Assessing the health risks of heavy metals and seasonal minerals fluctuations in Camellia sinensis cultivars during their growth seasons.

The risk assessment of heavy metals in tea is extremely imperative for the health of tea consumers. However, the effects of varietal variations and seasonal fluctuations on heavy metals and minerals in tea plants remain unclear. Inductively coupled plasma optical emission spectrometry (ICP-OES) was used to evaluate the contents of aluminum (Al), manganese (Mn), magnesium (Mg), boron (B), calcium (Ca), copper (Cu), cobalt (Co), iron (Fe), sodium (Na), zinc (Zn), arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), and antimony (Sb) in the two categories of young leaves (YL) and mature leaves (ML) of tea (Camellia sinensis) cultivars throughout the growing seasons. The results showed significant variations in the contents of the investigated nutrients both among the different cultivars and growing seasons as well. Furthermore, the average concentrations of Al, Mn, Mg, B, Ca, Cu, Co, Fe, Na, Zn, As, Cd, Cr, Ni, and Sb in YL ranged, from 671.58-2209.12, 1260.58-1902.21, 2290.56-2995.36, 91.18-164.68, 821.95-5708.20, 2.55-3.80, 3.96-25.22, 37.95-202.84, 81.79-205.05, 27.10-69.67, 0.028-0.053, 0.065-0.127, 2.40-3.73, 10.57-12.64, 0.11-0.14 mg kg-1, respectively. In ML, the concentrations were 2626.41-7834.60, 3980.82-6473.64, 3335.38-4537.48, 327.33-501.70, 9619.89-13153.68, 4.23-8.18, 17.23-34.20, 329.39-567.19, 145.36-248.69, 40.50-81.42, 0.089-0.169, 0.23-0.27, 5.24-7.89, 18.51-23.97, 0.15-0.19 mg kg-1, respectively. The contents of all analyzed nutrients were found to be higher in ML than in YL. Target hazard quotients (THQ) of As, Cd, Cr, Ni, and Sb, as well as the hazard index (HI), were all less than one, suggesting no risk to human health via tea consumption. This research might provide the groundwork for essential minerals recommendations, as well as a better understanding and management of heavy metal risks in tea.

Plant extract preparation and green synthesis of silver nanoparticles using Swertia chirata: Characterization and antimicrobial activity against selected human pathogens.

Herbal medicinal plants have been used for centuries in traditional medicine, and it is interesting to see how modern research has identified the active compounds responsible for their therapeutic effects. The green synthesis of silver nanoparticles using herbal medicinal plants, such as Swertia chirata, is particularly noteworthy due to its antimicrobial properties. In the current study, the Swertia chirata plant was collected for the first time from the region of Murree, Punjab, Pakistan. After collection, extracts were prepared in different solvents (ethanol, methanol, chloroform, and distilled water), and silver nanoparticles were synthesized by reducing silver nitrate (AgNO3). The UV-visible spectrophotometer, SEM, and EDX were used to characterize the synthesized nanoparticles in terms of their size and shape. The phytochemical analysis of crude extract was performed to determine the presence of different kinds of phytochemicals. The antibacterial activity of plant extracts and the silver nanoparticles were then assessed using the agar well diffusion method against various pathogenic bacteria. The results showed that the plant contains several phytochemicals with remarkable antioxidant potential. The antibacterial analysis revealed that silver nanoparticles and the plant extracts exhibited a significant zone of inhibition against human pathogenic bacteria (Escherichia coli, S. capitis, B. subtilis, and Pseudomonas aeruginosa) as compared to the cefixime and norfloxacin. This implies that the nanoparticles have the potential to be used in nano-medicine applications, such as drug delivery systems, as well as for their antibacterial, antifungal, and antiviral activities. Additionally, the development and application of materials and technologies at the nanometer scale opens possibilities for the creation of novel drugs and therapies. Overall, the study highlights the promising potential of herbal medicinal plants found in Murree, Punjab, Pakistan, and green-synthesized silver nanoparticles in various fields of medicine and nanotechnology.

