Rapid cultivation of aerobic granular sludge by xanthan gum in SBR reactors.
This study focuses on the effect of xanthan gum on aerobic sludge granulation, through close monitoring of the physical and chemical changes of the aerobic granular sludge, and treatment performance. Two sequencing batch reactors (SBRs), R1 and R2, were seeded with activated sludge only (R1) and with a mixture of activated sludge and 40 mg/L of xanthan gum (R2). The results showed that granulation finished on the 20th day in R2, far faster than the granulation time of 30 days in R1. Meanwhile, there was a reliably higher sludge concentration, better settling properties and better particle mechanical strength in R2, and better removal performance of total nitrogen (TN) and chemical oxygen demand (COD). The results demonstrated that seeding xanthan gum enhanced the aerobic sludge granulation in the SBR. Maybe its anionic and hydrophilic surface characteristics facilitate interactions with cations and other polysaccharides, inducing stronger gelation, which promoted the formation of particles or increased the internal relationship between particles, thereby increasing the cohesion within the sludge, so that the granular sludge was not easily broken.


Bioactive effects of olive oil phenolic compounds in humans: reduction of heart disease factors and oxidative damage.
Oxidative stress is defined as an imbalance between the oxidant and antioxidant systems of the body, in favour of the oxidants. Oxidative stress produced by free radicals has been linked to the development of several diseases such as cardiovascular, cancer, and neurodegenerative diseases. Olive oil is the main source of fat of the Mediterranean diet which has been shown to be effective against oxidative stress associated diseases and also with the ageing. Besides its richness in monounsaturated fatty acid, the oleic acid, olive oil contains minor components with antioxidant properties. Here, we update the state of the art, and degree of evidence, of the body of knowledge concerning the protective role on lipids and lipid oxidative damage in humans of the olive oil phenolic compounds.


GUN4-porphyrin complexes bind the ChlH/GUN5 subunit of Mg-Chelatase and promote chlorophyll biosynthesis in Arabidopsis.
The GENOMES UNCOUPLED4 (GUN4) protein stimulates chlorophyll biosynthesis by activating Mg-chelatase, the enzyme that commits protoporphyrin IX to chlorophyll biosynthesis. This stimulation depends on GUN4 binding the ChlH subunit of Mg-chelatase and the porphyrin substrate and product of Mg-chelatase. After binding porphyrins, GUN4 associates more stably with chloroplast membranes and was proposed to promote interactions between ChlH and chloroplast membranes-the site of Mg-chelatase activity. GUN4 was also proposed to attenuate the production of reactive oxygen species (ROS) by binding and shielding light-exposed porphyrins from collisions with O₂. To test these proposals, we first engineered Arabidopsis thaliana plants that express only porphyrin binding-deficient forms of GUN4. Using these transgenic plants and particular mutants, we found that the porphyrin binding activity of GUN4 and Mg-chelatase contribute to the accumulation of chlorophyll, GUN4, and Mg-chelatase subunits. Also, we found that the porphyrin binding activity of GUN4 and Mg-chelatase affect the associations of GUN4 and ChlH with chloroplast membranes and have various effects on the expression of ROS-inducible genes. Based on our findings, we conclude that ChlH and GUN4 use distinct mechanisms to associate with chloroplast membranes and that mutant alleles of GUN4 and Mg-chelatase genes cause sensitivity to intense light by a mechanism that is potentially complex.


