12 months) and among male (62.2%). The most prevalent SGTs were 19 followed by 10, 14 and 7; 21 per cent of isolates belonging to serotype 10 (n=7) were 11 (n=4) were not covered in any of the conjugate vaccines currently available in Indian market. Resistance to co-trimoxazole, tetracycline, penicillin and erythromycin was observed in 91 per cent (n=48), 36 per cent (n=19), 17 per cent (n=9) and 9 per cent (n=5) isolates, respectively. All the penicillin resistant isolates were found to be intermediately resistant by E-Test. Multidrug resistance was observed in 19 per cent (n=10) isolates. INTERPRETATION & CONCLUSIONS: High level of antibiotic resistance was present in S. pneumoniae isolated from healthy children below age five. A pneumococcal conjugate vaccine with the prevailing SGTs would help to reduce the pool of antibiotic resistant pneumococci. Continued surveillance of serotypes and tracking susceptibility pattern of S. pneumoniae will help to introduce appropriate vaccination protocols.

Determinants of prakriti, the human constitution types of Indian traditional medicine and its correlation with contemporary science.

BACKGROUND: Constitutional type of an individual or prakriti is the basic clinical denominator in Ayurveda, which defines physical, physiological, and psychological traits of an individual and is the template for individualized diet, lifestyle counseling, and treatment. The large number of phenotype description by prakriti determination is based on the knowledge and experience of the assessor, and hence subject to inherent variations and interpretations. OBJECTIVE: In this study we have attempted to relate dominant prakriti attribute to body mass index (BMI) of individuals by assessing an acceptable tool to provide the quantitative measure to the currently qualitative ayurvedic prakriti determination. MATERIALS AND METHODS: The study is cross sectional, multicentered, and prakriti assessment of a total of 3416 subjects was undertaken. Healthy male, nonsmoking, nonalcoholic volunteers between the age group of 20-30 were screened for their prakriti after obtaining written consent to participate in the study. The prakriti was determined on the phenotype description of ayurvedic texts and simultaneously by the use of a computer-aided prakriti assessment tool. Kappa statistical analysis was employed to validate the prakriti assessment and Chi-square, Cramer's V test to determine the relatedness in the dominant prakriti to various attributes. RESULTS: We found 80% concordance between ayurvedic physician and software in predicting the prakriti of an individual. The kappa value of 0.77 showed moderate agreement in prakriti assessment. We observed a significant correlations of dominant prakriti to place of birth and BMI with Chi-square, P < 0.01 (Cramer's V-value of 0.156 and 0.368, respectively). CONCLUSION: The present study attempts to integrate knowledge of traditional ayurvedic concepts with the contemporary science. We have demonstrated analysis of prakriti classification and its association with BMI and place of birth with the implications to one of the ways for human classification.

Intestinal Cryptosporidiosis and the Profile of the CD4 Counts in a Cohort of HIV Infected Patients.

BACKGROUND: Cryptosporidium is an infectious enteric pathogen which is capable of causing life-threatening illnesses in immunocompromised patients. AIMS: This prospective study was planned to know the frequency of intestinal cryptosporidiosis in HIV infected patients and its correlation with their immune status. Also, the conventional diagnostic methods were compared with the copro-antigen detection test by using Enzyme Linked Immuno Sorbent Assay (ELISA). SETTINGS AND DESIGN: This was a prospective cohort study. METHODS AND MATERIAL: Three consecutive stool samples which were collected from 90 HIV seropositive patients and 50 seronegative controls were screened for cryptosporidiosis by wet mount, direct modified ZN (Ziehl Neelsen) staining, modified ZN staining with formol ether concentration and copro-antigen detection by ELISA. Their immune statuses were measured by CD4 + cell counting. Statistical Analytical Tests which were Used: Odds ratio, Chi square test, Fisher extract test. RESULTS: Cryptosporidiosis was detected in 15 HIV seropositive cases. 13 cases had CD4 cell counts of < 100 cells/ µL. The formol ether concentration technique resulted in an increased number of oocysts/oil immersion field in 8 cases. ELISA was positive in 2 cases which were shown to be negative by modified ZN staining. All the controls were negative for cryptosporidium. CONCLUSIONS: Cryptosporidiosis is an opportunistic infection in HIV infected people who present with diarrhoea. The wet mount technique, though it is simple and inexpensive, is insensitive for the detection of cryptosporidium. The conventional modified ZN staining and the modified ZN staining with concentration have a sensitivity and a specificity of 85.71% and 98.84% respectively. The copro antigen detection by ELISA which has a greater sensitivity and specificity, is a useful tool in epidemiological studies.

