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.

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.).

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.).

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.

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.

Simultaneous estimation of E- and Z-isomers of guggulsterone in rabbit plasma using liquid chromatography tandem mass spectrometry and its application to pharmacokinetic study.

A sensitive and selective liquid chromatography/tandem mass spectrometric method was developed for simultaneous determination of E- and Z-guggulsterone isomers (antihyperlipidemic drug) in rabbit plasma. Both the isomers were resolved on a Symmetry-Shield C(18) (5 µm, 4.6 × 150 mm) column, using gradient elution comprising a mobile phase of methanol, 0.5% v/v formic acid and acetonitrile. With dexamethasone as internal standard, plasma samples were extracted by an automated solid-phase extraction method using C(18) cartridges. Detection was performed by electrospray ionization in multiple reaction monitoring (MRM) in positive mode. The calibration curve was linear over the concentration range of 1.56-200 ng/mL (r(2) ≥ 0.998) for both analytes. The intra-day and inter-day accuracy and precision were within -0.96 to 4.12 (%bias) and 2.73 to 8.00 (%RSD) respectively. The analytes were stable after three freeze-thaw cycles. The method was successfully applied to study steriospecific pharmacokinetics of E- and Z-guggulsterone in NZ rabbit.

Bioanalytical method development and validation of novel antithrombotic agent S002-333 by LC-MS/MS and its application to pharmacokinetic studies.

A rapid, sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using an electrospray ionization (ECI) source for the quantification of novel anti-thrombotic agent S002-333 [2-(4-methoxy-benzenesulfonyl)-2,3,4,9-tetrahydro-1H-ß-carboxylic acid amide] in rabbit plasma was developed and validated. The extraction from plasma was carried out by simple protein precipitation extraction method. The chromatographic separation was performed on an Ultramex Cyno, (150 x 4.6 mm, 5 µm) with a guard column, using acetonitrile-water (75:25,v/v) with flow rate of 0.6 mL/min as the mobile phase. The tandem mass spectrometer was tuned in the multiple reaction monitoring mode to monitor the m/z transitions 386.4/215.4 for S002-333 and m/z 393.4/171 for the internal standard dexamethasone, using positive ion mode. The MS/MS response was linear over the concentration range from 1.56 to 200 ng/mL, with a lower limit of detection of 0.78 ng/mL. The accuracy and precision of the method were within the acceptable limit of ±20% at the lower limit of quantitation and ±15% at other concentrations and showed no significant matrix effect. The validated method can be used in most or all stages of the screening and optimizing process for future method validation of pharmacokinetic studies.

Assessment of urban air pollution and it's probable health impact.

The present study deals with the quantitative effect of vehicular emission on ambient air quality during May 2006 in urban area of Lucknow city. In this study SPM, RSPM, SO2, NOx and 7 trace metals associated with RSPM were estimated at 10 representative locations in urban area and one village area for control. Beside this, air quality index (AQI), health effects of different metals and mortality were assessed. The 24 hr average concentration of SPM, RSPM, SO2 and NOx was found to be 382.3, 171.5, 24.3 and 33.8 microg m(-3) respectively in urban area and these concentrations were found to be significantly (p < 0.01) higher by 94.8, 134.8, 107.4 and 129.6% than control site respectively The 24 hr mean of SPM and RSPM at each location of urban area were found to be higher than prescribed limit of National Ambient Air Quality Standard (NAAQS) except SPM for industrial area. The 24 hr mean concentration of metals associated with RSPM was found to be higher than the control site by 52.3, 271.8, 408.9, 75.81, 62.7, 487.54 and 189.5% for Fe, Cu, Pb, Zn, Ni, Mn and Cr respectively. The inter correlation of metals Pb with Mn, Fe and Cr; Zn with Ni and Cr; Ni with Cr; Mn with Fe and Cu with Cr showed significant positive relation either at p < 0.05 or p < 0.01 level. Metals Pb, Mn and Cr (p < 0.01) and Cu (p < 0.05) showed significant positive correlation with RSPM. These results indicate that ambient air quality in the urban area is affected adversely due to emission and accumulation of SPM, RSPM, SO2, NOx and trace metals. These pollutants may pose detrimental effect on human health, as exposure of these are associated with cardiovascular and respiratory diseases, neurological impairments, increased risk of preterm birth and even mortality and morbidity.

Evaluation of hypoglycemic and anti-hyperglycemic potential of Tridax procumbens (Linn.).

