STATISTICAL DESIGN AND DEVELOPMENT OF A LIQUID ORAL FLOATING IN SITU GEL OF METFORMIN HYDROCHLORIDE FOR SUSTAINED RELEASE: PHARMACODYNAMIC AND TOXICITY (HISTOPATHOLOGY) STUDIES

Objective: To statistically design, optimize and evaluate a liquid oral, floating in situ gel of metformin hydrochloride (MH) to increase the gastric residence time (the absorption window being the upper part of the duodenum), sustain and modulate the release behavior of the drug. No liquid oral SR formulations of MH are yet available in the market. Methods: A simple mixing based ionic cross-linking method was used for the formulation. A Two-square Factorial Design was employed and the effect of sodium alginate and three categorical levels of HPMC (K4M, K100M, E50) on the response variables were studied. Results: The optimized formulation gelled instantaneously in simulated gastric fluid and showed>24 h floating. The drug release in 1h was 37.98 %, followed by a moderate sustained release for 12 h. Pharmacodynamic studies showed a significant reduction in blood glucose levels in Wistar rats. Short term preclinical safety studies revealed no toxicity to pancreatic tissues. On the contrary, faster regeneration of the β cells of the islets of Langerhans was observed with the group treated with the optimized formulation. Stability studies revealed a 2-year shelf life. Conclusion: An elegant, needle-free, in situ gelling, SR liquid oral of metformin hydrochloride could be developed with drug release modulated as per official specifications for SR formulations of MH. This would be an interesting alternative for geriatric patients who find it difficult to swallow bulky tablets

Response of rice (Oryza sativa L.) to Azotobacter inoculation.

In trials with rice cv. Suhasini given 120 kg N + 75 kg P2O5 + 50 kg K2O/ha, seed inoculation with Azotobacter strains isolated from the rhizosphere of 2 rice cultivars, sorghum, Pennisetum typhoides [= P. americanum] and wheat gave paddy yields of 2.51-3.17 t/ha compared with 1.79 t without seed inoculation; inoculation with Azotobacter from the rhizosphere of the same rice cultivar (Suhasini) gave the highest yield

Nature and dynamics of climate variability in the uganda cattle corridor

The study was conducted in the districts of Nakaseke and Nakasongola stratified into four farming systems of crop dominancy, pastoralists, mixed crop and livestock and fishing. The study was guided by two research questions: (1) how do community residents perceive climate change/variability? (2) What is the trend and nature of climate variability and how does it compare with people’s perceptions? Ninety eight percent (98%) of the respondents reported that the routine patterns of weather and climate had changed in the last 5 to 10 years and it has become less predictable with sunshine hours being extended and rainfall amounts being reduced. This compared well with the analyzed secondary data. Over 78% respondents perceived climate change and variability to be caused by tree cutting other than the known scientific reasons like increase in industrial fumes or increased fossil fuel use. Climate data showed that over the period 1961 to 2010 the number of dry spells within a rainfall season had increased with the most significant increase observed in the first rainfall season of March to May as compared to the season of September to November. The first dry season of June/July to August is short while the second dry season of December to February is long during the study period. The two rainfall seasons of March to May and September to November seem to be merging into one major season from May to November. Temperature data shows a significant increasing trend in mean annual temperatures with the most increase observed in the mean annual minimum temperatures than the maximum temperatures.Key words: Climate variability, community perceptions, Uganda cattle corridor, dry spells

Physicochemical Characteristics Of The Effluents Of The University Private Clinics Of Kinshasa Treated In Upflow Anaerobic Sludge Blanket (UASB)

The uses of water at the hospital are very varied: ¶use food, medical, technical and therapeutic;¶and thus various types of effluents generate. ¶To have a first approach on the current situation of the rejection of the effluents of the CUK, it is necessary to identify the origin of the rejections and to then know the risks which they can generate. ¶The chemical substances used in the hospitals for the activities of care and medical research are generally found in the liquid effluents. ¶This research has like objective to characterize the physicochemical pollution of the effluents of the university private clinics of Kinshasa, to appreciate the intensity of this pollution in order to estimate its impacts on those, in order to carry out a pilot treatment by engine UASB. ¶System UASB pilot set up gave satisfactory results. ¶All the physicochemical parameters of the effluents underwent an improvement in occurrence the DCO which passed from 6250 mg/l to 20 mg/l and the DBO5 of 200 mg/l with 0 mg/l on figure 8. ¶That goes in the same way with the pH, turbidity, dissolved oxygen, them MY, the Nitrate, as well as conductivity. This system in addition to the lowering of organic and mineral pollution, allows the production of the biogas, which in great scale can be used for the power supply of the generating establishment of the effluents.¶

