INNOVATIONS IN FOCUS: MECHANISTIC DISEASE THEORIES, CLIMATE DYNAMICS, AND HOST-PARASITE ADAPTATIONS.

Infectious illnesses are predicted to experience a range of intricate responses from climate change, with some likely to rise, others to fall and many expected to undergo changes in prevalence. The study uses extensive data on global temperature variations and infectious illness transmission in people and animals. We now know a lot more about how the temperature changes across the world and whether or not the spread of infectious diseases impacts people as well as animals. Three primary topics of research are investigated in this paper: improving mechanical disease modelling, investigating the role of environmental variation in sickness dynamics, and understanding the consequences of temperature imbalances between parasites and hosts. By incorporating the latest data stemming from these advancements into weather-disease models and bridging critical knowledge gaps, enhancing our ability to forecast the probable effect of rising temperatures on the prevalence of diseases among both human and animal communities is possible. Through the establishment of important information gaps and the incorporation of new findings into models of climate-disease relationships, it will be possible to predict the effects of changes in climatic averages, variations and extremes on people and wildlife health.

There is a Minimal Difference in Ankle Functional Outcomes After Peroneus Longus Harvest: Systematic Review and Meta-analysis.

Importance: Recently, peroneus longus (PL) autograft as a graft choice for ligament surgeries have attracted interest due to studies showing good clinical outcomes and minimal donor site morbidity. There remain concerns related to these grafts, especially the potential impact on ankle functions. Aims/Objective: The purpose of this review and meta-analysis is to summarize the available evidence for ankle functional outcomes after PL harvest. This will provide objective clinical evidence for surgical decision making. Evidence Review: Cochrane, Embase, Medline, and Google Scholar were all searched for articles published between January 2001 and May 2021. For the aim of a systematic review, certain inclusion and exclusion criteria were adopted in accordance with PRISMA recommendations. The primary outcome measure was the assessment of ankle functional outcomes using validated instruments (such as AOFAS score, FADI score etc.). Findings: A total of twelve studies representing pooled patient populations of 537 patients were included in this review. The average follow-up duration was 17 months (range; 6-32 months) across all studies. All twelve studies assessed AOFAS score and six studies also additionally assessed FADI score. The pooled mean outcomes measured showed a slight decrease in post-operative as compared to pre-operative AOFAS and FADI score (mean difference of AOFAS 1.92, 95% CI 1.021-3.123, p value < 0.05 and mean difference for FADI 1.50, 95% CI 0.561-2.445, p value < 0.05). Though statistically significant the magnitude of variance implies minimal clinical impact. Conclusion and Relevance: This review and meta-analysis found that PL autograft harvest leads to statistically significant but minimal impact on ankle functional outcomes. This, in conjunction with various studies on ankle parameters after PL harvest, shows that PL harvest leads to minimal impact on ankle outcomes and function. Level of Evidence: Systematic review Level III.

Is Follow-up Co-Morbidity Assessment via Laboratory Investigations in Older High Energy Trauma Patients Justified? - A Prospective-Retrospective Study.

Introduction: The objective of the current study was to test our hypothesis that older patients sustaining high energy trauma need to be evaluated for their comorbidities similar to geriatric patients sustaining low energy trauma. Materials and methods: This study was a retrospective-prospective analysis of 173 patients of more than 50 years of age enrolled between November 2017 and December 2018. Herewith, we have compared retrospectively collected laboratory investigations of 124 fragility fracture patients with prospectively collected laboratory investigations of 49 patients with high energy trauma. The laboratory investigations, including the liver function tests, renal function tests, indices of calcium metabolism, serum electrolytes, complete blood counts, and bone mineral density (BMD) scores. Results: Both groups were similar to each other as far as baseline demographic characteristics were concerned. The proportion of female patients and patients with non-osteoporotic range BMD (T-score >-2.5) was significantly higher in the high-energy fracture group (P value <0.05). Hypoalbuminemia (<3.4gm/dl) 17.3%, abnormalities sodium (<135mmol/L or >148mmol/L) 23.2%, Anaemia (<10g/dl) 12.7%, Hypercalcemia (>10.4mg/dl) 16.3%, Vitamin D deficiency (<20ng/ml) 17.3% are the common laboratory abnormality found in study population. No statistically significant difference was found among the two groups in terms of laboratory investigation abnormalities. Conclusion: The laboratory investigation abnormality in an older patient with a clinical fracture is independent of the mechanism of injury. The results of the current study emphasise the need for a comprehensive laboratory workup in older patients with either high- energy fractures or fragility fractures.

