Respiratory health and the Syrian conflict: a scoping literature review.

Conflict adversely affects respiratory health in both direct and indirect ways among populations whose health is already compromised through the compounding effects of conflict. Our aim is to review academic and grey literature relevant to respiratory health in the Syrian conflict (now more than a decade in duration) to explore its impacts on populations across Syria. We performed a scoping literature review of academic and grey literature on respiratory health in Syria between March 2011 (taken as the start of the conflict for practicality) and December 2023. Of 11,472 papers screened, 34 met the inclusion criteria, of which 29 were peer reviewed. Key themes identified included the impact of conflict on asthma diagnosis and management; the burden of respiratory tract infections (RTIs) and COVID-19; the impact of chemical weapon use and the impact of destruction and interruptions to the health system(s) across Syria on respiratory health. This review highlights the need for more in-depth exploration of the impact of conflict on respiratory health in Syria with focus on social determinants, for example, shelter, public health interventions, smoking cessation, and supporting early diagnosis and treatment of respiratory conditions to counter the effects that conflict has had on respiratory health.

Higher intake of ß-glucan impairs reproduction in a female teleost, Tor putitora (Hamilton, 1822).

Although the immuno-modulatory and stress-relieving properties of ß-glucan is well elucidated in humans and other animal models, including fish, its role as a dietary supplement on reproduction is extremely scarce. Therefore, in this study, adult female fish were fed one of four test diets having 0 (control), 0.5, 1, and 1.5% ß-D-glucan for 130 days and its effect on reproductive performance, ovarian and liver histology, sex hormones, and transcript abundance of selected reproduction-related genes was assessed. Low dietary intake of ß-glucan improved fertilization and hatching rates (p<0.05). The relative fecundity and percentage of spawning females were higher (non-significant) in 0.5% ß-glucan-fed groups. Surprisingly, even after 130 days, spawning did not occur in 1.5% ß-glucan-fed individuals. Irrespective of ß-glucan intake, all the brooders recorded similar plasma 17ß-estradiol and maturation-inducing hormone (p>0.05). Higher intake of ß-glucan (1.5%) upregulated aromatase genes without a parallel increase in 17ß-estradiol. However, plasma vitellogenin increased with increasing ß-glucan up to 1.0% then declined at 1.5% (p<0.05). The fish that received control, 0.5, and 1.5% ß-glucan recorded similar vitellogenin levels in their plasma. Significantly higher plasma cortisol was evidenced in 1.5% ß-glucan fed brooders (p<0.05). Histologically, higher follicular atresia and leaking of yolk material was evidenced in 1.5% ß-glucan-fed group. Liver histology revealed the highest nutrient/lipid accumulation in fish that received 1.0% and 1.5% ß-glucan. This study demonstrated the stimulatory effect of ß-glucan intake at a lower dose (0.5%) on reproduction. However, higher intake (1.5%) could perturb normal reproductive function in a fish model and caused an increased number of atretic follicles leading to spawning/reproductive failure.

Naturally manufactured biochar materials based sensor electrode for the electrochemical detection of polystyrene microplastics.

In recent times, microplastics have become a disturbance to both aquatic and terrestrial ecosystems and the ingestion of these particles can have severe consequences for wildlife, aquatic organisms, and even humans. In this study, two types of biochars were manufactured through the carbonization of naturally found starfish (SF-1) and aloevera (AL-1). The produced biochars were utilized as sensing electrode materials for the electrochemical detection of ∼100 nm polystyrene microplastics (PS). SF-1 and AL-1 based biochars were thoroughly analyzed in terms of morphology, structure, and composition. The detection of microplastics over biochar based electrodes was carried out by electrochemical studies. From electrochemical results, SF-1 based electrode exhibited the detection efficiency of ∼0.2562 µA/µM∙cm2 with detection limit of ∼0.44 nM whereas, a high detection efficiency of ∼3.263 µA/µM∙cm2 was shown by AL-1 based electrode and detection limit of ∼0.52 nM for PS (100 nm) microplastics. Process contributed to enhancing the sensitivity of AL-1 based electrode might associate to the presence of metal-carbon framework over biochar's surfaces. The AL-1 biochar electrode demonstrated excellent repeatability and detection stability for PS microplastics, suggesting the promising potential of AL-1 biochar for electrochemical microplastics detection.

