Protection and controlled release of vitamin C by different micro/nanocarriers.

Ascorbic acid, known as vitamin C, is an important antioxidant and food ingredient, and highly sensitive to environmental conditions, which makes its incorporation into food, cosmetic and pharmaceutical products more difficult. The evaluation of its nano/microencapsulation enables the improvement of its stability and controlled release. There are various investigations regarding ascorbic acid encapsulation; however, a deep study related to the scale-up of encapsulation process, its application into food products and digestibility study are still needed. This review highlights the main physicochemical and health properties of vitamin C, recent advances of its encapsulation into micro/nanocarriers, and application in food products. Also, the controlled release and bioavailability of encapsulated forms within different carriers is underlined. The results of published studies clearly show that vitamin C can be successfully protected within micro/nanoencapsulation systems and it can be applied as an efficient ingredient in the formulation of various food products such as bakery goods.

Arthropathy in hereditary haemochromatosis segregates with elevated erythrocyte mean corpuscular volume.

Objective: To evaluate the relationship between erythrocyte parameters and the presence or absence of arthritis in HFE C282Y homozygous hereditary haemochromatosis (HH) subjects compared to control groups of non-HH subjects with arthritis.Method: Erythrocyte and arthritis parameters [mean corpuscular volume (MCV) and mean cell haemoglobin (MCH)] were obtained from consecutive HH subjects (n = 119) who were referred for initial evaluation and management. For comparison, MCV and MCH values were collected from randomly selected non-HH subjects with rheumatoid arthritis (n = 100) and osteoarthritis (n = 100), consisting of equal numbers of men and women. Two other comparison groups comprised 16 men and women who were heterozygous for C282Y with arthritis, and 38 non-HH subjects with type 2 polyarticular osteoarthritis (T2POA).Results: MCV values were significantly higher in HH subjects with arthritis (95 ± 0.56 fL) than in HH subjects without arthritis (92.75 ± 0.50 fL, p = 0.037). HH subjects with or without arthritis demonstrated a higher mean MCV than the control groups of non-HH osteoarthritis (90.12 ± 0.46 fL, p < 0.001) and non-HH rheumatoid arthritis (90.94 ± 0.57 fL, p < 0.001). HH subjects with arthritis also demonstrated a higher MCV than heterozygous C282Y subjects with arthritis (93.18 ± 1.55 fL, p = 0.025) and non-HH subjects with a similar pattern of arthritis, notably T2POA (91.13 ± 0.50 fL, p < 0.01). An MCV of ≥ 97.85 fL provided a likelihood ratio of 2.2 for development of arthritis in HH subjects.Conclusion: This study demonstrated a relationship between elevated MCV and arthritis in incident cases of HH.

Phageome-based vaccination and human innate immune modulation could be a useful strategy to control human Coronavirus infections.

Human Coronavirus (CoV) infections, including SARS-COV, MERS-COV, and SARS-CoV-2, usually cause fatal lower and upper respiratory tract infections due to exacerbated expression of pro-inflammatory cytokines and chemokines. We aim to summarize different aspects, such as CoV immune evasion mechanisms and host innate immune response to these infections, and their role in pathogenesis. We have also elaborated the up-to-date findings on different vaccine development strategies and progress against CoVs in both humans and non-human models. Most importantly, we have described the Phageome-human immune interaction, its therapeutic usage as anti-viral, anti-inflammatory agent, and implications for multiple vaccine development systems. The data suggest that endogenous phages might play a vital role in eliminating the infection and regulating the body's immune system. Considering the innate-immune-induced pathogenesis against CoVs and the therapeutic aptitude of phageome, we propose that the prophylactic administration of phages and phage-based vaccines could be a useful strategy to control the emerging CoV infections.

Effects of Maternal Suicidal Ideation on Child Cognitive Development: A Longitudinal Analysis.

