Physicochemical properties and dissolution studies of dexamethasone acetate-beta-cyclodextrin inclusion complexes produced by different methods.
Inclusion complexes between dexamethasone acetate (DMA), a poorly water soluble drug, and beta-cyclodextrin (betaCD) were obtained to improve the solubility and dissolution rate of this drug. Phase-solubility profile indicated that the solubility of DMA was significantly increased in the presence of betaCD (33-fold) and was classified as A(L)-type, indicating the 1:1 stoichiometric inclusion complexes. Solid complexes prepared by different methods (kneading, coevaporation, freeze drying) and physical mixture were characterized by differential scanning calorimetry, thermogravimetry, infrared absorption and optical microscopy. Preparation methods influenced the physicochemical properties of the products. The dissolution profiles of solid complexes were determined and compared with those DMA alone and their physical mixture, in three different mediums: simulated gastric fluid (pH 1.2), simulated intestinal fluid (pH 7.4) and distilled water. The dissolution studies showed that in all mediums DMA presented an incomplete dissolution even in four hours. In contrast, the complexes formed presented a higher dissolution rate in simulated gastric fluid (SGF pH 1.2), which indicate that these have different ionization characteristics. According to the results, the freeze-dried and kneaded products exhibited higher dissolution rates than the drug alone, in all the mediums.


Seeing Voices: A Dynamic, Interprofessional Approach to Teaching Performing Arts and Speech-Language Pathology Students About Vocal Anatomy and Physiology.
Seeing Voices was an interprofessional, technology-enabled, large-scale, teaching and learning event developed to address the need to improve voice students' knowledge of laryngeal anatomy and physiology toward understanding and maintaining vocal health. Seeing Voices trialed a novel interprofessional educational approach, collected both quantitative and qualitative data about student experiences of laryngostroboscopic examination, and built a databank of laryngeal recordings for future student learning. Seeing Voices involved two 3-hour seminars in a large, university lecture space, run by an interprofessional team (speech-language pathologists, vocal coach, Ear Nose and Throat consultant) with quality equipment projecting laryngeal images to large screens with expert commentary in real time. Participants were 18 students who volunteered for laryngeal examination (9 per seminar) and student attendees (n = 175) from performing arts courses (classical singing, contemporary, jazz, musical theater, acting) and a speech-language pathology course. A quantitative evaluation of knowledge gained was undertaken using a Qualtrics survey. Results from pre (n = 175; performing arts = 120; speech-language pathology (SLP) = 55) and postevent (n = 99; performing arts = 56; SLP = 43) questionnaires were received from the students who attended. Interviews were collected from 15 of the 18 student volunteers about their experiences of nasendoscopic evaluation and data were analyzed using qualitative description and qualitative content analysis. Quantitative results demonstrated a strong trend toward increased knowledge following attendance at the event across year cohorts for both student groups. Qualitative interviews highlighted the value in seeing multiple examples of normal laryngeal functioning across different vocal techniques in real time. For those undertaking nasendoscopic examination, simultaneously seeing and feeling laryngeal maneuvers used in training appeared to promote understanding of their own vocal mechanism and the purpose of different vocal techniques. Seeing Voices offers a novel way to improve interprofessional collaboration, and engagement with, and understanding of, laryngeal anatomy and vocal health by students in performing arts and speech-language pathology courses.


[Isolation of viable human tumor cells and their characteristics during culturing in diffusion chambers].
Methodical approaches for obtaining the viable tumour cells from solid human tumours are developed. Combination of the short-term enzymatic treatment of the tumour tissue pieces and their gradual rubbing through the metal sieve with the decreasing pore sizes permitted obtaining a large number of isolated tumour cells with the high percentage of viability.


The pathological, ultrasonographic and computerized tomographic characteristics of chronic hematocele.
We report a case of a chronic hematocele and describe its characteristics. The specific pathological lesion of a chronic hematocele consists of several neovascular formations covered by layers of fibrin. These lesions give characteristic ultrasonic and computerized tomographic images, consisting of several sharply circumscribed small spherical areas of soft tissue. When correctly interpreted before the initiation of surgical treatment, these images will obviate an orchiectomy, which is not always necessary.


Abnormal course, abnormal flow, and systolic compression of the septal perforator associated with impaired myocardial perfusion in hypertrophic cardiomyopathy.
The septal perforators in hypertrophic cardiomyopathy (HCM) show systolic compression. The compression is thought to be related to the malpositioned septal perforators, but its relation to the development of myocardial ischemia remains controversial. We examined echocardiographically the blood flow and course of the major septal perforator in 142 consecutive patients with HCM; of these, 94 underwent coronary angiography to assess systolic compression of the septal perforators and 110 had thallium-201 scintigraphy. We then analyzed the relation of the findings in comparison with the results in 15 patients with valvular aortic stenosis (AS). The major septal perforator was visualized in 82 patients with HCM and in 8 patients with AS. The visualization did not depend on the pressure gradient between the left ventricle and aorta in the HCM patients, but did in the AS patients. In AS the perforator always showed a normal course near to, and convexly toward, the right ventricle. In 71 of the 82 HCM patients, the perforator was distant from the right-sided endocardium of the ventricular septum and often convex toward the left. The greater the leftward deviation, the higher was the grade of compression. In 48 of the 82 patients with HCM and in all of the 8 patients with AS who showed the flow signal, the septal perforator showed systolic retrograde flow; in the patients with HCM there was a significant correlation (r = 0.54, P <.05) between the peak velocity and the degree of leftward deviation. Furthermore, higher degrees of the leftward deviation and higher degrees of the systolic compression of the major perforator were each associated with a higher incidence of exercise-induced defect of thallium-201. The echocardiographic, angiographic, and scintigraphic findings in HCM may be closely related to one another. We speculate that the series of abnormalities is initiated by a high intramural pressure and impedance on the septal perforators due to their deviation toward the left.


The thermal aggregation of ovalbumin as large particles decreases its allergenicity for egg allergic patients and in a murine model.
Most egg-allergic children can tolerate extensively cooked eggs. Ovalbumin, a major allergen in egg whites, is prone to aggregate upon heating. This study compares ovalbumin's allergenicity when it is aggregated as large particles to ovalbumin in its native form. Immunoglobulins (Ig)-binding and the degranulation capacities of native and aggregated ovalbumin were measured with sera from egg-allergic children and from mice sensitized to native or aggregated ovalbumin. The influence of ovalbumin structure on Ig production upon sensitization and elicitation potency by challenge was also studied. We showed that heat aggregation of ovalbumin as large particles enhances IgG production and promotes IgG2a production (a shift toward the T helper 1 profile). Aggregated ovalbumin displayed lower Ig-binding and basophil-activation capacities for sera from both allergic patients and mice. This work illustrates the links between ovalbumin structure after heating and allergenicity potential using parameters from both the sensitization and elicitation phases of the allergic reaction.


Silver Pharmacology: Past, Present and Questions for the Future.
Silver pharmacology is at the cross-roads. It has a long history as a chemosterilent but is currently denigrated by some vested interests and other 'knowledge monopolies'. It deserves better--particularly in these critical times of ever mounting incidence of antibiotic resistance. This reappraisal outlines some approaches to a dispassionate debate as to why we should, or should not, be reconsidering silver as an addition to (not a substitute for) other antibiotics at the front line of medicine. This will require more understanding about (i) the chemistry of silver in a biological environment; (ii) the different physical and bio-reactive properties of ionised silver (Ag(I)) and nanoparticulate metallic silver (Ag(o)); (iii) the antibiotic potential of both Ag(I) and Ag(o); and (iv) establishing objective Quality Controls for potential silver therapies. Six appendices (A-F) provide some technical data and focus further upon the need to clearly define (a) procedures for manufacturing nanoparticulate metallic silver (NMS); and (b) the purity and properties of NMS preparations--especially stability, antibiotic efficacy and safety of products offered for clinical evaluation. A further appendix (G) deals with some political considerations currently impeding impartial clinical research on silver therapeutics.


Rhodium(III)-catalyzed redox-neutral coupling of N-phenoxyacetamides and alkynes with tunable selectivity.
Give it a tweak: A novel oxidizing directing group was developed for a rhodium(III)-catalyzed CH functionalization of N-phenoxyacetamides with alkynes. A small change in the reaction conditions leads to either ortho-hydroxyphenyl-substituted enamides or cyclization to deliver benzofurans with high selectivity (see scheme; Cp*=C5 Me5 ).


Multi-stage mental process for economic choice in capuchins.
We studied economic choice behavior in capuchin monkeys by offering them to choose between two different foods available in variable amounts. When monkeys selected between familiar foods, their choice patterns were well-described in terms of relative value of the two foods. A leading view in economics and biology is that such behavior results from stimulus-response associations acquired through experience. According to this view, values are not psychologically real; they can only be defined a posteriori. One prediction of this associative model is that animals faced for the first time with a new pair of foods learn to choose between them gradually. We tested this prediction. Surprisingly, we find that monkeys choose as effectively between new pairs of foods as they choose between familiar pairs of foods. We therefore, propose a cognitive model in which economic choice results from a two-stage mental process of value-assignment and decision-making. In a follow-up experiment, we find that the relative value assigned to three foods in sessions in which we tested them against each other combine according to transitivity.


Parallel quantitation of salt dioctyl sodium sulfosuccinate (DOSS) and fingerprinting analysis of dispersed oil in aqueous samples.
In many jurisdictions, dispersants are included in contingency plans as a viable countermeasure that can help reduce the overall environmental impact of marine oil spills. When used, it is imperative to monitor the progression of dispersant and oil to assess their environmental fate and behaviour. Amphiphilic salt dioctyl sodium sulfosuccinate (DOSS) is the major effective component of the most commonly available dispersants, such as Corexit® EC9500A. Without proper sample preparation, dispersed oil in water samples could interfere with the accurate analysis of DOSS and easily contaminate the LC-MS system. In this work, solid phase extraction (SPE) weak anion exchange (WAX) cartridges were used to separate oil and DOSS in aqueous samples. DOSS was accurately determined by liquid chromatography coupled with a high resolution Orbitrap mass spectrometer (LC-HRMS). Oil fingerprinting analysis was conducted and total petroleum hydrocarbons (TPHs), polycyclic aromatic hydrocarbons (PAHs), and petroleum biomarkers were determined by gas chromatography-flame ionization detection (GC-FID) and mass spectrometry (GC-MS). This SPE-LC/GC-MS method was used for the analysis of oil-dispersant water samples containing a mixture of Corexit® EC9500A and a selection of crude oils and refined petroleum products. Nearly a 100% DOSS recovery was obtained for various oil-surfactant conditions. Parallel quantitation of oils with dispersants was achieved using this method. A portion of the TPH loss was possibly attributed to oil retained by the SPE column. Chemical fingerprints and diagnostic ratios of target compounds in recovered dispersed oil overall remain unchanged compared with those of all studied oils.