Synthesis and evaluation of 2-phenylamino-1, 4-naphthoquinones derivatives as potential hypoglycaemic agents / Síntese e avaliação de derivados de 2-fenilamino-1, 4-naftoquinonas como potenciais agentes hipoglicemiantes

Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of 'chloro' group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Em razão dos graves efeitos colaterais causados pela maioria dos medicamentos antidiabéticos atualmente utilizados, continua a busca por novos medicamentos seguros para o controle do diabetes. As naftoquinonas, que possuem fortes propriedades antioxidantes, têm sido empregadas como candidatas à terapia do diabetes. O presente estudo visa encontrar o potencial antioxidante e hipoglicemiante de alguns novos derivados de 2-fenilamino-1,4-naftoquinonas (PAN), incluindo derivados de cloro, nitro, metil e bromo (5a-d) sintetizados por experimento em pote único. Os cristais do produto foram purificados por TLC e caracterizados por FT-IR. O potencial antioxidante dos compostos foi testado por meio de atividades de sequestro de radicais DPPH e redução de energia observada como absorção no UV-vis. O ensaio DPPH mostrou a poderosa atividade antioxidante dos derivados nitro e bromo, enquanto o derivado nitro mostrou o potencial de redução significativo para o ensaio FRAP. O potencial hipoglicêmico dos compostos foi estudado em modelo animal de rato. Todos os compostos sintetizados revelaram melhor atividade hipoglicemiante; no entanto, o derivado cloro apresentou atividade hipoglicêmica mais potente, com redução de 43% nos níveis médios de glicose no sangue dos animais tratados. Como a biorredução de naftoquinonas pode ser influenciada pela alteração de suas propriedades redox, notou-se que o efeito da doação eletrônica por ressonância (+R) do grupo "cloro" tem sido significativo na atividade biológica por meio da estabilização de sua forma imina, que limita o potencial de geração de radicais livres durante a biorredução de quinonas, e, portanto, tem sido proposto como a razão de sua atividade hipoglicemiante. Estudos futuros empregando as propriedades de grupos de doação eletrônica de PAN podem otimizar a interação droga-receptor para melhor planejamento de medicamentos e estratégias de desenvolvimento de medicamentos contra o diabetes e também para os ensaios clínicos.

Synthesis and evaluation of 2-phenylamino-1,4-naphthoquinones derivatives as potential hypoglycaemic agents

Abstract Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of chloro group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Resumo Em razão dos graves efeitos colaterais causados pela maioria dos medicamentos antidiabéticos atualmente utilizados, continua a busca por novos medicamentos seguros para o controle do diabetes. As naftoquinonas, que possuem fortes propriedades antioxidantes, têm sido empregadas como candidatas à terapia do diabetes. O presente estudo visa encontrar o potencial antioxidante e hipoglicemiante de alguns novos derivados de 2-fenilamino-1,4-naftoquinonas (PAN), incluindo derivados de cloro, nitro, metil e bromo (5a-d) sintetizados por experimento em pote único. Os cristais do produto foram purificados por TLC e caracterizados por FT-IR. O potencial antioxidante dos compostos foi testado por meio de atividades de sequestro de radicais DPPH e redução de energia observada como absorção no UV-vis. O ensaio DPPH mostrou a poderosa atividade antioxidante dos derivados nitro e bromo, enquanto o derivado nitro mostrou o potencial de redução significativo para o ensaio FRAP. O potencial hipoglicêmico dos compostos foi estudado em modelo animal de rato. Todos os compostos sintetizados revelaram melhor atividade hipoglicemiante; no entanto, o derivado cloro apresentou atividade hipoglicêmica mais potente, com redução de 43% nos níveis médios de glicose no sangue dos animais tratados. Como a biorredução de naftoquinonas pode ser influenciada pela alteração de suas propriedades redox, notou-se que o efeito da doação eletrônica por ressonância (+R) do grupo cloro tem sido significativo na atividade biológica por meio da estabilização de sua forma imina, que limita o potencial de geração de radicais livres durante a biorredução de quinonas, e, portanto, tem sido proposto como a razão de sua atividade hipoglicemiante. Estudos futuros empregando as propriedades de grupos de doação eletrônica de PAN podem otimizar a interação droga-receptor para melhor planejamento de medicamentos e estratégias de desenvolvimento de medicamentos contra o diabetes e também para os ensaios clínicos.