Environmental differences between Japan and Indonesia provide endophyte diversity associated with Artemisia plant and variety of artemisinin derivatives in microbial conversion.

We compared the endophytic compositions of Artemisia plant from different environments (Japan and Indonesia) to demonstrate that the endophytic filamentous fungi in both species differed based on their environments. To prove that the species were identical, both Artemisia plants were identified by comparing the scanning electron micrographs of their pollens, as well as the nucleotide sequences (ribosomal internal transcribed spacer and mitochondrial maturase K) of the two gene regions. After isolating the endophytic filamentous fungi from each plant, we observed that those from Japan and Indonesia comprised 14 and 6 genera, respectively. We assumed that the genera, Arthrinium and Colletotrichum, which exist in both Artemisia species, were species-specific filamentous fungi, while the other genera were environment-dependent. In the microbial-conversion reaction with artemisinin as a substrate using Colletotrichum sp., the peroxy bridge of artemisinin, which is an active site for achieving antimalarial effect, was converted into an ether bond. However, the reaction using the environment-dependent endophyte did not eliminate the peroxy bridge. These endophytic reactions indicated the different roles of endophytes within Artemisia plants.

Fresh evidence on connectedness between prominent markets during COVID-19 pandemic.

Various empirical studies have examined the nexus between financial markets, but this study focused on the comovement among prominent markets. Our study examines the interrelationship among main financial markets, i.e., stock, oil, and commodity during the recent pandemic. The interconnections among the selected markets are investigated using a battery of wavelet coherence tools and the Granger causality test. From the wavelet coherence analysis, our findings indicate strong co-movements among the VIX, oil volatility, and commodity prices during pandemic and localized in all scales and over the sample period. The dependency strength among the considered economies is noted to increase in pandemic, which implies increased short- and long-term benefits for the investors. Moreover, Our result exhibits a feedback causality between OVIX and crude oil, VIX and S&P 500, and gasoline and VIX. Interestingly, a unidirectional causality exists between VIX and crude oil, S&P 500 and crude oil, Brent and crude oil, gasoline, crude oil, and VIX and OVIX. We advocate that the findings will be helpful for portfolio managers, investors, and officials around the world.

Seasonal Variations of Fine Root Dynamics in Rubber-Flemingia macrophylla Intercropping System in Southwestern China.

Intercropping cover crops with trees enhance land productivity and improves the soil's physio-chemical properties while reducing the negative environmental impact. However, there is a lack of quantitative information on the relationships between fine root biomass and available soil nutrients, e.g., nitrogen (N), phosphorus (P), and potassium (K), especially in the rubber-Flemingia macrophylla intercropping system. Therefore, this study was initiated to explore the seasonal variation in fine root biomass and available soil nutrients at different stand ages (12, 15, and 24 years) and management systems, i.e., rubber monoculture (mono) and rubber-Flemingia macrophylla intercropping. In this study, we sampled 900 soil cores over five seasonal intervals, representing one year of biomass. The results showed that the total fine root biomass was greater in 12-year-old rubber monoculture; the same trend was observed in soil nutrients P and K. Furthermore, total fine root biomass had a significant positive correlation with available N (p < 0.001) in rubber monoculture and intercropping systems. Thus, it suggests that fine root growth and accumulation is a function of available soil nutrients. Our results indicate that fine root biomass and soil nutrients (P and K) may be determined by the functional characteristics of dominant tree species rather than collective mixed-species intercropping and are closely linked to forest stand type, topographic and edaphic factors. However, further investigations are needed to understand interspecific and complementary interactions between intercrop species under the rubber-Flemingia macrophylla intercropping system.

Biochemical changes and macrophage polarization of a silane-based endodontic irrigant in an animal model.