Antagonistic action of Lactobacillus lactis toward Salmonella spp. and Escherichia coli O157:H7 during growth and refrigerated storage.
Cells of Lactobacillus lactis were added to trypticase soy broth that contained cells of Escherichia coli O157:H7 or cells of Salmonella spp. in order to determine if L. lactis inhibited the pathogens. The inhibition of all pathogens was examined during growth at 37 degrees C for 24 h. Inhibition of Salmonella spp. was also examined at refrigeration temperatures (6 degrees C) for 5 days. One strain each of E. coli O157:H7, Salmonella Typhimurium, and Salmonella Enteritidis was examined. E. coli was enumerated on violet red bile agar, and Salmonella spp. were enumerated on brilliant green agar. In all experiments at 37 degrees C, the L. lactis completely inhibited all pathogens, producing numbers that were not detectable after 24 h of incubation. There were significant (P > 0.05) increases in numbers of the pathogens in the control samples containing no L. lactis. There were significant (P < 0.05) declines in the pH of both control and L. lactis inoculated samples. There was a significantly (P < 0.05) larger decline in the pH of samples inoculated with L.lactis. Interaction studies with pH-neutralized broth indicated that acid production by L lactis was primarily responsible for the inhibition. Numbers of Salmonella spp. incubated at 6 degrees C did not decline significantly (P > 0.05) for control or inoculated samples, which suggests that this strain of L. lactis does not inhibit Salmonella spp. at refrigeration temperatures. Additionally, there were no significant (P > 0.05) changes in pH or in numbers of L. lactis during refrigerated storage.


Selective in vitro response of thymus-derived lymphocytes from Treponema pallidum-infected rabbits.
The blastogenic response of nylon wool-separated peripheral-blood lymphocytes from Treponema pallidum-infected rabbits was tested in vitro with mitogens and T. pallidum antigens. The mitogenic response of the enriched T-cell population to concanavalin A and phytohemagglutinin was depressed during the first 3 to 4 weeks of infection, similar to the pattern observed with unfractionated cells. Shortly thereafter, levels of blastogenesis returned to values of uninfected cultures. Enhanced blast transformation was seen immediately when purified T-cells from infected rabbits were exposed in vitro to T. pallidum antigens. Although these relatively high levels of blastogenesis were maintained for the duration of the experiment, cultures of unfractionated lymphocytes from infected rabbits did not exhibit an increased blastogenic response to the same antigen preparation until 3 to 4 weeks after infection. Autologous serum from infected rabbits decreased the lymphocyte response to T. pallidum antigen. The stimulatory effects of anti-immunoglobulin G and lipopolysaccharide on nylon wool-fractionated or unfractionated lymphocytes from both infected and control rabbits were similar throughout the course of infection. During the first 6 weeks of experimental disease, there was a 25 to 31% increase in the number of lymphocytes circulating in the peripheral blood of T. pallidum-infected rabbits.


Response to selection for feed conversion ratio in Japanese quail.
We investigated the effect of selection for 4-wk feed conversion ratio (FCR) on genetic improvement of FCR, BW, weight gain (WG), feed intake (FI), and residual FI (RFI) in Japanese quail. The F line was selected for reduced FCR and the C line was maintained as a randombred control. In each generation, 35 sires and 70 dams were used as parents for the next generation. Three generations of selection were performed. Realized heritability for FCR was calculated as the ratio of cumulative selection response to the cumulative selection differential, and additionally, genetic response was quantified as the difference between the means of selection and control lines. The results showed that realized heritability for FCR after 3 generations of selection was 0.67. The mean FCR in F line and C line in the last generation was 2.13 and 2.61, respectively. This is 18.4% cumulative genetic improvement, or 6.1% improvement per generation. In the last generation, the means of F and C lines were 193 and 166 g for BW at age 28 d (16.4% total increase, or 5.5% per generation), 184 and 158 g for WG (17.2% total higher gain and 5.7% per generation), 393 and 413 g for FI (4.9% total higher consumption and 1.6% per generation), and -24.5 and 10.2 for RFI (-34.7 g of cumulative gain; -11.6 g per generation), respectively. These results show that selection to decrease FCR increases BW and WG and decreases FI and RFI as a correlated response.


