Carotenoid Extraction from Plant Tissues.

Carotenoids are the natural pigments available in nature and exhibit different colors such as yellow, red, and orange. These are a class of phytonutrients that have anti-cancer, anti-inflammatory, anti-oxidant, immune-modulatory, and anti-aging properties. These were used in food, pharmaceutical, nutraceutical, and cosmetic industries. They are divided into two classes: carotenes and xanthophylls. The carotenes are non-oxygenated derivatives and xanthophylls are oxygenated derivatives. The major source of carotenoids are vegetables, fruits, and tissues. Carotenoids also perform the roles of photoprotection and photosynthesis. In addition to the roles mentioned above, they are also involved and act as precursor molecules for the biosynthesis of phytohormones such as strigolactone and abscisic acid. This chapter briefly introduces carotenoids and their extraction method from plant tissue. Proposed protocol describes the extraction of carotenoid using solvents chloroform and dichloromethane. Reverse-phase HPLC can be performed with C30 columns using gradient elution. The column C30 is preferred to the C18 column because the C30 column has salient features, which include selective nature in the separation of structural isomers and hydrophobic, long-chain compounds, and shows the best compatibility with highly aqueous mobile phases. A complete pipeline for the extraction of carotenoids from plant tissue is given in the present protocol.

Sample Preparation from Plant Tissue for Gas Chromatography-Mass Spectrometry (GC-MS)we.

Metabolites are intermediate products formed during metabolism. Metabolites play different roles, including providing energy, supporting structure, transmitting signals, catalyzing reactions, enhancing defense, and interacting with other species. Plant metabolomics research aims to detect precisely all metabolites found within tissues of plants through GC-MS. This chapter primarily focuses on extracting metabolites using chemicals such as methanol, chloroform, ribitol, MSTFA, and TMCS. The metabolic analysis method is frequently used according to the specific kind of sample or matrix being investigated and the analysis objective. Chromatography (LC, GC, and CE) with mass spectrometry and NMR spectroscopy is used in modern metabolomics to analyze metabolites from plant samples. The most frequently used method for metabolites analysis is the GC-MS. It is a powerful technique that combines gas chromatography's separation capabilities with mass spectrometry, offering detailed information, including structural identification of each metabolite. This chapter contains an easy-to-follow guide to extract plant-based metabolites. The current protocol provides all the information needed for extracting metabolites from a plant, precautions, and troubleshooting.

Fully Automated Agatston Score Calculation From Electrocardiography-Gated Cardiac Computed Tomography Using Deep Learning and Multi-Organ Segmentation: A Validation Study.

To evaluate deep learning-based calcium segmentation and quantification on ECG-gated cardiac CT scans compared with manual evaluation. Automated calcium quantification was performed using a neural network based on mask regions with convolutional neural networks (R-CNNs) for multi-organ segmentation. Manual evaluation of calcium was carried out using proprietary software. This is a retrospective study of archived data. This study used 40 patients to train the segmentation model and 110 patients were used for the validation of the algorithm. The Pearson correlation coefficient between the reference actual and the computed predictive scores shows high level of correlation (0.84; P < .001) and high limits of agreement (±1.96 SD; -2000, 2000) in Bland-Altman plot analysis. The proposed method correctly classifies the risk group in 75.2% and classifies the subjects in the same group. In total, 81% of the predictive scores lie in the same categories and only seven patients out of 110 were more than one category off. For the presence/absence of coronary artery calcifications, the deep learning model achieved a sensitivity of 90% and a specificity of 94%. Fully automated model shows good correlation compared with reference standards. Automating process reduces evaluation time and optimizes clinical calcium scoring without additional resources.

Adaptive STDP-based on-chip spike pattern detection.