Silane-based/fully hydrolyzed, endodontic irrigant exhibiting antimicrobial properties, is prepared, and is hypothesized to control macrophage polarization for tissue repair. Albino wistar rats were injected with 0.1 ml root canal irrigant, and bone marrow cells procured. Cellular mitochondria were stained with MitoTracker green along with Transmission Electron Microscopy (TEM) performed for macrophage extracellular vesicle. Bone marrow stromal cells (BMSCs) were induced for M1 and M2 polarization and Raman spectroscopy with scratch assay performed. Cell counting was used to measure cytotoxicity, and fluorescence microscopy performed for CD163. Scanning Electron Microscopy (SEM) was used to investigate interaction of irrigants with Enterococcus faecalis. K21 specimens exhibited reduction in epithelium thickness and more mitochondrial mass. EVs showed differences between all groups with decrease and increase in IL-6 and IL-10 respectively. 0.5%k21 enhanced wound healing with more fibroblastic growth inside scratch analysis along with increased inflammation-related genes (ICAM-1, CXCL10, CXCL11, VCAM-1, CCL2, and CXCL8; tissue remodelling-related genes, collagen 1, EGFR and TIMP-2 in q-PCR analysis. Sharp bands at 1643 cm-1 existed in all with variable intensities. 0.5%k21 had a survival rate of BMSCs comparable to control group. Bacteria treated with 0.5%k21/1%k21, displayed damage. Antimicrobial and reparative efficacy of k21 disinfectant is a proof of concept for enhanced killing of bacteria across root dentin acquiring functional type M2 polarization for ethnopharmacological effects.

Range expansion decreases the reproductive fitness of Gentiana officinalis (Gentianaceae).

Plants living at the edge of their range boundary tend to suffer an overall decline in their fitness, including growth and reproduction. However, the reproductive performance of plants in artificially expanded habitats is rarely investigated, although this type of study would provide a better understanding of range limitations and improved conservation of ex situ plants. In the current study, we transplanted a narrowly dispersed species of Gentiana officinalis H. Smith (Gentianaceae) from its natural area of distribution to two different elevations and natural elevation to comprehensively study its pollination biology, including flowering phenology and duration, floral display, reproductive allocation, pollinator activity, and seed production. The findings indicated that the starting point and endpoint of the flowering phenology of G. officinalis were earlier at the low elevation, but the peak flowering periods did not differ significantly between any of the experimental plots. When transplanted, the flowering duration, especially the female phase, was reduced; the floral display, including spray numbers, flower numbers, and flower size (length and width), decreased, especially at high elevations. Moreover, the pollen numbers and pollen-ovule ratio were decreased at both high and low elevations, although the ovule numbers showed no change, and aboveground reproductive allocation was decreased. Furthermore, pollinator richness and activity were significantly decreased, and the seed-set ratio decreased under both natural conditions and with supplemental pollination. Finally, more severe pollen limitation was found in transplanted individuals. These results indicated an overall decrease in reproductive fitness in plants living outside their original area of distribution when the geographical range of G. officinalis was expanded.

Endophytic fungi inhabiting Physalis angulata L. plant: diversity, antioxidant, and antibacterial activities of their ethyl acetate extracts.

OBJECTIVES: Endophytic fungi are an essential source of biologically active compounds. They have the ability to synthesize secondary metabolites which are the same or have a high degree of similarity to their host plants. In this study, we aimed to explore the biodiversity and the bioactivities of active metabolites produced by 14 endophytic fungi isolated from the medicinal plant Physalis angulata L. (PA). METHODS: Fourteen endophytic fungi were isolated from the flowers, stems, leaves, and fruit husks of PA. The endophytic fungi were cultured and incubated in the PDB medium at room temperature. After three weeks, the cultures were extracted using ethyl acetate and dried using a rotary evaporator. The antioxidant activity was evaluated against DPPH while antibacterial activity was evaluated against Escherichia coli and Staphylococcus aureus using microdilution technique. TLC analysis was also done to profile the active compounds within the extract. RESULTS: Hyphomycetes fungus isolated from the flower of PA exhibited a moderate antioxidant activity with an antioxidant index value of 0.59 (IC50 = 52.43 µg/mL). Six isolates have strong antibacterial activity against E. coli and S. aureus with minimum inhibitory concentration (MIC) value ranging from 8-64 µg/mL. These endophytic fungi are one Hyphomycetes fungus isolated from the flower, one Fusarium sp. isolated from the stem, and four Colletotrichum sp. isolated from leaf and fruit husk of PA. CONCLUSIONS: Endophytic fungi isolated from PA are potential novel sources of active metabolites especially for antibacterial compounds.

