Development of a decision-making pathway for utilizing standalone lateral lumbar interbody fusion.
To develop a decision-making pathway for primary SA-LLIF. Furthermore, we analyzed the agreement of this pathway and compared outcomes of patients undergoing either SA-LLIF or 360-LLIF. A decision-making pathway for SA-LLIF was created based on the results of interviews/surveys of senior spine surgeons with over 10 years of experience. Internal validity was retrospectively evaluated using consecutive patients undergoing either SA-LLIF or 360-LLIF between 01/2018 and 07/2020 with 3D-printed Titanium cages. An outcome assessment looking primarily at revision surgery and secondary at cage subsidence, changes in disk and foraminal height, global and segmental lumbar lordosis, duration of surgery, estimated blood loss, and length of stay was carried out. 78 patients with 124 treated levels (37 SA-LLIF, 41 360-LLIF) were retrospectively analyzed. The pathway showed a direct agreement (SA-LLIF) of 100.0% and an indirect agreement (360-LLIF) of 95.1%. Clinical follow-up averaged 13.5 ± 6.5 months including 4 revision surgeries in the 360-LLIF group and none in the SA-LLIF group (p = 0.117). Radiographic follow-up averaged 9.5 ± 4.3 months, with no statistically significant difference in cage subsidence rate between the groups (p = 0.440). Compared to preoperative images, patients in both groups showed statistically significant changes in disk height (p < 0.001), foraminal height (p < 0.001), as well as restoration of segmental lordosis (p < 0.001 and p = 0.018). The SA-LLIF group showed shorter duration of surgery, less estimated blood loss and shorter LOS (p < 0.001). The proposed decision-making pathway provides a guide to adequately select patients for SA-LLIF. Further studies are needed to assess the external applicability and validity. Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.


Biosynthesis of rat insulin-like growth factor II. I. Immunochemical demonstration of a approximately 20-kilodalton biosynthetic precursor of rat insulin-like growth factor II in metabolically labeled BRL-3A rat liver cells.
BRL-3A rat liver cells synthesize mature 7484-dalton rat insulin-like growth factor II (rIGF-II) as a approximately 22-kDa precursor, presumably prepro-rIGF-II. In the present study, we have biosynthetically labeled intact BRL-3A cells with [35S]cysteine and immunoprecipitated cell lysates and media with antisera to rIGF-II. A approximately 20-kDa protein was identified in immunoprecipitates of cell lysates having properties consistent with pro-rIGF-II. The approximately 20-kDa protein is precipitated by immune sera but not by nonimmune serum. Its immunoprecipitation is specifically inhibited by unlabeled rIGF-II but not by insulin. It is not precipitated from labeled lysates of a subclone of BRL-3A cells (BRL-3A2) that does not synthesize rIGF-II. The approximately 20-kDa protein is rapidly labeled intracellularly (10 min) but is not detected in BRL-3A media. In pulse-chase experiments, radioactivity in the approximately 20-kDa protein disappears during the chase and appears, at later times, in specifically immunoprecipitated approximately 19-, approximately 10-, approximately 8-, and approximately 7-kDa proteins in media and, to a limited extent, intracellularly. A protein with electrophoretic mobility identical to that of the approximately 20-kDa protein observed in cell lysates is immunoprecipitated from 35S-proteins whose synthesis is directed by BRL-3A RNA in a reticulocyte lysate cell-free translation system supplemented with microsomal membranes, and presumably arises by cotranslational removal of the signal peptide from approximately 22-kDa prepro-rIGF-II. Processing of the approximately 20-kDa protein in intact BRL-3A cells to intermediate and mature rIGF-II species appears to occur at the time of secretion and/or shortly thereafter, with the different forms appearing at approximately the same time.


Intrathecal cryptococcal lesion of the cauda equina successfully treated with intrathecal amphotericin B: A case report.
A case of an intrathecal cryptococcal granuloma in the cauda equina is reported. Successful and minimally toxic therapy with intrathecal amphotericin B and oral 5-fluorocytosine, preceded by surgery, is described.


Membrane assembly of the functional KcsA potassium channel in a vesicle-based eukaryotic cell-free translation system.
The potassium channel KcsA was heterologously expressed in a eukaryotic cell-free system. Both, the expression yields and functional analysis of the protein were reported. Qualitative and quantitative analyses of KcsA expression were performed by using (14)C-labeled leucine as one of the amino acids supplemented in the cell-free reaction mixture. There was a time dependent increase in the protein yield as well as the intensity of the native tetramer band in insect cell derived microsomes. Electrophysiology measurements demonstrated the functional activity of the microsomes harboring KcsA showing single-channel currents with the typical biophysical characteristics of the ion channel. The channel behavior was asymmetric and showed positive rectification with larger currents towards positive voltages. KcsA channel currents were effectively blocked by potassium selective barium (Ba(2+)). This functional demonstration of an ion channel in eukaryotic cell-free system has a large potential for future applications including drug screening, diagnostic applications and functional assessment of complex membrane proteins like GPCRs by coupling them to ion channels in cell-free systems. Furthermore, membrane proteins can be expressed directly from linear DNA templates within 90 min, eliminating the need for additional cloning steps, which makes this cell-free system fast and efficient.


Silver Nitrate Staining of Nucleolar Organizer Regions (Ag-NORs) in Plant Chromosomes.
Silver nitrate staining to evidence the location of nucleolar organizer regions (Ag-NORs) in chromosomes is widely used as a classical method in plant cytogenetics. Here, we present the most used procedures and highlight some aspects in terms of their replicability by plant cytogeneticists. Some technical features described are materials and methods used, procedures, protocol modifications, and precautions in order to obtain positive signals. The methods to obtain Ag-NOR signals have different degrees of replicability, but do not require any sophisticated technology or equipment for their application.


Design of electromagnetic metasurface using two dimensional crystal nets.
Metasurfaces are of great interest as they exhibit unique electromagnetic properties. Currently, metasurface design focuses on generating new meta-atoms and their combinations. Here a topological database, reticular chemistry structure resource (RCSR), is introduced to bring a new dimension and more possibilities for metasurface design. RCSR has over 200 two-dimensional crystal nets, among which 72 are identified as suitable for metasurface design. Using a simple metallic cross as the metaatom, 72 metasurfaces are constructed from the atom positions and lattice vectors of the crystal nets templates. The transmission curves of all the metasurfaces are calculated using the finite-difference time-domain method. The calculated transmission curves have good diversity, showing that the crystal nets approach is a new engineering dimension for metasurface design. Three clusters are found for the calculated curves using the K-means algorithm and principal component analysis. The structure-property relationship between metasurface topology and transmission curve is investigated, but no simple descriptor has been found, indicating that further work is still needed. The crystal net design approach developed in this work can be extended to three-dimensional design and other types of metamaterials like mechanical materials.


Gender differences in the acceptance of wife-beating: evidence from 30 countries in Sub-Saharan Africa.
The World Health Organization (WHO) has cited domestic violence as an urgent global maternal and child health priority. Gender differences in the acceptance of wife-beating have not been explored at the multi-country level in sub-Saharan Africa (SSA) where the occurrence of wife-beating (36%) is greater than the global average (30%). It is against this backdrop that we examine the gender differences in the acceptance of wife beating in SSA. We used Demographic and Health Survey data from 30 SSA countries. Acceptance of wife beating among women and men was the principal outcome variable of interest. We employed Multiple correspondence analysis and logistic regression model as the primary estimation methods for this study. The descriptive statistics show that women had a higher acceptance rate (44%) of wife beating than men (25%). For the women sample, Mali, Democratic Republic of Congo, Chad, and Guinea had higher rates of acceptance of the wife beating (80.6%, 78.4%, 77.1% and 70.3% respectively) For the men, only Guinea had an acceptance rate above 50 percent. We found that all else equal, women's acceptance of wife beating is higher for male-headed households than for female-headed households. Women without formal education were 3.1 times more likely to accept wife beating than those with higher education. Men with no formal education were 2.3 times more likely to accept wife beating than men with higher education. We found that polygamous women were comparable to polygamous men. Polygamous women were 1.2 times more likely to accept wife beating than those in monogamous marriages. Women were 1.2 times more likely to accept wives beating if they had extramarital relationships. Contrarily, men who engaged in extramarital affairs were 1.5 times more likely to justify wife beating. We also found that women's acceptance of wife beating decreases as they age. Men who decide on major household purchases and spending decisions on their earnings are more likely to accept wife beating. Corollary, women with similar gender and employment roles also accept wife beating. Finally, exposure to mass media is significantly associated with lower acceptance of wife beating for women and men. We conclude that women have a higher acceptance rate of wife beating than men in SSA. Acceptance of wife beating differs significantly by country. Given the same level of education, women are more likely to accept wife beating than men. If women and men have similar levels of employment and gender roles, acceptance of wife beating is higher when men make major household purchasing decisions and and it is still higher even when the woman makes these decisions. Acceptance of wife beating is higher among young women and men, the uneducated, those in polygamous marriages, women, and men who engage in extra marital affairs, poor households and in rural areas. The findings indicate the need for policies and programs by SSA countries to truncate the high acceptance rate of wife beating, especially among women.


Phase diagrams of self-assembled mono-tethered nanospheres from molecular simulation and comparison to surfactants.
We perform Brownian dynamics simulations on model 3-D systems of mono-tethered nanospheres (TNS) to study the equilibrium morphologies formed by their self-assembly in a selective solvent. We predict that in contrast to flexible amphiphiles the nanospheres are locally ordered and there is an increase in the local order with an increase in concentration or relative nanoparticle diameter. We present the temperature vs concentration phase diagram for a system of TNS and propose a dimensionless scaling factor F(v) (headgroup volume/tether volume) that allows a comparison between the morphologies formed from TNS and traditional surfactants.


Validation of the Wisconsin Brief Pain Questionnaire in a multilingual South African population.
Assessment of pain intensity and its effect on quality of life is important for proper management of pain, but no validated pain assessment tools that assess pain intensity and the interference pain has on daily life are available in indigenous South African languages. Therefore, the aim of this study was to validate translated versions of the Wisconsin Brief Pain Questionnaire (WBPQ) in South African HIV-positive patients. The WBPQ was translated into three indigenous South African languages, Setswana, isiZulu, and Xitsonga. We interviewed 452 ambulatory HIV-positive patients (327 urban and 125 rural patients) between the ages of 20 and 76 years old. Factor analysis to assess construct validity identified a two-factor structure (pain intensity and pain interference) for the isiZulu (n=132), Xitsonga (n=125), and Setswana (n=66) versions of the WBPQ, whereas a three-factor structure (pain intensity, mood interference, and activity interference) was identified for the English (completed by English second-language speakers, n=129) version of the WBPQ. Cronbach alphas, calculated to assess the reliability of the pain intensity and pain interference scales, were greater than 0.70 for all scales in all four versions of the WBPQ, showing internal consistency within the dimensions. These results provide evidence of validity for an easily administered questionnaire, which assesses pain intensity and pain interference, in three indigenous South African languages, and for English second-language speakers, in a population of South African HIV-positive patients.