BACKGROUND: Diabetes is a metabolic disorder affecting carbohydrate, fat and protein metabolism. Tridax procumbens Linn. (Family-Asteraceae; common name-Dhaman grass) is common herb found in India. Traditionally, the tribal inhabitants of Udaipur district in Rajasthan (India) uses the leaf powder (along with other herb) orally to treat diabetes. There is a need to evaluate extracts of this plant in order to provide scientific proof for it's application in traditional medicine system. METHODS: Extraction of whole plant of T. procumbens using 50%methanol. The extract was tested for acute and sub-chronic anti-hyperglycemic activity in alloxan induced diabetic rats and for acute toxicity test among normal rats. Observations on body weight as well as on the oral glucose tolerance levels were also recorded. RESULTS: Oral administration of acute and sub chronic doses (250 and 500 mg/kg b.wt.) of T. procumbens extract showed a significant (p < 0.05) reduction in fasting blood glucose levels in diabetic rats, however the decline in blood sugar levels in normal rats was not observed. In acute study the maximum percent blood glucose reduction (68.26% at 250 mg/kg and 71.03% at 500 mg/kg body weight) in diabetic rats was observed at 6 h. The anti-hyperglycemic effects were not dependent of dose and the OGTT and Body weight supported the antihyperglycemic action of the drug. The results of anti-diabetic effect of T. procumbens were compared with the reference standard drug Glibenclamide (10 mg/kg b.wt.). CONCLUSION: These test results support traditional medicinal use of, T. procumbens for the treatment of diabetes mellitus with corrections in body weight and oral glucose tolerance and no visible signs or symptoms of toxicity in normal rats indicating a high margin of safety. These results warrant follow-up through bioassay-directed isolation of the active principles.

Where do lymph and tissue fluid accumulate in lymphedema of the lower limbs caused by obliteration of lymphatic collectors?

Obliteration of lymphatic collecting trunks of limbs by infective processes, trauma, oncologic surgery and irradiation bring about retention of lymph and tissue fluid in tissues. Knowledge as to where excess lymph is produced and accumulates as tissue fluid is indispensable for rational physical therapy. So far, this knowledge has been based on lymphoscintigraphic, ultrasonographic and MR images. None of these modalities provides distinct images of dilated lymphatics and fluid expanded tissue spaces in dermis, subcutis and muscles. Only anatomical dissection and histological processing of biopsy material can demonstrate the remnants of the lymphatic network and the sites of accumulation of mobile tissue fluid. We visualized and calculated the volume of the "tissue fluid and lymph" space in skin and subcutaneous tissue of foot, calf, and thigh in various stages of lymphedema, using special coloring techniques in specimens obtained during lymphatic microsurgical procedures or tissue debulking. When the collecting trunks were obliterated, lymph was present only in the subepidermal lymphatics, while mobile tissue fluid accumulated in the spontaneously formed spaces in the subcutaneous tissue, around small veins, and in the muscular fascia. Deformation of subcutaneous tissue by free fluid led to formation of interconnecting channels. In obstructive lymphedema caused by obliteration of collectors, lymph is present mainly in subepidermal lymphatics, and the bulk of stagnant tissue fluid accumulates in subcutis between fibrous septa and fat globules as well as above and underneath muscular fascia. These observations provide useful clues for designing pneumatic devices and rational manual lymphatic massage to move stagnant tissue fluid toward the non-swollen regions.

Wound healing in guinea pigs after topical application of starfish Pentaceraster regulus extract.

OBJECTIVE: To investigate the healing efficacy of Pentaceraster regulus (starfish) aqueous-methanol extract on cutaneous wounds in guinea pigs. METHOD: Freshly collected starfish were washed with distilled water and soaked in methanol for transportation. After filtering, soaking and concentration, the extract was fractionated into chloroform soluble (5g), 50% aqueous-methanol soluble (20g) and insoluble fractions (25g). Primary screening demonstrated moderate wound-healing activity in male Swiss-strain guinea pigs, so further fractionation into chloroform, 50% aqueous-methanol and insoluble fractions was undertaken.Wound-healing activity was concentrated only in the aqueous-methanol fraction, so this was used for the study. Animals received either 1% aqueous-methanol extract, the vehicle alone or 5% providone-iodine. The following were measured: wound area,wound tensile strength, DNA, total protein and hydroxyproline levels in excised granulation tissue. Histological changes were observed under microscope. RESULTS: Extract-treated wounds healed faster, indicated by a significant contraction in wound area (42%). Cellular proliferation and collagen synthesis at the wound site increased, demonstrated by increase in DNA (33%), protein (29%) and hydroxyproline (37%) content when compared with the controls and povidone-iodine-treated animals (standard care). These findings were confirmed by histological examination. Proper folding of collagen was demonstrated by a significant increase in tensile strength (34%). CONCLUSION: The results suggest that the aqueous-methanol extract of starfish P. regulus promotes wound-healing activity.