Influence of Nitrogen to Phosphorus Ratio and CO2 Concentration on Lipids Accumulation of Scenedesmus dimorphus for Bioenergy Production and CO2 Biofixation.

The potential of Scenedesmus dimorphus microalgae for CO2 biofixation and lipid biosynthesis for bioenergy applications was evaluated in this study. Batch experiments were conducted using synthetic tertiary municipal wastewater samples at several nitrogen to phosphorus (NP) ratios (1 : 1 to 8 : 1) and CO2 concentrations (∼0%, 2%, 4%, and 6% CO2 in supplied air). Scenedesmus dimorphus was cultivated for 25 days and the growth is highly dependent on the CO2 concentration and the NP ratio. An NP ratio of 2 : 1 produces a biomass yield of 733 mg/L when the microalga culture was supplied with air enriched with 2% CO2 . The maximum CO2 biofixation rate of 49.6 mg L-1 d-1 is at an NP ratio of 8 : 1 with 4% CO2 . A colorimetric technique depending on sulpho-phospho-vanillin (SPV) was utilized for the determination of the intracellular lipid content. The highest lipid content of 31.6% as the dry weight of the biomass is at an NP ratio of 1 : 1 and 6% CO2 . These results indicate that supplementation of suitable CO2 with favorable NP ratio has a considerable effect on lipid accumulation in the microalgae Scenedesmus dimorphus biomass.

The Resurgence of Measles Infection and its Associated Complications in Early Childhood at a Tertiary Care Hospital in Peshawar, Pakistan.

Measles infection is of substantial interest to immunologists due to its paradoxical interaction with the immune system. After the acquisition of the measles infection, secondary infection plays a pivotal role in measles-related deaths. A cross-sectional study conducted between December 2018 and July 2019 is presented here. A total of one hundred children of both genders presented with measles complications were included following WHO criteria. Measles confirmation was done by quantitative determination of anti-measles antibodies (IgM) in patients' sera while patient-related demographic data, vaccination status, and other clinical information were obtained on a separate form. The number of female patients (52%) slightly exceeded the number of males (48%). 43% of patients' parents were illiterate, and half of the patients (50%) were from a poor background. The majority of children (76%) who presented with the complications did not receive a measles vaccine. 56% of children were breastfed while 58% received vitamin A supplements but developed complications. The elevated levels of anti-measles IgM were observed in 77% of cases. In both genders, the major complications were pneumonia, lower respiratory tract infection (LRTI), acute diarrhea, diarrhea and LRTI, pneumonia and diarrhea, otitis media and pneumonia, myocarditis and LRTI, and pneumothorax. The majority of the infected children (n = 48) under 12 months of age had associated complications. It has been observed that the measles virus strikes early age children in the northwestern region of Pakistan, which is an alarming situation and is associated with the aforementioned complications, especially in unvaccinated children. Anti-measles IgM is an important serological parameter for early diagnosis of measles infection.Measles infection is of substantial interest to immunologists due to its paradoxical interaction with the immune system. After the acquisition of the measles infection, secondary infection plays a pivotal role in measles-related deaths. A cross-sectional study conducted between December 2018 and July 2019 is presented here. A total of one hundred children of both genders presented with measles complications were included following WHO criteria. Measles confirmation was done by quantitative determination of anti-measles antibodies (IgM) in patients' sera while patient-related demographic data, vaccination status, and other clinical information were obtained on a separate form. The number of female patients (52%) slightly exceeded the number of males (48%). 43% of patients' parents were illiterate, and half of the patients (50%) were from a poor background. The majority of children (76%) who presented with the complications did not receive a measles vaccine. 56% of children were breastfed while 58% received vitamin A supplements but developed complications. The elevated levels of anti-measles IgM were observed in 77% of cases. In both genders, the major complications were pneumonia, lower respiratory tract infection (LRTI), acute diarrhea, diarrhea and LRTI, pneumonia and diarrhea, otitis media and pneumonia, myocarditis and LRTI, and pneumothorax. The majority of the infected children (n = 48) under 12 months of age had associated complications. It has been observed that the measles virus strikes early age children in the northwestern region of Pakistan, which is an alarming situation and is associated with the aforementioned complications, especially in unvaccinated children. Anti-measles IgM is an important serological parameter for early diagnosis of measles infection.