Defects mediated weak ferromagnetism in Zn1-yCyO (0.00 ≤ y ≤ 0.10) nanorods semiconductors for spintronics applications.

A series of carbon-doped ZnO [Zn1-yCyO (0.00 ≤ y ≤ 0.10)] nanorods were synthesized using a cost-effective low-temperature (85 °C) dip coating technique. X-ray diffractometer scans of the samples revealed the hexagonal structure of the C-doped ZnO samples, except for y = 0.10. XRD analysis confirmed a decrease in the unit cell volume after doping C into the ZnO matrix, likely due to the incorporation of carbon at oxygen sites (CO defects) resulting from ionic size differences. The morphological analysis confirmed the presence of hexagonal-shaped nanorods. X-ray photoelectron spectroscopy identified C-Zn-C bonding, i.e., CO defects, Zn-O-C bond formation, O-C-O bonding, oxygen vacancies, and sp2-bonded carbon in the C-doped ZnO structure with different compositions. We analyzed the deconvoluted PL visible broadband emission through fitted Gaussian peaks to estimate various defects for electron transition within the bandgap. Raman spectroscopy confirmed the vibrational modes of each constituent. We observed a stronger room-temperature ferromagnetic nature in the y = 0.02 composition with a magnetization of 0.0018 emu/cc, corresponding to the highest CO defects concentration and the lowest measured bandgap (3.00 eV) compared to other samples. Partial density of states analysis demonstrated that magnetism from carbon is dominant due to its p-orbitals. We anticipate that if carbon substitutes oxygen sites in the ZnO structure, the C-2p orbitals become localized and create two holes at each site, leading to enhanced p-p type interactions and strong spin interactions between carbon atoms and carriers. This phenomenon can stabilize the long-range order of room-temperature ferromagnetism properties for spintronic applications.

Selectivity of Sol-Gel and Hydrothermal TiO2 Nanoparticles towards Photocatalytic Degradation of Cationic and Anionic Dyes.

Titanium dioxide (TiO2) nanoparticles have been extensively studied for catalyzing the photo-degradation of organic pollutants, the photocatalyst being nonselective to the substrate. We, however, found that TiO2 nanoparticles prepared via the sol-gel and hydrothermal synthetic routes each possess a definite specificity to the charge of the substrate for photodegradation. The nanoparticles were characterized by SEM, FTIR, XRD, TGA, and UV-visible spectra, and the photocatalytic degradation under UV-B (285 nm) irradiation of two model compounds, anionic methyl Orange (MO) and cationic methylene blue (MB) was monitored by a UV-visible spectrophotometer. Untreated sol-gel TiO2 nanoparticles (Tsg) preferentially degraded MO over MB (90% versus 40% in two hours), while after calcination at 400 °C for two hours (Tsgc) they showed reversed specificity (50% MO versus 90% MB in one hour). The as-prepared hydrothermal TiO2 nanoparticles (Tht) behaved in the opposite sense of Tsg (41% MO versus 91% MB degraded in one and a half hours); calcination at 400 °C (Thtc) did not reverse the trend but enhanced the efficiency of degradation. The study indicates that TiO2 nanoparticles can be made to degrade a specific class of organic pollutants from an effluent facilitating the recycling of a specific class of pollutants for cost-effective effluent management.