[False acute large bowel obstruction]. / Falesná akutní pseudoobstrukce tlustého streva.

Acute pseudobstruction of the large intestine is also termed the "Ogilvie" syndrome. The life- threatening condition without obvious mecha nical obstruction of the intestine, results from a major enlargement of the large intestine, which, if no therapy is initiated on time, may result in perforation of the right- sided colon, most commonly of the caecum. In this case study, the patient underwent urgent surgery for incipient caecal perforation. Nor the preoperative plain abdominal x- ray examination, abdominal CT, nor the laparotomy procedure detected any mechanical bowel obstruction. The condition was diagnosed as the Ogilvie syndrome in a chronic renal disorder of the patient. The procedure included transversostomy, drainage of the peritoneal cavity and complex management, and the patient was discharged to homecare on the ninth postoperative day. However, two weeks later, the patient was rehospitalized for bleeding from the stoma site. Colonoscopy detected a small stenosing tumor in the lienal flexure of the large intestine. The case study highlights failure of both the CT and x-ray abdominal examinations (air up to the sigmoid), as well as of the surgical exploration. Therefore, it may be concluded that not all pseudoobstructions are truely "pseudo".

Distribution of lovastatin to bone and its effect on bone turnover in rats.

Statins, the widely used lipid-lowering drugs, are inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, which catalyses a rate-limiting step in the biosynthesis of cholesterol. Many previous reports show that statins can act both as bone anabolic and as anti-resorptive agents but their beneficial effects on bone turnover are still controversial. Considering their high liver specificity and low oral bioavailability, the distribution of statins to the bone microenvironment is questionable. In this study, the distribution of lovastatin and its active metabolites to bone, with respect to plasma and liver compartments, was examined after oral and intravenous administration in female rats. As compared with oral administration, the distribution of lovastatin to the bone compartment was significantly enhanced after intravenous administration. Further, the effect of lovastatin on bone turnover was studied in-vitro and in-vivo to assess its anti-osteoporotic potential. Lovastatin acid but not lovastatin was found to inhibit parathyroid-hormone-induced bone resorption in an in-vitro chick embryo bone assay. Oral, as well as intravenous, short-term lovastatin treatment significantly reduced the serum total cholesterol, serum total alkaline phosphatase and urinary crosslinks in ovariectomized rats. In accordance with its increased distribution to the bone compartment, intravenously administered lovastatin was more effective in reducing the ovariectomy-induced increase in markers of bone metabolism, especially urinary crosslinks. The findings of this study suggest that statins inhibit bone resorption and that their anti-resorptive efficacy can be increased by administering them by routes other than oral so as to achieve their enhanced concentration in bone.

A time course study for the development of an immunocompromised wound model, using hydrocortisone.

Although wound healing is essentially a physiologic process, some chronic wounds exhibit considerable delay in healing. Often these do not heal perfectly in individuals with low immune profiles. Thus, the present study was undertaken to develop an excision wound model in the immunocompromised state induced by pretreatment with hydrocortisone (HC) 40 mg/kg intramuscularly in male rats. Wounds of 8-mm diameter were made on the preshaved dorsal surface of rats using an Acuderm biopsy punch, following pretreatment with HC. After 14 days HC-treated animals exhibited atrophy of spleen and adrenal glands and a significant reduction of circulating lymphocytes and increase in neutrophils; these changes are indicative of immunosuppressive state of animals. The cell proliferation was significantly affected as shown by decreases in DNA (23%) and protein (11%). Furthermore, there were also significant reductions in tensile strength (37%) and hydroxyproline (33%) contents. These results were further supported by lack of contraction of wound edges. It is concluded that animals primed with HC 1 week prior to wounding developed prolonged immunosuppression, which significantly impaired the wound healing as compared with other groups. Thus, this can be experimentally employed as an immunocompromised wound model for evaluating compounds as novel wound healers suitable for immunocompromised subjects.