Hypnosis regulation in propofol anaesthesia employing super-twisting sliding mode control to compensate variability dynamics.

Regulation of hypnosis level on bi-spectral index monitor (BIS) during a surgical procedure in propofol anaesthesia administration is a challenging task for an anaesthesiologist in multi-tasking environment of the operation theater. Automation in anaesthesia has the potential to solve issues arising from manual administration. Automation in anaesthesia is based on developing the three-compartmental model including pharmacokinetics and pharmacodynamic of the silico patients. This study focuses on regulation of the hypnosis level in the presence of surgical stimulus including skin incision, surgical diathermy and laryngoscopy as well as inter-patient variability by designing super-twisting sliding mode control (STSMC). The depth of the hypnosis level is maintained to 50 on the BIS level in the maintenance phase after improving the induction phase to 60 s using the conventional sliding mode control and 30 s with STSMC. The proposed scheme also compensates the inter-patient variability dynamics including height, age and weight of the different silico patients. Moreover, the surgical stimuli direct the hypnosis level towards the state of consciousness and stimulate the controller to provide continuous drug infusion during the interval 80-90 s. Simulation results witness that the oscillatory behaviour is observed in drug infusion to ensure the moderate level of hypnosis (40-60) for general surgery.

Provitamin A biofortification of cassava enhances shelf life but reduces dry matter content of storage roots due to altered carbon partitioning into starch.

Storage roots of cassava (Manihot esculenta Crantz), a major subsistence crop of sub-Saharan Africa, are calorie rich but deficient in essential micronutrients, including provitamin A ß-carotene. In this study, ß-carotene concentrations in cassava storage roots were enhanced by co-expression of transgenes for deoxy-d-xylulose-5-phosphate synthase (DXS) and bacterial phytoene synthase (crtB), mediated by the patatin-type 1 promoter. Storage roots harvested from field-grown plants accumulated carotenoids to ≤50 µg/g DW, 15- to 20-fold increases relative to roots from nontransgenic plants. Approximately 85%-90% of these carotenoids accumulated as all-trans-ß-carotene, the most nutritionally efficacious carotenoid. ß-Carotene-accumulating storage roots displayed delayed onset of postharvest physiological deterioration, a major constraint limiting utilization of cassava products. Large metabolite changes were detected in ß-carotene-enhanced storage roots. Most significantly, an inverse correlation was observed between ß-carotene and dry matter content, with reductions of 50%-60% of dry matter content in the highest carotenoid-accumulating storage roots of different cultivars. Further analysis confirmed a concomitant reduction in starch content and increased levels of total fatty acids, triacylglycerols, soluble sugars and abscisic acid. Potato engineered to co-express DXS and crtB displayed a similar correlation between ß-carotene accumulation, reduced dry matter and starch content and elevated oil and soluble sugars in tubers. Transcriptome analyses revealed a reduced expression of genes involved in starch biosynthesis including ADP-glucose pyrophosphorylase genes in transgenic, carotene-accumulating cassava roots relative to nontransgenic roots. These findings highlight unintended metabolic consequences of provitamin A biofortification of starch-rich organs and point to strategies for redirecting metabolic flux to restore starch production.