Isotope hydrology tools in the assessment of arsenic contamination in groundwater: An overview.

Groundwater is important for the survival of humanity and the demand for the same is drastically increasing globally. The precious water resources are under constant threat, either as a result of natural processes or due to the influence of the anthropogenic activities. Arsenic contamination of groundwater is one of those threats that have affected approximately over 500 million people in 107 countries globally. Although, many studies (∼1000 Nos.) have been carried out on arsenic hydrogeobiochemistry, only a few have reported, on the use of different isotopes in understanding the arsenic hydrochemistry, and its release mechanism and mobilization. Determination of the isotopic composition of a groundwater sample and its dissolved compounds enable a better insight into the hydrological processes that control the distribution and migration of arsenic in the subsurface hydrological system. The environmental isotopes of water molecules (δ18O and δ2H) have been widely used to assess the groundwater origin, its recharge mechanisms, the rock-water interactions and quality. The stable isotopes of dissolved compounds of water (δ34S, δ15N, δ13C, δ56Fe etc.) give better information on the reaction processes within these elements and thus act as a tracer for contaminants, while the radioactive isotopes, such as 14C, 3H, 81Kr, 36Cl, 39Ar etc., can be used to assess the residence time of groundwater and its renewability. This article reviews the different uses of environmental isotopes as tools for providing critical information on various hydrological processes in the arsenic contaminated regions that can't be obtained through conventional tools for better management of the groundwater resources.

Investigating miRNA subfamilies: Can they assist in the early diagnosis of acute myocardial infarction?

This report focuses on small non-coding RNA molecules (miRNAs), which have emerged as potential biomarkers with variable diagnostic values and false-positives in different conditions that limit their clinical preference. Current investigations focus on small non-coding RNA molecules (miRNAs), which have emerged as potential biomarkers with variable diagnostic values and false-positives in different conditions that limit their clinical preference. We thoroughly scrutinize the leading pathology of myocardial infarction and contemporary alterations in miRNAs for their specificity, stability and significant prognostic value at the early stage of acute myocardial infarction (AMI). Based on secondary data analysis, we explore common biomarkers and further investigate included miRNA biomarkers for their specificity, stability and area under the curve (AUC) values. We conclude that a group of novel biomarkers, including miRNA-1, miRNA-208a/b and miRNA-499, could help predict the emergence of AMI at an early stage.

Occlusion of the infarct-related coronary artery presenting as acute coronary syndrome with and without ST-elevation: impact of inflammation and outcomes in a real-world prospective cohort.

