Implication and utility of DAS-28 squeeze in rheumatoid arthritis: an Indian experience.

The purpose of this study was to compare and correlate disease activity score including 28 joints counts (DAS-28) Squeeze with DAS-28 and clinical disease activity index (CDAI) to assess disease activity (DA) in rheumatoid arthritis (RA) patients. A total of 100 RA patients were included in the study. All subjects were evaluated for disease activity using the DAS-28 Squeeze, DAS-28, and CDAI. Spearman's rho (ρ) was calculated to determine the correlation between DAS-28 Squeeze, DAS-28, and CDAI. Cross-tabulation was performed to compare and calculate the kappa coefficient for the link between two indices. For each scale, Cronbach's alpha was also calculated to test dependability. The average age of the study group was 43.9±11.3. The mean scores on the DAS-28 Squeeze, DAS-28, and CDAI were, respectively, 3.58±1.06, 5.06±1.56, and 22.81±14.92. p=0.001 indicated a significant correlation between DAS-28 Squeeze and DAS-28 (ρ=0.986) and CDAI (ρ=0.939) for DAS-28 Squeeze. There was a considerable correlation between all three measures at various DA levels. Cronbach's alpha for DAS-28 Squeeze, DAS-28, and CDAI were respectively 0.716, 0.663, and 0.734. DAS-28 Squeeze exhibited a substantial positive association with DAS-28 and CDAI for assessing disease activity and appears to be a more useful and reliable method than DAS-28 and CDAI for monitoring disease activity in RA patients.

Endophytes enhance the production of root alkaloids ajmalicine and serpentine by modulating the terpenoid indole alkaloid pathway in Catharanthus roseus roots.

AIM: The aim of this study was to identify and characterize promising endophytes capable of enhancing the content of root alkaloids ajmalicine and serpentine in low alkaloid yielding genotype of Catharanthus roseus cultivar Prabal and the possible mechanisms involved. METHOD AND RESULT: Of the four strains isolated from alkaloid-rich genotype of C. roseus cultivar Dhawal, endophytic strains CATDLF5 (Curvularia sp.) and CATDLF6 (Choanephora infundibulifera) enhanced serpentine content by 211·7-337·6%, while CATDRF2 (Aspergillus japonicus) and CATDS5 (Pseudomonas sp.) increased the content of ajmalicine by 123·4-203·8% in cultivar Prabal. Upregulated expression of key genes, geraniol 10-hydroxylase, tryptophan decarboxylase and strictosidine synthase involved in terpenoid indole alkaloid (TIA) biosynthetic pathway was observed in endophyte inoculated plants. Upregulated Octadecanoid-derivative Responsive Catharanthus AP2/ERF domain transcription activators like ORCA3 while, and downregulation of transcriptional repressor, ZCTs (Cys2/His2-type zinc finger protein family) enhanced the expression of genes for secondary metabolite production in endophyte-inoculated plants. CONCLUSION: The present work concluded that the selected endophytes of C. roseus can enhance the ajmalicine and serpentine contents by modulating the expression of structural and regulatory genes of TIA biosynthetic pathway in root. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytes can play an important role to enhance in planta content of pharmaceutically important alkaloids in C. roseus and can therefore be useful in reducing the cost of production of important alkaloids.

ACC deaminase-containing plant growth-promoting rhizobacteria protect Papaver somniferum from downy mildew.

AIMS: The aim of this study was to determine whether ACC (1-aminocyclopropane-1-carboxylic acid) deaminase-containing bacterial treatments could enhance the tolerance of poppy (Papaver somniferum L.) plants against biotic stress of downy mildew caused by Peronospora sp. METHODS AND RESULTS: Three different genotypes of P. somniferum, that is, Sampada, J-16 and I-14 were included in the experiment. The ACC deaminase-containing bacteria Pseudomonas putida (WPTe) reduced the downy mildew disease severity and significantly improved the growth and yield of P. somniferum plants. The chlorophyll content, photosynthetic rate, stomatal conductance and transpiration rate were modulated upon WPTe treatments in the poppy plants. We observed reduced synthesis of ethylene precursor (ACC) and abscisic acid (ABA), and enhanced production of indole acetic acid (IAA) in P. somniferum plants upon WPTe treatments. Moreover, WPTe treatment reduced proline and lipid peroxidation in plant leaves. CONCLUSION: These results highlight that the ACC deaminase-containing plant growth-promoting rhizobacteria (PGPR) enhance the tolerance of P. somniferum plant against downy mildew. SIGNIFICANCE AND IMPACT OF THE STUDY: ACC deaminase-containing PGPR may be used against phytopathogens which apart from protecting the plants from the disease could also be useful in reducing ethylene-induced damages in the event of abiotic stresses.