CaIPF19998 reduces drug susceptibility by enhancing the ability of biofilm formation and regulating redox homeostasis in Candida albicans.
CaIPF19998, a functionally unknown gene in Candida albicans, was identified by its homology to Saccharomyces cerevisiae AIF1 gene, which is involved in cell apoptosis. In this study, ipf19998 null mutant was generated with the URA-blaster method and the construction of overexpression of CaIPF19998 was measured by quantitative RT-PCR. Minimal inhibitory concentrations determination showed that the ipf19998 overexpressed strains was more resistant to the antifungals tested than the wildtype (strain CAI4). The 2,3-bis (2-methoxy-4-nitro-5-sulfo-phenyl)-2Htetrazolium-5-carboxanilide reduction assay showed that CaIPF19998 could enhance the capacity of C. albicans biofilms formation. On Candida biofilms mode, intracellular levels of reactive oxygen species were significantly decreased and real-time RT-PCR showed that some important redox-related genes, including ALD5, CIT1, PIL1, AHP1, TRX1 and TSA1, were up-regulated in the CaIPF19998 overexpressed strains. These results demonstrate that CaIPF19998 played an important role in C. albicans biofilms formation and intracellular redox homeostasis, therefore led to a close relationship between CaIPF19998 and drug susceptibility in C. albicans.


[Podiatric risk screening in patients with type 2 diabetes in Antananarivo].
Diabetic foot disease heavily weighs upon diabetics, being a significant cause of morbidity and severe disability. Their prevention is indispensable. Our study aimed to reduce the rate of amputations in diabetics. We conducted a retrospective, descriptive, cross-sectional, multicenter study of podiatric risk screening in patients with type 2 diabetes in the Endocrinology Department at the University Hospital of Befelatanana and at the Amadia Clinic, Faravohitra, over a period of 6 months. The average age of our patients was 54.43 years. Male sex predominated (60%). The patients suffered from diabetes which had evolved, on average, over a period of 7.35 years. The most common patient's history was smoking and chronic ulcerations of the foot. More than half of patients had an imbalance of diabetes, microalbuminuria and retinopathy. 56.50% of patients were aware of their risk but less than 46% of patients gave specific examples of appropriate behaviour. Only 13.33% of patients had undergone foot examination before this study. Their podiatric risk was very high. Predictive factors for ulceration included smoking, a history of chronic ulcer of the lower limbs, an imbalance of diabetes and foot deformity. Effective prevention strategies for amputations should include the screening and the identification of population at risk of ulceration.


Distribution of faecal indicator bacteria in tropical waters of Peninsular Malaysia and their decay rates in tropical seawater.
We investigated the appropriateness of faecal indicator bacteria in tropical waters. We compared total coliform (undetectable to 7.2 × 105 cfu 100 mL-1), faecal coliform (undetectable to 6.1 × 105 cfu 100 mL-1) and enterococci (undetectable to 3.1 × 104 cfu 100 mL-1) distribution in Peninsular Malaysia. Faecal indicator bacteria was highest in freshwater, and lowest in seawater (q > 4.18, p < 0.01). We also measured the decay rates of Escherichia coli and Enterococcus faecium in microcosms. In seawater, average decay rate for E. coli was 0.084 ± 0.029 h-1, and higher than E. faecium (0.048 ± 0.024 h-1) (t = 2.527, p < 0.05). Grazing accounted for 54 % of both E. coli and E. faecium decay. E. coli decayed in the <0.02 μm seawater fraction (0.023 ± 0.012 h-1) but E. faecium sometimes grew. Seawater warming further uncoupled the response from both E. coli and E. faecium as E. faecium grew and E. coli decayed with warming. Our results suggested that the prevalence of faecal indicator bacteria in tropical waters was not due to faecal pollution alone, and this will have serious implications towards the use of these faecal indicator bacteria.


Machine learning algorithms identify hypokalaemia risk in people with hypertension in the United States National Health and Nutrition Examination Survey 1999-2018.
Hypokalaemia is a side-effect of diuretics. We aimed to use machine learning to identify features predicting hypokalaemia risk in hypertensive patients. Participants with hypertension in the United States National Health and Nutrition Examination Survey 1999-2018 were included for analysis. To select the most suitable algorithm, we tested and evaluated five machine learning algorithms commonly employed in epidemiological studies: Logistic Regression, k-Nearest Neighbor, Random Forest, Recursive Partitioning and Regression Trees, and eXtreme Gradient Boosting. These algorithms were accessed using a set of 38 screened features. We then selected the key hypokalaemia-associated features in the hypertension group and their cardiovascular diseases (CVD) subgroup using the SHapley Additive exPlanations (SHAP) values. Using SHAP values, the key features and their impact pattern on hypokalaemia risk were determined. A total of 25,326 hypertensive participants were included for analysis, of whom 4,511 had known CVD. The Random Forest algorithm had the highest AUROC (hypertension dataset: 0.73 [95%CI, 0.71-0.76]; CVD subgroup: 0.72 [95%CI, 0.66-0.78]). Moreover, the nomogram based on the top twelve key features screened by random forest retained good performance: age, sex, race, poverty income ratio, body mass index, systolic and diastolic blood pressure, non-potassium-sparing diuretics use and duration, renin-angiotensin blockers use and duration, and CVD history in hypertension dataset; while in CVD subgroup, the additional key features were comorbid diabetes, education level, smoking status, and use of bronchodilators. Our predictive model based on the random forest algorithm performed best among the tested and evaluated five algorithms. Hypokalaemia-associated key features have been identified in hypertensive patients and the subgroup with CVD. These findings from machine learning facilitate the development of artificial intelligence to highlight hypokalaemia risk in hypertension patients.


Unusual in vivo rearrangements of the Y-chromosome in two males.
In the present paper two male patients with dic Y-chromosomes are reported with special attention to the identical and peculiar Y-chromosome rearrangements. Different cell types with variable morphology of the rearranged Y-chromosomes were found in both patients.


A species difference between Rana and Xenopus in the occurrence of intertectal neuronal plasticity.
In anuran amphibians, a system of neuronal connections links the two optic tecta and is involved in projections of the binocular visual field to the optic tecta. Electrophysiological studies have shown that in the frog, Xenopus laevis, the pattern of connections may be modified by procedures such as larval rotation of one eye. This modification appears to be effected by visual experience. Workers in other laboratories, however, found no evidence of such a modification in the related frog Rana pipiens. This difference in results may have been due to different rearing conditions and different recording techniques or may reflect a true species difference, in this respect, between Rana and Xenopus. In the present experiments, an attempt was made to distinguish between these possibilities by performing eye rotations in Rana and Xenopus, rearing them as identically as possible and recording from them under identical conditions. It was found that while Xenopus displayed the modification of intertectal connections, Rana did not. It is concluded that the different responses of the intertectal systems to larval eye rotation in Xenopus and Rana reflect a species difference.


Relative versus absolute modulation of growth in the fusionless treatment of experimental scoliosis.
Absolute and relative growth modulation of apical spinal segments were measured during creation and correction of an experimental scoliosis in a goat model. To differentiate relative and absolute changes in growth on the concavity and convexity of an experimental scoliosis treated with anterior vertebral stapling. The creation and correction of vertebral wedge deformities have been previously described in a rat tail model using external fixation as well as in a goat model using anterior vertebral body stapling. Progressive, structural, scoliotic curves convex to the right in the thoracic spine were created in 14 Spanish Cross-X female goats using a posterior asymmetric tether. After 7-13 weeks, all tethers were removed, and goats were randomized into stapled (n = 8) and untreated (n = 6) groups. Stapled goats underwent anterior vertebral stapling with 4 shape memory alloy staples (Medtronic Sofamor Danek, Memphis, TN) along the convexity of the maximal curvature. All goats were observed for an additional 7-13 weeks. There were 12 additional goats matched for age, sex, and weight used as growth controls throughout the study. Serial radiographs were used to document progression or correction of the maximal scoliotic deformity, and changes in relative and absolute growth at the apical spinal segment T9-10 (2 adjacent vertebrae and the intervening disc). All tethered goats had progressive, structural, scoliotic curves of significant magnitude during the tethering period (average 61.4 degrees, range 49 degrees to 73 degrees) (P = 0.001). There was 1 goat from each group eliminated from the study because its apical spinal segment did not match the T9-10 level used to establish normal growth in controls. During the treatment period, stapled goats had a correction of -6.9 degrees (P = 0.03), whereas untreated goats had little change (-1.4 degrees). Apical spinal segment wedging progressed in all tethered goats, from 11.1 degrees to 22.4 degrees, during the tethering period (P = 0.001). During the treatment period, wedging corrected -2.2 degrees (range 22.5 degrees to 20.3 degrees) in the stapled goats but progressed +3.5 degrees (range 22.3 degrees to 25.8 degrees) in the untreated goats (P < 0.05). Apical spinal segment growth in all tethered goats was decreased on the concavity by 78% and increased on the convexity by 33% when compared to growth controls (P < 0.001). During the treatment period, growth on the concavity of the apical spinal segment of the stapled goats was decreased by 10% but increased in the untreated goats by 37% when compared to growth controls. On the convexity, apical spinal segment growth at T9-10 was decreased in the stapled goats by 18% and increased in the untreated goats by 29% when compared to growth controls (P < 0.04). Data in this study show the ability to modulate relative and absolute growth, according to the Hueter-Volkmann law, at the apical spinal segment of a progressive experimental scoliosis. However, anterior vertebral stapling, although able to control progressive wedging and scoliosis at the apical spinal segment, was not able to reverse fully the Hueter-Volkmann effect.