Acute shoulder-girdle neuralgic amyotrophy (Parsonage-Turner syndrome with saphenous nerve involvement.
Parsonage-Turner syndrome (PTS) is a relatively rare cause of upper extremity weakness and pain. There is currently no effective treatment for PTS although corticosteroids are recommended. Here we report the case of a man with acute PTS and exceptional involvement of both saphenous nerves, advantageously treated with intravenous immunoglobulin.


Correction: Two-year efficacy of varenicline tartrate and counselling for inpatient smoking cessation (STOP study): A randomized controlled clinical trial.
[This corrects the article DOI: 10.1371/journal.pone.0231095.].


Home Scholarly Culture, Book Selection Reason, and Academic Performance: Pathways to Book Reading Interest among Secondary School Students.
Although studies have explored the predictors of book reading interest among children, little is known about the underlying mechanism that helps children become interested in reading books. This study attempt to demonstrate: (1) how book-reading interest is driven by reasons for choosing books (recommendation or personal preference), (2) how students with high and low academic achievements are motivated by different thinking pathways, and (3) how home scholarly culture improves book-reading interest through such pathways. Using Bayesian analysis on a dataset of survey responses from 4966 Vietnamese secondary students (11-15 years old, sixth to ninth grade), we found: (i) Reading interest is positively associated with a book recommendation and parental book reading activities (parents read books to children); (ii) High-achieving students are more interested in reading books if they can choose those books according to personal preferences; (iii) Parental book reading activities can promote book reading interest through recommendations and also by understanding children's personal preferences. We advocate a more personalized approach in educational policymaking, curriculum design, and home scholarly culture based on students' abilities and perceptions.


Comparative analyses of industrial-scale human platelet lysate preparations.
Efforts are underway to eliminate fetal bovine serum from mammalian cell cultures for clinical use. An emerging, viable replacement option for fetal bovine serum is human platelet lysate (PL) as either a plasma-based or serum-based product. Nine industrial-scale, serum-based PL manufacturing runs (i.e., lots) were performed, consisting of an average ± standard deviation volume of 24.6 ± 2.2 liters of pooled, platelet-rich plasma units that were obtained from apheresis donors. Manufactured lots were compared by evaluating various biochemical and functional test results. Comprehensive cytokine profiles of PL lots and product stability tests were performed. Global gene expression profiles of mesenchymal stromal cells (MSCs) cultured with plasma-based or serum-based PL were compared to MSCs cultured with fetal bovine serum. Electrolyte and protein levels were relatively consistent among all serum-based PL lots, with only slight variations in glucose and calcium levels. All nine lots were as good as or better than fetal bovine serum in expanding MSCs. Serum-based PL stored at -80°C remained stable over 2 years. Quantitative cytokine arrays showed similarities as well as dissimilarities in the proteins present in serum-based PL. Greater differences in MSC gene expression profiles were attributable to the starting cell source rather than with the use of either PL or fetal bovine serum as a culture supplement. Using a large-scale, standardized method, lot-to-lot variations were noted for industrial-scale preparations of serum-based PL products. However, all lots performed as well as or better than fetal bovine serum in supporting MSC growth. Together, these data indicate that off-the-shelf PL is a feasible substitute for fetal bovine serum in MSC cultures.


Transcriptomics-based analysis of sex-differentiated mechanisms of hepatotoxicity in zebrafish after long-term exposure to bisphenol AF.
Bisphenol AF (BPAF) is an emerging endocrine-disrupting chemical (EDC) prevalent in the environment as one of the main substitutes for bisphenol A. Sex-specific effects of EDCs have been commonly reported and closely linked to sexually dimorphic patterns of hormone metabolism and related gene expression during different exposure windows, but our understanding of these mechanisms is still limited. Here, following 28-day exposure of adult zebrafish to an environmentally relevant concentration of BPAF at 10 μg/L, the global transcriptional networks applying RNA sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) were respectively investigated in the male and female fish liver, connecting the sex-dependent toxicity of the long-term exposure of BPAF to molecular responses. As a result, more differentially expressed genes (DEGs) were detected in males (811) than in females (195), and spermatogenesis was the most enriched Gene Ontology (GO) functional classification in males, while circadian regulation of gene expression was the most enriched GO term in females. The expression levels of selected DEGs were routinely verified using qRT-PCR, which showed consistent alterations with the transcriptional changes in RNA-seq data. The causal network analysis by IPA suggested that the adverse outcomes of BPAF in males including liver damage, apoptosis, inflammation of organ, and liver carcinoma, associated with the regulation of several key DEGs detected in RNA-seq, could be linked to the activation of upstream regulatory molecules ifnα, yap1, and ptger2; while, the inhibition of upstream regulators hif1α, ifng, and igf1, leading to the down-regulated expression of several key DEGs, might be involved in BPAF's effects in females. Furthermore, BPAF exposure altered hepatic histological structure and inhibited antioxidant capability in both male and female livers. Overall, this study revealed different regulation networks involved in the sex-dependent effects of BPAF on the fish liver, and these detected DEGs upon BPAF exposure might be used as potential biomarkers for further assessing sex-specific hepatotoxicity following environmental EDC exposure.


Sources of geogenic arsenic in well water associated with granitic bedrock from Nova Scotia, Canada.
Arsenic toxicity in drinking water is a global issue, with chronic exposure causing cancer and other health concerns. Groundwater from geochemically similar granites from mainland Nova Scotia, Canada, can have high and low levels of arsenic. The origin of this variation is uncertain, but different mineral hosts for arsenic could explain the disparity. The lability of arsenic from different minerals was assessed using laser ablation inductively coupled plasma mass spectrometry combined with calculations based upon well water data. Pyrite has the highest arsenic concentration (mean: 2300 μg/g, n = 9), is unstable in the groundwater system, and can release arsenic during oxidation. However, oxidation products replacing pyrite can adsorb arsenic, modifying the amount released. Cordierite has low arsenic concentrations (mean: 7.3 μg/g, n = 5) but is abundant and relatively soluble. Thus, cordierite could be a previously unrecognized source of arsenic in metapelitic rocks from metamorphic terranes. Pyrite from one of the granites studied was not oxidized, which in addition to the absence of cordierite in these same granites could account for the lower arsenic levels observed in associated well water. The results of this study can be used to identify potential geogenic sources of arsenic in other granitic terranes and reduce the risk of exposure through drinking water.


Osteoblasts impair cholesterol synthesis in chondrocytes via Notch1 signalling.
Previous reports have proposed the importance of signalling and material exchange between cartilage and subchondral bone. However, the specific experimental evidence is still insufficient to support the effect of this interdependent relationship on mutual cell behaviours. In this study, we aimed to investigate cellular lipid metabolism in chondrocytes induced by osteoblasts. Osteoblast-induced chondrocytes were established in a Transwell chamber. A cholesterol detection kit was used to detect cholesterol contents. RNA sequencing and qPCR were performed to assess changes in mRNA expression. Western blot analysis was performed to detect protein expression. Immunofluorescence staining was conducted to show the cellular distribution of proteins. Cholesterol levels were significantly decreased in chondrocytes induced by osteoblasts. Osteoblasts reduced cholesterol synthesis in chondrocytes by reducing the expression of a series of synthetases, including Fdft1, Sqle, Lss, Cyp51, Msmo1, Nsdhl, Sc5d, Dhcr24 and Dhcr7. This modulatory process involves Notch1 signalling. The expression of ncstn and hey1, an activator and a specific downstream target of Notch signalling, respectively, were decreased in chondrocytes induced by osteoblasts. For the first time, we elucidated that communication with osteoblasts reduces cholesterol synthesis in chondrocytes through Notch1 signalling. This result may provide a better understanding of the effect of subchondral bone signalling on chondrocytes.


Empowerment interventions designed for persons living with chronic disease - a systematic review and meta-analysis of the components and efficacy of format on patient-reported outcomes.
Empowerment approaches are essential for building the capacity of individuals with chronic disease to be in control of their health. Reviews of empowerment interventions have been focused on specific chronic diseases, thereby limiting the scope of findings. This study had three aims: 1) to describe the characteristics of empowerment interventions covering a broad range of chronic diseases, 2) to clarify consistency with the World Health Organization`s (WHO) definition of empowerment as a process composed of four fundamental components and 3) to summarize outcome measures and estimate the effects in group and individual intervention formats. Systematic literature review and meta-analysis. CINAHL, Medline, Embase, PsycINFO, Web of Science, COCHRANE and Central Register of Controlled Trials were searched using Chronic Disease, NCD, Empowerment, as MeSH terms. Eligible randomized and quasi randomized controlled trials were included. Review Manager 5.4 was used to conduct the meta-analysis. Risk of bias was assessed with the Cochrane risk-of-bias tool (ROB 2). Thirty-nine articles representing 8,011 participants were included in the review. A majority (82%) of studies reported robust evidence for changes on study-defined outcome measures in favor of interventions. Intervention content was assessed against WHO's four fundamental components of empowerment, showing that all studies incorporated one component, but none targeted all components. Components reflecting knowledge acquisition, patient engagement with their health care providers and facilitating environment were scarcely reported. Meta-analyses found evidence for positive effects of group-format interventions measuring empowerment, HbA1c, and self-efficacy. Effects on empowerment were also found in some individual-format interventions. High levels of heterogeneity and variability among the conceptual frameworks were identified. Empowerment interventions in group-format were most efficient, however, considerable conceptual inconsistencies were identified. Future studies should consolidate conceptual understandings by using WHO's empowerment framework to ensure that fundamental components of empowerment are explicitly included in intervention design. Furthermore, there is a need to clarify the role of empowerment through pathways that include patient activation, self- management, and clinical outcomes. This systematic review will inform the clinicians and researchers who aim to develop novel empowerment interventions to assist patients in the process of gaining control of their health. PROSPERO: International Prospective register of systematic reviews ID=CRD42020178286.