This study aimed to assess the association between suicidal ideation among mothers living with HIV in Zimbabwe and the cognitive development of their children. Participants were mother-child dyads recruited from two rural districts in Zimbabwe. Data were collected at baseline and 12 months follow-up. Suicidal ideation was assessed using item-10 from the Edinburgh postnatal depression scale. Mixed-effects linear regression was used to assess the association of child cognitive outcomes at follow-up (using the Mullen scales of early learning) with maternal suicidal ideation. Mothers with suicidal ideation at baseline (n = 171) tended to be younger, unmarried, experienced moderate to severe hunger, had elevated parental stress and depression symptoms compared with non-suicidal mothers (n = 391). At follow-up, emerging maternal suicidal ideation was associated with poorer child cognitive outcomes (adjusted mean difference - 6.1; 95% CI - 10.3 to - 1.8; p = 0.03). Suicidal ideation affects child cognitive development and should be addressed, particularly in HIV positive mothers.

Patient characteristics and predictors of mortality in 470 adults admitted to a district general hospital in England with Covid-19.

Understanding risk factors for death from Covid-19 is key to providing good quality clinical care. We assessed the presenting characteristics of the 'first wave' of patients with Covid-19 at Royal Oldham Hospital, UK and undertook logistic regression modelling to investigate factors associated with death. Of 470 patients admitted, 169 (36%) died. The median age was 71 years (interquartile range 57-82), and 255 (54.3%) were men. The most common comorbidities were hypertension (n = 218, 46.4%), diabetes (n = 143, 30.4%) and chronic neurological disease (n = 123, 26.1%). The most frequent complications were acute kidney injury (AKI) (n = 157, 33.4%) and myocardial injury (n = 21, 4.5%). Forty-three (9.1%) patients required intubation and ventilation, and 39 (8.3%) received non-invasive ventilation. Independent risk factors for death were increasing age (odds ratio (OR) per 10 year increase above 40 years 1.87, 95% confidence interval (CI) 1.57-2.27), hypertension (OR 1.72, 95% CI 1.10-2.70), cancer (OR 2.20, 95% CI 1.27-3.81), platelets <150 × 103/µl (OR 1.93, 95% CI 1.13-3.30), C-reactive protein ≥100 µg/ml (OR 1.68, 95% CI 1.05-2.68), >50% chest radiograph infiltrates (OR 2.09, 95% CI 1.16-3.77) and AKI (OR 2.60, 95% CI 1.64-4.13). There was no independent association between death and gender, ethnicity, deprivation level, fever, SpO2/FiO2, lymphopoenia or other comorbidities. These findings will inform clinical and shared decision making, including use of respiratory support and therapeutic agents.

A pilot study on the rational use of medicines in four tertiary care hospitals through validated World Health Organization prescribing drugs indicators.

BACKGROUND: Appropriate utilization of therapeutic agents is a basic component of the quality of health outcomes for the patients and the community. A pilot study was conducted to evaluate the rational use of medicines and antibiotics, based on World Health Organization (who) prescribing indicators. STUDY DESIGN: We performed a retrospective, descriptive, cross-sectional pilot study in the medical outpatient departments in four tertiary care hospitals of Islamabad, Pakistan, in order to verify the correct prescribing of medicines according to the validated indicators prepared by the World Health Organization (who). METHODS: The Registries of all the prescriptions formulated during the period April 02 2017 - April 01 2018 by the outpatient departments of four tertiary care hospitals (two government funded hospitals (GH-A and GH-B) and two private funded hospitals (PH-C and PH-D) were considered. According to the World Health Organization recommendations, during the following month (April 02 2018 to May 1 2018), 600 prescriptions (150 per hospital) were collected by a random sampling method, verified and analyzed through a statistical tool (SPSS version 22.0). RESULTS: Mean number of medicines per prescription were 4.6 (Optimal value ≤ 2), with the highest value observed in GH-B hospital. Out of these, 350 (58.3%) (Optimal value < 30%) prescriptions consisted of antibiotics and 340 (56.6%) (Optimal value < 25%) prescriptions consisted of injectable medicines, with marked differences between hospitals. About 550 (19.6%) medicines were prescribed by generic name in all selected prescriptions with the lowest value observed in PH-D (9.9%) (Optimal value = 100%). Overall, 88% medicines were prescribed from National essential medicine list/formulary (Optimal value = 100%). All the prescribing core indicators showed significant difference between hospitals (P = 0.001). The most commonly prescribed antibiotic was ceftriaxone (37.4%), followed by ciprofloxacin (15.1%). CONCLUSIONS: Poor adherence to WHO prescribing indicators were observed in all medical outpatient departments in selected hospitals. WHO recommended core interventions should be implemented on trial basis to develop strategies to achieve long-lasting benefits.

