Efficacy and safety of curcumin in maintaining remission during disease-modifying antirheumatic drug withdrawal in rheumatoid arthritis at 52 weeks: a phase III double-blind, randomized placebo-controlled trial.

Curcumin has anti-inflammatory properties but current evidence is limited to advocate its use in rheumatoid arthritis (RA). We explored whether curcumin could maintain remission in patients with RA while tapering conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARD). In this patient-and investigator-blinded trial, adults with RA in sustained remission for more than six months were randomized to oral curcumin (1 g) with piperine (5 mg) twice daily or matching placebo. Patients who had received biological DMARDs or curcumin supplements in the last 6 months were excluded. csDMARD were tapered and stopped sequentially as per a fixed protocol. The primary outcome was flare-free survival at 52 weeks. The secondary outcomes were flare rate, correlation of serum curcuminoid levels with flares and safety. 200 patients (100 per arm) entered the trial with comparable baseline characteristics. Per protocol analysis included 92 and 93 participants in the curcumin and the placebo group, respectively. Flare-free survival at week 52 was similar between both groups (60% versus 64%; p = 0.76). The median time to flare was similar [Curcumin: 219 days (IQR: 123) versus placebo: 214 days (95.8); p = 0.067]. Cox proportionate regression modelling showed that the flare-free survival was independent of serum curcuminoid levels [adjusted HR = 0.99 (95% CI: 0.97-1.0)]. The model showed that flare-free survival was not associated with age, gender, seropositivity, or csDMARD used at baseline. No serious adverse effects were noted. Curcumin did not impact the flare-free survival in patients with RA in remission during the tapering of csDMARDs despite achieving adequate serum levels.Trial registration: CTRI/2018/04/013279.

Comparative analysis of biochemical, hormonal, and mineral compositions of preovulatory and cystic ovarian follicles in buffalo during the non-breeding season.

This study is a comparative analysis of the biochemical, hormonal, and mineral compositions of follicular fluid in preovulatory and cystic follicles of water buffalo (Bubalus bubalis). In total, reproductive tracts from 215 buffalo along with intact ovaries were collected randomly from an abattoir. The incidence of cystic conditions found in this study was 3.72% (8/215), involving the right ovary in 62.5% of instances and the left ovary in 37.5% of instances during the non-breeding season. Follicular fluid was aspirated from preovulatory follicles (12-15 mm diameter, oestrogen-active, follicular phase or stage IV corpus luteum on one of the two ovaries, n = 10) and cystic follicles (at least 20 mm diameter, no corpus luteum on any one of the two ovaries, n = 8). The follicular fluid samples were assayed for biochemical components (uric acid, creatinine, blood urea nitrogen, cholesterol, total protein, glucose, ascorbic acid, and alkaline phosphatase), hormones (progesterone, estradiol, and insulin), and minerals (calcium, magnesium, phosphorus, copper, zinc, and cobalt). Cystic follicles had greater (P < 0.05) concentrations of creatinine, blood urea nitrogen, cholesterol, progesterone, copper, zinc, and cobalt, and lesser (P < 0.05) concentrations of uric acid, glucose, ascorbic acid, estradiol, insulin, calcium, magnesium, and phosphorus compared with preovulatory follicles. These results indicated the marked differences in follicular fluid composition between preovulatory and cystic follicles in buffalo. Some of the changes were indicative of oxidative stress and disturbed steroidogenesis, two important mechanisms shown to be associated with cystic ovarian disease in various species. Further studies are warranted to investigate whether these differences are directly or indirectly involved in the formation of cystic follicles or are mere manifestations of the condition.

Is COVID-19 another case of the obesity paradox? Results from an international ecological study on behalf of the REPROGRAM Consortium Obesity study group.