The role of a novel fungal strain Trichoderma atroviride RVF3 in improving humic acid content in mature compost and vermicompost via ligninolytic and celluloxylanolytic activities.

AIMS: With the rising concerns about indiscriminate use of chemical fertilizers and accumulation of agro-industrial wastes in huge quantities, the present experiment was conducted to elucidate the effect of a novel fungal strain of Trichoderma atroviride in hastening the compost/vermicompost production process and for the production of humic acid (HA) rich compost and vermicompost. METHODS AND RESULTS: Rice (Oryza sativa) straw and distillation waste of geranium (Pelargonium graveolens), two important agricultural/industrial crop wastes were subjected to composting and vermicomposting. T. atroviride strains GVF10 (cellulase and xylanase producing), and RVF3 (ligninase and celluloxylanase producing) were inoculated alone or in combination. The HA content was found to increase maximally in rice vermicompost treated with ligninase producing strain RVF3 (85% with respect to HA standard) followed by geranium vermicompost + RVF3. The addition of the strain GVF10 increased HA content to about 35-62% with respect to HA standard. The addition of the fungal inoculum reduced the composting/vermicomposting time from 110 to 90 days. CONCLUSIONS: Our results indicate that the use of selected fungal strain(s) hold potential to produce qualitatively superior compost and vermicompost with high HA content in a shorter period. SIGNIFICANCE AND IMPACT OF THE STUDY: Use of appropriate fungal strains may increase the efficiency of composting/vermicomposting processes producing compost and vermicompost with higher HA content, and alleviating the problems of solid waste accumulation and declining soil fertility.

A natural plant growth promoter calliterpenone from a plant Callicarpa macrophylla Vahl improves the plant growth promoting effects of plant growth promoting rhizobacteria (PGPRs).

Experiments were conducted to evaluate the efficacy of calliterpenone, a natural plant growth promoter from a shrub Callicarpa macrophylla Vahl., in enhancing the growth and yield promoting effects of plant growth promoting rhizobacteria (PGPRs), in menthol mint (Mentha arvensis L).This study is based on our previous results indicating the microbial growth promotion by calliterpenone and assumption that application of calliterpenone along with PGPRs will improve the population of PGPRs resulting in higher impacts on plant growth and yield. Of the 15 PGPRs (identified as potent ones in our laboratory), 25 µl of 0.01 mM calliterpenone (8.0 µg/100 ml) was found to be useful in improving the population of nine PGPRs in culture media. The five selected strains of PGPRs exhibiting synergy with calliterpenone in enhancing growth of maize compared to PGPR or calliterpenone alone were selected and tested on two cultivars (cvs. Kosi and Kushal) of M. arvensis. Of the five strains, Bacillus subtilis P-20 (16S rDNA sequence homologous to Accession No NR027552) and B. subtilis Daz-26 (16SrDNA sequence homologuos to Accession No GU998816) were found to be highly effective in improving the herb and essential oil yield in the cultivars Kushal and Kosi respectively when co-treated with calliterpenone. The results open up the possibilities of using a natural growth promoter along with PGPRs as a bio-agri input for sustainable and organic agriculture.

Nutritional and toxicological assessment of white-rot fermented animal feed.

The fungal fermented wheat straws as animal feeds have been evaluated for its toxicological and nutritional status in male rats (Holtzman strain). Digestibility of dry matter and other nutrients as well as fiber fractions were found significantly higher (P < 0.05) in straw fermented with either Ganoderma sp. rckk02 (T3) or Crinipellis sp. RCK-1 (T4) than unfermented straw (T1) or straw fermented with Pycnoporus cinnabarinus (T2). The aflatoxin B1, B2, G1 and G2 were either absent or present in permissive levels in T3 and T4 diets and exhibited normal stress enzyme activity in case of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) enzymes whereas, rats fed on T2 diet showed elevated levels of stress enzymes (ALT, AST and LDH activity), 100% high morbidity and 8.3% mortality. This study suggests that Ganoderma sp. rckk02 and Crinipellis sp. RCK-1 are efficient in improving the nutritive value of poor quality straw and do not posses any threat for their subsequent use as ruminant feed.