Functional expression of a highly-reducing polyketide synthase of Emericella variecolor IFM42010, an asteltoxin-producing strain, resulted in production of two polyenoic β-ketolactones with opposite stereochemistry.
The asteltoxin-producing fungus Emericella variecolor IFM42010 possesses 22 highly-reducing polyketide synthase (HR-PKS) genes. Of these, an HR-PKS with a methyltransferase domain but lacking an enoylreductase domain could be involved in the biosynthesis of asteltoxin and related compounds. From six such candidate HR-PKS genes, Ev460pks was analyzed by gene disruption in E. variecolor and heterologous expression in Aspergillus oryzae. The Ev460pks-disrupted strain retained asteltoxin production ability, indicating that Ev460pks is not involved in asteltoxin biosynthesis. The A. oryzae transformant harboring the Ev460pks gene produced compounds 1 and 2, along with several unidentified products possibly decomposed from 2. Spectroscopic analyses revealed that 1 was a 4-methyl-β-ketolactone with a methylheptatriene side-chain at the C-5 position, and 2 was also a 4-methyl-β-ketolactone, bearing a dimethyltetradecahexaene side-chain at the same position. The relative configuration at C-4 in compounds 1 and 2 was opposite.


First stage of labour duration and associated risk of adverse neonatal outcomes.
Prior evidence evaluating the benefits and harms of expectant labour duration during active first stage is inconclusive regarding potential consequences for the neonate. Population-based cohort study in Stockholm-Gotland region, Sweden, including 46,040 women (Robson 1), between October 1st, 2008 and June 15th, 2020. Modified Poisson regression was used for the association between active first stage of labour duration and adverse neonatal outcomes. 94.2% experienced a delivery with normal neonatal outcomes. Absolute risk for severe outcomes increased from 1.9 to 3.0%, moderate outcomes increased from 2.8 to 6.2% (> 10.1 h). Compared to the reference, (< 5.1 h; median), the adjusted relative risk (aRR) of severe neonatal outcome significantly increased beyond 10.1 h (> 90th percentile) (aRR 1.53, 95% CI 1.26, 1.87), for moderate neonatal outcome the aRR began to slowly increase beyond 5.1 h (≥ 50 percentile; aRR 1.40, 95% CI 1.24, 1.58). Mediation analysis indicate that most of the association was due to a longer active first stage of labour, 13% (severe neonatal outcomes) and 20% (moderate neonatal outcomes) of the risk was mediated (indirect effect) by longer second stage of labour duration. We report an association between increasing active first stage duration and increased risk of adverse neonatal outcomes. We did not observe a clear labour duration risk threshold.


Antibody binding to greater than 50% of sperm at the tail tip does not impair male fertility.
A prospective study was conducted with a man displaying 57.5 +/- 13.4% tail tip-directed ASAs to relate results of in vitro tests with attempts to conceive. Tests of seminal quality, penetration of zona-free hamster oocytes, and in vitro penetration of preovulatory cervical mucus were normal. A pregnancy was achieved by natural intercourse during the first cycle in which conception was attempted. More than 50% of sperm were bound by ASAs during the cycle in which conception occurred. These results suggest that ASA binding to certain regions of the sperm surface have no adverse effect on fertility. Therefore, when diagnosing the fertility status of males with ASAs, it appears prudent to use tests that permit determination of the regional distribution of ASA binding to sperm, rather than tests that only permit determination of the presence or absence of ASAs in test fluids.


Hepatic microsomal enzymes in Schistosoma mansoni-infected mice: I. Effect of duration of infection and lindane administration on dimethylnitrosamine demethylases.
The prevalence of schistosomiasis in Egypt, its suspected relationship to carcinoma of the bladder, and the inevitable exposure of schistosomal patients to insecticides prompted the undertaking of this study. Dimethylnitrosamine (DMN) demethylases, responsible for the activation of DMN, were assessed in the hepatic microsomes from albino mice under the influence of Schistosoma mansoni infection and/or lindane administration. DMN-demethylase I responded to infection by an early increase in activity, reaching a peak 30 days after disease induction and declining sharply afterwards. DMN-demethylase II followed the same general pattern, but it reached its peak 20 days after infection and declined at a slower rate than DMN-demethylase I. The effects of lindane, an organochlorine insecticide, were also studied on these two enzymes in uninfected mice and in S. mansoni-infected animals after different durations of disease induction. Given orally, in a dose of 40 mg/kg/day for 3 consecutive days, lindane increased the activity of both enzymes. Since DMN requires metabolic activation for its hepatotoxic and carcinogenic actions, alterations in its activating enzymes, as a consequence to schistosomiasis and/or exposure to lindane, may change susceptibility to its toxic and carcinogenic potentials.


Using valve gape analysis to compare sensitivity of native Mytilus edulis to invasive Magallana gigas when exposed to heavy metal contamination.
Coastal ecosystems are ecologically and economically important but are under increasing pressure from numerous anthropogenic sources of stress. Both heavy metal pollution and invasive species pose major environmental concerns that can have significant impacts on marine organisms. It is likely that many stresses will occur simultaneously, resulting in potential cumulative ecological effects. The aim of this study was to compare the relative resilience of an invasive oyster Magallana gigas and a native mussel Mytilus edulis to heavy metal pollution, utilising their valve gape response as an indicator. The gape activity of bivalves has been utilised to monitor a range of potential impacts, including for example oil spills, increased turbidity, eutrophication, heavy metal contamination etc. In this study, Hall effect sensors were used on both the native blue mussel (M. edulis) and the pacific oyster (M. gigas), invasive to Ireland. Mussels were shown to be more responsive to pollution events than oysters, where all heavy metals tested (copper, cadmium, zinc, lead) had an effect on transition frequency though significant differences were only observed for lead and cadmium (Control; > Copper, p = 0.0003; >lead, p = 0.0002; >Cadmium, p = 0.0001). Cadmium had an apparent effect on mussels with specimens from this treatment remaining closed for an average of 45.3% of the time. Similarly, significant effects on the duration of time mussels spent fully open was observed when treated with lead and cadmium (Control; > lead, p = 0.03, > cadmium, p = 0.02). In contrast, oysters displayed no significant difference for any treatment for number of gapes, or duration spent open or closed. Though there was an effect of both zinc and copper on the amount of time spent closed, with averages of 63.2 and 68.7% respectively. This indicates oysters may be potentially more resilient to such pollution events; further boosting their competitive advantage. Future mesocosm or field studies are required to quantify this relative resilience.


Electrocardiographic findings in heat stroke and exhaustion: A study on Makkah pilgrims.
Over two million pilgrims perform annual rituals in Makkah region, which when coincides with summer months, exposes them to outdoor temperatures exceeding 45 °C and humidity approaching 80%. Accordingly, heat illnesses are common including explicit heat strokes and heat exhaustion. No previous studies elaborated on electrocardiographic changes among this unique cohort. To compare electrocardiographic changes in three groups exposed to high outdoor temperatures, namely, patients with heat stroke compared to patients with heat exhaustion and a control group exposed to the same outdoor temperatures without clinical manifestations. Through case control design, two case groups of patients were selected. The first group (G1) was 34 patients admitted to the cooling units with clinical picture of heat stroke and the second group (G2) comprised 28 patients admitted with heat exhaustion. The control group (G3) included 31 patients selected from relatives of patients and outdoor workers. The outcome for comparison was 12-lead electrocardiographic changes done for all selected individuals. For (G1), the ECG was done while they were prepared for cooling or immediately when cooling was started. In G1, 18 were females and 16 males with ages of 20-76 years (59 ± 11 years). Their heart rates ranged from 64 to 160 beats per minute (mean 120 ± 24 per minute). Only 5/34 ECGs were completely normal. Sinus tachycardia was present in 27/34 patients (79%), with ischemic changes in 9/34 ECGs. In G2, 24 were males and four females with ages of 25-80 (mean 47 ± 15 years), the heart rate ranged from 64 to 170 per minute (mean 97 ± 16 per minute). Seven out of 28 ECGs were normal (25%) while 21/28 had some abnormalities. None had ischemic changes. Control group (G3), was five females and 26 males ages 18-80 years (mean 38 ± 15 years), 22/31 had normal ECGs (71%). All had normal sinus rhythm, 56-98 beats per minute (74 ± 11). Nine patients had some electrocardiographic abnormalities but none had ischemic changes. We conclude that electrocardiographic abnormalities occur with a high frequency in patients with heat stroke and heat exhaustion, with sinus tachycardia and ischemic changes occurring more frequently in patients with heat stroke.


Metastatic melanoma in the older patient: special considerations.
Cancer is a disease of older age where genomic instability, impaired DNA repair, and weakened immune surveillance against cancer are recognized to play a causative role. Because the incidence of melanoma is increasing at a very fast pace in the elderly and there is a rapid expansion of the aging population, a large number of elderly patients with metastatic melanoma will be encountered in clinical practice. As a result, significant burden is expected to be placed on health care resources as effective treatment of this condition is sought. Because melanoma is an immunogenic tumor and promising immune-based treatments have acquired approval for treatment of metastatic melanoma, their successful use in elderly patients will require knowledge about aging and associated alterations in immune function. The spotlight will likely remain on antitumor immunity, its regulation and quality, and the profiles of the cytokines that shape the tumor microenvironment.


Syndrome of ankylosis, facial anomalies and pulmonary hypoplasia.
A newly recognized syndrome, with a pattern of malformations (fixation of joints, facial anomalies, and pulmonary hypoplasia) is reported from Zambia Central Africa in an African child. Additional features of deafness and cataract are included in the congenital abnormalities and it is suggested that a form of gentic abnormality is responsible for this condition.


Exploring the impact of CYP11A1's missense SNPs on the interaction between CYP11A1 and cholesterol: A comprehensive structural analysis and MD simulation study.
The process of steroidogenesis plays a vital role in human physiology as it governs the biosynthesis of mineralocorticoids, glucocorticoids, and androgens. These three classes of steroid hormones are primarily produced in the adrenal and gonadal glands through steroidogenesis pathways. Initiated by the side chain cleavage of cholesterol (CLR), this process leads to the conversion of cholesterol into pregnenolone and isocaproic aldehyde. The enzyme CYP11A1, encoded by the CYP11A1 gene, plays a key role in catalyzing the side chain cleavage of CLR. Several single nucleotide polymorphisms (SNPs) have been identified in the CYP11A1 gene, which may predispose carriers to disorders associated with abnormal steroidogenesis. Specifically, missense SNPs in the CYP11A1 gene have the potential to negatively impact the interaction between CYP11A1 and CLR, thus affecting the overall metabolome of steroid hormones. In this computational study, we focused on a specific set of missense SNPs reported in the CYP11A1 gene, aiming to identify variants that directly impact the interaction between CYP11A1 and CLR. The three-dimensional structure of the CYP11A1-CLR complex was obtained from the RCSB Protein Data Bank, while missense SNPs in the CYP11A1 gene were retrieved from Ensembl. To predict the most deleterious variants, we utilized the ConSurf server, SIFT, and PolyPhen. Furthermore, we assessed the impact of induced amino acid (AA) substitutions on the CYP11A1-CLR interaction using the PRODIGY server, PyMol, and Ligplot programs. Additionally, molecular dynamics (MD) simulations were conducted to analyze the effects of deleterious variants on the structural dynamics of the CYP11A1-CLR complex. Among the 8096 retrieved variants, we identified ten missense SNPs (E91K, W147G, R151W, R151Q, S391C, V392M, Q395K, Q416E, R460W, and R460Q) as deleterious for the interaction between CYP11A1 and CLR. MD simulations of the CYP11A1-CLR complexes carrying these deleterious AA substitutions revealed that Q416E, W147G, R460Q, and R460W had the most pronounced impacts on the structural dynamics of the complex. Consequently, these missense SNPs were considered the most deleterious ones. Further functional tests are recommended to assess the impact of these four missense SNPs on the enzymatic activity of CYP11A1. Moreover, Genome-Wide Association Studies (GWAS) should be conducted to determine the significance of their association with abnormal steroidogenesis diseases in various patient groups.