A spiking neural network (SNN) is a bottom-up tool used to describe information processing in brain microcircuits. It is becoming a crucial neuromorphic computational model. Spike-timing-dependent plasticity (STDP) is an unsupervised brain-like learning rule implemented in many SNNs and neuromorphic chips. However, a significant performance gap exists between ideal model simulation and neuromorphic implementation. The performance of STDP learning in neuromorphic chips deteriorates because the resolution of synaptic efficacy in such chips is generally restricted to 6 bits or less, whereas simulations employ the entire 64-bit floating-point precision available on digital computers. Previously, we introduced a bio-inspired learning rule named adaptive STDP and demonstrated via numerical simulation that adaptive STDP (using only 4-bit fixed-point synaptic efficacy) performs similarly to STDP learning (using 64-bit floating-point precision) in a noisy spike pattern detection model. Herein, we present the experimental results demonstrating the performance of adaptive STDP learning. To the best of our knowledge, this is the first study that demonstrates unsupervised noisy spatiotemporal spike pattern detection to perform well and maintain the simulation performance on a mixed-signal CMOS neuromorphic chip with low-resolution synaptic efficacy. The chip was designed in Taiwan Semiconductor Manufacturing Company (TSMC) 250 nm CMOS technology node and comprises a soma circuit and 256 synapse circuits along with their learning circuitry.

Assessing the SpO2 in a random population - Looking for the best among fingers.

Context: Pulse oximetry is one of the most revolutionary methods used to monitor the patients in the clinical setting, particularly intensive care and anesthesia. We usually use the index or middle finger to measure SpO2 values, but little is known about the inter-digital differences that exist between the fingers. Aim: We aim to compare the peripheral capillary oxygen saturation among fingers of both hands. A total of 93 healthy volunteers aged between 18 and 50 years participated in the study. Materials and Methods: Their SpO2 values were recorded from each finger with at least 1 minute of resting interval. Their blood pressure, heart rate, and body temperature were recorded as well. Result: A total of 930 measurements were obtained from 93 volunteers. The highest average SpO2 value of right-handed volunteers was measured from the left little finger (98.48 ± 0.62) of right-handed volunteers, and it was statistically significant when compared with the right ring finger, right little finger, left thumb, left index, left middle finger, and left ring finger. The highest average SpO2 from left-handed volunteers was obtained from the right index finger, but it was statistically insignificant. Conclusion: We assume ethnic and climatic differences to play a role in contradictory results noted from previous studies conducted, and this needs to be investigated further. It is recommended that multiple readings may be obtained from other fingers as well before coming to any conclusion as inter-finger variability cannot be ignored.

A Conductance-Based Silicon Synapse Circuit.

Neuron, synapse, and learning circuits inspired by the brain comprise the key components of a neuromorphic chip. In this study, we present a conductance-based analog silicon synapse circuit suitable for the implementation of reduced or multi-compartment neuron models. Compartmental models are more bio-realistic. They are implemented in neuromorphic chips aiming to mimic the electrical activities of the neuronal networks in the brain and incorporate biomimetic soma and synapse circuits. Most contemporary low-power analog synapse circuits implement bioinspired "current-based" synaptic models suited for the implementation of single-compartment point neuron models. They emulate the exponential decay profile of the synaptic current, but ignore the effect of the postsynaptic membrane potential on the synaptic current. This dependence is necessary to emulate shunting inhibition, which is thought to play important roles in information processing in the brain. The proposed circuit uses an oscillator-based resistor-type element at its output stage to incorporate this effect. This circuit is used to demonstrate the shunting inhibition phenomenon. Next, to demonstrate that the oscillatory nature of the induced synaptic current has no unforeseen effects, the synapse circuit is employed in a spatiotemporal spike pattern detection task. The task employs the adaptive spike-timing-dependent plasticity (STDP) learning rule, a bio-inspired learning rule introduced in a previous study. The mixed-signal chip is designed in a Taiwan Manufacturing Semiconductor Company 250 nm complementary metal oxide semiconductor technology node. It comprises a biomimetic soma circuit and 256 synapse circuits, along with their learning circuitries.

Efficacy of Individualized Homeopathic Medicines in the Treatment of Atopic Dermatitis in Adults: A Double-Blind, Randomized, Placebo-Controlled, Preliminary Trial.