BACKGROUND: Patients with ST-segment elevation typically feature total coronary occlusion (TCO) of the infarct-related artery (IRA) on angiography, which may result in worse outcomes. Yet, relying solely on electrocardiogram (ECG) findings may be misleading and those presenting with non-ST-segment elevation acute coronary syndromes (NSTE-ACSs) may have TCO as well. Herein, we aimed to delineate clinical characteristics and outcomes of patients with ACS stratified by IRA location. METHODS: A total of 4787 ACS patients were prospectively recruited between 2009 and 2017 in SPUM-ACS (ClinicalTrials.gov Identifier: NCT01000701). The primary endpoint was major adverse cardiovascular events (MACEs), a composite of all-cause death, non-fatal myocardial infarction and non-fatal stroke at 1 year. Multivariable-adjusted survival models were fitted using backward selection. RESULTS: A total of 4412 ACS patients were included in this analysis, 56.0% (n = 2469) ST-elevation myocardial infarction (STEMI) and 44.0% (n = 1943) NSTE-ACS. The IRA was the right coronary artery (RCA) in 33.9% (n = 1494), the left-anterior descending coronary artery (LAD) in 45.6% (n = 2013), and the left circumflex (LCx) in 20.5% (n = 905) patients. In STEMI patients, TCO (defined as TIMI 0 flow at angiography) was observed in 55% of cases with LAD, in 63% with RCA, and in 55% with LCx. In those presenting with NSTE-ACS, TCO was more frequent in those with LCx and RCA as compared to the LAD (27 and 24%, respectively, vs. 9%, P < 0.001). Among patients with NSTE-ACS, occlusion of the LCx was associated with an increased risk of MACE during 1 year after the index ACS (fully adjusted hazard ratio 1.68, 95% confidence interval 1.10-2.59, P = 0.02; reference: RCA and LAD). Features of patients with NSTE-ACS associated with TCO of the IRA included elevated lymphocyte and neutrophil counts, higher levels of high-sensitivity C reactive protein (hs-CRP) and high-sensitivity cardiac troponin T, lower eGFR, and notably a negative history of MI. CONCLUSION: In NSTE-ACS, both LCx and RCA involvement was associated with TCO at angiography despite the absence of ST-segment elevation. Involvement of the LCx, but not the LAD or RCA, as the IRA represented an independent predictor of MACE during 1-year follow-up. Hs-CRP, lymphocyte, and neutrophil counts were independent predictors of total IRA occlusion, suggesting a possible role of systemic inflammation in the detection of TCO irrespective of ECG presentation.

A high-fidelity quantum matter-link between ion-trap microchip modules.

System scalability is fundamental for large-scale quantum computers (QCs) and is being pursued over a variety of hardware platforms. For QCs based on trapped ions, architectures such as the quantum charge-coupled device (QCCD) are used to scale the number of qubits on a single device. However, the number of ions that can be hosted on a single quantum computing module is limited by the size of the chip being used. Therefore, a modular approach is of critical importance and requires quantum connections between individual modules. Here, we present the demonstration of a quantum matter-link in which ion qubits are transferred between adjacent QC modules. Ion transport between adjacent modules is realised at a rate of 2424 s-1 and with an infidelity associated with ion loss during transport below 7 × 10-8. Furthermore, we show that the link does not measurably impact the phase coherence of the qubit. The quantum matter-link constitutes a practical mechanism for the interconnection of QCCD devices. Our work will facilitate the implementation of modular QCs capable of fault-tolerant utility-scale quantum computation.

Catalytic oxidation of ibuprofen over bulk heterojunction photocatalysts based on conjugated donor-acceptor configured benzoselenadiazole molecule.

The use of photocatalysts for acquiring direct photon energy from sunlight is a promising way to clean the environment, particularly the remediation of contaminants from water. In this work, firstly π-conjugated organic semiconductor configuring benzoselenadiazole, 4-(3,5-bis(trifluoromethyl) phenyl)-7-(5'-hexyl-[2,2'-bithiophen]-5-yl)-benzo [c] (Kümmerer, 2009; Chen et al., 2018; Randeep et al., 201) selenadiazole, abbreviated as (RTh-Se-F), was synthesized. The designed RTh-Se-F with an extended π-conjugation showed good optical properties in the visible region and estimated a low optical band gap of ∼2.02 eV . The molecular orbitals i.e. HOMO (-5.33 eV) and LUMO (-3.31 eV) for RTh-Se-F organic semiconductor were suitably aligned to energy levels of (Madhavan et al., 2010Madhavan et al., 2010)-Phenyl-C71-butyric acid methyl esters (PC71BM) which resulted in the broadening of absorption and covering of entire visible region. RTh-Se-F was integrated with varied weight percentages (wt %) of PC71BM to obtain bulk heterojunction (BHJ) and applied as efficient visible light driven BHJ photocatalyst for an effective oxidation of ibuprofen. RTh-Se-F@PC71BM (1:2, wt %) BHJ photocatalyst showed the superior ibuprofen degradation of ∼93% within 90 min under visible light illumination. The maximum degradation rate by BHJ photocatalyst might be accredited to the broadening of absorption capacity and improved lifetime of photogenerated electron-hole pairs which might be resulted from high absorption properties of RTh-Se-F organic semiconductor.