Molecular epidemiology, associated risk factors, and phylogenetic analysis of anaplasmosis in camel.

Camel Anaplasmosis is caused by members of family Anaplasmatacae, a tick transmitted, obligate intracellular bacteria. The etiological bacteria are transmitted by ixodid tick species. The species have multi host range distribution that is why it is crucial to diagnose it timely. The aim of present study was to investigate the molecular epidemiology i.e. prevalence and risk factors analysis of camel anaplasmosis. Furthermore, variations in hematological standards were also evaluated. The study found an overall 13.33% prevalence in camels. The confirmation of PCR positive samples for Anaplasma spp. was made through sequencing, the study isolatesshowed high homology with Iranian, Chinese, Philippines and South African isolates of Anaplasmatacae (Accession numbers'; KX765882, KP062964, KY242456, LC007100 and U54806) on BLAST queries. The phylogenetic analysis revealedthree study isolates of present study clustered with each other and the cluster was found closer to Chinese isolate of A. phagocytophilum (KY242456), A. marginale (KU586048), and Mongolian isolates of A. ovis (LC194134). Two of the isolates resembled Iranian isolate of Candidatus Anaplasmacamelii (KX765882), while one isolate resembled with Chinese isolates of A. Platys (KX987336) and Croatian isolates of A. Platys (KY114935). The key risk factors odds ratio (OR>1) identified for occurrence of camel anaplasmosis using regression model found sex and age of animal, previous tick history, tick infestation and tick control status, housing type, cracks in walls, rearing system and other species in surrounding as the key risk factors. The hematological parameters like lymphocytes, monocytes, granulocytes and platelets count were significantly decreased (p < 0.05) in diseased camels than healthy. This is the first ever molecular data on camel anaplasmosis in Pakistan. The disease should be monitored unceasingly as the etiologies have multi host distribution. Prompt attention should be offered to animals because neutropenia, lymphopenia and thrombocytopenia can exacerbate the disease by making the animal predisposed to otherdiseases.

Mutations of SGO2 and CLDN14 collectively cause coincidental Perrault syndrome.

Perrault syndrome (PS) is a genetically heterogeneous disorder characterized by primary ovarian insufficiency (POI) in females and sensorineural hearing loss in males and females. In many PS subjects, causative variants have not been found in the five reported PS genes. The objective of this study was to identify the genetic cause of PS in an extended consanguineous family with six deaf individuals. Whole exome sequencing (WES) was completed on four affected members of a large family, and variants and co-segregation was confirmed by Sanger sequencing. All hearing impaired individuals, including the proband, are homozygous for a pathogenic variant of CLDN14, but this only explains the deafness. The PS proband is also homozygous for a frameshift variant (c.1453_1454delGA, p.(Glu485Lysfs*5)) in exon 7 of SGO2 encoding shugoshin 2, which is the likely cause of her concurrent ovarian insufficiency. In mouse, Sgol2a encoding shugoshin-like 2a is necessary during meiosis in both sexes to maintain the integrity of the cohesin complex that tethers sister chromatids. Human SGO2 has not previously been implicated in any disorder, but in this case of POI and perhaps others, it is a candidate for unexplained infertility.

Nutritional status is the major factor affecting grip strength of African HIV patients before and during antiretroviral treatment.