A Review of Modern Control Strategies for Clinical Evaluation of Propofol Anesthesia Administration Employing Hypnosis Level Regulation.

Regulating the depth of hypnosis during surgery is one of the major objectives of an anesthesia infusion system. Continuous administration of Propofol infusion during surgical procedures is essential but it unduly increases the load of an anesthetist working in a multitasking scenario in the operation theatre. Manual and target controlled infusion systems are not appropriate to handle instabilities like blood pressure and heart rate changes arising due to interpatient and intrapatient variability. Patient safety, large interindividual variability, and less postoperative effects are the main factors motivating automation in anesthesia administration. The idea of automated system for Propofol infusion excites control engineers to come up with more sophisticated systems that can handle optimum delivery of anesthetic drugs during surgery and avoid postoperative effects. A linear control technique is applied initially using three compartmental pharmacokinetic and pharmacodynamic models. Later on, sliding mode control and model predicative control achieve considerable results with nonlinear sigmoid model. Chattering and uncertainties are further improved by employing adaptive fuzzy control and H∞ control. The proposed sliding mode control scheme can easily handle the nonlinearities and achieve an optimum hypnosis level as compared to linear control schemes, hence preventing mishaps such as underdosing and overdosing of anesthesia.

Regulation of hypnosis in Propofol anesthesia administration based on non-linear control strategy / Controle da hipnose na administração de propofol com base na estratégia de controle não linear

Abstract Continuous adjustment of Propofol in manual delivery of anesthesia for conducting a surgical procedure overburdens the workload of an anesthetist who is working in a multi-tasking scenario. Going beyond manual administration and Target Controlled Infusion, closed-loop control of Propofol infusion has the potential to offer several benefits in terms of handling perturbations and reducing the effect of inter-patient variability. This paper proposes a closed-loop automated drug administration approach to control Depth Of Hypnosis in anesthesia. In contrast with most of the existing research on anesthesia control which makes use of linear control strategies or their improved variants, the novelty of the present research lies in applying robust control strategy i.e. Sliding Mode Control to accurately control drug infusion. Based on the derived patient's model, the designed controller uses measurements from EEG to regulate DOH on Bispectral Index by controlling infusion rate of Propofol. The performance of the controller is investigated and characterized with real dataset of 8 patients undergoing surgery. Results of this in silico study indicate that for all the patients, with 0% overshoot observed, the steady state error lies in between ±5. Clinically, this implies that in all the cases, without any overdose, the controller maintains the desired DOH level for smooth conduction of surgical procedures.

Resumo O ajuste contínuo de propofol na administração manual de anestesia para um procedimento cirúrgico onera a carga de trabalho de anestesistas que trabalham em ambiente multitarefa. Indo além da administração manual e da infusão alvo-controlada (IAC), o controle de circuito fechado da infusão de propofol tem o potencial de oferecer vários benefícios em termos de manejo das perturbações e reduzir o efeito da variabilidade interpaciente. Este artigo propõe uma abordagem para a administração automatizada de drogas em circuito fechado para controlar a profundidade da hipnose (PDH) em anestesia. Em contraste com a maioria das pesquisas existentes sobre o controle da anestesia que usam estratégias de controle linear ou de suas variantes melhoradas, a novidade da presente pesquisa reside na aplicação de uma estratégia de controle consistente; isto é, o Controle por Modos Deslizantes (CMD) para controlar com precisão a infusão da droga. Com base no modelo derivado do paciente, o controlador projetado usa as medições do EEG para regular a PDH no Bispectral Index (BIS), controla a taxa de infusão de propofol. O desempenho do controlador é investigado e caracterizado com um conjunto de dados reais de oito pacientes submetidos à cirurgia. Os resultados deste estudo in silico indicam que, para todos os pacientes, com 0% de excesso observado, o erro de estado estacionário fica entre ± 5. Clinicamente, isso implica que em todos os casos, sem qualquer sobredosagem, o controlador mantém o nível desejado de PDH para a condução tranquila dos procedimentos cirúrgicos.

