Tuberculosis (TB) has been repeatedly shown to have socioeconomic impacts in both individual-level and ecological studies; however, much less is known about this effect among children and adolescents ...and the extent to which being affected by TB during childhood and adolescence can have life-course implications. This paper describes the results of the development of a conceptual framework and scoping review to review the evidence on the short- and long-term socioeconomic impact of tuberculosis on children and adolescents.
To increase knowledge of the socioeconomic impact of TB on children and adolescents.
We developed a conceptual framework of the socioeconomic impact of TB on children and adolescents, and used scoping review methods to search for evidence supporting or disproving it. We searched four academic databases from 1 January 1990 to 6 April 2021 and conducted targeted searches of grey literature. We extracted data using a standard form and analysed data thematically.
Thirty-six studies (29 qualitative, five quantitative and two mixed methods studies) were included in the review. Overall, the evidence supported the conceptual framework, suggesting a severe socioeconomic impact of TB on children and adolescents through all the postulated pathways. Effects ranged from impoverishment, stigma, and family separation, to effects on nutrition and missed education opportunities. TB did not seem to exert a different socioeconomic impact when directly or indirectly affecting children/adolescents, suggesting that TB can affect this group even when they are not affected by the disease. No study provided sufficient follow-up to observe the long-term socioeconomic effect of TB in this age group.
The evidence gathered in this review reinforces our understanding of the impact of TB on children and adolescents and highlights the importance of considering effects during the entire life course. Both ad-hoc and sustainable social protection measures and strategies are essential to mitigate the socioeconomic consequences of TB among children and adolescents.
A suppository for rectal administration of carbamazepine has been developed for situations in which it is unsuitable to use the oral route of administration. In an open, controlled, within-patient ...study, the pharmacokinetics, clinical efficacy, and tolerability of carbamazepine slow-release tablets were compared with those of carbamazepine suppositories in children with epilepsy. The pharmacokinetic part of the study comprised 22 children, and an additional nine children were included in the clinical part of the study. Treatment with slow-release tablets was replaced for 7 days with carbamazepine suppositories in bioequivalent dosage. Clinical factors such as the rate of seizures and the local tolerability were studied, and an overall assessment of efficacy was made. In the pharmacokinetic part, 24-hour plasma concentration curves for carbamazepine and carbamazepine-10,11-epoxide were recorded. The plasma concentration profiles (minimum, maximum, and mean concentrations, fluctuation index, and area under the curve) for carbamazepine and the other metabolites did not show any significant differences between oral and rectal administration when the suppository dose was increased by 25% compared to the tablets. No increase in seizure frequency was detected, and the overall assessment was very good to good in 25 of the 29 epileptic children. Increased flatulence during treatment with suppositories was noted in two children, one had anal irritation, and one had nausea/vomiting. Treatment with carbamazepine slow-release tablets in children with epilepsy can be replaced by carbamazepine suppositories in 25% higher dosage, with good clinical effect and appropriate pharmacokinetic values, when it is unsuitable to use the common oral route of administration.
In order to overcome the problems of interdosage fluctuations of body fluid concentrations of carbamazepine, a slow-release formulation has been developed. In an open, controlled, within-patient ...study, the diurnal plasma concentrations of carbamazepine and its 10,11-epoxide were measured in 25 epileptic children first treated with conventional carbamazepine tablets (Tegretol) and then with the Tegretol slow-release preparation. The diurnal plasma concentration curves during treatment with the slow-release formulation showed significantly less variation over 24 hours than during treatment with the ordinary preparation, as measured by the fluctuation index. Mean concentration values also differed significantly, which is explained by a somewhat reduced bioavailability (22% less) of the slow-release formulation. There were no differences in efficacy and tolerability between the two formulations, but there was a clear-cut reduction of reported side effects, especially tiredness, on treatment with the slow-release formulation. For that reason, the slow-release formulation should be a major advantage in treating children with epilepsy, in order to avoid interference with cognitive functions. In 12 children, simultaneous measurements of the concentration of carbamazepine and its epoxide in saliva were made and compared with the plasma values. As expected, the concentration curves corresponded, indicating that saliva sampling is an appropriate alternative for monitoring the concentration of carbamazepine. All children remained on the slow-release preparation after the trial and were followed up for 12 months or more.
The effect of daylight on the compound eye was investigated in the deep-water crustacean isopod Cirolana borealis Lilljeborg. The animals were captured and fixed at night ('dark-exposed', i.e. not ...exposed to light) and day ('daylight-exposed'), respectively. Changes in light and darkness have an effect on the retinula cells; the ultrastructure of dark-exposed eyes is characterized by well-preserved organelles and cytoplasm. The photoreceptor membranes covering the microvilli are regularly aligned, and the outline of the villi is smooth. Electron-dense pigment granules are evenly distributed in the cytoplasm of the retinula cell outside the rhabdom. Daylight-exposed eyes differ from the dark-exposed eyes in the following aspects: (i) the microvilli are disrupted, (ii) retinula-cell pigment is found in the rhabdom, and (iii) the cytoplasm of retinula cells is vesiculated. These results are interpreted as retinal damage caused by excess exposure to light.
We tested whether intervention with atorvastatin affects the prostate beneficially compared with placebo in men with prostate cancer in a randomized clinical trial. A total of 160 statin-naïve ...prostate cancer patients scheduled for radical prostatectomy were randomized to use 80mg atorvastatin or placebo daily from recruitment to surgery for a median of 27 d. Blinding was maintained throughout the trial. In total, 158 men completed the follow-up, with 96% compliance. Overall, atorvastatin did not significantly lower tumor proliferation index Ki-67 or serum prostate-specific antigen (PSA) compared with placebo. In subgroup analyses, after a minimum of 28 d of atorvastatin use, Ki-67 was 14.1% lower compared with placebo (p = 0.056). Among high-grade cases (International Society of Urological Pathology Gleason grade 3 or higher), atorvastatin lowered PSA compared with placebo: median change –0.6 ng/ml; p = 0.024. Intraprostatic inflammation did not differ between the study arms (p = 0.8). Despite a negative overall result showing no effect of statins on Ki67 or PSA overall, in post hoc exploratory analyses, there appeared to be benefit after a minimum duration of 28 d. Further studies are needed to verify this.