Electrochemical disinfection of bacteria-laden water using antimony-doped tin-tungsten-oxide electrodes.
Electrochemical disinfection has been shown to be an efficient method with a shortrequired contact time for treatment of drinking water supplies, industrial raw water supplies, liquid foodstuffs, and wastewater effluents. In the present work, the electrochemical disinfection of saline water contaminated with bacteria was investigated in chloride-containing solutions using Sb-doped Sn80%-W20%-oxide anodes. The influence of current density, bacterial load, initial chloride concentration, solution pH, and the type of bacteria (E. coli D21, E. coli O157:H7, and E. faecalis) on disinfection efficacy was systematically examined. The impact of natural organic matter and a radical scavenger on the disinfection process was also examined. The electrochemical system was highly effective in bacterial inactivation for a 0.1 M NaCl solution contaminated with ∼107 CFU/mL bacteria by applying a current density ≥1 mA/cm2 through the cell.100% inactivation of E. coli D21 was achieved with a contact time of less than 60 s and power consumption of 48 Wh/m3, by applying a current density of 6 mA/cm2 in a 0.1 M NaCl solution contaminated with ∼107 CFU/mL. Reactive chlorine species as well as reactive oxygen species (e.g. hydroxyl radicals) generated in situ during the electrochemical process were determined to be responsible for inactivation of bacteria.


Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.
Description of the condition Malaria, an infectious disease transmitted by the bite of female mosquitoes from several Anopheles species, occurs in 87 countries with ongoing transmission (WHO 2020). The World Health Organization (WHO) estimated that, in 2019, approximately 229 million cases of malaria occurred worldwide, with 94% occurring in the WHO's African region (WHO 2020). Of these malaria cases, an estimated 409,000 deaths occurred globally, with 67% occurring in children under five years of age (WHO 2020). Malaria also negatively impacts the health of women during pregnancy, childbirth, and the postnatal period (WHO 2020). Sulfadoxine/pyrimethamine (SP), an antifolate antimalarial, has been widely used across sub-Saharan Africa as the first-line treatment for uncomplicated malaria since it was first introduced in Malawi in 1993 (Filler 2006). Due to increasing resistance to SP, in 2000 the WHO recommended that one of several artemisinin-based combination therapies (ACTs) be used instead of SP for the treatment of uncomplicated malaria caused by Plasmodium falciparum (Global Partnership to Roll Back Malaria 2001). However, despite these recommendations, SP continues to be advised for intermittent preventive treatment in pregnancy (IPTp) and intermittent preventive treatment in infants (IPTi), whether the person has malaria or not (WHO 2013). Description of the intervention Folate (vitamin B9) includes both naturally occurring folates and folic acid, the fully oxidized monoglutamic form of the vitamin, used in dietary supplements and fortified food. Folate deficiency (e.g. red blood cell (RBC) folate concentrations of less than 305 nanomoles per litre (nmol/L); serum or plasma concentrations of less than 7 nmol/L) is common in many parts of the world and often presents as megaloblastic anaemia, resulting from inadequate intake, increased requirements, reduced absorption, or abnormal metabolism of folate (Bailey 2015; WHO 2015a). Pregnant women have greater folate requirements; inadequate folate intake (evidenced by RBC folate concentrations of less than 400 nanograms per millilitre (ng/mL), or 906 nmol/L) prior to and during the first month of pregnancy increases the risk of neural tube defects, preterm delivery, low birthweight, and fetal growth restriction (Bourassa 2019). The WHO recommends that all women who are trying to conceive consume 400 micrograms (µg) of folic acid daily from the time they begin trying to conceive through to 12 weeks of gestation (WHO 2017). In 2015, the WHO added the dosage of 0.4 mg of folic acid to the essential drug list (WHO 2015c). Alongside daily oral iron (30 mg to 60 mg elemental iron), folic acid supplementation is recommended for pregnant women to prevent neural tube defects, maternal anaemia, puerperal sepsis, low birthweight, and preterm birth in settings where anaemia in pregnant women is a severe public health problem (i.e. where at least 40% of pregnant women have a blood haemoglobin (Hb) concentration of less than 110 g/L). How the intervention might work Potential interactions between folate status and malaria infection The malaria parasite requires folate for survival and growth; this has led to the hypothesis that folate status may influence malaria risk and severity. In rhesus monkeys, folate deficiency has been found to be protective against Plasmodium cynomolgi malaria infection, compared to folate-replete animals (Metz 2007). Alternatively, malaria may induce or exacerbate folate deficiency due to increased folate utilization from haemolysis and fever. Further, folate status measured via RBC folate is not an appropriate biomarker of folate status in malaria-infected individuals since RBC folate values in these individuals are indicative of both the person's stores and the parasite's folate synthesis. A study in Nigeria found that children with malaria infection had significantly higher RBC folate concentrations compared to children without malaria infection, but plasma folate levels were similar (Bradley-Moore 1985). Why it is important to do this review The malaria parasite needs folate for survival and growth in humans. For individuals, adequate folate levels are critical for health and well-being, and for the prevention of anaemia and neural tube defects. Many countries rely on folic acid supplementation to ensure adequate folate status in at-risk populations. Different formulations for folic acid supplements are available in many international settings, with dosages ranging from 400 µg to 5 mg. Evaluating folic acid dosage levels used in supplementation efforts may increase public health understanding of its potential impacts on malaria risk and severity and on treatment failures. Examining folic acid interactions with antifolate antimalarial medications and with malaria disease progression may help countries in malaria-endemic areas determine what are the most appropriate lower dose folic acid formulations for at-risk populations. The WHO has highlighted the limited evidence available and has indicated the need for further research on biomarkers of folate status, particularly interactions between RBC folate concentrations and tuberculosis, human immunodeficiency virus (HIV), and antifolate antimalarial drugs (WHO 2015b). An earlier Cochrane Review assessed the effects and safety of iron supplementation, with or without folic acid, in children living in hyperendemic or holoendemic malaria areas; it demonstrated that iron supplementation did not increase the risk of malaria, as indicated by fever and the presence of parasites in the blood (Neuberger 2016). Further, this review stated that folic acid may interfere with the efficacy of SP; however, the efficacy and safety of folic acid supplementation on these outcomes has not been established. This review will provide evidence on the effectiveness of daily folic acid supplementation in healthy and malaria-infected individuals living in malaria-endemic areas. Additionally, it will contribute to achieving both the WHO Global Technical Strategy for Malaria 2016-2030 (WHO 2015d), and United Nations Sustainable Development Goal 3 (to ensure healthy lives and to promote well-being for all of all ages) (United Nations 2021), and evaluating whether the potential effects of folic acid supplementation, at different doses (e.g. 0.4 mg, 1 mg, 5 mg daily), interferes with the effect of drugs used for prevention or treatment of malaria. To examine the effects of folic acid supplementation, at various doses, on malaria susceptibility (risk of infection) and severity among people living in areas with various degrees of malaria endemicity. We will examine the interaction between folic acid supplements and antifolate antimalarial drugs. Specifically, we will aim to answer the following. Among uninfected people living in malaria endemic areas, who are taking or not taking antifolate antimalarials for malaria prophylaxis, does taking a folic acid-containing supplement increase susceptibility to or severity of malaria infection? Among people with malaria infection who are being treated with antifolate antimalarials, does folic acid supplementation increase the risk of treatment failure? Criteria for considering studies for this review Types of studies Inclusion criteria Randomized controlled trials (RCTs) Quasi-RCTs with randomization at the individual or cluster level conducted in malaria-endemic areas (areas with ongoing, local malaria transmission, including areas approaching elimination, as listed in the World Malaria Report 2020) (WHO 2020) Exclusion criteria Ecological studies Observational studies In vivo/in vitro studies Economic studies Systematic literature reviews and meta-analyses (relevant systematic literature reviews and meta-analyses will be excluded but flagged for grey literature screening) Types of participants Inclusion criteria Individuals of any age or gender, living in a malaria endemic area, who are taking antifolate antimalarial medications (including but not limited to sulfadoxine/pyrimethamine (SP), pyrimethamine-dapsone, pyrimethamine, chloroquine and proguanil, cotrimoxazole) for the prevention or treatment of malaria (studies will be included if more than 70% of the participants live in malaria-endemic regions) Studies assessing participants with or without anaemia and with or without malaria parasitaemia at baseline will be included Exclusion criteria Individuals not taking antifolate antimalarial medications for prevention or treatment of malaria Individuals living in non-malaria endemic areas Types of interventions Inclusion criteria Folic acid supplementation Form: in tablet, capsule, dispersible tablet at any dose, during administration, or periodically Timing: during, before, or after (within a period of four to six weeks) administration of antifolate antimalarials Iron-folic acid supplementation Folic acid supplementation in combination with co-interventions that are identical between the intervention and control groups. Co-interventions include: anthelminthic treatment; multivitamin or multiple micronutrient supplementation; 5-methyltetrahydrofolate supplementation. Exclusion criteria Folate through folate-fortified water Folic acid administered through large-scale fortification of rice, wheat, or maize Comparators Placebo No treatment No folic acid/different doses of folic acid Iron Types of outcome measures Primary outcomes Uncomplicated malaria (defined as a history of fever with parasitological confirmation; acceptable parasitological confirmation will include rapid diagnostic tests (RDTs), malaria smears, or nucleic acid detection (i.e. polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), etc.)) (WHO 2010). This outcome is relevant for patients without malaria, given antifolate antimalarials for malaria prophylaxis. Severe malaria (defined as any case with cerebral malaria or acute P. falciparum malaria, with signs of severity or evidence of vital organ dysfunction, or both) (WHO 2010). This outcome is relevant for patients without malaria, given antifolate antimalarials for malaria prophylaxis. Parasite clearance (any Plasmodium species), defined as the time it takes for a patient who tests positive at enrolment and is treated to become smear-negative or PCR negative. This outcome is relevant for patients with malaria, treated with antifolate antimalarials. Treatment failure (defined as the inability to clear malaria parasitaemia or prevent recrudescence after administration of antimalarial medicine, regardless of whether clinical symptoms are resolved) (WHO 2019). This outcome is relevant for patients with malaria, treated with antifolate antimalarials. Secondary outcomes Duration of parasitaemia Parasite density Haemoglobin (Hb) concentrations (g/L) Anaemia: severe anaemia (defined as Hb less than 70 g/L in pregnant women and children aged six to 59 months; and Hb less than 80 g/L in other populations); moderate anaemia (defined as Hb less than 100 g/L in pregnant women and children aged six to 59 months; and less than 110 g/L in others) Death from any cause Among pregnant women: stillbirth (at less than 28 weeks gestation); low birthweight (less than 2500 g); active placental malaria (defined as Plasmodium detected in placental blood by smear or PCR, or by Plasmodium detected on impression smear or placental histology). Search methods for identification of studies A search will be conducted to identify completed and ongoing studies, without date or language restrictions. Electronic searches A search strategy will be designed to include the appropriate subject headings and text word terms related to each intervention of interest and study design of interest (see Appendix 1). Searches will be broken down by these two criteria (intervention of interest and study design of interest) to allow for ease of prioritization, if necessary. The study design filters recommended by the Scottish Intercollegiate Guidelines Network (SIGN), and those designed by Cochrane for identifying clinical trials for MEDLINE and Embase, will be used (SIGN 2020). There will be no date or language restrictions. Non-English articles identified for inclusion will be translated into English. If translations are not possible, advice will be requested from the Cochrane Infectious Diseases Group and the record will be stored in the "Awaiting assessment" section of the review until a translation is available. The following electronic databases will be searched for primary studies. Cochrane Central Register of Controlled Trials. Cumulative Index to Nursing and Allied Health Literature (CINAHL). Embase. MEDLINE. Scopus. Web of Science (both the Social Science Citation Index and the Science Citation Index). We will conduct manual searches of ClinicalTrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the United Nations Children's Fund (UNICEF) Evaluation and Research Database (ERD), in order to identify relevant ongoing or planned trials, abstracts, and full-text reports of evaluations, studies, and surveys related to programmes on folic acid supplementation in malaria-endemic areas. Additionally, manual searches of grey literature to identify RCTs that have not yet been published but are potentially eligible for inclusion will be conducted in the following sources. Global Index Medicus (GIM). African Index Medicus (AIM). Index Medicus for the Eastern Mediterranean Region (IMEMR). Latin American & Caribbean Health Sciences Literature (LILACS). Pan American Health Organization (PAHO). Western Pacific Region Index Medicus (WPRO). Index Medicus for the South-East Asian Region (IMSEAR). The Spanish Bibliographic Index in Health Sciences (IBECS) (ibecs.isciii.es/). Indian Journal of Medical Research (IJMR) (journals.lww.com/ijmr/pages/default.aspx). Native Health Database (nativehealthdatabase.net/). Scielo (www.scielo.br/). Searching other resources Handsearches of the five journals with the highest number of included studies in the last 12 months will be conducted to capture any relevant articles that may not have been indexed in the databases at the time of the search. We will contact the authors of included studies and will check reference lists of included papers for the identification of additional records. For assistance in identifying ongoing or unpublished studies, we will contact the Division of Nutrition, Physical Activity, and Obesity (DNPAO) and the Division of Parasitic Diseases and Malaria (DPDM) of the CDC, the United Nations World Food Programme (WFP), Nutrition International (NI), Global Alliance for Improved Nutrition (GAIN), and Hellen Keller International (HKI). Data collection and analysis Selection of studies Two review authors will independently screen the titles and abstracts of articles retrieved by each search to assess eligibility, as determined by the inclusion and exclusion criteria. Studies deemed eligible for inclusion by both review authors in the abstract screening phase will advance to the full-text screening phase, and full-text copies of all eligible papers will be retrieved. If full articles cannot be obtained, we will attempt to contact the authors to obtain further details of the studies. If such information is not obtained, we will classify the study as "awaiting assessment" until further information is published or made available to us. The same two review authors will independently assess the eligibility of full-text articles for inclusion in the systematic review. If any discrepancies occur between the studies selected by the two review authors, a third review author will provide arbitration. Each trial will be scrutinized to identify multiple publications from the same data set, and the justification for excluded trials will be documented. A PRISMA flow diagram of the study selection process will be presented to provide information on the number of records identified in the literature searches, the number of studies included and excluded, and the reasons for exclusion (Moher 2009). The list of excluded studies, along with their reasons for exclusion at the full-text screening phase, will also be created. Data extraction and management Two review authors will independently extract data for the final list of included studies using a standardized data specification form. Discrepancies observed between the data extracted by the two authors will be resolved by involving a third review author and reaching a consensus. Information will be extracted on study design components, baseline participant characteristics, intervention characteristics, and outcomes. For individually randomized trials, we will record the number of participants experiencing the event and the number analyzed in each treatment group or the effect estimate reported (e.g. risk ratio (RR)) for dichotomous outcome measures. For count data, we will record the number of events and the number of person-months of follow-up in each group. If the number of person-months is not reported, the product of the duration of follow-up and the number of children evaluated will be used to estimate this figure. We will calculate the rate ratio and standard error (SE) for each study. Zero events will be replaced by 0.5. We will extract both adjusted and unadjusted covariate incidence rate ratios if they are reported in the original studies. For continuous data, we will extract means (arithmetic or geometric) and a measure of variance (standard deviation (SD), SE, or confidence interval (CI)), percentage or mean change from baseline, and the numbers analyzed in each group. SDs will be computed from SEs or 95% CIs, assuming a normal distribution of the values. Haemoglobin values in g/dL will be calculated by multiplying haematocrit or packed cell volume values by 0.34, and studies reporting haemoglobin values in g/dL will be converted to g/L. In cluster-randomized trials, we will record the unit of randomization (e.g. household, compound, sector, or village), the number of clusters in the trial, and the average cluster size. The statistical methods used to analyze the trials will be documented, along with details describing whether these methods adjusted for clustering or other covariates. We plan to extract estimates of the intra-cluster correlation coefficient (ICC) for each outcome. Where results are adjusted for clustering, we will extract the treatment effect estimate and the SD or CI. If the results are not adjusted for clustering, we will extract the data reported. Assessment of risk of bias in included studies Two review authors (KSC, LFY) will independently assess the risk of bias for each included trial using the Cochrane 'Risk of bias 2' tool (RoB 2) for randomized studies (Sterne 2019). Judgements about the risk of bias of included studies will be made according to the recommendations outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021). Disagreements will be resolved by discussion, or by involving a third review author. The interest of our review will be to assess the effect of assignment to the interventions at baseline. We will evaluate each primary outcome using the RoB2 tool. The five domains of the Cochrane RoB2 tool include the following. Bias arising from the randomization process. Bias due to deviations from intended interventions. Bias due to missing outcome data. Bias in measurement of the outcome. Bias in selection of the reported result. Each domain of the RoB2 tool comprises the following. A series of 'signalling' questions. A judgement about the risk of bias for the domain, facilitated by an algorithm that maps responses to the signalling questions to a proposed judgement. Free-text boxes to justify responses to the signalling questions and 'Risk of bias' judgements. An option to predict (and explain) the likely direction of bias. Responses to signalling questions elicit information relevant to an assessment of the risk of bias. These response options are as follows. Yes (may indicate either low or high risk of bias, depending on the most natural way to ask the question). Probably yes. Probably no. No. No information (may indicate no evidence of that problem or an absence of information leading to concerns about there being a problem). Based on the answer to the signalling question, a 'Risk of bias' judgement is assigned to each domain. These judgements include one of the following. High risk of bias Low risk of bias Some concerns To generate the risk of bias judgement for each domain in the randomized studies, we will use the Excel template, available at www.riskofbias.info/welcome/rob-2-0-tool/current-version-of-rob-2. This file will be stored on a scientific data website, available to readers. Risk of bias in cluster randomized controlled trials For the cluster randomized trials, we will be using the RoB2 tool to analyze the five standard domains listed above along with Domain 1b (bias arising from the timing of identification or recruitment of participants) and its related signalling questions. To generate the risk of bias judgement for each domain in the cluster RCTs, we will use the Excel template available at https://sites.google.com/site/riskofbiastool/welcome/rob-2-0-tool/rob-2-for-cluster-randomized-trials. This file will be stored on a scientific data website, available to readers. Risk of bias in cross-over randomized controlled trials For cross-over randomized trials, we will be using the RoB2 tool to analyze the five standard domains listed above along with Domain 2 (bias due to deviations from intended interventions), and Domain 3 (bias due to missing outcome data), and their respective signalling questions. To generate the risk of bias judgement for each domain in the cross-over RCTs, we will use the Excel template, available at https://sites.google.com/site/riskofbiastool/welcome/rob-2-0-tool/rob-2-for-crossover-trials, for each risk of bias judgement of cross-over randomized studies. This file will be stored on a scientific data website, available to readers. Overall risk of bias The overall 'Risk of bias' judgement for each specific trial being assessed will be based on each domain-level judgement. The overall judgements include the following. Low risk of bias (the trial is judged to be at low risk of bias for all domains). Some concerns (the trial is judged to raise some concerns in at least one domain but is not judged to be at high risk of bias for any domain). High risk of bias (the trial is judged to be at high risk of bias in at least one domain, or is judged to have some concerns for multiple domains in a way that substantially lowers confidence in the result). The 'risk of bias' assessments will inform our GRADE evaluations of the certainty of evidence for our primary outcomes presented in the 'Summary of findings' tables and will also be used to inform the sensitivity analyses; (see Sensitivity analysis). If there is insufficient information in study reports to enable an assessment of the risk of bias, studies will be classified as "awaiting assessment" until further information is published or made available to us. Measures of treatment effect Dichotomous data For dichotomous data, we will present proportions and, for two-group comparisons, results as average RR or odds ratio (OR) with 95% CIs. Ordered categorical data Continuous data We will report results for continuous outcomes as the mean difference (MD) with 95% CIs, if outcomes are measured in the same way between trials. Where some studies have reported endpoint data and others have reported change-from-baseline data (with errors), we will combine these in the meta-analysis, if the outcomes were reported using the same scale. We will use the standardized mean difference (SMD), with 95% CIs, to combine trials that measured the same outcome but used different methods. If we do not find three or more studies for a pooled analysis, we will summarize the results in a narrative form. Unit of analysis issues Cluster-randomized trials We plan to combine results from both cluster-randomized and individually randomized studies, providing there is little heterogeneity between the studies. If the authors of cluster-randomized trials conducted their analyses at a different level from that of allocation, and they have not appropriately accounted for the cluster design in their analyses, we will calculate the trials' effective sample sizes to account for the effect of clustering in data. When one or more cluster-RCT reports RRs adjusted for clustering, we will compute cluster-adjusted SEs for the other trials. When none of the cluster-RCTs provide cluster-adjusted RRs, we will adjust the sample size for clustering. We will divide, by the estimated design effects (DE), the number of events and number evaluated for dichotomous outcomes and the number evaluated for continuous outcomes, where DE = 1 + ((average cluster size 1) * ICC). The derivation of the estimated ICCs and DEs will be reported. We will utilize the intra-cluster correlation coefficient (ICC), derived from the trial (if available), or from another source (e.g., using the ICCs derived from other, similar trials) and then calculate the design effect with the formula provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021). If this approach is used, we will report it and undertake sensitivity analysis to investigate the effect of variations in ICC. Studies with more than two treatment groups If we identify studies with more than two intervention groups (multi-arm studies), where possible we will combine groups to create a single pair-wise comparison or use the methods set out in the Cochrane Handbook to avoid double counting study participants (Higgins 2021). For the subgroup analyses, when the control group was shared by two or more study arms, we will divide the control group (events and total population) over the number of relevant subgroups to avoid double counting the participants. Trials with several study arms can be included more than once for different comparisons. Cross-over trials From cross-over trials, we will consider the first period of measurement only and will analyze the results together with parallel-group studies. Multiple outcome events In several outcomes, a participant might experience more than one outcome event during the trial period. For all outcomes, we will extract the number of participants with at least one event. Dealing with missing data We will contact the trial authors if the available data are unclear, missing, or reported in a format that is different from the format needed. We aim to perform a 'per protocol' or 'as observed' analysis; otherwise, we will perform a complete case analysis. This means that for treatment failure, we will base the analyses on the participants who received treatment and the number of participants for which there was an inability to clear malarial parasitaemia or prevent recrudescence after administration of an antimalarial medicine reported in the studies. Assessment of heterogeneity Heterogeneity in the results of the trials will be assessed by visually examining the forest plot to detect non-overlapping CIs, using the Chi2 test of heterogeneity (where a P value of less than 0.1 indicates statistical significance) and the I2 statistic of inconsistency (with a value of greater than 50% denoting moderate levels of heterogeneity). When statistical heterogeneity is present, we will investigate the reasons for it, using subgroup analysis. Assessment of reporting biases We will construct a funnel plot to assess the effect of small studies for the main outcome (when including more than 10 trials). Data synthesis The primary analysis will include all eligible studies that provide data regardless of the overall risk of bias as assessed by the RoB2 tool. Analyses will be conducted using Review Manager 5.4 (Review Manager 2020). Cluster-RCTs will be included in the main analysis after adjustment for clustering (see the previous section on cluster-RCTs). The meta-analysis will be performed using the Mantel-Haenszel random-effects model or the generic inverse variance method (when adjustment for clustering is performed by adjusting SEs), as appropriate. Subgroup analysis and investigation of heterogeneity The overall risk of bias will not be used as the basis in conducting our subgroup analyses. However, where data are available, we plan to conduct the following subgroup analyses, independent of heterogeneity. Dose of folic acid supplementation: higher doses (4 mg or more, daily) versus lower doses (less than 4 mg, daily). Moderate-severe anaemia at baseline (mean haemoglobin of participants in a trial at baseline below 100 g/L for pregnant women and children aged six to 59 months, and below 110 g/L for other populations) versus normal at baseline (mean haemoglobin above 100 g/L for pregnant women and children aged six to 59 months, and above 110 g/L for other populations). Antimalarial drug resistance to parasite: known resistance versus no resistance versus unknown/mixed/unreported parasite resistance. Folate status at baseline: Deficient (e.g. RBC folate concentration of less than 305 nmol/L, or serum folate concentration of less than 7nmol/L) and Insufficient (e.g. RBC folate concentration from 305 to less than 906 nmol/L, or serum folate concentration from 7 to less than 25 nmol/L) versus Sufficient (e.g. RBC folate concentration above 906 nmol/L, or serum folate concentration above 25 nmol/L). Presence of anaemia at baseline: yes versus no. Mandatory fortification status: yes, versus no (voluntary or none). We will only use the primary outcomes in any subgroup analyses, and we will limit subgroup analyses to those outcomes for which three or more trials contributed data. Comparisons between subgroups will be performed using Review Manager 5.4 (Review Manager 2020). Sensitivity analysis We will perform a sensitivity analysis, using the risk of bias as a variable to explore the robustness of the findings in our primary outcomes. We will verify the behaviour of our estimators by adding and removing studies with a high risk of bias overall from the analysis. That is, studies with a low risk of bias versus studies with a high risk of bias. Summary of findings and assessment of the certainty of the evidence For the assessment across studies, we will use the GRADE approach, as outlined in (Schünemann 2021). We will use the five GRADE considerations (study limitations based on RoB2 judgements, consistency of effect, imprecision, indirectness, and publication bias) to assess the certainty of the body of evidence as it relates to the studies which contribute data to the meta-analyses for the primary outcomes. The GRADEpro Guideline Development Tool (GRADEpro) will be used to import data from Review Manager 5.4 (Review Manager 2020) to create 'Summary of Findings' tables. The primary outcomes for the main comparison will be listed with estimates of relative effects, along with the number of participants and studies contributing data for those outcomes. These tables will provide outcome-specific information concerning the overall certainty of evidence from studies included in the comparison, the magnitude of the effect of the interventions examined, and the sum of available data on the outcomes we considered. We will include only primary outcomes in the summary of findings tables. For each individual outcome, two review authors (KSC, LFY) will independently assess the certainty of the evidence using the GRADE approach (Balshem 2011). For assessments of the overall certainty of evidence for each outcome that includes pooled data from included trials, we will downgrade the evidence from 'high certainty' by one level for serious (or by two for very serious) study limitations (risk of bias, indirectness of evidence, serious inconsistency, imprecision of effect estimates, or potential publication bias).