INTRODUCTION: Individualized homeopathy (IH) in atopic dermatitis (AD) remained under-researched. OBJECTIVE: We aimed at evaluating efficacy of IH in AD. METHODS: A double-blind, randomized, placebo-controlled, short-term, preliminary trial was conducted in an Indian homeopathy hospital. Patients were randomized to either IH (n = 30) or identical-looking placebo (n = 30) using computerized randomization and allocation. Outcomes were patient-oriented scoring of AD (PO-SCORAD; primary end point), Dermatological Life Quality Index (DLQI) score, and AD burden score for adults (ADBSA; secondary end points), measured monthly for 3 months. An intention-to-treat sample was analyzed after adjusting baseline differences. RESULTS: On PO-SCORAD, improvement was higher in IH against placebo, but nonsignificant statistically (pmonth 1 = 0.433, pmonth 2 = 0.442, pmonth 3 = 0.229). Secondary outcomes were also nonsignificant - both DLQI and ADBSA (p > 0.05). Four adverse events (diarrhea, injury, common cold) were recorded. CONCLUSIONS: There was a small, but nonsignificant direction of effect towards homeopathy, which renders the trial inconclusive. A properly powered robust trial is indicated.

Older patients (aged ≥60 years) with previously untreated advanced-stage classical Hodgkin lymphoma: a detailed analysis from the phase III ECHELON-1 study.

Effective and tolerable treatments are needed for older patients with classical Hodgkin lymphoma. We report results for older patients with classical Hodgkin lymphoma treated in the large phase III ECHELON-1 study of frontline brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Modified progression-free survival per independent review facility for older versus younger patients (aged ≥60 vs. <60 years) was a pre-specified subgroup analysis; as the ECHELON- 1 study was not powered for these analyses, reported P-values are descriptive. Of 1,334 enrolled patients, 186 (14%) were aged ≥60 years (A+AVD: n=84, ABVD: n=102); results below refer to this age group. Modified progression-free survival per independent review facility was similar in the two arms at 24 months (A+AVD: 70.3% [95% confidence interval (CI): 58.4-79.4], ABVD: 71.4% [95% CI: 60.5-79.8], hazard ratio (HR)=1.00 [95% CI: 0.58-1.72], P=0.993). After a median follow-up of 60.9 months, 5-year progression-free survival per investigator was 67.1% with A+AVD versus 61.6% with ABVD (HR=0.820 [95% CI: 0.494-1.362], P=0.443). Comparing A+AVD versus ABVD, grade 3/4 peripheral neuropathy occurred in 18% versus 3%; any-grade febrile neutropenia in 37% versus 17%; and any-grade pulmonary toxicity in 2% versus 13%, respectively, with three (3%) pulmonary toxicity-related deaths in patients receiving ABVD (none in those receiving A+AVD). Altogether, A+AVD showed overall similar efficacy to ABVD with survival rates in both arms comparing favorably to those of prior series in older patients with advanced-stage classical Hodgkin lymphoma. Compared to ABVD, A+AVD was associated with higher rates of neuropathy and neutropenia, but lower rates of pulmonary-related toxicity. Trials registered at ClinicalTrials.gov identifiers: NCT01712490; EudraCT number: 2011-005450-60.

An Adaptive STDP Learning Rule for Neuromorphic Systems.

The promise of neuromorphic computing to develop ultra-low-power intelligent devices lies in its ability to localize information processing and memory storage in synaptic circuits much like the synapses in the brain. Spiking neural networks modeled using high-resolution synapses and armed with local unsupervised learning rules like spike time-dependent plasticity (STDP) have shown promising results in tasks such as pattern detection and image classification. However, designing and implementing a conventional, multibit STDP circuit becomes complex both in terms of the circuitry and the required silicon area. In this work, we introduce a modified and hardware-friendly STDP learning (named adaptive STDP) implemented using just 4-bit synapses. We demonstrate the capability of this learning rule in a pattern recognition task, in which a neuron learns to recognize a specific spike pattern embedded within noisy inhomogeneous Poisson spikes. Our results demonstrate that the performance of the proposed learning rule (94% using just 4-bit synapses) is similar to the conventional STDP learning (96% using 64-bit floating-point precision). The models used in this study are ideal ones for a CMOS neuromorphic circuit with analog soma and synapse circuits and mixed-signal learning circuits. The learning circuit stores the synaptic weight in a 4-bit digital memory that is updated asynchronously. In circuit simulation with Taiwan Semiconductor Manufacturing Company (TSMC) 250 nm CMOS process design kit (PDK), the static power consumption of a single synapse and the energy per spike (to generate a synaptic current of amplitude 15 pA and time constant 3 ms) are less than 2 pW and 200 fJ, respectively. The static power consumption of the learning circuit is less than 135 pW, and the energy to process a pair of pre- and postsynaptic spikes corresponding to a single learning step is less than 235 pJ. A single 4-bit synapse (capable of being configured as excitatory, inhibitory, or shunting inhibitory) along with its learning circuitry and digital memory occupies around 17,250 µm2 of silicon area.