Regulation of hypnosis in Propofol anesthesia administration based on non-linear control strategy.

Continuous adjustment of Propofol in manual delivery of anesthesia for conducting a surgical procedure overburdens the workload of an anesthetist who is working in a multi-tasking scenario. Going beyond manual administration and Target Controlled Infusion, closed-loop control of Propofol infusion has the potential to offer several benefits in terms of handling perturbations and reducing the effect of inter-patient variability. This paper proposes a closed-loop automated drug administration approach to control Depth Of Hypnosis in anesthesia. In contrast with most of the existing research on anesthesia control which makes use of linear control strategies or their improved variants, the novelty of the present research lies in applying robust control strategy i.e. Sliding Mode Control to accurately control drug infusion. Based on the derived patient's model, the designed controller uses measurements from EEG to regulate DOH on Bispectral Index by controlling infusion rate of Propofol. The performance of the controller is investigated and characterized with real dataset of 8 patients undergoing surgery. Results of this in silico study indicate that for all the patients, with 0% overshoot observed, the steady state error lies in between ±5. Clinically, this implies that in all the cases, without any overdose, the controller maintains the desired DOH level for smooth conduction of surgical procedures.

[Regulation of hypnosis in Propofol anesthesia administration based on non-linear control strategy]. / Controle da hipnose na administração de propofol com base na estratégia de controle não linear.

Continuous adjustment of Propofol in manual delivery of anesthesia for conducting a surgical procedure overburdens the workload of an anesthetist who is working in a multi-tasking scenario. Going beyond manual administration and Target Controlled Infusion, closed-loop control of Propofol infusion has the potential to offer several benefits in terms of handling perturbations and reducing the effect of inter-patient variability. This paper proposes a closed-loop automated drug administration approach to control Depth Of Hypnosis in anesthesia. In contrast with most of the existing research on anesthesia control which makes use of linear control strategies or their improved variants, the novelty of the present research lies in applying robust control strategy i.e. Sliding Mode Control to accurately control drug infusion. Based on the derived patient's model, the designed controller uses measurements from EEG to regulate DOH on Bispectral Index by controlling infusion rate of Propofol. The performance of the controller is investigated and characterized with real dataset of 8 patients undergoing surgery. Results of this in silico study indicate that for all the patients, with 0% overshoot observed, the steady state error lies in between ±5. Clinically, this implies that in all the cases, without any overdose, the controller maintains the desired DOH level for smooth conduction of surgical procedures.

Implementation of the ANISA Study in Karachi, Pakistan: Challenges and Solutions.

BACKGROUND: Aetiology of Neonatal Infection in South Asia (ANISA) is a multicenter study in Bangladesh, India and Pakistan exploring the incidence and etiology of neonatal infections. A periurban site in Karachi was selected for its representativeness of the general population in neonatal health indicators. An established demographic surveillance system and other infrastructure needed for conducting the study already existed at this site. ANISA presents a unique challenge because of the need to capture every birth outcome in the community within a few hours of delivery to reliably estimate the incidence and etiology of early-onset sepsis in a setting where home births and deaths are common. CONTEXTUAL CHALLENGES: Major challenges at the Karachi site are related to early birth reporting and newborn assessment for births outside the catchment areas, parental refusal to participate, diverse ethnicity of the population, collection of biological specimens from healthy controls, political instability and crime, power outages and blood culture contamination. Some of the remedial actions taken include prolonging working hours; developing counseling skills of field workers; hiring staff with different linguistic abilities from within the study community; liaising with health facilities, key community informants, Lady Health Workers and traditional birth attendants; hiring community mobilizers; enhancing community sensitization; developing contingency plans for field work interruptions and procuring backup generators. The specimen contamination rate has decreased through training, supervision and video monitoring of blood collection procedures with individualized counseling of phlebotomists. CONCLUSION: ANISA offers lessons for successful implementation of complex study protocols in areas of high child mortality and challenging social environments.