Simple and rapid colorimetric detection of cofactors of aptazymes using noncrosslinking gold nanoparticle aggregation.
We developed a method for simply and rapidly detecting cofactors of aptazymes with high sensitivity using unique noncrosslinking gold nanoparticle aggregation. Applying this method to a theophylline-dependent aptazyme, 100 microM, 10 microM, and 1 microM theophylline were detected easily by the naked eye within 10 min, 20 min, and 65 min, respectively. This method is also applicable to other cleavase-aptazymes without altering the probe-DNA sequence on the gold nanoparticle.


A Propensity Score Matching Analysis of the Effects of Special Education Services.
We sought to quantify the effectiveness of special education services as naturally delivered in U.S. schools. Specifically, we examined whether children receiving special education services displayed (a) greater reading or mathematics skills, (b) more frequent learning-related behaviors, or (c) less frequent externalizing or internalizing problem behaviors than closely matched peers not receiving such services. To do so, we used propensity score matching techniques to analyze data from the Early Childhood Longitudinal-Study Kindergarten Cohort, 1998-1999, a large scale, nationally representative sample of U.S. schoolchildren. Collectively, results indicate that receipt of special education services has either a negative or statistically non-significant impact on children's learning or behavior. However, special education services do yield a small, positive effect on children's learning-related behaviors.


New vertebral osteoporotic compression fractures after percutaneous vertebroplasty: retrospective analysis of risk factors.
To investigate risk factors for new vertebral compression fractures (VCFs) after vertebroplasty. The authors analyzed the occurrence of new VCFs in 70 patients who had previously undergone vertebroplasty for the treatment of one VCF. The following covariates were analyzed: age, sex, body weight, height, body mass index (BMI), treated vertebral level, relative distance between treated vertebrae and new VCFs, pre-existing untreated VCFs, gas-containing vertebrae before treatment, and surgical approach. Surgical variables, including cement leakage into the disk, anterior vertebral height restoration, and kyphosis correction of treated vertebrae were also analyzed. A Cox proportional hazards regression analysis was used to determine the relative risk of new adjacent VCFs. The Kaplan-Meier method was used to calculate mean fracture-free rate over time. Seventy patients were reviewed, with a mean follow-up of 20.0 months +/- 10.2 (range, 6-48 months). We identified 22 new fractures in 19 of the 70 patients (27%), with 16 adjacent and six nonadjacent VCFs. The mean time to new fracture was 10.6 months +/- 9.5, and there was no significant difference in time to adjacent or nonadjacent VCF. Increased risk of VCF was associated with proximity to the treated vertebra, greater kyphosis correction, and low patient BMI. The 1-year fracture-free rate was 79.5%. New VCFs are common in patients with a low BMI, which suggests osteoporosis as a mechanism of fracture.


A Comparative Study of Various Office Procedures for the Management of Small to Medium Size Tympanic Membrane Perforations.
A hospital based prospective study to compare and evaluate the efficacy and convenience of various office procedures like chemical cauterization, fat plug myringoplasty and butterfly cartilage tympanoplasty. This interventional, prospective, longitudinal study carried out on 300 patients in the ENT department of a tertiary care medical college hospital in central India between January 2009 and January 2015. The success rate was found to be 94.54, 91.12 and 97% in chemical cauterization, fat plug and butterfly cartilage tympanoplasty respectively (p value 0.246). In all the groups there were significant improvement in terms of hearing in decibels and AB gap postoperatively. No statistically significant association was found in between the failure rates in all the groups. From this study we conclude that all the procedures were simple, rapid, reliable, cost effective, takes less time and minimum hospital stay (day care) than conventional tympanoplasty. We strongly recommend these procedures in place of tympanoplasty in small to medium size central tympanic membrane perforations according to condition and convenience of the patients.