Effect of aging biosolids with soils of contrasting pH on subsequent concentrations of Cu and Zn in pore water and on their plant uptake.
The study examines if a short period of reaction after addition of biosolids to soils can reduce the solubility and potential phytotoxicity of biosolid-borne Zn and Cu. The effects of period of aging (zero, 60, and 120 days) of biosolids (applied at 0, 10, 20, and 30 g kg⁻¹) with an acid, neutral, or alkaline soil on pH and concentrations of Zn, Cu, and dissolved organic C in solution over a 60-day growth period of spinach were investigated using Rhizon pore water samplers. In the acid and neutral soils, increasing aging period markedly reduced the concentrations of Zn and Cu in solution and there were concomitant increases in solution pH. The effect was much less pronounced in the alkaline soil. Soluble Zn and Cu concentrations were generally positively correlated with dissolved organic C concentrations, negatively correlated with pH in the alkaline and neutral soils but positively correlated with pH in the acid soil. Spinach yields were lower in the acid than neutral and alkaline soils and tended to increase with increasing rates of biosolids in all three soils. The concentrations of tissue Zn and Cu were notably high in shoots of plants grown in the acid soil. For all biosolid-amended soils, the concentrations of tissue Cu were lower in plants grown after 60 days rather than no aging. Following biosolids applications to soils, an aging period of only a few months is likely to lower the solubility, and potential phytotoxicity, of biosolid-borne Zn and Cu particularly in acid and neutral soils.


Solid versus liquid phase assays in detection of insulin antibodies. Influence of iodination site on labelled insulin binding.
On type 1 newly diagnosed and on insulin treated diabetic patients, anti-insulin autoantibodies (IAA) and antibodies (IA) having the same specificity are respectively induced. Such immune response may be evaluated either by radiobinding assay (RBA) or enzyme-linked immunosorbent assay (ELISA). Both methodologies have been compared at previous International Workshops, which pointed out discrepancies in results. In this work, IAA/IA prevalence was assessed by displacement RBA and ELISA, in normal subjects, type 2 (treated with hypoglycaemic agents), insulin treated and newly diagnosed type 1 diabetic patients. Results showed a lack of RBA-ELISA agreement. An attempt was then made to determine whether such results were, at least in part, attributable to iodination site in Tyr-A14. For this purpose parallel RBA assays were carried out by using radiolabelled insulin at A14 and A19 Tyr residues. Control sera and samples from insulin treated and type 1 newly diagnosed diabetic patients were tested. Our results suggest that labelling position is not involved in artifactual binding of tracers, at least as a systematic phenomenon. In the majority of cases the variability in RBA-ELISA signal ratios are best explained in terms of differences in the basic principles operating in both methods instead of artifacts due to tracer preparation.


In vivo imaging of the immune response in the eye.
The immune system is governed by dynamic events involving in part direct intercellular interactions between an immune cell and other cells or the cell's environment. Owing to its unique optical characteristics, the eye offers remarkable opportunities for the analysis of the immune system by intravital microscopy. In this review, we present a brief overview of the current state of knowledge of leukocyte trafficking in each of three anatomically distinct and medically important regions of the eye (cornea, iris, retina) as determined by the application of intravital microscopy to animal models of disease. Additionally, we discuss the use of ocular imaging in patients and volunteers. Finally, we examine the future prospects for this field in terms of its potential for impacting our understanding of fundamental immunological phenomena.


Imaging of Bowel Wall Thickening in the Hospitalized Patient.
Bowel wall thickening in the hospitalized patient can be due to myriad etiologies. Familiarity with the optimal study protocols and a structured approach for evaluation are important. Understanding the pathology and knowing the imaging features of most common entities (ischemia, shock bowel, hemorrhage, infection, graft-versus-host disease, and fluid overload) enable radiologists to provide unique value to clinical management.


Can the UK AQ-10 be applicable to Chinese samples with autism spectrum disorder in Hong Kong? Cross-cultural similarities and differences.
The current study aimed at testing and developing alternative short versions of autism spectrum quotient (AQ-10) (adult [self-report], adult [parent-report], adolescent, and child versions) for use in Hong Kong. First, the various versions of AQ-10 developed in the United Kingdom (the AQ-10-UK) were applied to Hong Kong Chinese samples and demonstrated satisfactory discriminative power (AUCs 0.77-0.94). Second, the Hong Kong Chinese versions of AQ-10 (AQ-10-HK) were developed, using the same methodology as in the original UK study. There were some changes in the choice of items and cut-offs. The AQ-10-HK demonstrated slightly greater discriminative power (AUCs 0.88-0.97) to that of the AQ-10-UK, but the differences in AUCs were not statistically significant. Compared to the corresponding full-length versions, both the UK and HK short forms did not seem to lose any significant discriminative power. Yet, the various versions of AQ, be they the full-length or AQ-10, appeared to consistently exhibit slightly smaller AUCs with the Hong Kong Chinese samples than with the UK samples. So, this study found both cross-cultural similarities and differences. The AQ-10-HK was recommended for local practice to maximize the advantage gained. Yet, for international multi-site research collaboration, involving the UK and HK, the original AQ-10-UK can be used for direct comparison of data.


Histologic response of dose-intense chemotherapy with preoperative hypofractionated radiotherapy for patients with high-risk soft tissue sarcomas.
The authors studied a dose-intense regimen of epirubicin and ifosfamide with hypofractionated preoperative radiotherapy for high-risk soft tissue sarcomas. The primary objective was estimation of the rate of >or=95% pathologic necrosis. Twenty-five patients with intermediate-grade or high-grade, localized soft tissue sarcomas of the extremity or body wall measuring >5 cm were treated with epirubicin at a dose of 30 mg/m(2)/day on Days 1 to 4 and ifosfamide at a dose of 2.5 g/m(2)/day on Days 1 to 4 every 21 days for 3 preoperative and 3 postoperative cycles. A total of 28 grays of radiation was administered over 8 fractions during Cycle 2 of preoperative therapy (epirubicin was omitted). Sixteen patients (64%) completed all chemotherapy cycles and the average delivered dose intensity relative to intended therapy was 69%. Twenty-one patients (84%) experienced grade 4 toxicity (using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 2.0]), which was predominantly hematologic. Notable toxicities included neutropenic fever (40%), ifosfamide-induced encephalopathy (24%), and grade 3/4 anemia (64%). Postoperative wound complications requiring a surgical procedure occurred in 20% of patients. The rate of >or=95% pathologic necrosis was 40% (95% confidence interval [95% CI], 21-59%). Estimates of 2-year overall and disease-free survival were 84% (95% CI, 66-100%) and 62% (95% CI, 37-86%), respectively. A high rate of >or=95% pathologic necrosis was noted with this aggressive chemoradiotherapy regimen. The occurrence of significant acute toxicities limited the delivery of the intended dose intensity.


The inhibitory effect of Corynebacterium parvum and Pasteurella multocida pretreatment on staphylococcal synovitis in turkeys.
Corynebacterium parvum and Pasteurella multocida were shown to be immunostimulants in turkeys, increasing the ability of whole blood to kill Staphylococcus aureus and prolonging the incubation time of experimental staphylococcal synovitis.


Asthma in schoolchildren in Monroe county, Florida: school-based needs assessment.
Asthma is the most common chronic pediatric condition (14%) and the leading cause of school absenteeism in the USA. However, little is known about asthma prevalence and distribution in schoolchildren in the Florida Keys region (Monroe County). Thus, the objectives of this study were to assess asthma prevalence, symptoms, cost and distribution in schoolchildren in the Florida Keys region and to pinpoint where asthma management services are most needed. Cross-sectional survey data on asthma prevalence, symptoms and socio-demographics was collected and analyzed by race, sex, grade and zip code. A total of 2313 parents of schoolchildren in the Florida Keys completed the adapted Harlem Empowerment Zone Asthma Initiative Questionnaire. The questionnaire was distributed to school principals, who sent them home with students to be filled out by parents or caregivers. We also analyzed data from the online Monroe County 2012 Florida Youth Tobacco Survey, the 2011 Florida CHARTS, the Medical Expenditures Panel Survey, and emergency departments (ED). Data were analyzed by race, sex, and grade. In total 14.5% of respondents had been told their child had asthma and 9.6% reported their child had wheezing in the last 12 months. The prevalence was higher in the Lower Keys and Key West regions. Parents from households where anyone smoked cigarettes (OR 1.52, 95% CI 1.11-2.09) and those who had a male child (1.53, 1.17-2.00) more often reported that their child had asthma. The rate of asthma-related ED visits for Black non-Hispanic schoolchildren (1202 per 100,000) was substantially higher than the numbers for White (250.2 per 100,000) and Hispanic schoolchildren (325.1 per 100,000). Most of the direct cost of asthma was concentrated in children in grades four through seven ($1236.02-$2147.02 per child). The asthma prevalence in a sample of schoolchildren in the Florida Keys region was comparable to the nationwide prevalence. Black non-Hispanic schoolchildren had more asthma-related ED visits that White and Hispanic schoolchildren. Most of the direct cost of asthma is concentrated in children in late elementary through early middle school grades. Interventions are needed, particularly targeting Black schoolchildren in late elementary through early middle school grades in Lower Keys and Key West region.