Antibiotic utilization, sensitivity, and cost in the medical intensive care unit of a tertiary care teaching hospital in Nepal.

BACKGROUND: High utilization and irrational use of antibiotics in an intensive care unit increases microbial resistance, morbidity, mortality, and costs. OBJECTIVE: This study aimed to evaluate the utilization, sensitivity and cost analysis of antibiotics used in the medical intensive care unit of a tertiary care teaching hospital of Nepal. METHODS: A prospective cohort study was conducted on patients admitted to the medical intensive care unit at a tertiary care teaching hospital in central Nepal from July to September 2016. Antibiotic utilization, defined daily dose per 100 bed-days and the cost of antibiotics per patient were calculated. Descriptive statistics were performed using IBM-SPSS 20.0. RESULTS: A total of 365 antibiotics were prescribed in 157 patients during the study period, with an average of 2.34 prescriptions per patient. Total antibiotic utilization in terms of defined daily dose per 100 bed-days was 49.5. Piperacillin/tazobactam (45.2%) was the most commonly prescribed antibiotic, and meropenem was the most expensive antibiotics (US$4440.70). The median (interquartile range) cost of antibiotics used per patient was US$47.67 (US$63.73). Escherichia coli, Acinetobacter, and Pseudomonas sp. were the common organisms isolated and were found to be resistant to some of the commonly used antibiotics. CONCLUSION: This study suggests that the utilization and cost of antibiotics are high in medical intensive care unit of the hospital and E. coli was resistant to multiple antibiotics. The findings highlight an urgent need for the implementation of antibiotic stewardship program in order to improve antibiotic utilization in such hospital settings.

A retrospective study to assess the risk of bladder cancer in type-2 diabetic patients treated with pioglitazone.

INTRODUCTION: Pioglitazone has been a cornerstone of oral hypoglycemic therapy. Concerns have been raised about its association with urinary bladder cancer. Considering the wide usage of this drug, concrete and multiple population-based studies are needed to establish the safety of this drug. The present retrospective study is aimed to assess the association of pioglitazone with urinary bladder cancer. MATERIALS AND METHODS: Clinical records of 4170 patients (2085 pioglitazone users and similar number of nonpioglitazone users) attending the diabetes clinic at a tertiary level teaching hospital were accessed, and the patients were subjected to symptom-directed questionnaire, urine examination, and cystoscopy and bladder biopsy (whenever clinically indicated). The risk of bladder cancer was also assessed with respect to cumulative dose and duration of pioglitazone. RESULTS: We did not observe any increased risk of bladder malignancy with pioglitazone exposure; furthermore, there was no association with cumulative dose and duration of pioglitazone therapy. Pioglitazone was found to be effective and safe in managing glycemic control in diabetic patients.

Brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine in patients with advanced-stage, classical Hodgkin lymphoma: A prespecified subgroup analysis of high-risk patients from the ECHELON-1 study.