Molecular characterization of four innate immune genes in Tor putitora and their comparative transcriptional abundance during wild- and captive-bred ontogenetic developmental stages.

The current study was designed to characterize immune genes and compare their expression during ontogenetic developmental stages in progenies of wild-collected and captive-matured T. putitora. The full-length cDNA sequences of Tptlr2, Tpmyd88, Tpcd36, and Tpil8 were 2814, 1545, 1807, and 653 bp in length, with ORFs of 2379 bp, 855 bp, 1410 bp, and 297 bp, encoding for putative peptides of 793, 284, 469 and 98 amino acids, respectively. The predicted peptide sequences of the genes had high sequence homology and structural conservation with other teleost fishes, especially cyprinids. The expression of Tptlr2 was relatively low in both wild- and captive-bred offsprings during the early embryonic stages, but significantly increased later in development. The mRNA abundance of the Tpmyd88 gene was significantly low until the blastula stage, then increased notably from the gastrula stage to the advanced fry stage. The Tpcd36 expression elevated during later developmental stages, peaking at advanced fry stage in both. On the other hand, expression of Tpil8 was relatively low until the blastula stage and showed a moderate increase from the organogenesis stage onwards in wild-bred offsprings, whereas a significant upregulation was seen in the captive-bred offsprings from the organogenesis stage until the advanced fry stage, with its maximum expression at the pre-metamorphosis stage. Overall, the findings suggest the crucial role of Tpmyd88, Tptlr2, Tpcd36, and Tpil8 in inducing innate immunity in embryonic and larval stages of T. putitora. Further, the considerably higher expression of the immune genes in the embryonic and larval stages of captive-bred offsprings may indicate a stronger immune system.

Improving outcomes for amputees: The health-related quality of life and cost utility analysis of osseointegration prosthetics in transfemoral amputees.

AIM: Some amputees are unable to adequately ambulate using conventional socket prosthetics, osseointegrated prosthetics have been described as an alternative strategy in this patient group. This paper aims to assess the effect of osseointegrated prosthetics, commonly simply referred to as osseointegration, in transfemoral amputees on health-related quality of life and cost analysis. METHODS: Two centre analysis of patients receiving transcutaneous femoral osseointegration using The Osseointegration Group of Australia Osseointegration Prosthetic Limb (OGAP-OPL) implant. Retrospective health utility and cost analysis of prospectively collected patient reported health outcome data. Osseointegration cost was compared with the yearly cost of a poorly fitting conventional prosthetic determining cost/Quality Adjusted Life Year. RESULTS: Eighty amputees received osseointegration. Mean age was 39 years (range 20-57) and 66% were male (n = 53). The majority of subjects underwent unilateral (n = 62, 77.5%) rather than bilateral surgery (n = 18, 22.5%). Trauma was the most common indication (n = 59, 74%). Maximum follow up was 10.5-years. Mean preoperative EQ5D HUV in pooled data was 0.64 (SEM 0.025) increasing to 0.73 (0.036) at 5-years and 0.78 (0.051) at 6 years with continued improvement up to 10.5-years. In subgroup analysis those with a starting EQ5D HUV <0.60 reached a cost/QALY of <£30,000 at 5-years postoperatively and show statistically significant improvement in EQ5D HUV. The UK military experience was wholly positive with a mean starting EQ5D HUV of 0.48 (0.017) with significant (p < 0.05) improvement in EQ5D HUV at each time point and a resultant reducing cost/QALY at each time point being £28,616.89 at 5 years. CONCLUSION: There is both a quality of life and financial argument in favour of osseointegration in select patients with above transfemoral amputations. In those unable to mobilise satisfactorily with traditional prostheses and a pre-intervention score of <0.60, a consistent cost effectiveness and quality of life benefit can be seen. Such patients should be considered for osseointegration as these patients reap the maximum benefit and cost effectiveness of the device. This evidence lends strongly to the debate advocating the use of osseointegration through centrally funded resources, including the NHS.

