Endoplasmic reticulum stress in adipose tissue augments lipolysis

The endoplasmic reticulum (ER) is an organelle important for protein synthesis and folding, lipid synthesis and Ca²⁺ homoeostasis. Consequently, ER stress or dysfunction affects numerous cellular processes and has been implicated as a contributing factor in several pathophysiological conditions. Tunicamycin induces ER stress in various cell types in vitro as well as in vivo. In mice, a hallmark of tunicamycin administration is the development of fatty livers within 24–48 hrs accompanied by hepatic ER stress. We hypothesized that tunicamycin would induce ER stress in adipose tissue that would lead to increased lipolysis and subsequently to fatty infiltration of the liver and hepatomegaly. Our results show that intraperitoneal administration of tunicamycin rapidly induced an ER stress response in adipose tissue that correlated with increased circulating free fatty acids (FFAs) and glycerol along with decreased adipose tissue mass and lipid droplet size. Furthermore, we found that in addition to fatty infiltration of the liver as well as hepatomegaly, lipid accumulation was also present in the heart, skeletal muscle and kidney. To corroborate our findings to a clinical setting, we examined adipose tissue from burned patients where increases in lipolysis and the development of fatty livers have been well documented. We found that burned patients displayed significant ER stress within adipose tissue and that ER stress augments lipolysis in cultured human adipocytes. Our results indicate a possible role for ER stress induced lipolysis in adipose tissue as an underlying mechanism contributing to increases in circulating FFAs and fatty infiltration into other organs.     

The use of hydrogenated Schiff base ligands in the synthesis of multi-metallic compounds

The synthetic utility of tris-((2-hydroxybenzyl)-aminoethyl)amine (H6TrenSal) and tris-((2-hydroxy-5-bromobenzyl)-aminoethyl)amine (H6Tren5BrSal) are investigated. A range of monomeric complexes with general formula [(H6TrenSal)M][NO₃] with nickel, copper and zinc are reported and crystallographically analysed. Nickel adopts three motifs which are different to that observed for copper and zinc. The use of these species as platforms for the synthesis of more complex systems in conjunction with the lanthanoids are explored. Copper and zinc do not follow a similar reaction pathway to nickel. While nickel forms the expected trimetallic motif [{(TrenSal)Ni}₂Ln(HOMe)]⁺, copper forms a copper trimetallic motif. In contrast to both nickel and copper, reactions with [(H6TrenSal)Zn]⁺ produce lanthanoid based products namely [(H6Tren5BrSal)Gd(NO₃)₃] and [{(H6TrenSal)Ce}₂-μ²-O₂].     

Phytochemical analysis and toxicological evaluation of the ethanolic Leaves extract of Hypoestes rosea on the morphology and biochemical indices of the Kidneys of albino Wistar Rats

BackgroundHypoestes rosea (family: Acanthacea), has been harnessed and utilized for treatment of several ailments. However, there is the paucity of available data on nephrotoxicity associated with this herb. Here, we investigated the phytochemical profile and toxicological effect of H. rosea on Wistar Rats.MethodsTwenty rats (weight range: 75–100 g) were assigned into five study groups, viz; (a) control (without treatment) (b) treatment group 1, orally administered with 50 mg/kg (c) treatment group 2, orally administered with 100 mg/kg (d) treatment group 3, orally administered with 250 mg/kg, and (e) treatment group 4, orally administered with 300 mg/kg of H. rosea, respectively for 28 days of four rats per group. The rats were made unconscious by using oral administration of chloroform. Cardiac punctures were made, and blood samples collected into 10 ml labeled plain container, allowed to clot and spun to harvest serum for determination of sodium, potassium, chloride, bicarbonate, urea and creatinine using colorimetric, back-titrimetric, Urease-Berthelot and Jaffe’s reaction methods respectively. Kidneys of rats were harvested, weighed and immediately fixed in 10% neutral buffered formalin for histological analysis.ResultMean serum sodium (p = 0.049), potassium (p = 0.007), and urea (p < 0.001) levels were significantly higher among the treatment groups compared to controls. Histopathological findings of kidney sections revealed mild glomerular infiltration in treatment groups 2–4. Additionally, sclerosis was observed in groups 3–4. Phytochemical analysis of H. rosea revealed presence of alkaloids, flavonoids, saponins, tannins, terpenoids, steroids and reducing sugars.ConclusionFrom the findings in this study, H. rosea leaf extract causes significant damage to the kidneys of Wistar rats at higher doses. Of which, the damages were dose-dependent in direct proportionality manner. To better determine the safe dosage and ideal duration of consumption, there is the need for further studies on H. rosea.     