Assessment of left ventricular enlargement from planar thallium-201 images.
Although a subjective assessment of left ventricular (LV) size can be made from planar thallium images, the validity of this practice had not been critically assessed. The objective of this study was to determine the accuracy of planar thallium imaging in the assessment of LV size by using two-dimensional guided M-mode echocardiographic measurements as the standard. Consecutive patients (n = 100) who had clinically indicated stress thallium and echocardiography done within a time interval of 1 month were selected. LV size was classified as dilated or normal on immediate and 4-hour-delayed thallium scans by the consensus of two blinded observers. When present, perfusion defects were noted. LV end-diastolic internal diameter (LVIDd) was measured on M-mode images. The mean LVIDd was 5.7 cm in patients with dilated LVs compared with 5.0 cm in those with normal LVs (p < 0.01). By using an LVIDd of 5.6 cm as the upper limit of normal, the sensitivity and specificity of planar thallium imaging for detection of left ventricle enlargement were 87% and 86%, respectively. Corresponding positive and negative predictive accuracies in this population were 65% and 96%, respectively. There was a higher incidence of fixed defects in group 1 (p < 0.01). We conclude that LV enlargement can be easily and reliably determined from routine planar thallium images.


Comparative Sacral Morphology in Spondylolisthesis Patients.
Retrospective comparative case series. Evaluation of sacral morphology in spondylolisthesis patients compared with asymptomatic controls. Patients with spondylolisthesis are known to differ from asymptomatic controls in sagittal plane anatomy, but few studies examine the coronal and axial plane differences in these cohorts. This is a retrospective evaluation of magnetic resonance imaging of the lumbosacral spine in 29 spondylolisthesis patients and an asymptomatic cohort (n = 154). Measurements of the linear distance and angular position of L5 and sacrum were performed in the sagittal, coronal, and axial planes. Receiver operating characteristic (ROC) curve analysis quantified these associations. High- and low-grade spondylolisthesis patients were compared with two-sample t-tests. All p-values are two-sided and considered significant when p < .05. Axial measurements showed the distance of the right to left anterior ala and the L5 body width did not differ between the cohorts. Sacroiliac (SI) joint angles in the spondylolisthesis cohort were closer to the true sagittal plane than in the controls 109° versus 121° (p < .001). In the sagittal plane, the linear measurement of the ratio of the midpoint anteroposterior width L5 to the sacral end plate was larger in the high-grade patients than the low-grade patients and controls. In addition, the kyphosis between S1-S2 and S2-S3 was larger in the spondylolisthesis cohort. The SI joints in patients with spondylolisthesis were orientated closer to the sagittal plane than in the controls. An awareness of this positioning may be important in surgical implant insertion as well as rehabilitation of hip extensor weakness. The main anatomical differences found in this study were in the sagittal plane. Sacral end plate abnormalities were well visualized and consistent with radiographic findings in the literature. Level III, diagnostic.


Applying Interactive Mobile health to Asthma Care in Teens (AIM2ACT): Development and design of a randomized controlled trial.
Early adolescents have difficulties performing asthma self-management behaviors, placing them at-risk for poor asthma control and reduced quality of life. This paper describes the development and plans for testing an interactive mobile health (mHealth) tool for early adolescents, ages 12-15years, and their caregivers to help improve asthma management. Applying Interactive Mobile health to Asthma Care in Teens (AIM2ACT) is informed by the Pediatric Self-management model, which posits that helpful caregiver support is facilitated by elucidating disease management behaviors and allocating treatment responsibility in the family system, and subsequently engaging in collaborative caregiver-adolescent asthma management. The AIM2ACT intervention was developed through iterative feedback from an advisory board composed of adolescent-caregiver dyads. A pilot randomized controlled trial of AIM2ACT will be conducted with 50 early adolescents with poorly controlled asthma and a caregiver. Adolescent-caregiver dyads will be randomized to receive the AIM2ACT smartphone application (AIM2ACT app) or a self-guided asthma control condition for a 4-month period. Feasibility and acceptability data will be collected throughout the trial. Efficacy outcomes, including family asthma management, lung function, adolescent asthma control, asthma-related quality of life, and self-efficacy for asthma management, will be collected at baseline, post-treatment, and 4-month follow-up. Results from the current study will inform the utility of mHealth to foster the development of asthma self-management skills among early adolescents.


Devising and validating a pen-side hematological formula for hemoglobin estimation in Cholistani cattle.
The present study has been designed to devise a pen-side hematological formula for estimation of hemoglobin (Hb) from packed cell volume (PCV) in Cholistani breed of cattle being reared under pastoralism in Cholistan desert, Pakistan. It also aims to validate the soundness of rule of calculating Hb concentration as one-third of PCV and vice versa as being used in human medicine. Cholistani cattle (n = 364) were bled for PCV determination (microhematocrit) method and Hb estimation (hematology analyzer) (HbD) as well as through calculation being one-third of PCV (HbC). The independent-sample t-test was implied for deducing difference between HbD and HbC, and between HbD and corrected Hb (CHb) for all study groups. The CHb was deduced through regression prediction equation attained from linear regression model. Scatter-plots were drawn and linear regression was carried out between various studied hematological attributes. Significantly (P ≤ 0.01) positive correlation coefficient was noticed for all study groups being highest for female adult stock (r = 0.893; adjusted R-square = 0.79) between HbD and PCV and between HbD and HbC. The regression equation for overall results attained, i.e., Hb = 0.13 (PCV) + 6.3 was used to deduce CHb. A non-significant (P ≥ 0.05) difference was noticed between HbD and CHb. In conclusion, a convention of human clinical medicine that Hb concentration is third of PCV and vice versa cannot be implied for Cholistani cattle. A different equation, i.e., Hb (g/dL) = 0.13 (PCV) + 6.3 may provide reliable results for Hb estimation from the PCV in cattle.


Needle Arthroscopic Inspection and Treatment of (Osteo)chondral Lesions of the Ankle in Unstable Syndesmotic Injuries Treated With Suture Button Fixation: A Standardized Approach.
Both acute and chronic syndesmotic injuries are associated with (osteo)chondral lesions of the ankle in at least 1 out of 5 patients. Having a common denominator of an acute traumatic injury being external rotation and forced dorsiflexion, the injury of a combined unstable syndesmotic injury and a potentially present concomitant (osteo)chondral lesion to the ankle warrants a thorough diagnostic and interventional approach. Furthermore, early diagnosis may prevent further damage to the joint through lifestyle changes and increase the chances of successful conservative or surgical treatment, potentially reducing the progression toward end-stage osteoarthritis. Consequently, technological advances and financial considerations have led to the development of a minimally invasive needle arthroscopic inspection and treatment of concomitant (osteo)chondral injuries of the ankle in the combined treatment of unstable syndesmotic injuries with suture button fixation. The present Technical Note describes this innovative minimally invasive assessment and concomitant treatment technique.


Responsive and self-healing structural color supramolecular hydrogel patch for diabetic wound treatment.
The treatment of diabetic wounds remains a great challenge for medical community. Here, we present a novel structural color supramolecular hydrogel patch for diabetic wound treatment. This hydrogel patch was created by using N-acryloyl glycinamide (NAGA) and 1-vinyl-1,2,4-triazole (VTZ) mixed supramolecular hydrogel as the inverse opal scaffold, and temperature responsive poly(N-isopropylacrylamide) (PNIPAM) hydrogel loaded with vascular endothelial cell growth factor (VEGF) as a filler. Supramolecular hydrogel renders hydrogel patch with superior mechanical properties, in which NAGA and VTZ also provide self-healing and antibacterial properties, respectively. Besides, as the existence of PNIPAM, the hydrogel patch was endowed with thermal-responsiveness property, which could release actives in response to temperature stimulus. Given these excellent performances, we have demonstrated that the supramolecular hydrogel patch could significantly enhance the wound healing process in diabetes rats by downregulating the expression of inflammatory factors, promoting collagen deposition and angiogenesis. Attractively, due to responsive optical property of inverse opal scaffold, the hydrogel patch could display color-sensing behavior that was suitable for the wound monitoring and management as well as guidance of clinical treatment. These distinctive features indicate that the presented hydrogel patches have huge potential values in biomedical fields.


Cerebral glycogenolysis and glycolysis in malathion-treated hyperglycaemic animals.
Treatment with malathion resulted in an increase in the level of blood glucose and lactate and reduced cerebral glycogen, 2 hr after its administration. The blood pyruvate level was not changed. The activities of glycogenolytic enzymes (glycogen phosphorylase and phosphoglucomutase) were increased significantly in the brain, whereas that of glucose-6-phosphatase remained unchanged. The activity of the glycolytic enzyme-hexokinase was increased significantly in malathion-treated animals, whereas those of the glucose-6-phosphate and lactate dehydrogenases were not significantly changed. The changes in enzyme activities may be a compensatory mechanism to provide energy in the form of glucose to cerebral tissue on account of stimulatory effects in malathion-treated animals.


Dynamic scintigraphy: calculatiion and imaging of regional distribution of quantitative parameters.
The theory and general method of calculation of the parametric (functional) images at dynamic studies is described briefly. This method is illustrated by a general program DYNAM. PARAM. PRESENT. created for Clincom apparatus. Moreover, the selection of parameters and algorithms for calculation, the problems associated with the filtration of data, the correction for dead time and for non-homogeneity are discussed. In addition to the general method, there are presented here the possible ways of application of the simplified methods of construction of the parametric images by means of algebraic operations between images in special cases. Some aspects of that method are completed by examples of practical parametric images of some organs.