Introduction: Obesity has emerged as one of the major risk factors of severe morbidity and cause-specific mortality among severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected individuals. Patients with obesity also have overlapping cardiovascular diseases and diabetes, which make them increasingly vulnerable. This novel ecological study examines the impact of obesity and/or body mass index (BMI) on rates of population-adjusted cases and deaths due to coronavirus disease 2019 (COVID-19). Material and methods: Publicly available datasets were used to obtain relevant data on COVID-19, obesity and ecological variables. Group-wise comparisons and multivariate logistic regression analyses were performed. The receiver operating characteristic curve (ROC) was plotted to compute the area under the curve. Results: We found that male BMI is an independent predictor of cause-specific (COVID-19) mortality, and not of the caseload per million population. Countries with obesity rates of 20-30% had a significantly higher (approximately double) number of deaths per million population to both those in < 20% and > 30% slabs. We postulate that there may be a U-shaped paradoxical relationship between obesity and COVID-19 with the cause-specific mortality burden more pronounced in the countries with 20-30% obesity rates. These findings are novel along with the methodological approach of doing ecological analyses on country-wide data from publicly available sources. Conclusions: We anticipate, in light of our findings, that appropriate targeted public health approaches or campaigns could be developed to minimize the risk and cause-specific morbidity burden due to COVID-19 in countries with nationwide obesity rates of 20-30%.

IoT Based Smart Assist System to Monitor Entertainment Spots Occupancy and COVID 19 Screening During the Pandemic.

The greatest threat to the word in recent days is the spread of COVID 19 virus throughout the world. To tackle this problem government of India has implemented various restrictions to be followed to stop the spread of the COVID 19 virus. But most of the time general public forget their responsibilities and don't follow these restrictions, especially in situations like when their favourite hero's movie releases in the theatre, and in spending time in hotels, malls and in other entertainment places in spite of governments occupancy restrictions in those places. In order to address this problem we propose an IoT based Smart System for monitoring the occupancy in such entertainment spots and screen the public entry if they dint follow the protocols such as if they dint wear mask or if they have body temperature. This proposed system is implemented on a Raspberry Pi 3B+ processor which runs on a Broadcom processor. For monitoring the occupancy and screen the visitors for mask, we use a Passive Infrared Sensors and Pi camera to count the person entering into the premises. And we use a MLX90614 Infrared temperature sensor for screening the public entry with high temperature. The complete system is implemented using python programming and the details will be uploaded to cloud, authorities can monitor this from a remote place so that the spread of COVID 19 can be restricted in pubic entertainment spots.

Banana Plant Disease Classification Using Hybrid Convolutional Neural Network.

Banana cultivation is one of the main agricultural elements in India, while the common problem of cultivation is that the crop has been influenced by several diseases, while the pest indications have been needed for discovering the infections initially for avoiding the financial loss to the farmers. This problem will affect the entire banana productivity and directly affects the economy of the country. A hybrid convolution neural network (CNN) enabled banana disease detection, and the classification is proposed to overcome these issues guide the farmers through enabling fertilizers that have to be utilized for avoiding the disease in the initial stages, and the proposed technique shows 99% of accuracy that is compared with the related deep learning techniques.

Fuzzy Guided Autonomous Nursing Robot through Wireless Beacon Network.

Robotics is one of the most emerging technologies today, and are used in a variety of applications, ranging from complex rocket technology to monitoring of crops in agriculture. Robots can be exceptionally useful in a smart hospital environment provided that they are equipped with improved vision capabilities for detection and avoidance of obstacles present in their path, thus allowing robots to perform their tasks without any disturbance. In the particular case of Autonomous Nursing Robots, major essential issues are effective robot path planning for the delivery of medicines to patients, measuring the patient body parameters through sensors, interacting with and informing the patient, by means of voice-based modules, about the doctors visiting schedule, his/her body parameter details, etc. This paper presents an approach of a complete Autonomous Nursing Robot which supports all the aforementioned tasks. In this paper, we present a new Autonomous Nursing Robot system capable of operating in a smart hospital environment area. The objective of the system is to identify the patient room, perform robot path planning for the delivery of medicines to a patient, and measure the patient body parameters, through a wireless BLE (Bluetooth Low Energy) beacon receiver and the BLE beacon transmitter at the respective patient rooms. Assuming that a wireless beacon is kept at the patient room, the robot follows the beacon's signal, identifies the respective room and delivers the needed medicine to the patient. A new fuzzy controller system which consists of three ultrasonic sensors and one camera is developed to detect the optimal robot path and to avoid the robot collision with stable and moving obstacles. The fuzzy controller effectively detects obstacles in the robot's vicinity and makes proper decisions for avoiding them. The navigation of the robot is implemented on a BLE tag module by using the AOA (Angle of Arrival) method. The robot uses sensors to measure the patient body parameters and updates these data to the hospital patient database system in a private cloud mode. It also makes uses of a Google assistant to interact with the patients. The robotic system was implemented on the Raspberry Pi using Matlab 2018b. The system performance was evaluated on a PC with an Intel Core i5 processor, while the solar power was used to power the system. Several sensors, namely HC-SR04 ultrasonic sensor, Logitech HD 720p image sensor, a temperature sensor and a heart rate sensor are used together with a camera to generate datasets for testing the proposed system. In particular, the system was tested on operations taking place in the context of a private hospital in Tirunelveli, Tamilnadu, India. A detailed comparison is performed, through some performance metrics, such as Correlation, Root Mean Square Error (RMSE), and Mean Absolute Percentage Error (MAPE), against the related works of Deepu et al., Huh and Seo, Chinmayi et al., Alli et al., Xu, Ran et al., and Lee et al. The experimental system validation showed that the fuzzy controller achieves very high accuracy in obstacle detection and avoidance, with a very low computational time for taking directional decisions. Moreover, the experimental results demonstrated that the robotic system achieves superior accuracy in detecting/avoiding obstacles compared to other systems of similar purposes presented in the related works.