Approximately one-third of patients diagnosed with Hodgkin lymphoma presenting with Stage IV disease do not survive past 5 years. We present updated efficacy and safety analyses in high-risk patient subgroups, defined by Stage IV disease or International Prognostic Score (IPS) of 4-7, enrolled in the ECHELON-1 study that compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as first-line therapy after a median follow-up of 37.1 months. Among patients treated with A + AVD (n = 664) or ABVD (n = 670), 64% had Stage IV disease and 26% had an IPS of 4-7. Patients with Stage IV disease treated with A + AVD showed consistent improvements in PFS at 3 years as assessed by investigator (hazard ratio [HR], 0.723; 95% confidence interval [CI], 0.537-0.973; p = 0.032). Similar improvements were seen in the subgroup of patients with IPS of 4-7 (HR, 0.588; 95% CI, 0.386-0.894; p = 0.012). The most common adverse events (AEs) in A + AVD-treated versus ABVD-treated patients with Stage IV disease were peripheral neuropathy (67% vs. 40%) and neutropenia (71% vs. 55%); in patients with IPS of 4-7, the most common AEs were peripheral neuropathy (69% vs. 45%), neutropenia (66% vs. 55%), and febrile neutropenia (23% vs. 9%), respectively. Patients in high-risk subgroups did not experience greater AE incidence or severity than patients in the total population. This updated analysis of ECHELON-1 shows a favorable benefit-risk balance in high-risk patients.

Developments and Prospects in Imperative Underexploited Vegetable Legumes Breeding: A Review.

Vegetable legumes are an essential source of carbohydrates, vitamins, and minerals, along with health-promoting bioactive chemicals. The demand for the use of either fresh or processed vegetable legumes is continually expanding on account of the growing consumer awareness about their well-balanced diet. Therefore, sustaining optimum yields of vegetable legumes is extremely important. Here we seek to present d etails of prospects of underexploited vegetable legumes for food availability, accessibility, and improved livelihood utilization. So far research attention was mainly focused on pulse legumes' performance as compared to vegetable legumes. Wild and cultivated vegetable legumes vary morphologically across diverse habitats. This could make them less known, underutilized, and underexploited, and make them a promising potential nutritional source in developing nations where malnutrition still exists. Research efforts are required to promote underexploited vegetable legumes, for improving their use to feed the ever-increasing population in the future. In view of all the above points, here we have discussed underexploited vegetable legumes with tremendous potential; namely, vegetable pigeon pea (Cajanus cajan), cluster bean (Cyamopsis tetragonoloba), winged bean (Psophocarpus tetragonolobus), dolichos bean (Lablab purpureus), and cowpea (Vigna unguiculata), thereby covering the progress related to various aspects such as pre-breeding, molecular markers, quantitative trait locus (QTLs), genomics, and genetic engineering. Overall, this review has summarized the information related to advancements in the breeding of vegetable legumes which will ultimately help in ensuring food and nutritional security in developing nations.

Should screening voluntary blood donors be used as strategy to diagnose diabetes and diabetic nephropathy?

INTRODUCTION AND AIM: The present study aims to assess the glycemic status during voluntary blood donation as a strategy to detect undiagnosed diabetes mellitus and diabetic nephropathy. MATERIAL AND METHOD: Study was conducted at a tertiary care hospital and medical college. All voluntary blood donors underwent random capillary blood glucose screening and patients who had random blood sugar exceeding 200 mg/dl were subjected to undergo oral glucose tolerance test (OGTT). The subjects thus detected diabetic by capillary blood sugar and OGTT underwent screening diabetic kidney disease with urine albumin to creatnine ratio (UACR). Data collected was statistically analyzed using SPSS 16 using Student's t test. RESULTS: Seven hundred and sixty five males and 443 females were enrolled for the study. Capillary blood sugar of 54 subjects was ≥200 mg/dl. 48 subjects gave consent for OGTT, stratified data showed 22 subjects (12 males and 10 females) were in range of 200-300 mg/dl. 20 subjects (12 males and 8 females) were in range of 300-400 mg/dl, whereas 6 subjects (5 males and 1 female) had blood sugar more than 400 mg/dl. The HbA1C ranges in respective glycemic groups were 200-300 mg/dl - 7.4% to 8.6% (mean - 8.05%), 300-400 mg/dl - 8.7% to 11.8% (mean 9.63%), more than 400 mg/dl - 11.8% to 14.2% (mean - 13%). Male preponderance was observed in all glycemic groups, though the difference was statistically insignificant. Of the 48 diabetic subjects, 13 (27.08%) were detected to have albuminuria, of these 11 (22.91%) had microalbuminuria (UACR 30 - 300 mg/gm), whereas 2 (4.16%) had overt proteinuria (UACR exceeding 300 mg/gm). CONCLUSION: Glycemic screening with random capillary blood glucose screening, 75 gm 2 hour OGTT and HbA1C amongst voluntary blood donors can be used to detect pre diabetes and undiagnosed diabetes mellitus and diabetic nephropathy.