From a case-control survey to a diagnostic viral gastroenteritis panel for testing of general practitioners' patients.
To evaluate the pathogenicity of a broad range of 11 possible gastroenteritis viruses, by means of statistical relationships with cases vs. controls, or Ct-values, in order to establish the most appropriate diagnostic panel for our general practitioner (GP) patients in the Netherlands (2010-2012). Archived stool samples from 1340 cases and 1100 controls were retested using internally controlled multiplex real-time PCRs for putative pathogenic gastroenteritis viruses: adenovirus, astrovirus, bocavirus, enterovirus, norovirus GI and GII, human parechovirus, rotavirus, salivirus, sapovirus, and torovirus. The prevalence of any virus in symptomatic cases and asymptomatic controls was 16.6% (223/1340) and 10.2% (112/1100), respectively. Prevalence of astrovirus (adjusted odds ratio (aOR) 10.37; 95% confidence interval (CI) 1.34-80.06) and norovirus GII (aOR 3.10; CI 1.62-5.92) was significantly higher in cases versus controls. Rotavirus was encountered only in cases. We did not find torovirus and there was no statistically significant relationship with cases for salivirus (aOR 1,67; (CI) 0.43-6.54)), adenovirus non-group F (aOR 1.20; CI 0.75-1.91), bocavirus (aOR 0.85; CI 0.05-13.64), enterovirus (aOR 0.83; CI 0.50-1.37), human parechovirus (aOR 1.61; CI 0.54-4.77) and sapovirus (aOR 1.15; CI 0.67-1.98). Though adenovirus group F (aOR 6.37; CI 0.80-50.92) and norovirus GI (aOR 2.22, CI: 0.79-6.23) are known enteropathogenic viruses and were more prevalent in cases than in controls, this did not reach significance in this study. The Ct value did not discriminate between carriage and disease in PCR-positive subjects. In our population, diagnostic gastroenteritis tests should screen for adenovirus group F, astrovirus, noroviruses GI and GII, and rotavirus. Case-control studies as ours are lacking and should also be carried out in populations from other epidemiological backgrounds.


A review of methods for interpretation of glycopeptide tandem mass spectral data.
Despite the publication of several software tools for analysis of glycopeptide tandem mass spectra, there remains a lack of consensus regarding the most effective and appropriate methods. In part, this reflects problems with applying standard methods for proteomics database searching and false discovery rate calculation. While the analysis of small post-translational modifications (PTMs) may be regarded as an extension of proteomics database searching, glycosylation requires specialized approaches. This is because glycans are large and heterogeneous by nature, causing glycopeptides to exist as multiple glycosylated variants. Thus, the mass of the peptide cannot be calculated directly from that of the intact glycopeptide. In addition, the chemical nature of the glycan strongly influences product ion patterns observed for glycopeptides. As a result, glycopeptidomics requires specialized bioinformatics methods. We summarize the recent progress towards a consensus for effective glycopeptide tandem mass spectrometric analysis.


Lymphocytic Choriomeningitis Virus Infections and Seroprevalence, Southern Iraq.
Acute febrile neurological infection cases in southern Iraq (N = 212) were screened for lymphocytic choriomeningitis virus (LCMV). Two LCMV IgM-positive serum samples and 2 cerebrospinal fluid samples with phylogenetically distinct LCMV strains were found. The overall LCMV seroprevalence was 8.8%. LCMV infections are common and associated with acute neurological disease in Iraq.


A classification of retrolental fibroplasia to evaluate vitamin E therapy.
A refined classification of the stages of the retinopathy of prematurity (RLF) based on the experience of over 7500 examinations during the past decade is presented. We have been using the basic elements of this classification since 1972 in order to evaluate the influence of vitamin E on retrolental fibroplasia (RLF). It is our impression that it provides a more accurate clinical method of following the course of the retinopathy and a tool for assessing the factors other than prematurity and hyperoxia that may play a subtle role in the development of RLF.


Perceived Impact of a Land and Property Rights Program on Violence Against Women in Rural Kenya: A Qualitative Investigation.
The current study focuses on a community-led land and property rights program in two rural provinces in western Kenya. The program was designed to respond to women's property rights violations to reduce violence against women and HIV risks at the community level. Through in-depth interviews with 30 women, we examine the perceived impact that this community-level property rights program had on violence against women at the individual and community level. We also examine perceptions as to how reductions in violence were achieved. Finally, we consider how our findings may aid researchers in the design of structural violence-prevention strategies.


Infection prevention and control in patients with cystic fibrosis (CF): Results from a survey in 35 German CF treatment centers.
This survey evaluates whether the Cystic Fibrosis (CF)-specific infection prevention and control (IPC) recommendations released by the Commission for Hospital Hygiene and Infection Prevention (KRINKO) in 2012 have been implemented in specialized German CF facilities. Of 35 participating centers (response rate 32.7%), 37% care for more than 100 patients and 44% treat mainly adults. Clinics for adult CF patients report a shortage of qualified personnel for intensified environmental cleaning. Some hospitals struggle to provide single patient rooms with an adjacent sanitary area to segregate CF patients strictly. Most centers offer at least one decolonization cycle (including systemic and inhalative antibiotics) to patients colonized with MRSA. In CF centers in Germany, the KRINKO IPC recommendations are considered helpful by the attending physicians and thoroughly implemented. There is room for improvement concerning strict segregation of inpatients with CF in single patient rooms, in particular in large CF centers mainly caring for adults.


Altered brain and muscle amino-acid levels due to remote injury during glutamine supplementation.
Glutamine (GLN) has aroused considerable interest among clinicians and nutritionists after studies demonstrated conclusively profound GLN depletion during critical illness. Although the brain plays an important role in GLN metabolism, little is known concerning changes in cerebral handling of GLN following injury. We have evaluated in a rat trauma (bilateral femur fractures) model, the nutritional efficacy of GLN-rich diet and the remote injury-induced changes in amino-acid (AA) contents of brain and muscle tissues. Both control and traumatised rats were starved for 2 days and then pair-fed for 4 days, either a basic liquid diet (BioServ # F1259) or an isonitrogenous test diet which contained the same basic diet from which 10% nitrogen (N) was replaced by GLN-N. Protein efficiency ratio as well as plasma levels of anabolic growth hormone and insulin did not change due to GLN-enriched diet. Remote injury-induced changes in GLN and glutamic acid (GLU) during GLN-rich diet were minimal in brain tissues; whereas GLN levels were decreased in plasma and muscle, GLU levels were increased in plasma and decreased in muscle tissues. The AA levels of brain tissues, in general, were maintained within narrow limits during GLN supplementation in control and injured rats. An increased influx of tryptophan and increased synthesis of the neurotransmitter serotonin were suggested due to GLN-enriched diet.


New diagnostic finding to assess para-Hisian pacing observed in a patient with a permanent form of junctional reciprocating tachycardia.
Para-Hisian pacing, a useful method to differentiate conduction over an accessory pathway from conduction over the AV node, is assessed essentially by comparing the timing of local atrial electrograms between His-bundle captured beats and His-bundle noncaptured beats. We describe the case of a patient with a permanent form of junctional reciprocating tachycardia, in whom an atrial double potential was recorded only during the tachycardia at the right posterior septum. During para-Hisian pacing, a morphologic change in the atrial electrogram at the posterior septum was also identified, as well as a change in the retrograde atrial sequence. Since the morphologic change of atrial electrograms during para-Hisian pacing cannot be demonstrated in a patient without an accessory pathway, this new finding could be considered a new additional diagnostic criterion suggesting the presence of an accessory pathway.


Experiences of siblings of children with chronic diseases revealed by the dramatic therapeutic play.
To understand, through dramatic therapeutic play, the experiences of siblings of children with chronic diseases. Phenomenological study, in the light of Heideggerian philosophical framework, conducted with 12 siblings of children with chronic diseases, aged between three and 11 years, accompanied in a public teaching hospital in the countryside of the state of São Paulo. The phenomenological interviews were audio-recorded and mediated by sessions of dramatic therapeutic play; later, interpreted from the Heideggerianphilosophical framework and thematic literature. The siblings demonstrated that they are affectively touched in the mode of sadness, longing and affection towards the sick child and, by the daily occupations imposed by the disease. The dramatic therapeutic play enabled the siblings of children with chronic diseases to expose their experiences permeated by the limitations of the child's chronic disease. Instituting actions for the inclusion of the sibling during the nursing care of the child with chronic disease is urgent to improve its quality.


Accelerated Diffusion-Weighted MR Image Reconstruction Using Deep Neural Networks.
Under-sampling in diffusion-weighted imaging (DWI) decreases the scan time that helps to reduce off-resonance effects, geometric distortions, and susceptibility artifacts; however, it leads to under-sampling artifacts. In this paper, diffusion-weighted MR image (DWI-MR) reconstruction using deep learning (DWI U-Net) is proposed to recover artifact-free DW images from variable density highly under-sampled k-space data. Additionally, different optimizers, i.e., RMSProp, Adam, Adagrad, and Adadelta, have been investigated to choose the best optimizers for DWI U-Net. The reconstruction results are compared with the conventional Compressed Sensing (CS) reconstruction. The quality of the recovered images is assessed using mean artifact power (AP), mean root mean square error (RMSE), mean structural similarity index measure (SSIM), and mean apparent diffusion coefficient (ADC). The proposed method provides up to 61.1%, 60.0%, 30.4%, and 28.7% improvements in the mean AP value of the reconstructed images in our experiments with different optimizers, i.e., RMSProp, Adam, Adagrad, and Adadelta, respectively, as compared to the conventional CS at an acceleration factor of 6 (i.e., AF = 6). The results of DWI U-Net with the RMSProp, Adam, Adagrad, and Adadelta optimizers show 13.6%, 10.0%, 8.7%, and 8.74% improvements, respectively, in terms of mean SSIM with respect to the conventional CS at AF = 6. Also, the proposed technique shows 51.4%, 29.5%, 24.04%, and 18.0% improvements in terms of mean RMSE using the RMSProp, Adam, Adagrad, and Adadelta optimizers, respectively, with reference to the conventional CS at AF = 6. The results confirm that DWI U-Net performs better than the conventional CS reconstruction. Also, when comparing the different optimizers in DWI U-Net, RMSProp provides better results than the other optimizers.