Dopamine D1 receptor-dependent inhibition of NaCl transport in the rat thick ascending limb: mechanism of action.
Our previous in vitro microperfusion studies established that dopamine inhibits sodium chloride transport in the rat medullary thick ascending limb. The present study was designed to determine the intracellular signaling pathway mediating this response. The dopamine D1 receptor agonist fenoldopam (1 microM) inhibited sodium chloride transport in the thick ascending limb by 42+/-5%. The dopamine D1 receptor antagonist R-(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-HCl (SCH-23390) completely blocked this effect of fenoldopam. Suppression of protein kinase A activity using either myristoylated protein kinase inhibitor (PKI) or N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide.2HCl (H-89), as well as suppression of phospholipase C activity using 1-(6-((17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U-73122), had no effect on fenoldopam-dependent inhibition of transport. In contrast, inhibition of phospholipase A2 activity using E-6-(Bromomethylene)tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one (HELSS) significantly attenuated the effect of fenoldopam by 74%. The cytochrome P-450 monooxygenase inhibitor 17-octadecynoic acid (17-ODYA) and the protein kinase C inhibitor staurosporine both significantly attenuated the effects of fenoldopam by 67%. Exposure to 20-Hydroxy-(5Z, 8Z, 11Z, 14Z)-eicosatetraenoic acid (20-HETE) inhibited transport by 31+/-5%, and this effect was significantly attenuated by 66% in the presence of staurosporine. We propose a signaling pathway in which dopamine activates a calcium-independent phospholipase A2 in the medullary thick ascending limb. Released arachidonic acid is then metabolized to 20-HETE which subsequently increases protein kinase C activity that acts as a final transport effector.


Identification, using cDNA macroarray analysis, of distinct gene expression profiles associated with pathological and virological features of hepatocellular carcinoma.
It is still unclear as to whether the gene expression profile in HCV- or HBV-related HCC exhibits a degree of specificity and whether the development of HCC in a context of cirrhosis influences this gene profile. To address these issues, the expression profiles of 15 cases of HCC were analysed using cDNA macroarray. A global analysis and hierarchical clustering, demonstrated the heterogeneity of HCC patterns, with a majority of down-regulated genes. Statistical analysis clearly showed a distinction between the gene expression profiles of HCV- and HBV-related HCC. HBV-associated HCC exhibited involvement of different cellular pathways, those controlling apoptosis, p53 signalling and G1/S transition. In HCV-related HCC we identified a more heterogenous pattern with an over-expression of the TGF-beta induced gene. In HCC developing on non-cirrhotic tissues, beta-catenin encoding gene and genes implicated in the PKC pathway were specifically up-regulated. In addition, our investigation highlighted a distinct profiles of TGF-beta superfamily encoding genes in well, moderately or poorly differentiated HCC. Overall, our study supports the hypothesis that despite the heterogeneity of the HCC pattern, the large-scale screening of gene expression may provide data significant to our understanding of the mechanism of liver carcinogenesis.


Giant fibroepithelial polyp of the perineum: Giant fibroepithelial polyp.
Fibroepitheial polyps (FEP) are among the most common benign skin lesions and definitive histology is often needed to exclude malignancy. These polyps are usually less than 5cm in size and are often seen in genito-urinary sites including the perineum. A small number can reach a significant size. A 46-year-old female patient presented with a pedunculated mass measuring 18cm in diameter, localized to the left perineum. The lesion was excised and the histopathological diagnosis was fibroepithelial polyp. We present this case as the third largest FEP recorded in the available literature.


The opening of high-speed rail and environmental pollution of the Yangtze River Delta Region in China-based on SDID model test.
In recent years, environmental problems have attracted attention at home and abroad, so exploring the causes of environmental pollution has become a research content for scholars. The opening of high-speed railway has improved the economic development of China's Yangtze River Delta, and with the economic growth, the construction of high-speed railway has also led to environmental pollution in China's Yangtze River Delta. Therefore, using the data from 41 prefecture-level cities in China's Yangtze River Delta from 2003 to 2020, the SDID model was constructed, and the comprehensive index of environmental pollution was calculated by factor analysis to calculate the impact of high-speed railway construction on environmental pollution in China's Yangtze River Delta. The conclusions are as follows: The opening of high-speed railway significantly reduces the overall pollution level in China's Yangtze River Delta. The opening of high-speed rail has played a role in restraining the environmental pollution of the first and second tier cities and the third and fourth tier cities, but the pollution level of the third and fourth tier cities has decreased significantly.


Allosteric inhibition of the protein-protein interaction between the leukemia-associated proteins Runx1 and CBFbeta.
The two subunits of core binding factor (Runx1 and CBFbeta) play critical roles in hematopoiesis and are frequent targets of chromosomal translocations found in leukemia. The binding of the CBFbeta-smooth muscle myosin heavy chain (SMMHC) fusion protein to Runx1 is essential for leukemogenesis, making this a viable target for treatment. We have developed inhibitors with low micromolar affinity which effectively block binding of Runx1 to CBFbeta. NMR-based docking shows that these compounds bind to CBFbeta at a site displaced from the binding interface for Runx1, that is, these compounds function as allosteric inhibitors of this protein-protein interaction, a potentially generalizable approach. Treatment of the human leukemia cell line ME-1 with these compounds shows decreased proliferation, indicating these are good candidates for further development.


Electrophoretic transfer of DNA from gels to filters by using a homemade apparatus.
Electroblotting is a rapid and high-efficiency method of transferring DNA from gels to the variety of membranes available, in very short time frames when compared with capillary-blotting techniques and with much less preparation required. A simple apparatus made of two food savers, one dialysis membrane, one sponge, and two removable electrodes was used to transfer DNA molecules up to 21 kb, from agarose gels to nitrocellulose filters, in less than 30 min. A recombinant pAT153 plasmid carrying the human cytomegalovirus BamH I-P fragment (7.2 kb) was rapidly identified by hybridization, using our simplified transfer procedure.


Comparison of two video-imaging instruments for measuring volumetric shrinkage of dental resin composites.
The purpose of this study was to measure the polymerization shrinkage of three dental resin composites using two commercially available video-imaging devices to determine if the devices produced equivalent results. Small, semi-spherical specimens of a microhybrid (Venus), microfill (Filtek A110), and flowable (Esthet*X Flow) resin composite were manually formed and light activated for 40s using a light-curing unit. The volumetric polymerization shrinkage of fifteen specimens of each brand of resin composite was measured using the AcuVol and the Drop Shape Analysis System model DSA10 Mk2 (DSAS) video-imaging devices. Mean volumetric shrinkage values were calculated for each resin composite and equivalence was evaluated using the two one-sided tests approach. Differences between the means that were less than approximately 5% of the observed shrinkage were considered indicative of clinical equivalence. Mean volumetric shrinkage values measured for the resin composites were: Venus (AcuVol, 3.07+/-0.07%; DSAS, 2.90+/-0.07%); Filtek A110 (AcuVol, 2.26+/-0.10%; DSAS, 2.25+/-0.09%); and Esthet*X Flow (AcuVol, 5.01+/-0.17%; DSAS, 5.14+/-0.11%). Statistical analysis revealed that the two imaging devices produced equivalent results for Filtek A110 and Esthet*X Flow but not for Venus. Video-imaging systems provide an easy method for measuring volumetric shrinkage of resin composites. As with other methods for measuring volumetric shrinkage, however, they are best used to comparatively measure different materials within the same laboratory.


Signal transduction: turning a switch into a rheostat.
MAP kinase cascades are inherently switch-like, but, during yeast mating, MAPK signaling is graded. A new study suggests that the Ste5 scaffold protein is responsible for making this switch less switch-like.


Excessive glycation of pericapillary pericytic matrix components is an essential mechanism of arterial hypertension development in hyperglycemia.
In patients with essential hypertension, inhibition of glucose utilization in tissues was detected similar to that in diabetics. High levels of glycated compounds were found in cerebral, cardiac, and renal tissues of patients dead from coronary heart disease complicated and not complicated from diabetes mellitus and essential hypertension compared to victims dead from traumas. Experimental studies on rabbits and rats showed that the content of glycoconjugates in tissues did not increase in short-term (exogenous or stress-associated) hyperglycemia, while accumulation of glycoconjugates in pericapillary, pericytic, and cellular structures in long-term hyperglycemia caused deformation of tissue ultrastructure. These disorders can impede capillary transudation, initiate and stabilize arterial hypertension, and lead to multiple organ failure.


A Distance-Based Framework for the Characterization of Metabolic Heterogeneity in Large Sets of Genome-Scale Metabolic Models.
Gene expression and protein abundance data of cells or tissues belonging to healthy and diseased individuals can be integrated and mapped onto genome-scale metabolic networks to produce patient-derived models. As the number of available and newly developed genome-scale metabolic models increases, new methods are needed to objectively analyze large sets of models and to identify the determinants of metabolic heterogeneity. We developed a distance-based workflow that combines consensus machine learning and metabolic modeling techniques and used it to apply pattern recognition algorithms to collections of genome-scale metabolic models, both microbial and human. Model composition, network topology and flux distribution provide complementary aspects of metabolic heterogeneity in patient-specific genome-scale models of skeletal muscle. Using consensus clustering analysis we identified the metabolic processes involved in the individual responses to endurance training in older adults.


New bisbenzylisoquinoline alkaloid, isolation and structure elucidation from Cocculus pendulus.
This paper describes phytochemical studies on aerial part of the Cocculus pendulus, which led to the identification of a new ingredient namely, 2 N-methylkohatine (1) along with four reported compounds Kohatine (2), 1,2-Dehydrokohatine (3) and 5'Hhydroxyapateline (4). Structures of the all Compounds were elucidated by using 1 D and 2 D NMR and mass spectroscopy furthermore the structure of new Compound 1 was also proved by synthesize from compound 2 (Kohatine).


Borophenes made easy.
To date, the scalable synthesis of elemental two-dimensional materials beyond graphene still remains elusive. Here, we introduce a versatile chemical vapor deposition (CVD) method to grow borophenes, as well as borophene heterostructures, by selectively using diborane originating from traceable byproducts of borazine. Specifically, metallic borophene polymorphs were successfully synthesized on Ir(111) and Cu(111) single-crystal substrates and conjointly with insulating hexagonal boron nitride (hBN) to form atomically precise lateral borophene-hBN interfaces or vertical van der Waals heterostructures. Thereby, borophene is protected from immediate oxidation by a single hBN overlayer. The ability to synthesize high-quality borophenes with large single-crystalline domains in the micrometer scale by a straight-forward CVD approach opens up opportunities for the study of their fundamental properties and for device incorporation.