Thermal hysteresis in microtubule assembly/disassembly dynamics: The aging-induced degradation of tubulin dimers.

The assembly/disassembly of biological macromolecules plays an important role in their biological functionalities. Although the dynamics of tubulin polymers and their super-assembly into microtubule structures is critical for many cellular processes, details of their cyclical polymerization/depolymerization are not fully understood. Here, we use a specially designed light scattering technique to continuously examine the effects of temperature cycling on the process of microtubule assembly/disassembly. We observe a thermal hysteresis loop during tubulin assembly/disassembly, consistently with earlier reports on the coexistence of tubulin and microtubules as a phase transition. In a cyclical process, the structural hysteresis has a kinetic component that depends on the rate of temperature change but also an intrinsic thermodynamic component that depends on the protein topology, possibly related to irreversible processes. Analyzing the evolution of such thermal hysteresis loops over successive cycles, we found that the assembly/disassembly ceases after some time, which is indicative of protein aging leading to its inability to self-assemble after a finite number of temperature cycles. The emergence of assembly-incompetent tubulin could have major consequences for human pathologies related to microtubules, including aging, neurodegenerative diseases and cancer.

Association of Vitamin D Levels with Incident All-Cause Dementia in Longitudinal Observational Studies: A Systematic Review and Meta-analysis.

BACKGROUND: The role of vitamin D is not only limited to bone health and pathogenesis of chronic diseases. Evidence now suggests that it is also involved in the development of various dementias and Alzheimer's disease (AD). OBJECTIVE: To carry out a systematic review and meta-analysis to evaluate the association between vitamin D levels and increased risk of incident all-cause dementia in longitudinal studies. DESIGN: We conducted a systematic review and meta-analysis using the electronic bibliographic databases PubMed and Scopus. SETTING: Prospective cohort studies. PARTICIPANTS: Community-dwelling older adults. MEASUREMENTS: Vitamin D serum concentrations were categorized in three groups: normal levels (>50 nmol/L), insufficient levels (25 - 49.9 nmol/L), and deficient levels (<25 nmol/L). We performed a meta-analysis using the general inverse variance method to calculate the pooled risk of AD and all-cause dementia according to vitamin D levels. Random-effects or fixed-effect model were used to calculate the pooled risk based on the heterogeneity analysis. RESULTS: Five studies were included in the meta-analysis. The pooled risk of all-cause dementia and AD was significantly higher in those with deficient serum vitamin D level compared to those with normal level (1.33, CI95% [1.15, 1.54], and 1.87, CI95% [1.03, 3.41], respectively). Those with insufficient level also had a higher pooled risk of all-cause dementia and AD, but the strength of association was less robust (1.14 CI95% [1.02, 1.27] and 1.25, CI95% [1.04 - 1.51], respectively). CONCLUSION: We found a gradient effect for the risk of all-cause dementia and AD according to the vitamin D level, with higher risk in those in the deficient levels group and intermediate risk in those with insufficient levels. Our findings were limited by the relatively small number of studies included in the meta-analysis and their geographic restriction.

The role of core needle biopsies in the management of neck lumps.

INTRODUCTION: King's College Hospital has proudly provided a one-stop neck lump clinic since 2012. These multidisciplinary clinics allow for rapid diagnoses due to in-clinic investigations. In April 2013, ultrasound-guided core needle biopsies were introduced as an alternative/adjunct to fine-needle aspiration cytology and open biopsies for obtaining histological diagnoses. The aim of the study was to assess the impact of core needle biopsies on the diagnosis of neck lumps compared with fine-needle aspiration cytology and open biopsies between April 2015 and May 2016. MATERIALS AND METHODS: Data were collected prospectively between April 2015 and May 2016 and analysed for numbers of fine-needle aspiration cytology, core needle biopsies and open biopsies performed and diagnoses made. RESULTS: A total of 190 patients were seen on the clinic; 51 had fine-needle aspiration cytology and 19 procedures gave a diagnosis. Of the remainder of these patients, 21 went on to have a core needle biopsy and 12 biopsies gave a diagnosis. An additional eight patients only had a core needle biopsy, of which five biopsies gave a diagnosis. Of the ten patients who had an open biopsy, four had a previous fine-needle aspiration cytology and core needle biopsy, three only a core needle biopsy, two had neither and one had fine-needle aspiration cytology. CONCLUSION: The introduction of core needle biopsies has reduced the number of open biopsies performed. With increasing acceptance of this minimally invasive technique, core needle biopsies appear to be forming the key diagnostic investigation in patients with neck lumps.