Sugarcane bagasse based biorefineries in India: potential and challenges

Sugarcane bagasse (SCB) is one of the world's most abundant agricultural residues and in an Indian context, ∼100 million tonnes per annum is produced. The current use of SCB is restricted to the cogeneration of steam and power; however considering its potential, cogeneration is not the best valorisation route. Furthermore, with falling electricity prices and reducing global sugar prices due to excess sugar stock, it is inevitable that the waste generated (SCB) by sugar mills are utilised for generating revenue sustainably. With this background, this review aims to put forth a biorefinery perspective based on SCB feedstock. Biogas and bioethanol are the Government of India's current focus with policies and subsidies clearly pointing towards a sizeable future market. Therefore, alongside these biofuels, high-value chemicals such as xylitol, succinic acid and lactic acid were identified as other desired products for biorefineries. This review firstly discusses SCB pre-treatment options based on end applications (saccharification or anaerobic digestion, AD). Next, state-of-the-art for each of these aspects was reviewed and our perspective on a profitable biorefinery is presented. We propose an AD based biorefinery where vortex-based hydrodynamic cavitation was found to be the best choice for pre-treatment. AD is considered not only a bioprocess for energy production here but also a ‘pre-treatment’, where partial conversion of holocellulose leads to a digestate rich in a loosened fibre matrix. This digestate rich in cellulose can be enzymatically hydrolysed and further valorised biochemically. This approach would be cost effective and provide a sustainable waste management route for sugar mills

Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies

Ebola virus (EBOV) is an enveloped, single-stranded RNA virus that can cause Ebola virus disease (EVD). It is thought that EVD survivors are protected against subsequent infection with EBOV and that neutralising antibodies to the viral surface glycoprotein (GP) are potential correlates of protection. Serological studies are vital to assess neutralising antibodies targeted to EBOV GP; however, handling of EBOV is limited to containment level 4 laboratories. Pseudotyped viruses can be used as alternatives to live viruses, which require high levels of bio-containment, in serological and viral entry assays. However, neutralisation capacity can differ among pseudotyped virus platforms. We evaluated the suitability of EBOV GP pseudotyped human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV) to measure the neutralising ability of plasma from EVD survivors, when compared to results from a live EBOV neutralisation assay. The sensitivity, specificity and correlation with live EBOV neutralisation were greater for the VSV-based pseudotyped virus system, which is particularly important when evaluating EBOV vaccine responses and immuno-therapeutics. Therefore, the EBOV GP pseudotyped VSV neutralisation assay reported here could be used to provide a better understanding of the putative correlates of protection against EBOV

Studies on Morphophysiological and Biochemical Parameters for Sucking Pest Tolerance in Organic Cotton

The demand for organic cotton is primarily driven by manufacturers and brands with a corporate focus on environmental and social responsibility. These entities strive to be responsible stewards by seeking organic cotton, which not only offers environmental benefits but also provides softer, more durable, and longer-lasting clothing. Unlike conventional cotton, organic cotton is processed without the use of harsh chemicals, making it more comfortable for individuals with sensitive skin. A study was conducted at the Center of Organic Agriculture Research and Training Center, Department of Agronomy, Dr. PDKV, Akola, Maharashtra, India to evaluate 22 cotton genotypes, including control samples, using a randomized block design with three replications during the kharif (June–October) season in the years 2019–2020 and 2020–2021, under complete organic conditions. During the initial year of the study (2019–2020), visual observations were made to assess the incidence of sucking pests on the cotton genotypes’ leaves, including the top, middle, and bottom portions. The observations indicated promising results, leading to a more detailed study in the subsequent year (2020–2021). This extended study identified several tolerant genotypes to sucking pests, such as AV-G11, PA-255, GA-8004, AV-C14, and AV-G13 from the arboreum species, as well as AKH-09-5, a hirsutum cultivar. Among the recorded data, it was found that the lowest mean aphid population occurred at 90 days after sowing (DAS), with only 1.53 aphids per leaf. Similarly, the lowest mean populations of Cicadellidae, thrips, and whitefly were recorded at 0.75, 0.97, and 0.63 per leaf, respectively, all at 30 DAS. Microscopic analysis of trichome density and gossypol glands revealed a negative and significant correlation with Aphis gossypi (aphids), Cicadellidae sp. (Cicadellidae), and Thrips tabaci (thrips). However, a positive and significant correlation was found with Bemesia tabaci (whitefly). Furthermore, the estimation of total soluble sugar using the Anthrone method, total nitrogen, and crude protein showed positive and significant correlations with aphids, Cicadellidae, and thrips, but negative, significant correlations with whitefly. The findings indicate that higher trichome density provides greater resistance to sucking pest infestation. It was concluded that G. arboreum genotypes exhibit greater tolerance to sucking pests compared to G. hirsutum varieties. This implies that G. arboreum varieties may require less intensive pest management, aligning with organic farming principles. The discovery of these genotypes opens up possibilities for utilizing them as sustainable and pest-resistant options in cotton cultivation, promoting environmentally friendly and organic farming practices in cotton fiber production

PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer.

The cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway detects cytosolic DNA to activate innate immune responses. Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA repair deficiencies such as those caused by BRCA1 mutations or ERCC1 defects. Using isogenic cell lines and patient-derived samples, we showed that ERCC1-defective non-small cell lung cancer (NSCLC) cells exhibit an enhanced type I IFN transcriptomic signature and that low ERCC1 expression correlates with increased lymphocytic infiltration. We demonstrated that clinical PARPi, including olaparib and rucaparib, have cell-autonomous immunomodulatory properties in ERCC1-defective NSCLC and BRCA1-defective triple-negative breast cancer (TNBC) cells. Mechanistically, PARPi generated cytoplasmic chromatin fragments with characteristics of micronuclei; these were found to activate cGAS/STING, downstream type I IFN signaling, and CCL5 secretion. Importantly, these effects were suppressed in PARP1-null TNBC cells, suggesting that this phenotype resulted from an on-target effect of PARPi on PARP1. PARPi also potentiated IFN-γ-induced PD-L1 expression in NSCLC cell lines and in fresh patient tumor cells; this effect was enhanced in ERCC1-deficient contexts. Our data provide a preclinical rationale for using PARPi as immunomodulatory agents in appropriately molecularly selected populations

Urban Movement and Alcohol Intake Strongly Predict Defaulting from Tuberculosis Treatment: An Operational Study

BACKGROUND: High levels of defaulting from treatment challenge tuberculosis control in many African cities. We assessed defaulting from tuberculosis treatment in an African urban setting. METHODS: An observational study among adult patients with smear-positive pulmonary tuberculosis receiving treatment at urban primary care clinics in Kampala, Uganda. Defaulting was defined as having missed two consecutive monthly clinic visits while not being reported to have died or continued treatment elsewhere. Defaulting patients were actively followed-up and interviewed. We assessed proportions of patients abandoning treatment with and without the information obtained through active follow-up and we examined associated factors through multivariable logistic regression. RESULTS: Between April 2007 and April 2008, 270 adults aged ≥15 years were included; 54 patients (20%) were recorded as treatment defaulters. On active follow-up vital status was established of 28/54 (52%) patients. Of these, 19 (68%) had completely stopped treatment, one (4%) had died and eight (29%) had continued treatment elsewhere. Extrapolating this to all defaulters meant that 14% rather than 20% of all patients had truly abandoned treatment. Daily consumption of alcohol, recorded at the start of treatment, predicted defaulting (adjusted odds ratio [OR(adj)] 4.4, 95%CI 1.8-13.5), as did change of residence during treatment (OR(adj) 8.7, 95%CI 1.8-41.5); 32% of patients abandoning treatment had changed residence. CONCLUSIONS: A high proportion of tuberculosis patients in primary care clinics in Kampala abandon treatment. Assessing change of residence during scheduled clinic appointments may serve as an early warning signal that the patient may default and needs adherence counseling

Effect of zinc on the treatment of Plasmodium falciparum malaria in children: A randomized controlled trial

Background: Zinc supplementation in young children has been associated with reductions in the incidence and severity of diarrheal diseases, acute respiratory infections, and malaria. Objective: The objective was to evaluate the potential role of zinc as an adjunct in the treatment of acute, uncomplicated falciparum malaria; a multicenter, double-blind, randomized placebo-controlled clinical trial was undertaken. Design: Children (n = 1087) aged 6 mo to 5 y were enrolled at sites in Ecuador, Ghana, Tanzania, Uganda, and Zambia. Children with fever and ≥ 2000 asexual forms of Plasmodium falciparum/μL in a thick blood smear received chloroquine and were randomly assigned to receive zinc (20 mg/d for infants, 40 mg/d for older children) or placebo for 4 d. Results: There was no effect of zinc on the median time to reduction of fever (zinc group: 24.2 h; placebo group: 24.0 h; P = 0.37), a ≥75% reduction in parasitemia from baseline in the first 72 h in 73.4% of the zinc group and in 77.6% of the placebo group (P = 0.11), and no significant change in hemoglobin concentration during the 3-d period of hospitalization and the 4 wk of follow-up. Mean plasma zinc concentrations were low in all children at baseline (zinc group: 8.54 ± 3.93 μmol/L; placebo group: 8.34 ± 3.25 μmol/L), but children who received zinc supplementation had higher plasma zinc concentrations at 72 h than did those who received placebo (10.95 ± 3.63 compared with 10.16 ± 3.25 μmol/L, P \u3c 0.001). Conclusion: Zinc does not appear to provide a beneficial effect in the treatment of acute, uncomplicated falciparum malaria in preschool children