Effects of ageing on responses of rabbit iris smooth muscles to agonists and field stimulation.
1. The pharmacological properties of contractile responses of sphincter and dilator to field stimulation did not change with age, so that innervation of both these muscles does not change apparently with age. 2. In the sphincter, no age-related change was observed in muscarinic cholinoceptor mechanisms. Tension induced by field stimulation increased with age from 5 to 13 weeks, decreased from 40 to 125 weeks and did not change thereafter. Age-related change in tension is due to change in the amount of acetylcholine released by stimulation. 3. In the dilator, the pD2 value of norepinephrine increased with age from 5 to 13 weeks, decreased from 13 to 125 weeks and did not change thereafter. The pD2 value of norepinephrine was proportional to the receptor reserve, suggesting that changes in alpha 1-adrenoceptor mechanisms are due to changes in receptor reserve. No age-related change was observed in affinity of alpha 1-adrenoceptors. 4. The tension of the dilator induced by field stimulation increased with age from 5 to 13 weeks did not change from 13 to 180 weeks. The age-related change in tension is due to change in the amount of norepinephrine released by stimulation.


An assessment of perioperative outcomes for open, laparoscopic, and robot-assisted pancreaticoduodenectomy in New York State.
Minimally invasive techniques for pancreaticoduodenectomy (PD) are increasing in practice, however, data remains limited regarding perioperative outcomes. Our study sought to compare patients undergoing open pancreaticoduodenectomy (OPD) with those undergoing laparoscopic (LPD) or robot-assisted pancreaticoduodenectomy (RPD). Patients who underwent PD during 2016-2018 were identified from the New York State Planning and Research Cooperative System database. Of the 1954 patients identified, 1708 (87.4%) underwent OPD, 165 (8.4%) underwent LPD, and 81 (4.2%) underwent RPD. The majority of patients were White (63.8%), males (53.3%) with a mean age of 65.4 years. RPD patients had a lower median Charlson Comorbidity Index (2) than OPD (3) or LPD (3, p = 0.01) and had a lower 30-day rate of complications (35.8% vs. 48.3% vs. 43.6% respectively, p = 0.05). After propensity-score matching, however, there were no differences between the groups regarding overall complications, surgical site infections, anastomotic leaks, or mortality (p = NS for all). OPD demonstrated a longer length of stay (median 8 days) compared to LPD (7 days) or RPD (7 days, p < 0.01). Patients undergoing LPD and RPD have a shorter length of hospital stay compared to OPD and there was no difference in overall morbidity or mortality when matched to similar patients.


Natural LILRB1 D1-D2 variants show frequency differences in populations and bind to HLA class I with various avidities.
Leukocyte immunoglobulin-like receptor B1 (LILRB1) is widely expressed on various immune cells and the engagement of LILRB1 to HLA class I and pathogen-derived proteins can modulate the immune response. In the current study, 108 LILRB1 alleles were identified by screening the LILRB1 locus from the 1000 Genomes Phase 3 database. Forty-six alleles that occurred in three or more individuals encode 28 LILRB1 allotypes, and the inferred LILRB1 allotypes were then grouped into 9 LILRB1 D1-D2 variants for further analysis. We found that variants 1, 2, and 3 represent the three most frequent LILRB1 D1-D2 variants and the nine variants show frequency differences in populations. The binding assay demonstrated that variant 1 bound to HLA class I with the highest avidity, and all tested LILRB1 D1-D2 variants bound to HLA-C with lower avidity than to HLA-A and -B. Locus-specific polymorphisms at positions 183, 189, and 268 in HLA class I and dimorphisms in HLA-A (positions 207 and 253) and in HLA-B (position 194) affect their binding to LILRB1. Notably, the electrostatic interaction plays a critical role in the binding of LILRB1 to HLA class I as revealed by electrostatic analysis and by comparison of different binding avidities caused by polymorphisms at positions 72 and 103 of LILRB1. In this paper, we present a comprehensive study of the population genetics and binding abilities of LILRB1. The data will help us better understand the LILRB1-related diversity of the immune system and lay a foundation for functional studies.


Synthesis, chemical and biochemical characterization of Lu2O3-iPSMA nanoparticles activated by neutron irradiation.
Among the nanomaterials, rare sesquioxides (lanthanide oxides such as Lu2O3) are of interest due to their adequate thermal conductivity, excellent chemical stability, and high light output. The prostate-specific membrane antigen (PSMA) is an integral multifunctional protein overexpressed in various types of cancer cells. The radiolabeled PSMA inhibitor peptides (iPSMA) have demonstrated their usefulness as specific probes in the treatment and detection of a wide variety of neoplasms, mainly due to their high in vivo recognition by the PSMA protein. The objective of this research was to synthesize Lu2O3-iPSMA nanoparticles (NPs) and characterize their physicochemical properties before and after neutron activation, as well as to assess their biodistribution profile and in vitro potential to target cells overexpressing PSMA. The Lu2O3 NPs were synthesized by the precipitation-calcination method and conjugated to the iPSMA peptide using DOTA (1,4,7,10-tetraazocyclodecane-N,N',N″,N‴-tetraacetic acid) as a linking agent. Results of the physicochemical characterization by FT-IR and UV-Vis spectroscopies, SEM, TEM, DLS, HRTEM, SAED, DSC-TGA, and X-ray diffraction indicated the formation of Lu2O3-iPSMA NPs (diameter of 29.98 ± 9.07 nm), which were not affected in their physicochemical properties after neutron activation. 177Lu2O3-iPSMA NPs showed high affinity (Kd = 5.7 ± 1.9 nM) for the PSMA protein, evaluated by the saturation assay on HepG2 hepatocellular carcinoma cells (PSMA-positive). The biodistribution profile of the nanosystem in healthy mice showed the main uptake in the liver. After irradiation, radioactive Lu2O3-iPSMA NPs exhibited radioluminescent properties, making the in vivo acquisition of their biodistribution, via optical imaging, possible. The results obtained from this research validate the execution of additional preclinical studies with the objective of evaluating the potential of the 177Lu2O3-iPSMA NPs for the targeted radiotherapy and in vivo imaging of tumors overexpressing the PSMA protein.


Correlation between olfactory responses, dispersal tendencies, and life-history traits of the predatory mite Neoseiulus womersleyi (Acari: Phytoseiidae) of eight local populations.
To investigate the relationship between foraging behavior and life-history traits of the predatory mite Neoseiulus womersleyi, the olfactory responses, dispersal ratios from a prey patch, predation rates, fecundity, and developmental times in eight local populations of N. womersleyi were investigated. Significant differences among local populations were found in all these traits except fecundity. None of the life-history traits correlated with foraging behavior. A significant positive correlation was found only between the olfactory response and the dispersal ratio. These results suggested that predatory mites with low olfactory responses would stay in a prey patch longer than predatory mites with high olfactory responses.


The endosperm and the embryo of Arabidopsis thaliana are independently transformed through infiltration by Agrobacterium tumefaciens.
Several experiments had indicated that in planta transformation of Arabidopsis thaliana by Agrobacterium involves the female germ line. In order to identify the precise stage at which transformation occurs we have monitored expression of a gusA reporter gene in the two products of the double fertilization of infiltrated plants. The plantlets and the remaining endosperm of seeds were separately tested after germination. It appeared that in the majority of cases only the plantlet or the endosperm were transformed. Based on transformation with two vectors borne by two different Agrobacterium strains, the minority of 'co-transformed' plantlets and endosperm can be explained by simultaneous but independent transformation events. These results indicate that mature female gametes could be the targets of T-DNA.


Effects of environmental factors on denitrifying bacteria and functional genes in sediments of Bohai Sea, China.
The ability of denitrifying microorganisms to respond to different ecological pressures remains unknown, especially in marine sediments rich in various heavy metals. Here, gene abundance and transcriptional abundance of five functional denitrification genes (narG, nirK, nirS, norB, and nosZ) in Bohai Sea sediments were examined, and high-throughput Illumina sequencing was used to analyze the community structure of nirK and nirS denitrifying bacteria. The nirS- and nirK-type denitrifying bacteria were classified into different genera. The heavy metal content in sediments was negatively correlated with transcriptional abundance of denitrifying genes, and RNA: DNA ratio for each gene was highest in central Bohai Sea. These results indicated the distribution of nitrite reductase denitrifying bacterial communities was affected by depth, total nitrogen, total phosphorus and sediment grain size. Heavy metal contamination in sediment environment may negatively regulate the transcriptional abundance of denitrifying genes and cause geographical differences in the denitrifying bacterial community structure.


High-Entropy Microdomain Interlocking Polymer Electrolytes for Advanced All-Solid-State Battery Chemistries.
All-solid-state polymer electrolytes (ASPEs) with excellent processivity are considered one of the most forward-looking materials for large-scale industrialization. However, the contradiction between improving the mechanical strength and accelerating the ionic migration of ASPEs has always been difficult to reconcile. Herein, a rational concept is raised of high-entropy microdomain interlocking ASPEs (HEMI-ASPEs), inspired by entropic elasticity well-known in polymer and biochemical sciences, by introducing newly designed multifunctional ABC miktoarm star terpolymers into polyethylene oxide for the first time. The tailor-made HEMI-ASPEs possess multifunctional polymer chains, which induce themselves to assemble into micro- and nanoscale dynamic interlocking networks with high topological structure entropy. HEMI-ASPEs achieve excellent toughness, considerable ionic conductivity, an appreciable lithium transference number (0.63), and desirable thermal stability (Td > 400 °C) for all-solid-state lithium metal batteries. The Li|HEMI-ASPE-Li|Li symmetrical cell shows a stable Li plating/stripping performance over 4000 h, and a LiFePO4 |HEMI-ASPE-Li|Li full cell exhibits a high capacity retention (≈96%) after 300 cycles. This work contributes an innovative design concept introducing high-entropy supramolecular dynamic networks for ASPEs.