Extraction of the Anticancer and Antimicrobial Agent, Prodigiosin, from Vibrio gazogenes PB1 and Its Identification by 1D and 2D NMR.

Prodigiosin is a secondary metabolite produced in several species of bacteria. It exhibits antimicrobial and anticancer properties. Methods for the extraction and identification of prodigiosin and their related derivatives from bacterial cultures typically depend on solvent-based extractions followed by NMR spectroscopy. The estuarine bacterium, V. gazogenes PB1, was previously shown to produce prodigiosin. This conclusion, however, was based on analytical data obtained from ultraviolet-visible absorption spectrophotometry and infrared spectroscopy. Complete dependence on these techniques would be considered inadequate for the accurate identification of the various members of the prodiginine family of compounds, which possess very similar chemical structures and near-identical optical properties. In this study, we extracted prodigiosin from a culture of Vibrio gazogenes PB1 cultivated in minimal media, and for the first time, confirmed the synthesis of prodigiosin Vibrio gazogenes PB1 using NMR techniques. The chemical structure was validated by 1H and 13C NMR spectroscopy, and further corroborated by 2D NMR, which included 1H-1H-gDQFCOSY, 1H-13C-gHSQC, and 1H-13C-gHMBC, as well as 1H-1H-homonuclear decoupling experiments. Based on this data, previous NMR spectral assignments of prodigiosin are reaffirmed and in some cases, corrected. The findings will be particularly relevant for experimental work relating to the use of V. gazogenes PB1 as a host for the synthesis of prodigiosin.

Development of cannabidiol nanoemulsion for direct nose to brain delivery: statistical optimization,in vitroandin vivoevaluation.

Cannabidiol (CBD) is a prescribed drug for epilepsy but has low oral bioavailability and gastric instability. Because of the direct link between the nasal cavity and the central nervous system, intranasal administration of CBD as nanoemulsions which are the small sized lipid carriers seem to improve the bioavailability. CBD-nanoemulsions (NEs) were made using Capryol 90, Tween 80, and Transcutol P as oil, surfactant, and co-surfactant, respectively, following aqueous titration approach. Then, using the Box-Behnken design, CBD-NE was statistically optimised for the selection of desirable excipient concentrations in order to create the optimal CBD-NE formulation. As independent variables in the statistical design, Capryol 90 (oil; coded asA), Tween 80 (surfactant; coded asB), and Transcutol P (co-surfactant; coded asC) were used. The dependent variables were droplet size (DS; coded asR1) and polydispersity index (PDI; coded asR2). The average DS, PDI, and the zeta potential of the optimized CBD-NEs were observed to be 88.73 ± 2.67 nm, 0.311 ± 0.015, and -2.71 ± 0.52 mV respectively. Pure CBD and lyophilized CBD-NEFourier-transform infraredspectra demonstrated no physicochemical interaction between excipients and the drug. Furthermore, differential scanning calorimetry and x-ray diffraction measurements revealed the amorphous CBD in the NE. As compared to pure CBD, the optimised CBD-NE showed considerably betterin vitrodrug release as well asex vivonasal permeability. The drug targeting efficiency and direct transport percentage of the optimised CBD-NEs were found to be 419.64% and 76.17%, respectively, in this research. Additionally, pharmacokinetic investigations after intranasal administration of CBD-NE revealed considerably higher drug concentrations in the brain with better brain targeting efficiency. As a result, the development of CBD-NE may be an excellent alternative for better intranasal delivery.