A Comparative Study of Quantitative Smartphone Usages among Controlled and Uncontrolled Type 2 Diabetes Mellitus Population.

BACKGROUND: Smartphones has significantly changed the lifestyle of people and considered as basic need for day to day work. But its usages beyond certain limits adversely affects physical and mental health. Aim of this study is to analyzes the quantitative usages of smartphone among controlled and uncontrolled type 2 diabetes patients. Objective is to correlate the pattern and duration of smartphone usages with the level of glycemic control. METHOD: "RealizD" is a mobile application that observes the pattern of mobile phone usages like 'screen time' (total duration of time spends watching mobile screen for any purpose) and number of times phone picked in a day. It graphically displays the hourly usages and longest duration of phone use in a single stretch. Subjects were patients of type 2 diabetes mellitus(T2DM) divided into 50 "case" with poor glycemic control and 50 "control" with good glycemic control. This application was installed in their smartphones to collect all above data. Subjects were observed for period of 3 months. Demographic data, blood glucose levels and HbA1c was recorded at first and again at second visit 3 months after. Data from application was recorded at second visit as described above. FINDINGS: The average screen time of cases was 160 ± 50.9 minutes per day whereas of controls was 107 ± 22.5 minutes. This difference in the screen time was statistically significant. Higher the screen time more was the HbA1c. The average of number of times a case picked his/her phone in a day was 70.2 ± 20.1 whereas by the controls was 57.3 ± 22.2. The difference was statistically significant. Also, Cases spend 37.3 % versus controls who spend 19.9 % of total screen time between 5 AM to 9 AM. The difference was statistically significant. This indicates that uncontrolled T2DM patients spend more time on phone in morning hours. INTERPRETATION: Smartphones could be best companion if used judiciously. Their unrestricted use adversely affects the health. Among diabetes patient unregulated smartphone usages leads to poor glycemic control and thus could be considered an important factor that need to be addressed.

Teneligliptin-induced hair loss: A case report.

Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the common phenotype of hyperglycemia secondary to various pathophysiologic mechanisms that include reduced insulin secretion, decreased glucose utilization, and increased glucose production. Individuals suffering from Type 2 DM (T2DM) tend to be at a higher risk for the development of both micro as well as macrovascular complications. Management strategy includes an armamentarium of drugs and lifestyle modifications. 35 years old male diagnosed with T2DM was started on a fixed-dose combination of 20 mg Teneligliptin and 1 g metformin once daily. After consuming this dose for a month, he observed no reduction in his blood sugar levels and consequently escalated the dose to twice daily without any consultation or supervision. Subsequently, on next visit OPD his blood sugar was controlled, however, he complained of hair loss from the scalp. This complaint was resolved with the discontinuation of Teneligliptin.

Primary prophylaxis with G-CSF may improve outcomes in patients with newly diagnosed stage III/IV Hodgkin lymphoma treated with brentuximab vedotin plus chemotherapy.

We investigate the impact of granulocyte-colony stimulating factor (G-CSF) primary prophylaxis (G-PP, N = 83) versus no G-PP (N = 579) on safety and efficacy of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) in the ECHELON-1 study of previously untreated stage III/IV classical Hodgkin lymphoma. G-PP was associated with lower incidence of ≥ grade 3 neutropenia (29% versus 70%) and febrile neutropenia (11% versus 21%). Fewer dose delays (35% versus 49%), reductions (20% versus 26%), and hospitalizations (29% versus 38%) were observed. Seven neutropenia-associated deaths occurred in the A + AVD arm; none received G-PP. A + AVD with G-PP was associated with decreased risk of a modified progression-free survival event by 26% compared with A + AVD alone (95% CI: 0.40-1.37). G-PP reduced the rate and severity of adverse events, including febrile neutropenia, reduced treatment delays, dose reductions, and discontinuations, and may thus improve efficacy outcomes. These data support G-PP for all patients treated with A + AVD.