Computer analysis of left ventricular dynamic geometry in man.
Analysis of left ventricular performance in 20 normal patients was undertaken using biplane cineangiography and a semiautomatic computer image processing system. The analysis included evaluation of volumes, ejection fraction, regional shortening, patterns of ejection and filling and, when simultaneous left ventricular pressure was recorded stroke work, stroke power, wall stress and internal myocardial work. All of these data were calculated from digitized images stored permanently on digital magnetic tape, and can be reproduced without reanalysis of the cine film. Normal left ventricular function is described by an end-diastolic volume index of 82 +/- 3 ml, an ejection fraction of 60 +/- 2 percent, left ventricular mass index of 97 +/- 6 g/m2, peak first derivative of volume (dV/dt) of 485 +/- 28 ml/sec, anterior shortening of 48 +/- 2.3 percent, inferior shortening of 33 +/- 1.7 percent, lateral shortening of 29 +/- 1.5 percent, anterior mean shortening velocity (Vcf, in percent of end-diastolic length [L]/sec) of 1.5 +/- 0.1 L/sec, inferior Vcf of 1.1 +/- 0.06 L/sec and lateral Vcf of 0.94 +/- 0.2 L/sec, stroke work of 1.33 +/- 0.21 joules, mean stroke power of 3.7 +/- 0.62 joules/sec, integrated left ventricular pressure (tension-time index) of 2,866 +/- 340 mm Hg-sec, and integrated stress (stress-time index) of 7,260 +/- 765 (X 10(3)) dynes sec/cm2. Internal myocardial work was calculated from the strain energy. More internal work was expended in circumferential than logitudinal shortening (circumferential, 0.69 +/- 0.1 joules; longitudinal, 0.41 +/- 0.08, P less than 0.01), because hoop stress was greater than meridian stress (hoop, 201 +/- 20 dynes/cm3 X 10(3); meridian, 126 +/- 13, P less than 0.001). This analysis of left ventricular performance provides a reliable means for identifying abnormal ventricular function and may be more sensitive than any one measurement alone. The use of digital image processing makes this complex functional analysis of left ventricular performance feasible.


Experimentally-induced osteoarthritis in guinea pigs: effect of surgical procedure and dietary intake of vitamin C.
The effect of variation in dietary ascorbic acid on surgically induced osteoarthritis was examined in the stifle joints of guniea pigs. Two different surgical procedures were used to induce osteoarthritis in the right stifle joint of these animals. Guinea pigs were maintained either on a high (150 mg/day) or low (2.4 mg/day) dietary intake of vitamin C. Regardless of the surgical procedure used to induce osteoarthritis, the animals maintained on the high level of vitamin C consistently showed severe joint damage than animals on the low level of the vitamin.


An unusual case of heart failure due to ANCA-negative vasculitis: A case report and focused review of the literature.
Heart failure due to ANCA-negative vasculitis, is a rare potentially life-threatening manifestation of ANCA vasculitis. Therefore, physicians must always pay attention to this manifestation for proper disease diagnosis and treatment. Less than 10% of primary vasculitides cause cardiac dysfunction, with Takayasu's arteritis, polyarteritis nodosa, and eosinophilic granulomatosis with polyangiitis being the most common cases. However, any cardiac tissue can be affected by ANCA vasculitis. We present a case of heart failure with reduced ventricular ejection fraction due to ANCA negative-vasculitis.


Model-based approaches to predict drug-drug interactions associated with hepatic uptake transporters: preclinical, clinical and beyond.
Membrane transporters have been recognized to play a key role in determining the absorption, distribution and elimination processes of drugs. The organic anion-transporting polypeptide (OATP)1B1 and OATP1B3 isoforms are selectively expressed in the human liver and are known to cause significant drug-drug interactions (DDIs), as observed with an increasing number of drugs. It is evident that DDIs involving hepatic transporters are capable of altering systemic, as well as tissue-specific, exposure of drug substrates resulting in marked differences in drug safety and/or efficacy. It is therefore essential to quantitatively predict such interactions early in the drug development to mitigate clinical risks. The role of hepatic uptake transporters in drug disposition and clinical DDIs has been reviewed with an emphasis on the current state of the models applicable for quantitative predictions. The readers will also gain insight into the in vitro experimental tools available to characterize transport kinetics, while appreciating the knowledge gaps in the in vitro-in vivo extrapolation (IVIVE), which warrant further investigation. Static and dynamic models can be convincingly applied to quantitatively predict drug interactions, early in drug discovery, to mitigate clinical risks as well as to avoid unnecessary clinical studies. Compared to basic models, which focus on individual processes, mechanistic models provide the ability to assess DDI potential for compounds with systemic disposition determined by both transporters and metabolic enzymes. However, complexities in the experimental tools and an apparent disconnect in the IVIVE of transport kinetics have limited the physiologically based pharmacokinetic modeling strategies. Emerging data on the expression of transporter proteins and tissue drug concentrations are expected to help bridge these gaps. In addition, detailed characterization of substrate kinetics can facilitate building comprehensive mechanistic models.


One year follow-up after cryoballoon isolation of the pulmonary veins in patients with paroxysmal atrial fibrillation.
Pulmonary vein isolation (PVI) with cryoenergy delivered through a balloon is a new approach in the treatment of atrial fibrillation (AF), but long-term follow-up is lacking. The aim of this study was to provide insight in the success rate and the incidence of recurrences. Patients with symptomatic AF despite anti-arrhythmic drugs (AADs) were treated with cryoballoon PVI. Daily transtelephonic ECG monitoring, 24 h Holter-ECG, and an arrhythmia-focused questionnaire were used to document AF. One hundred and forty-one patients completed a follow-up of 457 +/- 252 days. Before ablation, Holter-ECG showed AF in 45%, including 16% continuous AF throughout the recording. Event recording revealed a median AF burden of 26%. The questionnaire showed a median of weekly AF complaints lasting for hours. All but one patient had successful PVI with a single procedure. After ablation, AF (defined as lasting for more than 30 s) was seen in 11% of Holter-ECGs, with 1% continuous AF. The event recording showed an AF burden of 9%. The median patient reported no more AF-related symptoms. Recurrence during the first 3 months was predictive for later recurrence. A second procedure was performed in 24 patients. The freedom of AF was 59% without AADs after 1,2 procedures. Four right phrenic nerve paralyses occurred, all resolving within 6 months. No PV stenoses were observed. Pulmonary vein isolation with a cryothermal balloon is an effective treatment for paroxysmal AF, resulting in a clinical success rate comparable to studies involving radiofrequency ablation. Temporary right phrenic nerve paralysis is the most important complication.


Cross-Phenotype Association Analysis Using Summary Statistics from GWAS.
For over a decade, genome-wide association studies (GWAS) have been a major tool for detecting genetic variants underlying complex traits. Recent studies have demonstrated that the same variant or gene can be associated with multiple traits, and such associations are termed cross-phenotype (CP) associations. CP association analysis can improve statistical power by searching for variants that contribute to multiple traits, which is often relevant to pleiotropy. In this chapter, we discuss existing statistical methods for analyzing association between a single marker and multivariate phenotypes, we introduce a general approach, CPASSOC, to detect the CP associations, and explain how to conduct the analysis in practice.


Effect of nitric oxide synthase induction on the expression of mitochondrial respiratory chain enzyme subunits in mixed cortical and astroglial cell cultures.
In the present study we evaluated the effects of NO synthase (NOS) induction on the regulation of cytochrome c oxidase (CO) and F0F1-ATPase subunit expression in astroglial and mixed cortical cell cultures. In mixed cortical cell cultures, 18 h of treatment with lipopolysaccharide (LPS, 0.1 microgram/mL) plus interferon-gamma (INF-gamma, 10 U/mL) caused an increase of mRNAs for CO-I, F0F1-ATPase 6 and also for iNOS at 20 DIV. The induction of both CO-I and F0F1-ATPase 6 was abolished by the NOS inhibitor N-monomethyl-L-arginine (NMMA) or by the enzymatic scavenger superoxide dismutase/catalase (SOD/CAT). In primary astroglial cell cultures, treatment for 18 h with increasing concentrations of LPS and INF gamma, produced an increase in the amount of mitochondrial encoded CO-I and -II subunits, with no significant modifications of nuclear encoded subunit IV. An increase was also observed at level of transcription for CO-I and -II, and F0F1-ATPase 6 mRNAs. These effects were abolished by addition of NMMA or SOD/CAT. mRNA induction of CO-I was higher in mixed cortical than in astroglial cell cultures while that of F0F1-ATPase 6 was similar in both cell types. These results suggest that the expression of mitochondrial encoded subunits (CO-I, CO-II and F0F1-ATPase 6) is up-regulated in response to oxygen and NO reactive species. The activity of cytochrome c oxidase decreased after LPS/INF gamma treatment in both astroglial and mixed cortical cultures. The activity of ATP synthase was unmodified, while ATP content drastically decreased after LPS/INF gamma treatment, in both astroglial and mixed cortical cultures. The enzymatic activities of catalase and Mn-SOD (mitochondrial) showed a significant increase after LPS/INF gamma treatment, which was abolished by NMMA.


Design, synthesis and identification of novel substituted 2-amino thiazole analogues as potential anti-inflammatory agents targeting 5-lipoxygenase.
Human 5-Lipoxygenase (5-LOX) is a key enzyme targeted for asthma and inflammation. Zileuton, the only drug against 5-LOX, was withdrawn from the market due to several problems. In the present study, the performance of rationally designed conjugates of thiazole (2) and thiourea (3) scaffolds from our previously reported 2-amino-4-aryl thiazole (1) is reported. They are synthesized (total 31 derivatives), characterized, and tested against the 5-LOX enzyme in vitro and the mode of action of the most active ones are determined. Compound 2m exhibited an IC50 of 0.9 ± 0.1 μM acting through competitive (non-redox) mechanism, unlike Zileuton, and found to be devoid of radical scavenging properties. Computational studies are in good agreement with the experimental data supporting its mechanism of action. Another lead molecule from the thiourea series (3), 3f, exhibited an IC50 of 1.4 ± 0.1 μM against 5-LOX whose mode of action is redox type (non-competitive). It is promising to note that the activities displayed by both the lead inhibitors, 2m and 3f, are better than the commercial drug, Zileuton (IC50 = 1.5 ± 0.3 μM). These inhibitors could be further developed as drugs against inflammation.


Feasibility of multidisciplinary telehealth evaluations in atypical dementia.
While cognitive assessment by videoconference has become possible over the past decade, the COVID-19 pandemic underscores the critical need for expansion and examination of these methods, their appropriateness for various patient populations, and their benefits and limitations. Validity and reliability studies of tele-neuropsychological testing have been conducted in MCI or mild AD dementia patients (e.g., MMSE=25+); few studies have assessed the feasibility of neurologic examination by video, and none in atypical dementias, assuming that patients with some types (e.g., language, comportment) or greater severity of cognitive-behavioral impairment would be unable to participate. Here we report the feasibility of telehealth services for a multi-disciplinary dementia subspecialty clinic that include cognitive-behavioral and neurologic assessment with patients with atypical neurodegenerative syndromes. 104 patient-carepartner (P-C) dyads met with providers in the MGH FTD Unit by videoconference (March-December, 2020) for routine clinical care. P-Cs completed validated questionnaires assessing cognition-mood/behavior/function on REDCap prior to video clinical interview and cognitive assessment, including the MoCA and Boston Cognitive Exam (BCE2.0), a newly revised brief cognitive assessment battery adapted for telehealth. P-Cs met with a neurologist for a basic neurologic examination (including eye-movement examination), review of assessment results, and discussion of care plan. P-Cs completed a satisfaction survey. The 104 P-Cs included a range of atypical neurodegenerative disorders (bvFTD, PCA, PPA, CBS, PSP, eoAD, Multidomain syndrome) mild-to-severe impairment (CDR range: 0-3). 76% completed the MoCA (25% had CDR=2). 36% also completed the BCEv2. Comparison of remote assessment data to previous in-person testing is ongoing. Of P-Cs who completed a satisfaction survey, all reported being "very satisfied" with the appointment, with 93% open to participating in a remote visit again. 87% found the telehealth visit comparable to an in-person visit. 66% preferred a future combination of remote and in-person visits. Multi-disciplinary telehealth visits appear to be feasible with patients with atypical cognitive-behavioral syndromes of across the severity spectrum. P-Cs report a high degree of satisfaction with the telehealth visit and an openness to ongoing telehealth visits. Results have implications for increasing accessibility of multidisciplinary medical services for patients and families living with complex forms of dementia.