Effect of temperature on growth performance and immuno-biochemical changes in endangered golden mahseer, Tor putitora (Hamilton, 1923).

The present study to evaluated the effect of different thermal regimes on growth performance, oxidative stress, antioxidant enzymes, and immuno-biochemical responses of endangered golden mahseer, Tor putitora. A total of 144 healthy fingerlings were randomly distributed into four experimental groups (13 °C, 16 °C, 19 °C, 22 ± 0.5 °C) in triplicate rectangular fiberglass reinforced plastics tanks. The highest and lowest Growth rate, Specific growth rate, Daily growth index, Thermal growth coefficient, Viscera-somatic index, and Growth hormone were observed at 19 °C and 13 °C, respectively. The lowest SGR and VSI were observed at 22 °C. The feed conversion ratio was significantly higher in the control group (p < 0.05), whereas there was a significant decrease in all the treatment groups. The highest and lowest hepato-somatic index was observed at a temperature of 13 °C and 16 °C, respectively, while no significant (p > 0.05) impact of temperature regimes were observed on the length-weight relationship. Regarding hematological indices results, the hematocrit, hemoglobin, total erythrocyte count, and total leucocyte count were significantly higher at 13 °C, whereas the lowest was observed in all the treatment groups (p < 0.05). Higher myeloperoxidase activity and lysozyme activity were observed at 13 °C, whereas lowest at 22 °C. Anti-oxidant potential, SOD, and catalase (muscle) were significantly higher in the control group, whereas they gradually decreased with an increasing temperature. Catalase (liver) level was significantly higher at 22 °C. GST content was significantly higher at 22 °C compared to 13 °C, and GST content increased gradually with an increased temperature. The lipid peroxidation level in the liver and muscle was significantly higher at 22 °C and 13 °C, respectively. The present study concluded that the different phenotypic, antioxidative, and immuno-biochemical modulations of golden mahseer fingerlings in response to different temperature regimes could be used for better management and propagation.

Synthesis and evaluation of 2-phenylamino-1,4-naphthoquinones derivatives as potential hypoglycaemic agents.

Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of 'chloro' group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Secreted protein markers in oral squamous cell carcinoma (OSCC).

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a main cause of oral cancer mortality and morbidity in central south Asia. To improve the clinical outcome of OSCC patients, detection markers are needed, which are preferably non-invasive and thus independent of a tissue biopsy. METHODS: In the present study, we aimed to identify robust candidate protein biomarkers for non-invasive OSCC diagnosis. To this end, we measured the global protein profiles of OSCC tissue lysates to matched normal adjacent mucosa samples (n = 14) and the secretomes of nine HNSCC cell lines using LC-MS/MS-based proteomics. RESULTS: A total of 5123 tissue proteins were identified, of which 205 were robustly up- regulated (p-value < 0.01, fold change > + 2) in OSCC-tissues compared to normal adjacent tissues. The biological process "Secretion" was highly enriched in this set of proteins. Other upregulated biological pathways included "Unfolded Protein Response", "Spliceosomal complex assembly", "Protein localization to endosome" and "Interferon Gamma Response". Transcription factor analysis implicated Creb3L1, ESRRA, YY, ELF2, STAT1 and XBP as potential regulators. Of the 205 upregulated tissue proteins, 132 were identified in the cancer cell line secretomes, underscoring their potential use as non-invasive biofluid markers. To further prioritize our candidate markers for non-invasive OSCC detection, we integrated our data with public biofluid datasets including OSCC saliva, yielding 25 candidate markers for further study. CONCLUSIONS: We identified several key proteins and processes that are associated with OSCC tissues, underscoring the importance of altered secretion. Cancer-associated OSCC secretome proteins present in saliva have potential to be used as novel non-invasive biomarkers for the diagnosis of OSCC.