Is Follow-up Co-Morbidity Assessment via Laboratory Investigations in Older High Energy Trauma Patients Justified? - A Prospective-Retrospective Study

@#Introduction: The objective of the current study was to test our hypothesis that older patients sustaining high energy trauma need to be evaluated for their comorbidities similar to geriatric patients sustaining low energy trauma. Materials and methods: This study was a retrospectiveprospective analysis of 173 patients of more than 50 years of age enrolled between November 2017 and December 2018. Herewith, we have compared retrospectively collected laboratory investigations of 124 fragility fracture patients with prospectively collected laboratory investigations of 49 patients with high energy trauma. The laboratory investigations, including the liver function tests, renal function tests, indices of calcium metabolism, serum electrolytes, complete blood counts, and bone mineral density (BMD) scores. Results: Both groups were similar to each other as far as baseline demographic characteristics were concerned. The proportion of female patients and patients with nonosteoporotic range BMD (T-score >-2.5) was significantly higher in the high-energy fracture group (P value <0.05). Hypoalbuminemia (<3.4gm/dl) 17.3%, abnormalities sodium (<135mmol/L or >148mmol/L) 23.2%, Anaemia (<10g/dl) 12.7%, Hypercalcemia (>10.4mg/dl) 16.3%, Vitamin D deficiency (<20ng/ml) 17.3% are the common laboratory abnormality found in study population. No statistically significant difference was found among the two groups in terms of laboratory investigation abnormalities. Conclusion: The laboratory investigation abnormality in an older patient with a clinical fracture is independent of the mechanism of injury. The results of the current study emphasise the need for a comprehensive laboratory workup in older patients with either high- energy fractures or fragility fractures.

Assessment of Clinical Pharmacokinetic Drug-Drug Interaction of Antimalarial Drugs α/ß-Arteether and Sulfadoxine-Pyrimethamine.

Antimalarial drug combination therapy is now being widely used for the treatment of uncomplicated malaria. The objective of the present study was to investigate the effects of coadministration of intramuscular α/ß-arteether (α/ß-AE) and oral sulfadoxine-pyrimethamine (SP) on the pharmacokinetic properties of each drug as a drug-drug interaction study to support the development of a fixed-dose combination therapy. A single-dose, open-label, crossover clinical trial was conducted in healthy adult Indian male volunteers (18 to 45 years, n = 13) who received a single dose of AE or SP or a combination dose of AE and SP. Blood samples were collected up to 21 days postadministration, and concentrations of α-AE, ß-AE, sulfadoxine, and pyrimethamine were determined by using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated and statistically analyzed to calculate the geometric mean ratio and confidence interval. Following single-dose coadministration of intramuscular AE and oral SP, the pharmacokinetic properties of α/ß-AE were not significantly affected, and α/ß-AE had no significant effect on the pharmacokinetic properties of SP in these selected groups of healthy volunteers. However, more investigations are needed to explore this further. (This study has been registered in the clinical trial registry of India under approval no. CTRI/2011/11/002155.).

Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. METHODS: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. RESULTS: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). CONCLUSIONS: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

Chemically designed Pt/PPy nano-composite for effective LPG gas sensor.

Simultaneous in situ reduction of hexachloroplatinic acid by the amine group in the pyrrole monomer and oxidation of pyrrole to form polypyrrole (PPy) was examined. The reactions were performed at various temperatures to understand the degree of reduction of platinum precursor as well as doping of polypyrrole with Pt(II) chloro-complex. Spectroscopic images revealed different morphologies for the Pt/PPy nano-composite prepared at various temperatures. The as-prepared Pt/PPy nano-composite samples were tested for their ability to sense liquefied petroleum gas (LPG) which resulted in excellent sensing at relatively low temperature. The porous nature and ohmic contact between the PPy and platinum nanoparticles makes the as-prepared Pt/PPy nano-composite highly useful for sensors as well as electronic applications.