OBJECTIVES: Low grip strength is a marker of frailty and a risk factor for mortality among HIV patients and other populations. We investigated factors associated with grip strength in malnourished HIV patients at referral to ART, and at 12 weeks and 2-3 years after starting ART. METHODS: The study involved HIV-infected Zambian and Tanzanian participants recruited to the NUSTART trial when malnourished (body mass index <18.5 kg/m2 ) and requiring ART. The relationship of grip strength to nutritional, infectious and demographic factors was assessed by multivariable linear regression at referral for ART (n = 1742) and after 12 weeks (n = 778) and 2-3 years of ART (n = 273). RESULTS: In analyses controlled only for sex, age and height, most nutrition and infection-related variables were associated with grip strength. However, in multivariable analyses, consistent associations were seen for fat-free mass index, mid-upper arm circumference, haemoglobin and systolic blood pressure, and a variable association with fat mass index in men. C-reactive protein and CD4 count had limited independent effects on grip strength, while receiving tuberculosis treatment was associated with weaker grip strength. CONCLUSIONS: In this population of originally malnourished HIV patients, poor grip strength was more strongly and independently associated with nutritional than with infection and inflammation variables. Programmes to improve health and survival of HIV patients should incorporate nutritional assessment and management and could use grip strength as a functional indicator of improving nutrition.

Unresolved questions regarding human hereditary deafness.

Human hearing loss is a common neurosensory disorder about which many basic research and clinically relevant questions are unresolved. This review on hereditary deafness focuses on three examples considered at first glance to be uncomplicated, however, upon inspection, are enigmatic and ripe for future research efforts. The three examples of clinical and genetic complexities are drawn from studies of (i) Pendred syndrome/DFNB4 (PDS, OMIM 274600), (ii) Perrault syndrome (deafness and infertility) due to mutations of CLPP (PRTLS3, OMIM 614129), and (iii) the unexplained extensive clinical variability associated with TBC1D24 mutations. At present, it is unknown how different mutations of TBC1D24 cause non-syndromic deafness (DFNB86, OMIM 614617), epilepsy (OMIM 605021), epilepsy with deafness, or DOORS syndrome (OMIM 220500) that is characterized by deafness, onychodystrophy (alteration of toenail or fingernail morphology), osteodystrophy (defective development of bone), mental retardation, and seizures. A comprehensive understanding of the multifaceted roles of each gene associated with human deafness is expected to provide future opportunities for restoration as well as preservation of normal hearing.

Efficient use of artificial micro-RNA to downregulate the expression of genes at the post-transcriptional level in Arabidopsis thaliana.

Micro-RNAs are cellular components regulating gene expression at the post-transcription level. In the present study, artificial micro-RNAs were used to decrease the transcript level of two genes, AtExpA8 (encoding an expansin) and AHL25 (encoding an AT-hook motif nuclear localized protein) in Arabidopsis thaliana. The backbone of the Arabidopsis endogenous MIR319a micro-RNA was used in a site-directed mutagenesis approach for the generation of artificial micro-RNAs targeting two genes. The recombinant cassettes were expressed under the control of the CaMV 35S promoter in individual A. thaliana plants. Transgenic lines of the third generation were tested by isolating total RNA and by subsequent cDNA synthesis using oligo-dT18 primers and mRNAs as templates. The expression of the two target genes was checked through quantitative real-time polymerase chain reaction to confirm reduced transcript levels for AtExpA8 and AHL25. Downregulation of AtExpA8 resulted in the formation of short hypocotyls compared with those of the wild-type control in response to low pH and high salt concentration. This technology could be used to prevent the expression of exogenous and invading genes posing a threat to the normal cellular physiology of the host plant.

Effect of route of inoculation on replication of avian influenza virus (H9N2) and interferon gene expression in guinea fowl (Numida meleagridis).