Identification and analysis of putative homologues of mechanosensitive channels in pathogenic protozoa.
Mechanosensitive channels play important roles in the physiology of many organisms, and their dysfunction can affect cell survival. This suggests that they might be therapeutic targets in pathogenic organisms. Pathogenic protozoa lead to diseases such as malaria, dysentery, leishmaniasis and trypanosomiasis that are responsible for millions of deaths each year worldwide. We analyzed the genomes of pathogenic protozoa and show the existence within them of genes encoding putative homologues of mechanosensitive channels. Entamoeba histolytica, Leishmania spp., Trypanosoma cruzi and Trichomonas vaginalis have genes encoding homologues of Piezo channels, while most pathogenic protozoa have genes encoding homologues of mechanosensitive small-conductance (MscS) and K(+)-dependent (MscK) channels. In contrast, all parasites examined lack genes encoding mechanosensitive large-conductance (MscL), mini-conductance (MscM) and degenerin/epithelial Na(+) (DEG/ENaC) channels. Multiple sequence alignments of evolutionarily distant protozoan, amoeban, plant, insect and vertebrate Piezo channel subunits define an absolutely conserved motif that may be involved in channel conductance or gating. MscS channels are not present in humans, and the sequences of protozoan and human homologues of Piezo channels differ substantially. This suggests the possibility for specific targeting of mechanosensitive channels of pathogens by therapeutic drugs.


Comparison of regional cerebral blood flow with transcranial magnetic stimulation at different forces.
This study's objective was to investigate regional cerebral blood flow (rCBF) within the primary motor cortex (M1) and to compare it with thresholds of transcranial magnetic stimulation (TMS) and electromyographic recordings during exertion of different force levels with the right index finger. Quantitative electromyographic recordings, TMS, and positron emission tomography scans were performed while five and six volunteers, respectively, pressed a Morse key repetitively or with constant force with the right hand at five different force levels: 5, 10, 20, 40, and 60% of the individual's maximum voluntary contraction (MVC). Although at 5% MVC muscle activity was restricted to the first dorsal interosseus muscle, superficial finger flexors, and extensors, there was progressive involvement of proximal muscles during finger flexion with increasing force. rCBF increased logarithmically in the contralateral M1 with increasing force. In ipsilateral M1, rCBF decreased at 5% MVC and then increased logarithmically at higher force levels. TMS thresholds in the contralateral hemisphere declined logarithmically to reach a plateau at high force levels. The threshold in the ipsilateral hemisphere decreased slightly at high force levels. The logarithmic increase of rCBF and decrease of TMS thresholds in the contralateral hemisphere suggest related underlying physiological phenomena; increased cortical synaptic activity and increased excitability. It suggested that the pronounced ipsilateral rCBF alterations reflect transcallosal inhibition and are more prominent during repetitive movements (as used in the positron emission tomography study) than during the generation of a constant force (as exerted during TMS).


Longitudinal effect of antiretroviral therapy on markers of hepatic toxicity: impact of hepatitis C coinfection.
To characterize longitudinal hepatic toxicity of antiretroviral therapy in HIV-infected women with and without hepatitis C virus (HCV) infection, we measured alanine and aspartate aminotransferase values among women initiating highly active antiretroviral therapy (HAART). For 312 HIV/HCV coinfected women who received HAART for a mean of 1.8 years, the prevalence of elevated aminotransferase levels >3 times and >5 times the upper limit of normal (ULN) was low (<12% and <4%, respectively), and the prevalence of elevated aminotransferase levels declined over time. When we analyzed trends in aminotransferase levels according to type of HAART received among HCV-infected and uninfected women, we found that mean aminotransferase levels declined among 539 women receiving therapy with protease inhibitors (decreases of 5.34%-4.23% of the ULN per year; P values for trend of.007-.06), but mean values among 128 women receiving therapy with nonnucleoside reverse-transcriptase inhibitors remained stable (from decreases of 1.65% to increases of 7.57% of the ULN per year; P values of.19-.71). Our findings lend support to assertions that antiretroviral therapy is safe for women with HCV infection.