Isoformononetin, a methoxydaidzein present in medicinal plants, reverses bone loss in osteopenic rats and exerts bone anabolic action by preventing osteoblast apoptosis.

PURPOSE: Daidzein (Daid) has been implicated in bone health for its estrogen-'like' effects but low bioavailability, unfavorable metabolism and uterine estrogenicity impede its clinical potential. This study was aimed at assessing isoformononetin (Isoformo), a naturally occurring methoxydaidzein, for bone anabolic effect by overcoming the pitfalls associated with Daid. METHODS: Sprague-Dawley ovariectomized (OVx) rats with established osteopenia were administered Isoformo, 17ß-oestradiol (E2) or human parathyroid hormone. Efficacy was evaluated by bone microarchitecture using microcomputed tomography and determination of new bone formation by fluorescent labeling of bone. Osteoblast apoptosis was measured by co-labeling of bone sections with Runx-2 and TUNEL. Biochemical markers of bone metabolism were measured by ELISA. Plasma and bone marrow levels of Isoformo and Daid were determined by LC-MS-MS. Rat bone marrow stromal cells were harvested to study osteoblastic differentiation by Isoformo and Daid. New born rat pups were injected with Isoformo and Daid to study the effect of the compounds on the expression of osteogenic genes in the calvaria by real time PCR. RESULTS: In osteopenic rats, Isoformo treatment restored trabecular microarchitecture, increased new bone formation, increased the serum osteogenic marker (procollagen N-terminal propeptide), decreased resorptive marker (urinary C-terminal teleopeptide of type I collagen) and diminished osteoblast apoptosis in bone. At the most effective osteogenic dose of Isoformo, plasma and bone marrow levels were comprised of ~90% Isoformo and the rest, Daid. Isoformo at the concentration reaching the bone marrow achieved out of its most effective oral dosing induced stromal cell mineralization and osteogenic gene expression in the calvaria of neonatal rats. Isoformo exhibited uterine safety. CONCLUSIONS: Our study demonstrates that Isoformo reverses established osteopenia in adult OVx rats likely via its pro-survival effect on osteoblasts. Given its bone anabolic and anti-catabolic effects accompanied with safety at uterine level we propose its potential in the management of postmenopausal osteoporosis.

In vitro hyperglycemia enhances sodium currents in dorsal root ganglion neurons: an effect attenuated by carbamazepine.

Neuropathy is often seen in uncontrolled diabetes and the mechanisms involved for neuropathic pain are poorly understood. Hyperglycemia is a consequence of chronic uncontrolled diabetes and it is postulated to produce neuropathic pain. Therefore, in this study, we have investigated the effects of hyperglycemia on Na(+) channel kinetics in cultured dorsal root ganglion (DRG) neurons from neonatal rats using whole-cell patch-clamp technique. Hyperglycemia-induced increase in density of tetrodotoxin resistant (TTXr) Na(+) currents was increased in time- and concentration-dependent manner. The increase was maximal with 60 mM and 24 h. There was no change Na(+) current density in time-matched control neurons. The conductance curve of TTXr Na(+) current shifted leftward after 24 h exposure to 45 mM glucose. Carbamazepine (CBZ, 100 µM) depressed TTXr Na(+) current in neurons incubated with control (17.26), 45 and 60 mM of glucose. The depression observed with CBZ in the presence of high glucose, i.e., 45 mM (86.5±4.9%) was significantly greater than control (61.6±1.8%). Hyperglycemia also increased reactive oxygen species (ROS) activity and was attenuated by CBZ. These results suggest that short-term exposure of DRG neurons to high glucose concentrations enhance the Na(+) channel activity, and were attenuated by CBZ via ROS-dependent mechanisms.

Nano-titanium dioxide induces genotoxicity and apoptosis in human lung cancer cell line, A549.