Response of anestrous heifers fed local grass or oak foliage-based diet with two different mineral mixtures.

The effect of incorporation of two different mineral mixtures and/or oak leaves was studied on nutrient utilization and reproductive performance in anestrous heifers. Twenty-one anestrous heifers (18.2 ± 1.45 months; 229 ± 14.2 kg body weight) were randomly distributed into three similar groups. Heifers in control (T1) and first treatment group (T2) were fed concentrate mixture incorporated with Bureau of Indian Standards (BIS) specific mineral mixture and a customized mineral mixture developed specially for Kumaon hills (MMKH), respectively, along with local green grass (Pennisetum orientale). In the second treatment group (T3), concentrate mixture was the same as that of T2, while the source of roughage was local oak (Quercus leucotricophora) leaves containing 3.35% condensed tannin. A digestibility trial was conducted after 120 days of study. The feed intake was similar among the groups. Digestibility coefficient of crude protein (CP) was lower in T3 than T2 and comparable to T1. Feeding oak leaves improved absorption of calcium as compared to grass-fed animals. Bioavailability of copper and zinc was higher (P < 0.05) in oak leaves and MMKH fed group (T3) as compared to T1, but similar to T2. Conversely, absorption of iron had the reverse trend and was reflected in serum Fe concentration. Hematological, biochemical, enzyme and hormonal profiles were not influenced by any of the treatments. The relative occurrence of estrus cyclicity and conception rate was more in groups T2 and T3, respectively, than other groups. It was concluded that feeding oak foliage-based diet containing 1.87% tannin along with customized mineral mixture developed for Kumaon hills improved certain nutrient utilization and reproductive performance as compared to local green grass supplemented with BIS-specific mineral mixture or MMKH.

Systematic analysis of purified astrocytes after SCI unveils Zeb2os function during astrogliosis.

Spinal cord injury (SCI) is one of the most devastating neural injuries without effective therapeutic solutions. Astrocytes are the predominant component of the scar. Understanding the complex contributions of reactive astrocytes to SCI pathophysiologies is fundamentally important for developing therapeutic strategies. We have studied the molecular changes in the injury environment and the astrocyte-specific responses by astrocyte purification from injured spinal cords from acute to chronic stages. In addition to protein-coding genes, we have systematically analyzed the expression profiles of long non-coding RNAs (lncRNAs) (>200 bp), which are regulatory RNAs that play important roles in the CNS. We have identified a highly conserved lncRNA, Zeb2os, and demonstrated using functional assays that it plays an important role in reactive astrogliosis through the Zeb2os/Zeb2/Stat3 axis. These studies provide valuable insights into the molecular basis of reactive astrogliosis and fill the knowledge gap regarding the function(s) of lncRNAs in astrogliosis and SCI.

Hematological and serum biochemical profile in cattle experimentally infected with foot-and-mouth disease virus.