Circulating Serotypes and Trends in Antibiotic Resistance of Invasive Streptococcus Pneumoniae from Children under Five in Bangalore.

BACKGROUND: Globally, Streptococcus pneumoniae is estimated to be responsible for 1 to 2 million deaths annually, in extremes of age. Serotypic distribution of pneumococci varies with age, time, and geographical area. Limited data is available on serotypic prevalence and antimicrobial susceptibility patterns of pneumococci in India. AIM: To assess resistance trends to different groups of antimicrobials and serotypic prevalences of invasive pneumococci. SETTINGS AND DESIGN: A prospective, hospital based study was conducted for two years, at a tertiary care medical college hospital in south Bangalore. Forty invasive pneumococcal isolates from children who were ≤5 years, with a clinical and radiological diagnosis of invasive pneumococcal disease, (IPD) were evaluated. METHODS: Qualitative typing/grouping was performed by doing the capsular reaction test (Neufeld test). Antimicrobial susceptibility was tested by Minimum Inhibitory Concentration method using automated microdilution procedure. RESULTS: The predominant invasive pneumococcal serotypes were serogroups/types (SGTs) 6 (25%) and 14 (17.5%). 35%, 77.5% and 15% of isolates were resistant to Penicillin, Trimethoprim/Sulfamethoxazole (TMP-SMX) and Ceftriaxone respectively. Intermediate and high level resistances to penicillin were seen in 22.5% and 12.5% of S. pneumoniae isolates correspondingly. Multidrug resistance was observed in 20% of strains. CONCLUSION: This study reported presence of high level drug resistance in invasive pneumococcal isolates which were obtained from children. The serogroup/type distribution in our study and those in other Indian studies were not even. This calls for monitoring of resistance and mapping of serotype distribution.

Establishment of population-based surveillance for invasive pneumococcal disease in Bangalore, India.

BACKGROUND: Invasive pneumococcal disease (IPD) is vaccine-preventable but few data on the incidence of PD exist for Indian children. AIMS: To assess the feasibility of implementing prospective, population-based surveillance for PD among children less than five years of age. Settings and Design :Hospitals and health agencies, Bangalore, India. Retrospective review and analysis of hospitalization records as well as public health and demographic data. MATERIAL AND METHODS: Records for 2006 hospitalizations for pneumococcal disease-associated syndromes (meningitis, pneumonia and sepsis) were identified at three pediatric referral hospitals (Indira Gandhi Institute of Child Health, Kempegowda Institute of Child Health and Vani Vilas Hospital) in Bangalore using International Classification of Diseases, 9th revision codes. Hospital microbiology laboratory records were assessed to ensure capacity for identifying S. pneumoniae. Population data were identified from national census and polio surveillance data. RESULTS: The Bangalore city southern zone includes 33 wards occupying 51 Km 2 with 150,945 children between 0-5 years of age served by three referral pediatric hospitals. From January--December 2006, records of these three hospitals showed 2,219 hospitalizations of children less than five years of age (967 pneumonia, 768 sepsis, and 484 meningitis) with PD-associated diagnoses (southern zone area incidence: 0.15/100,000 PD-associated hospitalizations, less than five years of age). There were 178 deaths in children less than five years of age, of which 87 were attributable to sepsis, 56 to pneumonia and 35 to meningitis. CONCLUSION: Our analysis suggests that the PD-associated disease burden in Bangalore is high and local institutions have capacity for population-based surveillance. In a prospective study, systematic attention to potential barriers in identifying children with pneumococcal infections will improve estimation of IPD incidence in India.

Troglitazone prevents and reverses dexamethasone induced insulin resistance on glycogen synthesis in 3T3 adipocytes.