Dermoscopy diagnosis of cancerous lesions utilizing dual deep learning algorithms via visual and audio (sonification) outputs: Laboratory and prospective observational studies.

BACKGROUND: Early diagnosis of skin cancer lesions by dermoscopy, the gold standard in dermatological imaging, calls for a diagnostic upscale. The aim of the study was to improve the accuracy of dermoscopic skin cancer diagnosis through use of novel deep learning (DL) algorithms. An additional sonification-derived diagnostic layer was added to the visual classification to increase sensitivity. METHODS: Two parallel studies were conducted: a laboratory retrospective study (LABS, n = 482 biopsies) and a non-interventional prospective observational study (OBS, n = 63 biopsies). A training data set of biopsy-verified reports, normal and cancerous skin lesions (n = 3954), were used to develop a DL classifier exploring visual features (System A). The outputs of the classifier were sonified, i.e. data conversion into sound (System B). Derived sound files were analyzed by a second machine learning classifier, either as raw audio (LABS, OBS) or following conversion into spectrograms (LABS) and by image analysis and human heuristics (OBS). The OBS criteria outcomes were System A specificity and System B sensitivity as raw sounds, spectrogram areas or heuristics. FINDINGS: LABS employed dermoscopies, half benign half malignant, and compared the accuracy of Systems A and B. System A algorithm resulted in a ROC AUC of 0.976 (95% CI, 0.965-0.987). Secondary machine learning analysis of raw sound, FFT and Spectrogram ROC curves resulted in AUC's of 0.931 (95% CI 0.881-0.981), 0.90 (95% CI 0.838-0.963) and 0.988 (CI 95% 0.973-1.001), respectively. OBS analysis of raw sound dermoscopies by the secondary machine learning resulted in a ROC AUC of 0.819 (95% CI, 0.7956 to 0.8406). OBS image analysis of AUC for spectrograms displayed a ROC AUC of 0.808 (CI 95% 0.6945 To 0.9208). By applying a heuristic analysis of Systems A and B a sensitivity of 86% and specificity of 91% were derived in the clinical study. INTERPRETATION: Adding a second stage of processing, which includes a deep learning algorithm of sonification and heuristic inspection with machine learning, significantly improves diagnostic accuracy. A combined two-stage system is expected to assist clinical decisions and de-escalate the current trend of over-diagnosis of skin cancer lesions as pathological. FUND: Bostel Technologies. Trial Registration clinicaltrials.gov Identifier: NCT03362138.

Care seeking and treatment related delay among childhood tuberculosis patients in Delhi, India.

OBJECTIVE: To examine delays in treatment initiation among child tuberculosis (TB) patients and to identify associated factors. METHOD: A multistage cluster random sampling strategy was used to select 175 parents/care givers of childhood TB patients from eight district TB centres covered by the Revised National Tuberculosis Control Programme in Delhi for interview in a cross-sectional survey. Binary logistic regression analysis was used to identify associated factors. RESULTS: Median estimated patient and health system delay was respectively 3 (range 1-300) and 41 days (range 10-397). Median total delay was 52 days (range 12-553). Among cases with self-reported delay, 64% of care givers thought that the symptoms would subside without treatment. In pulmonary cases, patient's sex, age of the primary care giver, religion and community were associated with patient delay. The child's place of birth and household size were associated with delay among extra-pulmonary TB cases. Type of first provider and number of providers consulted were associated with health system delay. Those who lived at a greater distance from their first health facility (OR 2.2, 95%CI 1.18-4.07) were more likely to experience prolonged patient delay. CONCLUSIONS: As the considerable health system delays were related to the type and number of providers consulted, targeted strategies are required to bring the health system closer to these particularly vulnerable children and their care givers.