BACKGROUND AND AIM: Foot-and-mouth disease (FMD) is an acute viral infection affecting cloven-hoofed animals causing vesicular erosions in the oral cavity and interdigital space. The present study was undertaken to ascertain the time-dependent changes in clinical, hematological, and biochemical profiles in different breeds of cattle following experimental infection. MATERIALS AND METHODS: The animals were inoculated with 1.0×104 50% bovine tongue infectious dose (BTID50) by intradermolingual route. Clinical signs were observed, and blood/serum samples were collected at different time intervals. RESULTS: The white blood cell count declined sharply on days 7-13 and recovered on day 14 post-FMD infection. Biochemical analysis of serum markers for vital organ profile revealed no marked damage. However, a significant increase in blood urea nitrogen (BUN) value indicated pre-renal azotemia. Transient hyperthyroidism was indicated by the rise in T3 and T4 that can be correlated with a decrease in triglyceride and total cholesterol levels. In the cardiac damage assessment study, a distinct breed difference was observed wherein Malnad Gidda calves showed no cardiac damage. CONCLUSION: Except thyroid profile, BUN, and creatine kinase-myocardial band, all other serum biochemical parameters showed no significant abnormalities, whereas lymphopenia is the only hematological change and it is suggested that effective ameliorative measures should be targeted mainly on the feed/water intake, thyroid gland, and the level of lymphocytes.

Molecular analyses of genetic variability in the populations of Bergenia ciliata in Indian Himalayan Region (IHR).

Bergenia ciliata is an important medicinal plant species of Indian Himalayan Region (IHR). Genetic variability and population genetic structure of B. ciliata sampled from IHR was studied using two single primer amplification reaction (SPAR) methods (DAMD: Directed Amplification of Minisatellite region DNA; ISSR: Inter Simple Sequence Repeats). To provide a reasonable scientific basis for management and conservation of B. ciliata populations in IHR, genetic diversity analysis of 11 populations with 24 SPAR markers (15 ISSR and 9 DAMD) revealed significantly high level of (90.03%) polymorphism at species level. However, genetic variability was low at population level and KUL and BWS populations showed maximum while SHM population revealed least genetic diversity among the 11 populations. Analysis of molecular variance revealed highest percentage of variation (73%) within populations, followed by 17% among populations and least (10%) among the Himalayan regions. Clustering pattern obtained from UPGMA dendrogram was supported by STRUCTURE and principal coordinate analysis, segregating all the 11 natural populations of B. ciliata into two genetic clusters: Eastern and Western Himalayan populations. The clustering patterns of all the three statistical methods indicated that populations of B. ciliata have structured in response to the local micro-climates of the habitats in IHR, and therefore, it can be concluded that genetic variability is in congruence with the geographical diversity.

A pilot, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of a novel Boswellia serrata extract in the management of osteoarthritis of the knee.

A double-blind, placebo-controlled human trial was conducted to evaluate the safety and efficacy of a standardized oral supplementation of Boswellin®, a novel extract of Boswellia serrata extract (BSE) containing 3-acetyl-11-keto-ß-boswellic acid (AKBBA) with ß-boswellic acid (BBA). A total of 48 patients with osteoarthritis (OA) of the knee were randomized and allocated to the BSE and placebo groups for intervention. Patients were administered BSE or placebo for a period of 120 days. The trial results revealed that BSE treatment significantly improved the physical function of the patients by reducing pain and stiffness compared with placebo. Radiographic assessments showed improved knee joint gap and reduced osteophytes (spur) confirming the efficacy of BSE treatment. BSE also significantly reduced the serum levels of high-sensitive C-reactive protein, a potential inflammatory marker associated with OA of the knee. No serious adverse events were reported. This is the first study with BSE conducted for a period of 120 days, longer than any other previous clinical trial on patients with OA of the knee. The findings provide evidence that biologically active constituents of BSE, namely, AKBBA and BBA, act synergistically to exert anti-inflammatory/anti-arthritic activity showing improvement in physical and functional ability and reducing the pain and stiffness.

Transcriptional and translational abundance of Bone morphogenetic protein (BMP) 2, 4, 6, 7 and their receptors BMPR1A, 1B and BMPR2 in buffalo ovarian follicle and the role of BMP4 and BMP7 on estrogen production and survival of cultured granulosa cells.