The Accuracy of Web Sites and Cellular Phone Applications in Predicting the Fertile Window.
To evaluate the validity of fertility web sites and applications (apps) by comparing the predicted fertile window of these modalities to the actual fertile window of a standard 28-day cycle. This was a descriptive study. The top resulting free web sites and electronic apps downloadable to a cellular phone that provide calendars for fertility and ovulation prediction were assessed. Cycles were standardized to 28 days in length, 4 days of menses, and the last menstrual period was set to January 1, 2015. The predicted date of ovulation and fertility window generated were compared with an actual estimated date of ovulation on cycle day 15, January 15, and a fertile window consisting of cycle day 10 to cycle day 15, the day of ovulation plus the preceding 5 cycle days, January 10-15. Data from 20 web sites and 33 apps were collected. Of all the web sites and apps used, one web site and three apps predicted the precise fertile window. Web sites and electronic apps used by the general public to predict fertile windows are generally inaccurate, although the clinical effect of this inaccuracy is unknown. Although they all include the most fertile cycle day, the range of the fertility window varies widely. Patients who are trying to conceive with the assistance of calendars generated from web sites and electronic apps should be counseled on the inaccuracy of these modalities.


Use of ocular hypotensive prostaglandin analogues in patients with uveitis: does their use increase anterior uveitis and cystoid macular oedema?
A retrospective comparative case series was studied to determine whether the use of prostaglandin (PG) analogues to treat raised intraocular pressure (IOP) in patients with uveitis resulted in an increase in the frequency of anterior uveitis or cystoid macular oedema (CMO). 163 eyes of 84 consecutive patients with uveitis and raised IOP treated with a PG analogue at two tertiary referral uveitis clinics were identified over a 3-month period. Control eyes were selected as those uveitic eyes of the same patients, which were treated with topical IOP-lowering agent(s) other than a PG analogue. Pretreatment IOP was compared with the mean IOP during PG analogue treatment. The frequency of anterior uveitis and CMO during PG analogue treatment was compared with the frequency of these complications in the control eyes during non-PG IOP-lowering treatment. Significant IOP reductions were observed during PG analogue treatment. There was no significant difference in the frequency of anterior uveitis in those eyes treated with PG analogues and those treated with non-PG agents (p = 0.87, Fisher exact test). None of the 69 uveitic eyes without a previous history of CMO developed this complication. There was no increase in the frequency of visually significant CMO during PG treatment compared with that during non-PG treatment (p = 0.19, Fisher exact test). This study demonstrates that PG analogues are potent topical medications for lowering raised IOP in patients with uveitis and are not associated with increased risk of CMO or anterior uveitis.


Oral administration of Nigella sativa oil attenuates arsenic-induced redox imbalance, DNA damage, metabolic distress, and histopathological alterations in rat intestine.
Exposure to arsenic, a widespread environmental toxin, produces multiple organ toxicity, including gastrointestinal toxicity. Nigella sativa (NS) has long been revered for its numerous health benefits under normal and pathological states. In view of this, the present study attempts to evaluate the protective efficacy of orally administered Nigella sativa oil (NSO) against arsenic-induced cytotoxic and genotoxic alterations in rat intestine and elucidate the underlying mechanism of its action. Rats were categorized into the control, NaAs, NSO, and NaAs+NSO groups. After pre-treatment of rats in the NaAs+NSO and NSO groups daily with NSO (2 ml/kg bwt, orally) for 14 days, NSO treatment was further continued for 30 days, with and without NaAs treatment (5 mg/kg bwt, orally), respectively. Various biochemical parameters, such as enzymatic and non-enzymatic antioxidants, carbohydrate metabolic and brush border membrane marker enzyme activities were evaluated in the mucosal homogenates of all the groups. Intestinal brush border membrane vesicles (BBMV) were isolated, and the activities of membrane marker enzyme viz. ALP, GGTase, LAP, and sucrase were determined. Further, the effect on kinetic parameters viz KM (Michaelis-Menten constant) and Vmax of these enzymes was assessed. Integrity of enterocyte DNA was examined using the comet assay. Histopathology of the intestines was performed to evaluate the histoarchitectural alterations induced by chronic arsenic exposure and/or NSO supplementation. Arsenic accumulation in the intestine was studied by inductively coupled plasma-mass spectroscopy (ICP-MS). NaAs treatment caused substantial changes in the activities of brush border membrane (BBM), carbohydrate metabolism, and antioxidant defense enzymes in the intestinal mucosal homogenates. The isolated BBM vesicles (BBMV) also showed marked suppression in the marker enzyme activities. Severe DNA damage and mucosal arsenic accumulation were observed in rats treated with NaAs alone. In contrast, oral NSO supplementation significantly alleviated all the adverse alterations induced by NaAs treatment. Histopathological examination supported the biochemical findings. NSO, by improving the antioxidant status and energy metabolism, could significantly alter the ability of the intestine to protect against free radical-mediated arsenic toxicity in intestine. Thus, NSO may have an excellent scope in managing gastrointestinal distress in arsenic intoxication.


A Bonhoeffer-van der Pol oscillator model of locked and non-locked behaviors of living pacemaker neurons.
A recent investigation of the influence of periodic inhibitory trains on a crayfish pacemaker neuron showed not only well-known locked periodic responses but also intermittent, messy, and hopping responses. This communication studies the responses of the Bonhoeffer-van der Pol (BVP) model with self-sustained oscillation when exposed to periodic pulse trains inputs. The analysis is similar to that used in crayfish and reveals interesting features, both comparable and complementary to those seen in the living preparation.


Impact of speech rate and mouth opening on hypernasality and speech intelligibility in children with a cleft (lip and) palate.
this study evaluated the effectiveness of different speech techniques (i.e. modification of speech rate and/or mouth opening) for the rehabilitation of hypernasality in children with a cleft palate with or without a cleft lip (CP±L). The impact of speech rate and/or mouth opening was investigated on both hypernasality and speech intelligibility. thirteen patients with CP±L and perceived hypernasality (mean age: 10y5m) and 13 age and gender matched children without CP±L were included. Children were asked to read an oral and oronasal text passage in ten different speaking conditions where speech rate and/or mouth opening was manipulated. Outcome measures included instrumental measurements of hypernasality and perceptual ratings of speech intelligibility and hypernasality. speaking with a lower speech rate had a statistically significant, positive influence on objective measures of hypernasality in both groups, especially when elicited by a metronome. An increased mouth opening and the combination of both techniques was only effective in the control group. Moreover, it was found that children without CP ±L were less intelligible when speaking with a decreased mouth opening. a metronome-controlled decrease of speech rate had a positive influence on objective measures of hypernasality both in children with and without CP±L. However, present study could not provide any evidence that speaking with increased mouth opening reduces objective and perceptual measures of hypernasality in children with CP±L. Further research investigating the use of these techniques is necessary.


Psychosocial Factors and Personality Traits and the Prevalence of Arterial Hypertension Among 35- and 55-Year-Old Men and Women in Sweden and Estonia: a SWESTONIA Longitudinal Study.
Psychosocial factors influence the risk of developing hypertension. Personality traits have a modulating effect against the harmful influences of psychosocial factors. Through a longitudinal clinical study consisting of men and women aged 35 and 55 at the baseline in Estonia and Sweden, to assess the influence of psychosocial factors and personality traits resulting in arterial hypertension. Data analysis based on the cross-sectional study with 2 assessments over 13 years of a sample comprising 158 individuals from Estonia and 213 individuals from Sweden. The Pearlin Mastery Scale, Rosenberg Self-esteem Scale, Depression Model and Gothenburg Quality of Life Instrument were used. Throughout the follow-up period, a higher depressive mood and lower self-assessed quality of life score prevailed among the 35-year-old and 55-year-old Estonians compared with the Swedish study participants (p < 0.001). Among the 55-year-old Estonian study participants with diagnosed hypertension, but not among the Swedish, negative stressful life events had a significantly stronger effect (p < 0.001) on the risk of developing hypertension. In addition, lower mastery (p < 0.05) dominated among study participants diagnosed with hypertension. The combined effects of psychosocial factors and personality traits are important variables in predicting the risk of developing arterial hypertension. The study results are relevant to clinical practice and provide suggestions for employing successful preventive measures.


Cost effectiveness of first-line oral antiviral therapies for chronic hepatitis B : a systematic review.
Chronic hepatitis B is a common, progressive disease, particularly when viral replication is detected. Oral antivirals can suppress viral replication and prevent or delay the development of cirrhosis and liver-related complications. The aim of this study was to systematically review the quality of cost-effectiveness evidence on first-line treatment with entecavir (ETV) or tenofovir difumarate (TDF) for patients with chronic hepatitis B. We searched electronic databases and retrieved articles published up to October 2011, in which the cost effectiveness of ETV or TDF was compared with that of other oral antivirals. The quality of the studies identified was assessed with a standard checklist for critical appraisal. We selected 16 original papers, all published in the last 5 years. There was a conflict of interest in 12 of the 16 studies due to sponsorship by the corresponding pharmaceutical companies. According to the validity assessment, ten studies were classified as high quality. Five studies performed a cost-effectiveness analysis comparing ETV with TDF; they concluded that TDF dominates ETV. The other 11 studies compared ETV or TDF with other strategies; all concluded that ETV and TDF are both cost-effective interventions. This systematic review shows that there is valid evidence suggesting that ETV and TDF are cost-effective interventions for the treatment of patients with chronic hepatitis B in many health systems. In countries where both alternatives are available, it appears that TDF dominates ETV. These results could help decision makers and clinicians to understand economic issues regarding the available drugs for first-line treatment of hepatitis B.