The study was designed to investigate the replication of a re-assortant H9N2 avian influenza virus (AIV) and induction of the interferon (IFNγ) response after aerosol or intranasal inoculation with the virus in guinea fowl. To determine virus shedding pattern, oropharyngeal and cloacal swabs and tissue specimens of trachea, lungs, spleen and caecal tonsils were collected post-inoculation (pi). Infected guinea fowl showed mild clinical signs, while negative control guinea fowl remained healthy and active throughout the experiment irrespective of the inoculation route. However, the clinical signs were more prominent in guinea fowl infected through the aerosol route. Virus was detected in all oropharyngeal and cloacal swabs up to 7 d pi in guinea fowl from both inoculation groups. However, virus was detected more frequently and in higher titres in oropharyngeal swabs and specimens of trachea and lungs from the group exposed to aerosols than in the group given intranasal drops. In accordance with viral replication findings, expression of IFNγ was up-regulated on 1, 2 and 4 d pi to a significantly higher level in lung tissue specimens from the group exposed to virus aerosol than from controls treated with PBS intranasally. On the other hand, IFNγ was up-regulated above that of controls in lung tissue specimens from the group treated with intranasal drops of virus only on 4 d pi. These findings indicate that virus administered in aerosols was more efficient in infecting the lower respiratory tract and in inducing activity of the IFNγ gene than virus administered as intranasal drops. The results of this study suggest that virus aerosols cause more intense respiratory infection and increase the shedding of the H9N2 AIV in guinea fowl, highlighting the potential role of guinea fowl as a mixing bowl for transmission and maintenance of H9N2 AIV between poultry premises.

IDENTIFICATION OF QTLs ON CHROMOSOME 1B FOR GRAIN QUALITY TRAITS IN BREAD WHEAT (TRITICUM AESTIVUM L.).

The present study was designed considering the importance of grain quality traits, genetic diversity and marker-trait association analysis in wheat. A significant amount of genetic diversity was found for various seed traits though the genotypes included in the study were found structured. The extent of polymorphism was high with a range of 2-13 alleles and average of 6.5 alleles per locus. Population structure was detected with 30 unlinked SSRs that divided the population of 92 genotypes in three sub-populations. Extensive LD extent was found on chromosome 1B with 42 SSRs specific for 1B chromosome. Marker-trait associations were determined using mixed linear model, where, population structure and kinship calculated on the basis of unlinked markers were covariated with 1B specific markers and traits data. Eight QTLs for five traits including protein, gluten contents, test weight bread and chapati making quality. Protein content, test weight, bread quality and Glu-B1 were found significantly associated with primers WMC419 (32 cM); WMC128 (30 cM), WMC419 (32 cM); WMC818 (17 cM) and WMC416 (44 cM), respectively.

Updated Next-to-Next-to-Leading-Order QCD Predictions for the Weak Radiative B-Meson Decays.

Weak radiative decays of the B mesons belong to the most important flavor changing processes that provide constraints on physics at the TeV scale. In the derivation of such constraints, accurate standard model predictions for the inclusive branching ratios play a crucial role. In the current Letter we present an update of these predictions, incorporating all our results for the O(α_{s}^{2}) and lower-order perturbative corrections that have been calculated after 2006. New estimates of nonperturbative effects are taken into account, too. For the CP- and isospin-averaged branching ratios, we find B_{sγ}=(3.36±0.23)×10^{-4} and B_{dγ}=(1.73_{-0.22}^{+0.12})×10^{-5}, for E_{γ}>1.6 GeV. Both results remain in agreement with the current experimental averages. Normalizing their sum to the inclusive semileptonic branching ratio, we obtain R_{γ}≡(B_{sγ}+B_{dγ})/B_{cℓν}=(3.31±0.22)×10^{-3}. A new bound from B_{sγ} on the charged Higgs boson mass in the two-Higgs-doublet-model II reads M_{H^{±}}>480 GeV at 95% C.L.

Bottom-up fabrication of graphene on Ru(0001) via molecular self-assembly.