Reconstruction of severe burn contractures of the upper lip in males using a pedicled superficial temporal artery hair-bearing flap. Two case reports.
Severe burn contractures of the upper lip are usually treated either with full thickness skin grafts or flaps. Most authors recommend the free radial forearm flap as the flap of choice. In males, another free flap option is the use of the superficial temporal artery hair-bearing free flap. In this report, we demonstrate that the superficial temporal artery hair-bearing flap may be used as a pedicle flap (rather than a free flap) for the reconstruction of severe upper lip burn contractures in males. We show our method of flap delay and design to ensure that the distal part of the flap will survive; and this will be demonstrated in two case reports. The pedicled superficial temporal artery flap is much simpler to execute than free flaps. Severe post burn contractures of the upper lip in males may be reconstructed using the pedicled superficial temporal artery hair-bearing flap. In order for the flap to reach the contralateral side of the lip, it will have to cross the midline in the scalp. We demonstrate our method of flap delay and design to ensure flap safety and viability. We also show that concurrent burn deformities in close proximity of the upper lip should be treated prior to upper lip reconstruction. Finally, we stress on the principle of reconstructing the entire skin of the upper lip as one aesthetic unit.


Biexcitons in monolayer transition metal dichalcogenides tuned by magnetic fields.
We present time-integrated four-wave mixing measurements on monolayer MoSe2 in magnetic fields up to 25 T. The experimental data together with time-dependent density function theory calculations provide interesting insights into the biexciton formation and dynamics. In the presence of magnetic fields the coherence at negative and positive time delays is dominated by intervalley biexcitons. We demonstrate that magnetic fields can serve as a control to enhance the biexciton formation and help search for more exotic states of matter, including the creation of multiple exciton complexes and excitonic condensates.


Relation of Muscle Mass and Fat Mass to Cardiovascular Disease Mortality.
We evaluated the relation between components of body composition and mortality in patients with cardiovascular disease (CVD). Dual x-ray absorptiometry body composition data from the National Health and Nutrition Examination Survey 1999 to 2004 was linked to total and CVD mortality data 1999 to 2006 in 6,451 patients with CVD. Kaplan-Meier survival analysis for the end points of total and CVD mortality was plotted by quartiles of muscle mass, fat mass, and categories of body mass index (BMI). Subjects were stratified into 4 groups (low muscle/low fat mass, low muscle/high fat mass, high muscle/low fat mass, and high muscle/high fat mass). Adjusted Cox proportional hazards regression determined hazard ratios for total and CVD mortality. Rates of cardiovascular/total mortality were lower in higher quartiles of muscle mass, fat mass, and higher categories of BMI (p <0.001). The high muscle/low fat mass group had a lower risk of CVD and total mortality (risk-adjusted hazard ratios of 0.32, 95% confidence interval 0.14 to 0.73 and 0.38, 95% confidence interval 0.22 to 0.68, for CVD and total mortality, respectively). Thus, increasing fat mass, muscle mass, and BMI were all correlated with improved survival. The specific subgroup of high muscle and low fat mass had the lowest mortality risk compared with other body composition subtypes. This suggests the importance of body composition assessment in the prediction of cardiovascular and total mortality in patients with CVD.


Retinal detachment after neodymium:YAG laser posterior capsulotomy.
We reviewed the records of 397 patients who had undergone Nd:YAG laser posterior capsulotomy between July 1983 and August 1988. Of the 366 eyes that had been followed up for three months or more, 13 (3.6%) developed a retinal detachment after capsulotomy; of these 13 detachments, 11 (84.6%) occurred within the first year. The combination of male gender with axial myopia (greater than or equal to 25.00 mm), a history of lattice degeneration, or a history of retinal detachment in the fellow eye was a significant risk factor for the development of retinal detachment after YAG capsulotomy.


In vitro and in vivo anticancer activity of surface modified paclitaxel attached hydroxyapatite and titanium dioxide nanoparticles.
Targeted drug delivery using nanocrystalline materials delivers the drug at the diseased site. This increases the efficacy of the drug in killing the cancer cells. Surface modifications were done to target the drug to a particular receptor on the cell surface. This paper reports synthesis of hydroxyapatite and titanium dioxide nanoparticles and modification of their surface with polyethylene glycol (PEG) followed by folic acid (FA). Paclitaxel, an anticancer drug, is attached to functionalized hydroxyapatite and titanium dioxide nanoparticles. The pure and functionalised nanoparticles are characterised with XRD, TEM and UV spectroscopy. Anticancer analysis was carried out in DEN induced hepatocarcinoma animals. Biochemical, hematological and histopathological analysis show that the surface modified paclitaxel attached nanoparticles have an higher anticancer activity than the pure paclitaxel and surface modified nanoparticles without paclitaxel. This is due to the targeting of the drug to the folate receptor in the cancer cells.


A meta-analysis of associations of IL-10 gene polymorphisms with acute leukemia susceptibility.
Recently, increasing evidence has demonstrated that IL-10 single nucleotide polymorphisms (SNPs) are associated with the risk of acute leukemia (AL), but the findings of different articles remain controversial. Thus, we performed a meta-analysis to further investigate the exact roles of IL-10 SNPs in AL susceptibility. Six common Chinese and English databases were utilized to retrieve eligible studies. The strength of the association was assessed by calculating odds ratios and 95 % confidence intervals. All analyses were carried out using Review Manager (version 5.3) and STATA (version 15.1). The registered number of this research is CRD42022373362. A total of 6391 participants were enrolled in this research. The results showed that the AG genotype of rs1800896 increased AL risk in the heterozygous codominant model (AG vs. AA, OR = 1.41, 95 % CI = 1.04-1.92, P = 0.03) and overdominant model (AG vs. AA + GG, OR = 1.32, 95 % CI = 1.04-1.70, P = 0.03). In the subgroup analysis, associations between the G allele, GG genotype, AG genotype, AG + GG genotype of rs1800896 and increased AL risk were also observed in the mixed population based on allelic, homozygote codominant, heterozygous codominant, dominant, and overdominant models. Furthermore, an association between the AC genotype of rs1800872 and increased AL risk was observed in the Caucasian population in the overdominant model. However, the rs1800871, rs3024489 and rs3024493 polymorphisms did not affect AL risk. IL-10 rs1800896 and rs1800872 affected the susceptibility of AL and therefore may be biomarkers for early screening and risk prediction of AL.


Open aortic stent grafting and prosthetic bypass in a child.
Pseudoaneurysm is a major complication of percutaneous balloon angioplasty to treat recoarctation and restenosis after an interrupted aortic arch repair. Endovascular stent grafting to manage this complication has rarely been performed in children. We used a combination of open stent grafting and a prosthetic ascending aorta-to-descending aorta bypass to treat a pseudoaneurysm and ascending aorta stenosis in a 7-year-old child.


A closer look at nursing documentation on paper forms: preparation for computerizing a nursing documentation system.
A small scale documentation analysis was conducted to explore the medical and surgical nursing content of the patient record at a large teaching hospital affiliated with Partners Healthcare System (PHS), in preparation for a computerized documentation system. Through this study, we identified a number of problems associated with the paper record that require resolution in the new computerized system, including elimination of documentation redundancy, areas where more structure is needed to properly capture data on nursing practice, and various design considerations to support a more complete and accurate documentation of nursing care.


Morphological, ultrastructural and functional imaging of frozen/thawed and vitrified/warmed human ovarian tissue retrieved from oncological patients.
Which is the best method for human ovarian tissue cryopreservation: slow freezing/rapid thawing (SF/RT) or vitrification/warming (V/W)? The conventional SF/RT protocol used in this study seems to better preserve the morpho-functional status of human cryopreserved ovarian tissue than the used open carrier V/W protocol. Cryopreservation of human ovarian tissue is generally performed using the SF/RT method. However, reduction in the follicular pool and stroma damage are often observed. An emerging alternative procedure is represented by V/W which seems to allow the maintenance of the morphological integrity of the stroma. This is a retrospective cohort study including six patients affected by oncological diseases and enrolled from January to December 2014. Ovarian tissue was laparoscopically harvested from the right and left ovaries and was cryopreserved using a routinary SF/RT protocol or a V/W method, involving tissue incubation in two solutions (containing propylene glycol, ethylene glycol and sucrose at different concentrations) and vitrification in an open system. For each patient, three pieces from each ovary were collected at the time of laparoscopy (fresh tissue) and after storage (SF/RT or V/W) and processed for light microscopy (LM) and transmission electron microscopy (TEM), to assess the morphological and ultrastructural features of follicles and stroma, and for laser scanning confocal microscopy (LSCM), to determine the functional energetic/redox stroma status. The preservation status of SF/RT and V/W ovarian tissues was compared with that of fresh ones, as well as between them. By LM and TEM, SF/RT and V/W samples showed cryodamage of small entity. Interstitial oedema and increased stromal cell vacuolization and chromatin clumping were observed in SF/RT samples; in contrast, V/W samples showed oocyte nuclei with slightly thickened chromatin and irregular shapes. The functional imaging analysis by LSCM revealed that the mitochondrial activity and intracellular reactive oxygen species levels were reduced both in SF/RT and in V/W samples compared with fresh samples. The study also showed progressive dysfunction of the mitochondrial activity going from the outer to the inner serial section of the ovarian cortex. The reduction of mitochondrial activity of V/W samples compared with fresh samples was significantly higher in the inner section than in the outer section. The results report the bioenergetic and oxidative status assessment of fresh and cryopreserved human ovarian tissue by LSCM, a technique recently applied to tissue samples. The use of LSCM on human ovarian tissues after SF/RT or V/W is a new application that requires validation. The procedures for mitochondrial staining with functional probes and fixing are not yet standardized. Xenografting of the cryopreserved ovarian tissue in severe combined immunodeficient mice and in vitro culture have not yet been performed. The identification of a cryopreservation method able to maintain the morpho-functional integrity of the ovarian tissue and a number of follicles comparable with those observed in fresh tissue might optimize results in clinical practice, in terms of recovery, duration of ovarian function and increased delivery outcomes after replanting. The SF/RT protocol allowed better morpho-functional tissue integrity than the V/W procedure. Funding was provided by Fondazione del Monte di Bologna e Ravenna, Italy. Dr N.A.M. was granted by the project ONEV MIUR PONa3 00134-n.254/R&C 18 5 2011 and the project GR-2011-02351396 (Ministry of Health, Young Researchers Grant 2011/2012). There are no competing interests. Clinical trial 74/2001/0 (approved:13 2 2002): 'Pilot study on cryopreservation of human ovarian tissue: morphological and immunohistochemical analysis before and after cryopreservation'.