Safely resuming neglected tropical disease control activities during COVID-19: Perspectives from Nigeria and Guinea

Since its early spread in early 2020, the disease caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus Disease 2019 (COVID-19) has caused mass disruptions to health services. These have included interruptions to programs that aimed to prevent, control, and eliminate neglected tropical diseases (NTDs). In March 2020, the World Health Organization (WHO) released interim guidelines recommending the temporary cessation of mass drug administration (MDA), community-based surveys, and case detection, while encouraging continuation of morbidity management and vector control where possible. Over the course of the following months, national programs and implementing partners contributed to COVID-19 response efforts, while also beginning to plan for resumption of NTD control activities. To understand the challenges, opportunities, and recommendations for maximizing continuity of disease control during public health emergencies, we sought perspectives from Nigeria and Guinea on the process of restarting NTD control efforts during the COVID-19 pandemic. Through semistructured interviews with individuals involved with NTD control at the local and national levels, we identified key themes and common perspectives between the 2 countries, as well as observations that were specific to each. Overall, interviewees stressed the challenges posed by COVID-19 interruptions, particularly with respect to delays to activities and related knock-on impacts, such as drug expiry and prolonged elimination timelines, as well as concerns related to funding. However, respondents in both countries also highlighted the benefits of a formal risk assessment approach, particularly in terms of encouraging information sharing and increasing coordination and advocacy. Recommendations included ensuring greater availability of historical data to allow better monitoring of how future emergencies affect NTD control progress; continuing to use risk assessment approaches in the future; and identifying mechanisms for sharing lessons learned and innovations between countries as a means of advancing postpandemic health systems and disease control capacity strengthening.     

Allergic Complications of Meningococcal Disease I—Clinical Aspects

Out of 717 patients with meningococcal disease 53 showed one or more of the three allergic complications: 47 (6·6%) developed arthritis, 12 (1·7%) developed cutaneous vasculitis, and 6 developed episcleritis. These complications, which were often multiple, occurred six to nine days after the beginning of the illness and three to six days after the start of successful antibiotic therapy. Those patients with severe systemic disease were prone to the complications.Histological and bacteriological study of the arthritis and vasculitis showed that these lesions were probably not due to persisting infection and suggested that they might be due to immune complex disease.     

Optimisation of the Photonic Efficiency of TiO2 Decorated on MWCNTs for Methylene Blue Photodegradation

MWCNTs/TiO₂ nanocomposite was prepared by oxidising MWCNT in H₂SO₄/HNO₃ then decorating it with TiO₂-p25 nanopowder. The composites were characterised using XRD, TEM, FT-IR PL and UV−vis spectroscopy. The TEM images have shown TiO₂ nanoparticles immobilised onto the sidewalls of the MWCNTs. The UV-vis spectrum confirms that the nanocomposites can significantly absorb more light in the visible regions compared with the commercial TiO₂ (P25). The catalytic activity of these nanocomposites was determined by photooxidation of MB aqueous solution in the presence of visible light. The MWCNTs/TiO₂ (1:3) mass ratio showed maximum degradation efficiency. However, its activity was more favourable in alkaline and a neutral pH than an acidic medium.     