A bottom-up fabrication of graphene via molecular self-assembly of p-Terphenyl on Ru(0001) has been investigated by scanning tunneling microcopy and density functional theory. Upon annealing of the sample at 450 °C, the intermediate stage is observed, in which the adsorbed p-Terphenyl molecules and graphitized flakes converted from the molecules coexist, implying the onset of dehydrogenation of p-Terphenyl. At the annealing temperature of 480 °C, the graphitized flakes start to convert into graphene. An adsoption energy of 5.99 eV is calculated for an individual p-Terphenyl molecule on Ru(0001), denoting a strong interaction between the adsorbate and substrate. The intermolecular interaction brings an extra adsorption energy of 0.28 eV for each molecule in the di-molecule adsorption system. During the conversion process from adsorbed molecule into graphene, the intermolecular interaction leads to the increase of the dehydrogenation barrier from 1.52 to 1.64 eV.

Use of romiplostim in patients with chronic idiopathic thrombocytopenic purpura during perioperative period.

INTRODUCTION: In patients with chronic idiopathic thrombocytopenic purpura (cITP), the platelet count tends to be quite variable and, in the majority of cases, specific therapy is not warranted on a regular basis. However, patients with low platelet count (<30 nL) or with bleeding complications would require therapy, such as prednisolone, intravenous immunoglobulin infusions, splenectomy and/or immunosuppression. Romiplostim, a thrombopoietin agonist, has also proven to be useful in improving platelet counts. cITP can be associated with bleeding complications perioperatively. As such, a higher platelet count is warranted (approximately 80 nL), particularly for invasive surgeries, such as orthopaedic surgery, cardio-thoracic surgery, head and neck surgery and abdominal surgery, where risk of bleeding is quite high already. AIM: The aim of this study is to evaluate the safety and efficacy of short-term use of romiplostim, perioperatively. METHODS: Patients with chronic ITP requiring major surgical interventions were enrolled in the study. Patients with malignancies or myelodysplastic syndromes, major bleeding disorders, under 18 years of age or pregnancy were excluded. CONCLUSION: This study has shown that the use of romiplostim is safe and effective in improving platelet counts preoperatively and that this could achieve excellent haemostasis, with no associated bleeding complications or rebound thrombocytopenia. A larger study involving multiple centres is required to verify these findings.

Mitochondrial Transfer Between Mesenchymal Stem Cells and Cancer Cells.

Mitochondrial transfer (MT) is a biological process that allows a donor cell to horizontally share its own mitochondria with a recipient cell. Mitochondria are highly dynamic membrane-bound sub-cellular organelles prominently involved in the regulation of the cell energy balance, calcium homeostasis, and apoptotic machinery activation. They physiologically undergo fusion and fission processes in response to the cell requirement, with a continuous morphological re-arrangement. This structural and functional plasticity is at the basis of the MT, described in tissue regeneration, cardiac and neurological diseases, as well as in cancer. Here, the MT has been observed in the tumor micro-environment (TME) from the adipose-derived stem cells (ASCs) to the cancer cells, eventually reverting the lack of the mitochondria respiration function, or enhancing their motility and drug resistance. In this chapter, we outline some key protocols for evaluating this exciting phenomenon of MT. These methodological and technical approaches are very important, considering all the limitations that scientists constantly face, especially in this field of the research.

Cancer Stem Cells: Detection and Characterization from Solid Tumors.

Cancer stem cells (CSCs) have emerged as an attractive research interest due to their prominent role in development of the tumors. CSCs are rare dormant cells that can self-renew and maintain tumor development and heterogeneity. A better understanding of CSCs can improve tumor classification and contribute toward the development of novel therapeutic approaches to fight cancer. Hence, it is of immense importance to comprehend the basic function of CSCs in tumor formation, which can only be possible by devising perfected methodologies to isolate, detect, and characterize them. In this chapter, we outline the key protocols to culture, identify, and isolate CSCs from solid tumors to further advance basic and clinical investigation related to CSCs and their role in tumor biology.