Idiopathic Hypertrophie Pyloric Stenosis : Our Experience.

BACKGROUND: A typical infant with idiopathic hypertrophic pyloric stenosis is described as a male child, first in the order of birth with a positive family history. However our experience suggests otherwise which is presented in this report. Methods : A retrospective analysis of medical records of 8 infants, who were diagnosed to be suffering from idiopathic hypertrophic pyloric stenosis and subjected to surgical treatment, was undertaken. RESULTS: There were 5 (62.5%) males and 3 (37.5%) females. There was no family history and only one child (12.5%) was first born in the order of birth. One infant was preterm and one case (12.5%) had associated congenital anomaly (single kidney). Definitive diagnosis was established in 6 (75%) babies at admission whereas, other 2 cases (25%) required further evaluation. All the infants were in a state of moderate dehydration and in a varying state of hypochloremic alkalosis. The pH and serum chloride levels ranged from 7.52 to 7.67 and 86-94 mmol/L respectively. All were subjected to traditional Ramstedt's pyloromyotomy after having undergone vigorous correction of fluids and electrolytes for 24-48 hours. Intraoperatively, there was one iatrogenic mucosal perforation, which was closed with an omental patch. Postoperative feeding was initiated 12 hrs after surgery in 6 (75%) babies. CONCLUSION: Our series suggests a clinical profile of hypertrophic pyloric stenosis in our subset of patients which is different from what is described in literature.

Rhodococcus equi brain abscess in a patient without HIV.

Rhodococcus equi, a Gram positive organism, is a cause of infections in immunocompromised individuals. In humans, it mainly causes disease in those infected with human immunodeficiency virus (HIV), and generally presents as chronic pulmonary infection. It may also cause intracranial infections, which manifest as brain abscesses. This report describes a case of rhodococcus brain and pulmonary infection in a patient who did not have HIV or another disorder of cell mediated immunity. He was treated with intravenous imipenem, vancomycin, and rifampin for eight weeks and recovered from the infection.

Altered course of Plasmodium berghei infection by nifedipine treatment.

The effect of nifedipine (a calcium channel blocker) on the course of P. berghei infection was examined. It was observed that mice receiving a daily dose of 0.015 mg/kg of nifedipine had significantly shorter prepatent, patent and survival periods as compared to untreated P. berghei-infected animals (p < 0.001). This shows that the calcium channel blockers, in addition to possessing the property of reversing drug resistance during combined therapy with chloroquine, may also alter the pathophysiology of malaria infection. The decreased resistance of the host to the invading parasite suggests that the effect of CCB on the host-parasite interaction in human malaria needs to be investigated further before CCB can be used in combination with chloroquine for the treatment of chloroquine-resistant malaria or for chemoprophylaxis.

Generation of reactive oxygen species by blood monocytes in human Plasmodium falciparum and P. vivax infections.

Generation of reactive oxygen radicals by peripheral blood monocytes was measured by luminol-dependent chemiluminescence in 23 P. vivax- and 7 P. falciparum-infected patients. The chemiluminescence index (CLI) was not found to be significantly higher in P. vivax-infected cases than in healthy controls. But in patients with P. falciparum infection, the CLI was significantly higher compared to controls as well as to P. vivax-infected patients. In two severe and complicated P. falciparum-infected cases, CLI was found to be higher than in mild cases. As immunosuppression is more marked in falciparum malaria than in vivax cases, the role of oxygen radical generation in immunopathology and causation of immunosuppression in falciparum malaria needs further investigation.

Transforming growth factor beta 1 improves wound healing and random flap survival in normal and irradiated rats.