Computational Docking Study of p7 Ion Channel from HCV Genotype 3 and Genotype 4 and Its Interaction with Natural Compounds.

BACKGROUND: The current standard care therapy for hepatitis C virus (HCV) infection consists of two regimes, namely interferon-based and interferon-free treatments. The treatment through the combination of ribavirin and pegylated interferon is expensive, only mildly effective, and is associated with severe side effects. In 2011, two direct-acting antiviral (DAA) drugs, boceprevir and telaprevir, were licensed that have shown enhanced sustained virologic response (SVR) in phase III clinical trial, however, these interferon-free treatments are more sensitive to HCV genotype 1 infection. The variable nature of HCV, and the limited number of inhibitors developed thus aim in expanding the repertoire of available drug targets, resulting in targeting the virus assembly therapeutically. AIM: We conducted this study to predict the 3D structure of the p7 protein from the HCV genotypes 3 and 4. Approximately 63 amino acid residues encoded in HCV render this channel sensitive to inhibitors, making p7 a promising target for novel therapies. HCV p7 protein forms a small membrane known as viroporin, and is essential for effective self-assembly of large channels that conduct cation assembly and discharge infectious virion particles. METHOD: In this study, we screened drugs and flavonoids known to disrupt translation and production of HCV proteins, targeted against the active site of p7 residues of HCV genotype 3 (GT3) (isolatek3a) and HCV genotype 4a (GT4) (isolateED43). Furthermore, we conducted a quantitative structure-activity relationship and docking interaction study. RESULTS: The drug NB-DNJ formed the highest number of hydrogen bond interactions with both modeled p7 proteins with high interaction energy, followed by BIT225. A flavonoid screen demonstrated that Epigallocatechin gallate (EGCG), nobiletin, and quercetin, have more binding modes in GT3 than in GT4. Thus, the predicted p7 protein molecule of HCV from GT3 and GT4 provides a general avenue to target structure-based antiviral compounds. CONCLUSIONS: We hypothesize that the inhibitors of viral p7 identified in this screen may be a new class of potent agents, but further confirmation in vitro and in vivo is essential. This structure-guided drug design for both GT3 and GT4 can lead to the identification of drug-like natural compounds, confirming p7 as a new target in the rapidly increasing era of HCV.

Effects of CO2 Concentration and pH on Mixotrophic Growth of Nannochloropsis oculata.

This communication reports an experimental investigation of integrated CO2 bio-conversion, wastewater treatment, and biomass production by microalgae cultivation. In this regard, the effects of CO2 concentrations on mixotrophic growth kinetics of a microalgae strain (Nannochloropsis oculata) are conducted in a semi-batch photobioreactor. The concentration of CO2 in the feed stream is varied from 4 to 12 mol% by adjusting CO2-to-air ratio. The variation of pH of the synthetic wastewater culture media and nutrient uptake by the microalgae are also monitored. The experimental evaluation shows that 8 % CO2 gives the highest growth rate of N. oculata with a productivity of 0.088 g L(-1) day(-1). Under the studied conditions, the pH value of the culture media between 5.5 and 6.5 is favorable for the growth of N. oculata in mixotrophic condition. Among the nutrients available in the culture media, percentage of ammonia removal is found to be the highest (98.9 %) as compared that of other compounds such as nitrate (88.2 %) and phosphate (18.9 %). The thermochemical characteristics of the cultivated microalgae are assessed by thermogravimetric analysis in presence of air. The produced microalgae is thermally stable up to 200 °C. Following that, the microalgae biomass is sharply decomposed within 600 °C.