Protective role of TIRAP functional variant against development of coronary artery disease

Coronary artery disease (CAD) is the leading cause of sudden death worldwide. Inflammation is proved to be an important player in development of the CAD. Inflammation is directly regulated by the Toll like receptors (TLRs). Susceptibility of CAD is influenced by genetic variations within TLRs and the proteins involved in its signaling cascade. The TIRAP/MAL {TIR domain containing adaptor protein / MyD88 (myeloid differentiation primary response gene 88) adaptor-like} exhibits maximum genetic variations of all adaptor proteins involved in TLR signaling cascade. Susceptibility to a number of diseases can be influenced due to presence of S180L single nucleotide polymorphism (SNP) of TIRAP/MAL. This study was conducted to investigate the functional role of this well characterized S180L polymorphism on susceptibility to CAD among Pakistani patients. A total of 146 Pakistani CAD patients and 147 controls were genotyped by Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) and the data was analyzed by using 2-tailed Chi square (x²) test. The p value ≤ 0.05 was considered to be significant.Significantly high frequency of homozygous L180L genotype was observed among healthy subjects as compared to the CAD patients [24 (16%) vs 7 (5%); x² 11.85; p = 0.003]. Moreover, the allele frequency of the minor allele; 180L was observed to be significantly higher among controls than the CAD patients, having same direction of association [156 (53%) vs 131 (45%); OR (95% CI) = 0.7198 (0.520–0.996); p < 0.05).Our results indicate that protective effect of L180L; a coding variant of TIRAP/MAL against CAD is discernible.     

Phosphorus chemistry and bacterial community composition interact in brackish sediments receiving agricultural discharges

Background

External nutrient discharges have caused eutrophication in many estuaries and coastal seas such as the Baltic Sea. The sedimented nutrients can affect bacterial communities which, in turn, are widely believed to contribute to release of nutrients such as phosphorus from the sediment.

Methods

We investigated relationships between bacterial communities and chemical forms of phosphorus as well as elements involved in its cycling in brackish sediments using up-to-date multivariate statistical methods. Bacterial community composition was determined by terminal restriction fragment length polymorphism and cloning of the 16S rRNA gene.

Results and Conclusions

The bacterial community composition differed along gradients of nutrients, especially of different phosphorus forms, from the estuary receiving agricultural phosphorus loading to the open sea. This suggests that the chemical composition of sediment phosphorus, which has been affected by riverine phosphorus loading, influenced on bacterial communities. Chemical and spatial parameters explained 25% and 11% of the variation in bacterial communities. Deltaproteobacteria, presumptively sulphate and sulphur/iron reducing, were strongly associated to chemical parameters, also when spatial autocorrelation was taken into account. Sulphate reducers correlated positively with labile organic phosphorus and total nitrogen in the open sea sediments. Sulphur/iron reducers and sulphate reducers linked to iron reduction correlated positively with aluminium- and iron-bound phosphorus, and total iron in the estuary. The sulphate and sulphur/iron reducing bacteria can thus have an important role both in the mineralization and mobilization of nutrients from sediment.

Significance

Novelty in our study is that relationships between bacterial community composition and different phosphorus forms, instead of total phosphorus, were investigated. Total phosphorus does not necessarily bring out interactions between bacteria and phosphorus chemistry since proportions of easily usable mobile (reactive) phosphorus and immobile phosphorus forms in different sediments can vary. Our study suggested possible feedbacks between different forms of phosphorus and bacterial community composition.     

Control of snakebite envenoming: A mathematical modeling study

A mathematical model is designed to assess the impact of some interventional strategies for curtailing the burden of snakebite envenoming in a community. The model is fitted with real data set. Numerical simulations have shown that public health awareness of the susceptible individuals on snakebite preventive measures could reduce the number of envenoming and prevent deaths and disabilities in the population. The simulations further revealed that if at least fifty percent of snakebite envenoming patients receive early treatment with antivenom a substantial number of deaths will be averted. Furthermore, it is shown using optimal control that combining public health awareness and antivenom treatment averts the highest number of snakebite induced deaths and disability adjusted life years in the study area. To choose the best strategy amidst limited resources in the study area, cost effectiveness analysis in terms of incremental cost effectiveness ratio is performed. It has been established that the control efforts of combining public health awareness of the susceptible individuals and antivenom treatment for victims of snakebite envenoming is the most cost effective strategy. Approximately the sum of US$72,548 is needed to avert 117 deaths or 2,739 disability adjusted life years that are recorded within 21 months in the study area. Thus, the combination of these two control strategies is recommended.