BMPs and their receptors modulate the granulosa cell (GC) function in the follicle of domestic animals. Since little is known on BMPs in the buffalo, the present study was aimed to investigate the expression of BMP2, 4, 6, 7 and their receptors BMPR1A, BMPR1B, BMPR2 in the GC and theca cells (TC) of ovarian follicles and the role of BMP4 and BMP7 on buffalo GC. Follicles were classified into four groups based on size and E2 level in the follicular fluid as follows: (i) Group1(4-6 mm; <0.5 ng/mL) (ii) Group 2 (7-9 mm; 0.5-5 ng/mL) (iii) Group 3 (10-13 mm; 5-40 ng/mL) and (iv) Group 4 (dominant follicle) (>13 mm; >180 ng/mL). The results revealed that except BMP6, BMP2, 4 7 and receptors BMPR1A, BMPR1B and BMPR2 showed a minimum of 1.5-2 fold increase in mRNA expression in the GC of dominant follicle as compared to other follicle classes. In the dominant follicle, a two-fold increase in BMP4 and BMP7 expression was observed in the TC. At 100 ng/mL, the BMP4 and BMP7 either alone or in combination maximally down-regulated CASPASE3 and stimulated the transcripts of PCNA, FSHR and CYP19A1 that was supported by E2 secretion in the granulosa cell culture suggesting their role in cell survival and E2 production. In conclusion, GC and TC of dominant follicles express BMP 2, 4, 6, 7 and their receptors BMPR1A, BMPR1B and BMPR2. BMP4 and BMP7 stimulate E2 production and promote GC survival.

Major bioactive phenolics in Bergenia species from the Indian Himalayan region: Method development, validation and quantitative estimation using UHPLC-QqQLIT-MS/MS.

Bergenia species are important medicinal plants used in indigenous systems of medicine for their antilithiatic and diuretic properties. An ultra-high performance liquid chromatography coupled to hybrid linear ion trap triple quadrupole mass spectrometry (UHPLC-QqQLIT-MS/MS) method has been developed and validated for the estimation of quantitative variation of eight major bioactive phenolics in the rhizomes (150 samples) of four species of this herb, Bergenia (B. ciliata, B. ligulata, B. purpurascens and B. stracheyi). Chromatographic separation was obtained on a Waters ACQUITY UPLCTM BEH (ethylene bridged hybrid) C18 column with a mobile phase consisting of 0.1% (v/v) formic acid aqueous solution and acetonitrile under a gradient elution manner. A hybrid linear ion trap triple quadrupole mass spectrometer was operated in negative electrospray ionization mode with multiple reactions monitoring for detection and quantification of the eight compounds. The validated method demonstrated good linearity (r2 ≥ 0.9991), precision (RSD ≤ 1.87%) and accuracy (95.16-102.11%, RSD ≤ 1.83%) for all reference analytes. The quantitative results revealed that B. ligulata contains the highest amount of the major active marker-bergenin. The results also suggest that sensitive UHPLC-QqQLIT-MS/MS method, a sensitive, accurate and convenient one, could be helpful in identification of potential accession(s), rapid quality control and establishing authenticity of Bergenia species as raw material for pharmaceutical industries.

[Retracted] Epidermal growth factor-stimulated human cervical cancer cell growth is associated with EGFR and cyclin D1 activation, independent of COX-2 expression levels.

Following the publication of this article, which was concerned with the expression of phosphorylated epidermal growth factor receptor (pEGFR) and cyclin D1 activation independently of the expression levels of cyclo-oxygenase-2, an interested reader drew to our attention apparent anomalies associated with the western blot data shown in Fig. 2C. Following an internal investigation at the New York University School of Medicine, we were requested to produce the original film, or the scan of the image of the film, for verification. Unfortunately, we were unable to provide the original film or scanned image to disprove the allegation, since the original pEGFR image could not be found. Therefore, the Investigation Committee recommended that this article be retracted, and we are withdrawing the article in line with the request. All the authors agree to the retraction of this paper. We sincerely regret any inconvenience this has caused. [the original article was published in the International Journal of Oncology 40: 13-20, 2012; DOI: 10.3892/ijo.2011.1211].