The increased inhaled application of titanium dioxide nanoparticles (TiO(2) NPs) increases the potential pulmonary health risks. The present investigations were carried out to study the TiO(2) NPs-induced apoptosis, oxidative stress and genotoxicity in the human lung cancer cell line, A549, a widely used cell system for pulmonary toxicity studies. Tetrazolium bromide salt and lactate dehydrogenase release assays were used to study the cytotoxicity. The genotoxicity studies were carried out using cytokinesis block micronucleus assay. Apoptosis was confirmed by the formation of apoptotic bodies and altered expression (messenger RNA (mRNA) and protein) of markers such as P(53), P(21), Bax, Bcl(2) and cleaved caspase-3. Cells exposed to TiO(2) NPs (10 and 50 µg/ml) for 6-24 h shows significant induction in oxidative stress, that is, the production of reactive oxygen species and malondialdehyde and decrease in the activity of catalase and glutathione. TiO(2) NPs exposure also induces the formation of apoptotic bodies and micronucleus as marker of genotoxicity. A significant up-regulation in the expression of apoptosis markers such as P(53), P(21) and cleaved caspase-3 was observed, while the levels were down-regulated for Bcl(2) at both mRNA and protein levels. TiO(2) NPs exposure could not pose significant effects on Bax expression. Data indicate that nano-TiO(2) induces oxidative stress, genotoxicity and apoptosis in human lung cancer cell line, A549. Our result also identifies the mechanisms involved in TiO(2) NP-induced changes in A549 cells. Perhaps, reporting for the first time, the association of TiO(2) NPs-induced genotoxicity and apoptosis at transcriptional and translational level in the human lung cancer cell line, A549 cells.

Differential subcellular targeting of recombinant human α1-proteinase inhibitor influences yield, biological activity and in planta stability of the protein in transgenic tomato plants.

The response of protein accumulation site on yield, biological activity and in planta stability of therapeutic recombinant human proteinase inhibitor (α1-PI) was analyzed via targeting to different subcellular locations, like endoplasmic reticulum (ER), apoplast, vacuole and cytosol in leaves of transgenic tomato plants. In situ localization of the recombinant α1-PI protein in transgenic plant cells was monitored by immunohistochemical staining. Maximum accumulation of recombinant α1-PI in T0 and T1 transgenic tomato plants was achieved from 1.5 to 3.2% of total soluble protein (TSP) by retention in ER lumen, followed by vacuole and apoplast, whereas cytosolic targeting resulted into degradation of the protein. The plant-derived recombinant α1-PI showed biological activity for elastase inhibition, as monitored by residual porcine pancreatic elastase (PPE) activity assay and band-shift assay. Recombinant α1-PI was purified from transgenic tomato plants with high yield, homogeneity and biological activity. Purified protein appeared as a single band of ∼48-50 kDa on SDS-PAGE with pI value ranging between 5.1 and 5.3. Results of mass spectrometry and optical spectroscopy of purified recombinant α1-PI revealed the structural integrity of the recombinant protein comparable to native serum α1-PI. Enzymatic deglycosylation and lectin-binding assays with the purified recombinant α1-PI showed compartment-specific N-glycosylation of the protein targeted to ER, apoplast and vacuole. Conformational studies based on urea-induced denaturation and circular dichroism (CD) spectroscopy revealed relatively lower stability of the recombinant α1-PI protein, compared to its serum counterpart. Pharmacokinetic evaluation of plant derived recombinant and human plasma-purified α1-PI in rat, by intravenous route, revealed significantly faster plasma clearance and lower area under curve (AUC) of recombinant protein. Our data suggested significance of protein sorting sequences and feasibility to use transgenic plants for the production of stable, glycosylated and biologically active recombinant α1-PI for further therapeutic applications.

Effect of thickness on nanostructured SnO2 thin films by spray pyrolysis as highly sensitive H2S gas sensor.