OBJECTIVES: To evaluate the effect of chronic irradiation on wound healing and random flap survival (FV), and the effect of transforming growth factor beta 1 (TGF-beta 1) in this setting using an animal model. DESIGN: A randomized, controlled study with four groups of rats to study the effect of irradiation 4 months before surgical intervention. The effect of TGF-beta 1 on FV and wound healing also was evaluated in the irradiated and nonirradiated groups. SUBJECTS: Ninety-five rats were available for evaluation. Group 1 (n = 10) was the control; group 2 (n = 28) received TGF-beta 1; group 3 (n = 28) received radiation therapy; and group 4 (n = 29) received radiation therapy and TGF-beta 1. INTERVENTION: The irradiated groups received 15 Gy to their dorsal skin. Four months later all received McFarlane skin flaps. Groups 2 and 4 received topical TGF-beta 1, 4 micrograms, to the bed of the flap; groups 1 and 3 received saline. On postoperative day 7 all rats were evaluated for tensile strength and FV, and histologic staining with hematoxylin-eosin for collagen and TGF-beta 1 was done. The slides were evaluated in a "blinded" fashion. RESULTS: Irradiation decreased tensile strength and FV, but not to a notable degree. Transforming growth factor beta 1 improved tensile strength in the irradiated (P = .04, Student's t test) and nonirradiated groups (P = .05, Student's t test). Transforming growth factor beta 1 also improved FV in all groups, but significantly in the irradiation plus TGF-beta 1 group (P = .001, Student's t test). The TGF-beta 1 group had the most mature collagen present at the wound edge. No qualitative difference was seen in the immunohistochemical staining for the four groups. CONCLUSIONS: Transforming growth factor beta 1 improves wound healing and random FV in radiated and nonirradiated rat skin. Further study is needed to determine the radiation dose necessary to create an "impaired wound-healing model" in rats, and the optimum dose of TGF-beta 1 in this setting.

Effect of nifedipine on calcium status and chemiluminescence response of phagocytes during Plasmodium berghei infection in mice.

The macrophages and neutrophils from nifedipine-treated mice, both Plasmodium berghei-infected and uninfected, showed suppressed capacity to generate oxygen free radicals as compared with untreated controls. Nifedipine treatment did not affect resting state free calcium levels in these cells. But the rise in intracellular calcium levels of macrophages and neutrophils following P. berghei infection was significantly less (P < 0.05) in nifedipine-treated mice as compared with untreated groups at various parasitaemia levels. Probably this reflects a more potent effect of nifedipine on these cells in the depolarized state. Similarly, the rise in intracellular calcium levels of these cells following formyl-Met-Leu-Phe (fMLP) stimulation was also significantly less in nifedipine-treated groups than in untreated controls at different parasitaemia levels. A positive correlation between this fMLP-stimulated rise in calcium levels and the chemiluminescence response of macrophages and neutrophils was observed in nifedipine-treated and untreated groups at various parasitaemia levels. Thus the respiratory-burst responses of these cells during P. berghei infection depend on the calcium homeostasis in the cells. The disturbances of the calcium-regulating mechanisms by nifedipine treatment resulted in subnormal phagocytic cell responses which lead to more severe and rapidly fatal P. berghei infection in these animals.

Primary versus rescue percutaneous coronary intervention in patients with acute myocardial infarction.

OBJECTIVE: To compare angiographic and clinical outcomes of patients with acute myocardial infarction (AMI) who underwent primary percutaneous coronary intervention (PCI) versus rescue PCI following failed thrombolysis. BACKGROUND: Patients presenting with AMI are treated either with primary PCI or with thrombolysis. When thrombolysis fails, rescue PCI is performed. METHODS AND RESULTS: We compared the outcome of 105 consecutive patients with AMI who underwent either primary PCI (60 patients) or rescue PCI (45 patients) between January 1997 and January 1999. The patients were followed for up to 6 months. Time delay to reperfusion was significantly longer in the rescue PCI group (354 vs. 189 min; p < 0.001). The majority of patients received a stent (93%). Glycoprotein (GP) IIb/IIIa inhibitors were used in 53% of patients in the primary PCI group and in 22% in the rescue group. TIMI grade 3 flow was achieved in 93.3% of patients in the primary PCI group and in 88.8% in the rescue group (p = 0.08). Post-procedure ejection fraction was 53% in the primary PCI group and 47% in the rescue group (p = 0.014). A composite endpoint of death, recurrent MI, repeat PCI, coronary artery bypass grafting (CABG) and recurrent angina at 6 months occurred in 35% of the patients in the primary PCI group and 26.7% in the rescue group (p = 0.36). CONCLUSION: Despite a significant delay to reperfusion and a lower immediate post-procedure ejection fraction, the clinical outcome of patients treated with rescue PCI following failed thrombolysis appears to be similar to that of patients treated with primary PCI at 6 months.