Expression and functional role of Bone Morphogenetic Proteins (BMPs) in cyclical corpus luteum in buffalo (Bubalus bubalis).

The role of growth factors in the modulation of ovarian function is an interesting area of research in reproductive biology. Recently, we have shown the expression and role of IGF, EGF, VEGF and FGF in the follicle and CL. Here, we report the presence of Bone Morphogenetic Proteins (BMPs) and their functional receptors in the corpus luteum (CL) of buffalo. The bubaline CL was classified into four stages according to the morphology and progesterone (P4) concentration. The qPCR, immunoblot and immunohistochemistry studies revealed that BMP2 and BMP Receptors (BMPR1A, BMPR1B and BMPR2) were significantly upregulated during the mid stage whereas BMP4 and BMP7 were upregulated during the early stage of CL (P<0.05). Studies on primary luteal cell culture (LCC) using mid CL showed a significant time and concentration dependent effect of BMP4 and BMP7 (P<0.05). At 100ngml-1, the BMPs maximally stimulated the transcripts of StAR, CYP11A1 and 3ßHSD that paralleled with P4 accretion in the media (P<0.05). Further, the BMP4 as well as BMP7 upregulated the transcripts of PCNA and downregulated CASPASE3 in the LCC at the same concentration (P<0.05). Though the combined effect of BMP4 and 7 was significantly higher (P<0.05) than that of individual one, it was not additive. In conclusion, the expression of BMPs and their receptors were dependent on the stages of CL in the buffalo. Treatment of LCC with BMPs in vitro confirmed the presence of functional receptors that stimulated the P4 production and luteal cell survival. Moreover, the results support the concept that the upregulation of P4 and its biosynthetic pathway enzymes such as CYP11A1, StAR and 3ßHSD in the CL is likely due to the autocrine and /or paracrine effects of BMP4 and BMP7 under physiological milieu.

Platelet activating factor: A potential biomarker in acute coronary syndrome?

Platelet activating factor (PAF) is a potent pro-inflammatory negotiator that shows distinct spectrum of biological and pharmacological effects. Importantly, it participates in a wide range of pathophysiological conditions. In cardiovascular system, PAF has been shown to have an important role in platelet and neutrophil aggregation, vascular permeability, microvascular leakage, thrombus formation, leukocyte adhesion to the endothelial cells, and initiation and progression of atherosclerosis. The purpose of this article was to review the PAF, a family of lipids that is associated with the pathology of coronary artery diseases due to their association with leading etiological mechanisms such as inflammation, endothelial dysfunction, oxidative and nitrosative stress, and platelet reactivity. This review further provides information about PAF and its potential role as a key contributor to the pathogenesis of cardiovascular disorders.

Evaluating a murine model of endometritis using uterine isolates of Escherichia coli from postpartum buffalo.

Ascending infection of the uterus with Gram-negative bacteria is responsible for postpartum endometritis in cattle and buffalo and can adversely affect fertility. Development of a laboratory animal model for bovine endometritis would facilitate the understanding of the pathogenesis as it is difficult to conduct controlled experimentation in the native host. In the present study, 30 virgin Swiss Albino mice (5-8 weeks old) were used to evaluate the pathogenic potential of Escherichia coli, isolated from the normally calved postpartum buffalo to induce endometritis. Mice in the diestrus phase of the estrous cycle were randomly allotted to one of the following four intravaginal inoculation (100 µL) treatments: EG (experimental group)-1: sterile normal saline; EG-2, -3 and -4: E. coli@ 1.5 × 104, 105 and 106 CFU/ml, respectively. The animals were then scarified 36 h post-inoculation to study gross and microscopical lesions. Gross changes were confined to EG-4. Acute endometritis was recorded in 50% of the EG-3 and 66.7% of the EG-4. The rate of acute endometritis development was significantly higher in EG-4 (P<0.05) as compared to the other groups. The present study demonstrated that the animal model for bubaline endometritis can be developed in mice by intravaginal inoculation of E.coli@ 1.5 × 106 CFU/ml at diestrus. Ease of intravaginal inoculation, apparent absence of systemic involvement and high infective rate are the advantages of the model over other studies.