Troglitazone lowers blood glucose levels in Type II diabetic patients. To evaluate the insulin sensitizing action of troglitazone on glycogen synthesis we have used dexamethasone-treated 3T3 adipocytes as an in vitro model. Differentiated 3T3 adipocytes were incubated with 100 nM dexamethasone for 6 days. Troglitazone (1.0 microM) or metformin (1.0 mM) with or without 200 nM insulin was added during the last 4 days. At the end, insulin (100 nM) stimulated glycogen synthesis was determined using (14)C-glucose. Dexamethasone caused a 50% reduction in glycogen synthesis. Troglitazone caused an approximately 3 fold increase in glycogen synthesis from 43.9+/-3.4 to 120+/-16.2 nmols h(-1). Under identical conditions metformin had no significant effect. When cells were incubated with troglitazone and dexamethasone simultaneously for 6 days, troglitazone but not metformin completely prevented dexamethasone-induced insulin resistance. RU 486 (1.0 microM) also completely prevented the insulin resistance. Chronic incubation with dexamethasone and insulin resulted in a 73% reduction in glycogen synthesis. In these adipocytes, troglitazone was partially active with glycogen synthesis rising from 23.1+/-3.0 to 44.4+/-4.5 nmol h(-1), P<0.01 while metformin was inactive. Troglitazone stimulated 2-deoxyglucose uptake by 2 - 3 fold in dexamethasone-treated adipocytes. Metformin also increased glucose uptake significantly. Troglitazone did not affect insulin binding while a 2 fold increase was observed in normal adipocytes where it exhibited a modest effect. Since the effect of troglitazone was greater in dexamethasone-treated adipocytes, troglitazone is likely to act by preventing dexamethasone-induced alterations which may include (i) binding to glucocorticoid receptor and (ii) effect on glucose uptake. These data demonstrate the direct insulin sensitizing action of troglitazone on glycogen synthesis and suggest a pharmacological profile different from metformin.

Teaching headache management to medicine residents.

BACKGROUND: To evaluate the effect of teaching headache management to PG-1 medicine residents. DESIGN: Observational study using prerotation and postrotation ratings by residents of improvement in their knowledge of etiology, diagnosis, appropriate use of narcotics, and treatment of headache. SETTING: Veterans Affairs Outpatient Clinic. PARTICIPANTS: Twenty-two medicine residents. MEASUREMENTS AND RESULTS: There was small but significant improvement in the total knowledge score (P = .03) and in areas of etiology of headache (P = .02) and appropriate use of narcotics (P = .001). CONCLUSION: We found there were substantial increases in residents subjective levels of understanding, history-taking and in the diagnosis and treatment of headache (P < .0001) in contrast to the objective knowledge test.

Sinusitis. A review for generalists.

A frequent complication of the common cold, sinusitis is one of the most prevalent problems seen in general medical and emergency department practices. In addition, nosocomial sinus infection, particularly in intensive care units, is being recognized more frequently. Decision making about managing patients with sinusitis is based primarily on the history and, to a lesser extent, the findings of the physical examination.

Headaches.

Headaches are a common problem that can be disabling. The clinical features and treatment of migraine, cluster, and tension headaches are presented in this article. Emphasis is placed on the newer drugs available for acute and prophylactic treatment of these headaches. Features of headaches associated with intracranial aneurysms, temporal arteritis, cerebrovascular accidents, brain tumors, and temporomandibular disorders are also discussed.

Recent advances in the acute management of migraine and cluster headaches.

I have discussed the pharmacokinetics, efficacies, and side effects of the various nonnarcotic drugs available for the treatment of patients who have headache. Sumatriptan, the newest one, is expensive but may be cost-effective for those who have failed traditional migraine treatment, who visit the ER frequently, who have potential for drug abuse, or who have to miss time from school or work due to the headache. Studies are in progress to compare sumatriptan with other available drugs such as DHE-45 and to determine its possible role in the prophylaxis of migraine. A new 5-HT1D receptor agonist with more efficacy and fewer side effects may be developed in the future. When sumatriptan and DHE-45 are contraindicated due to hypertension or coronary artery disease, other drugs such as metoclopramide, ketorolac, and butorphanol can be used as alternatives.