Cholesterol-lowering atorvastatin does not lower prostate cancer proliferation rate compared with placebo overall, but exploratory analyses suggest a benefit in longer exposure.
Atorvastatin at a dose of 80mg/d does not significantly change prostate cancer Ki-67 or prostate-specific antigen (PSA) overall compared with placebo in a randomized trial. However, a minimum intervention duration of 28 d lowers Ki-67 by 14%. Among high-grade cases, atorvastatin lowers PSA compared with placebo,
Androgen deprivation therapy is the cornerstone treatment of advanced prostate cancer. Eventually prostate cancer cells overcome androgen deprivation therapy, giving rise to castration resistant ...prostate cancer (CRPC) characterized by increased androgen receptor (AR) activity. Understanding the cellular mechanisms leading to CRPC is needed for development of novel treatments. We used long-term cell cultures to model CRPC; a testosterone-dependent cell line (VCaP-T) and cell line adapted to grow in low testosterone (VCaP-CT). These were used to uncover persistent and adaptive responses to testosterone level. RNA was sequenced to study AR-regulated genes. Expression level changed due to testosterone depletion in 418 genes in VCaP-T (AR-associated genes). To evaluate significance for CRPC growth, we compared which of them were adaptive i.e., restored expression level in VCaP-CT. Adaptive genes were enriched to steroid metabolism, immune response and lipid metabolism. The Cancer Genome Atlas Prostate Adenocarcinoma data were used to assess the association with cancer aggressiveness and progression-free survival. Expressions of 47 AR-associated or association gaining genes were statistically significant markers for progression-free survival. These included genes related to immune response, adhesion and transport. Taken together, we identified and clinically validated multiple genes being linked with progression of prostate cancer and propose several novel risk genes. Possible use as biomarkers or therapeutic targets should be studied further.
Bioactive glasses (BAGs) have been studied for decades for clinical use, and they have found many dental and orthopedic applications. BAGs have also been shown to have an antibacterial effect e.g., ...on some oral microorganisms. In this extensive work we show that six powdered BAGs and two sol–gel derived materials have a clear antibacterial effect on 29 clinically important bacterial species. We also incorporated a rapid and accurate flow cytometric (FCM) method to calculate and standardize the numbers of viable bacteria inoculated in the suspensions used in the tests for antibacterial activity. In all materials tested growth inhibition could be demonstrated, although the concentration and time needed for the effect varied depending on the BAG. The most effective glass was S53P4, which had a clear growth-inhibitory effect on all pathogens tested. The sol–gel derived materials CaPSiO and CaPSiO II also showed a strong antibacterial effect. In summary, BAGs were found to clearly inhibit the growth of a wide selection of bacterial species causing e.g., infections on the surfaces of prostheses in the body after implantation.
Background
Diagnostic tests for fish allergy are hampered by the large number of under‐investigated fish species. Four salmon allergens are well‐characterized and registered with the WHO/IUIS while ...no catfish allergens have been described so far. In 2008, freshwater‐cultured catfish production surpassed that of salmon, the globally most‐cultured marine species. We aimed to identify, quantify, and compare all IgE‐binding proteins in salmon and catfish.
Methods
Seventy‐seven pediatric patients with clinically confirmed fish allergy underwent skin prick tests to salmon and catfish. The allergen repertoire of raw and heated protein extracts was evaluated by immunoblotting using five allergen‐specific antibodies and patients' serum followed by mass spectrometric analyses.
Results
Raw and heated extracts from catfish displayed a higher frequency of IgE‐binding compared to those from salmon (77% vs 70% and 64% vs 53%, respectively). The major fish allergen parvalbumin demonstrated the highest IgE‐binding capacity (10%‐49%), followed by triosephosphate isomerase (TPI; 19%‐34%) in raw and tropomyosin (6%‐32%) in heated extracts. Six previously unidentified fish allergens, including TPI, were registered with the WHO/IUIS. Creatine kinase from salmon and catfish was detected by IgE from 14% and 10% of patients, respectively. Catfish L‐lactate dehydrogenase, glyceraldehyde‐3‐phosphate dehydrogenase, pyruvate kinase, and glucose‐6‐phosphate isomerase showed IgE‐binding for 6%‐13% of patients. In salmon, these proteins could not be separated successfully.
Conclusions
We detail the allergen repertoire of two highly farmed fish species. IgE‐binding to fish tropomyosins and TPIs was demonstrated for the first time in a large patient cohort. Tropomyosins, in addition to parvalbumins, should be considered for urgently needed improved fish allergy diagnostics.
Catfish raw and heated extracts demonstrate higher prevalence and diversity of IgE‐binding as compared to salmon. PV, TM and TPI are the most prominent IgE‐binding fish proteins, followed by Eno, Ald and GAPDH. TM is the second most abundant protein, after PV, in heated extracts and up to 49% of 77 fish‐allergic children demonstrate IgE‐binding.
Abbreviations: Ald, aldolase; Eno, enolase; GAPDH, glyceraldehyde‐3‐phosphate dehydrogenase; MS, mass spectrometry, PV, parvalbumin, SDS‐PAGE, sodium dodecyl sulphate‐polyacrylamide gel electrophoresis; TM, tropomyosin, TPI, triosephosphate isomerase
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