Nanostructured SnO2 thin films were prepared by spray pyrolysis technique onto glass substrates with different thickness by varying quantity of precursor solution. The structural, optical and electrical properties of these films have been studied. The crystallographic structure of the films was studied by X-ray diffraction (XRD). It is found that the films are tetragonal with (110) orientation. The grain size increases with thickness. Atomic Force Microscopy (AFM) showed that the nanocrystalline nature of the films with porous nature. The grain size increased 14 to 29 nm with increase in film thickness. The studies on the optical properties show that the direct band gap value decreases from 3.75 to 3.50 eV. The temperature dependence of the electrical conductivity was studied. The activation energies of the films are calculated from the conductance temperature characteristics. The nanostructured SnO2 thin films were used as sensing layers for resistive gas sensors. The dependence of gas sensing properties on the thickness of SnO2 thin films was investigated. The gas response of the SnO2 thin films towards the H2S gas was determined at an operating temperature of 150 degrees C. The sensitivity towards H2S gas is strongly depending on surface morphology of the SnO2 thin films.

Sono-chemical synthesis of ZnO nano-particles and their application in hydrogen sulphide gas sensing.

Herein we describe synthesis of ZnO nanoparticles by using alkaline solution of ZnX2 (X = NO3, Cl) under ultrasound energy of 20 KHz. The reaction can be completed in about 1-2 hours. As prepared powders were analyzed by XRD measurement to find that the product is hexagonal phase pure ZnO. UV-Visible measurement of aq. solution showed absorption band at -365 nm and photoluminescence (PL) indicated multiple bands in visible region due to deep traps owing to high temperature sintering. The hydrophilicity can be imparted by use of a suitable polyelectrolyte. Freshly prepared samples showed good dispersion in aqueous and alcoholic medium. The thick films derived from the ZnO nano-particles showed excellent sensing for hydrogen sulphide gas.

Simultaneous estimation of 16α-hydroxycleroda-3,13(14) Z-dien-15,16-olide from Polyalthia longifolia and its metabolite in hamster plasma: application to pharmacokinetic study.

A selective and sensitive LC-MS-MS method was developed and validated for simultaneous estimation and pharmacokinetic studies of 16α-hydroxycleroda-3,13(14) Z-dien-15,16-olide (K-09) obtained from Polyalthia longifolia and its metabolite (K-9T), a novel antidyslipidemic agent. Sample clean-up involved liquid-liquid extraction of both the analytes and internal standard (rosuvastatin) from 200 µL of hamster plasma. The analytes were chromatographically separated on a Symmetry-Shield C18 (5 µm, 4.6 × 150 mm) column, using acetonitrile-0.1% aqueous formic acid (92:08, v/v) as the mobile phase. Detection was performed using negative ion electrospray ionization in multiple reaction monitoring mode. The MS/MS response was linear over the concentration range 1.56-200 ng/mL, with a correlation coefficient (r²) of 0.998 or better. The within- and between-batch precisions (relative standard deviation, %RSD) and the accuracy (percentage bias) were within acceptable limits as per FDA guidelines. The validated method was successfully applied to reveal the pharmacokinetic parameters of K-09 and metabolite after oral administration. This method will therefore be highly useful for future studies of K-09 and metabolite K-9T pharmacokinetics in preclinical and clinical studies.

Nano-silver mediated polymerization of pyrrole: synthesis and gas sensing properties of polypyrrole (PPy)/Ag nano-composite.

Thermal polymerization of pyrrole was performed using silver nitrate as source of silver ions followed by its conversion to Polypyrrole (PPy)/Ag nano-comoposites without using any external oxidizing agent or solvent. The formation of PPy was monitored by UV-Visible absorption spectroscopy showing a band at approximately 464 nm. XRD measurement confirmed characteristic peaks for face centered cubic (fcc) silver and presence of PPy at 2 theta of approximately 23 degrees suggesting the formation of PPy/Ag nanocomposite. Transmission electron microscopy (TEM) images showed non-aggregated spherical Ag nano-particles of about 5-10 nm. PPy/Ag thick film acts as a NH3 sensor at 100 degrees C, a H2S sensor at 250 degrees C and CO2 sensor at 350 degrees C. The thick films showed capability to recognize various gases at different operating temperature.