Local Anesthesia Injection in Upper Blepharoplasty Surgery: A Side at a Time or Both Sides at Once? A Prospective Randomized Study.
Perceived pain during local anesthesia injections can be effected by the injection sequence. We sought to compare pain levels during local anesthesia injections during upper lid blepharoplasty (ULB) using 2 surgical sequences. We conducted a prospective, randomized clinical trial. Patients with ULB were randomized to either have local anesthesia injection followed by ULB in the right eyelid and then in the left (Group A) or to have local anesthesia injection to both eyelids followed by ULB on both eyelids (Group B). Pain was assessed using a visual analog scale (VAS) for pain score of 0 to 10. Forty patients were included and randomized. The mean VAS score in Group A was 2.60 ± 1.84 and 3.30 ± 1.62 (right and left, respectively, p value = .035). The mean VAS score in Group B was 2.55 ± 1.63 and 2.80 ± 1.67 (right and left eyelids, respectively, p value = .258). No intergroup difference in pain was found. Patients having sequential anesthesia during ULB perceived more pain on injection to the second eyelid, whereas patients having local anesthesia followed by ULB perceived the same amount of pain in both eyes. Pain levels in both groups were similar. Local anesthesia injections in both groups were well tolerated.


Disclosure of human immunodeficiency virus status to children in South Africa: A comprehensive analysis.
The extent of disclosure of HIV status to children and adolescents and the context facilitating their disclosure process have received little attention. To assess disclosure and provide a comprehensive analysis of characteristics associated with disclosure to children (3-14 years) receiving antiretroviral treatment in a South African semi-urban clinic. This cross-sectional study used structured interview administered questionnaires which were supplemented with medical record data. Predictors included child, caregiver, clinical and socio-economic characteristics, viral suppression, immune response, adherence, health-related quality of life and family functioning. We included 190 children of whom 45 (23.7%) received disclosure about their HIV status, of whom 28 (14.7%) were partially disclosed and 17 (8.9%) were fully disclosed. Older age of the child and higher education of the caregiver were strongly associated with disclosure. Female caregivers, detectable viral load, syrup formulation, protease inhibitor (PI) regimens with stavudine and didanosine, and self-reported non-adherence were strongly associated with non-disclosure. When children do well on treatment, caregivers feel less stringent need to disclose. Well-functioning families, higher educated caregivers and better socio-economic status enabled and promoted disclosure. Non-disclosure can indicate a sub-optimal social structure which could negatively affect adherence and viral suppression. There is an urgent need to address disclosure thoughtfully and proactively in the long-term disease management. For the disclosure process to be beneficial, an enabling supportive context is important, which will provide a great opportunity for future interventions.


Histone demethylase JMJD1C regulates esophageal cancer proliferation Via YAP1 signaling.
Esophageal cancer (EC) is the most lethal cancer, and it is of significant concern worldwide, particularly in China. However, there are no effective treatments to cure it, such as chemotherapy, surgery, or radiotherapy. This is attributed to the lack of understanding of the molecular mechanisms of EC. Recently, the superfamily of Jmj-containing KDMs has been shown to play an important role in tumorigenesis in various cancers, including EC. In this study, we demonstrated that JMJD1C was upregulated in patient EC tissues and different EC cell lines. Furthermore, JMJD1C levels were positively correlated with the TNM stage. Moreover, the colony formation assay, CCK8, and cell number count assay showed that the knockdown of JMJD1C inhibited EC cell proliferation. Western blot analysis and the quantitative real-time polymerase chain reaction assay showed that the knockdown of JMJD1C repressed the protein and mRNA levels of YAP1 via regulating the H3K9me2 activity, but not the H3K9me1 activity. The colony formation assay, CCK8 analysis, and cell number count assay revealed that inhibition of EC cell proliferation by the knockdown of JMJD1C was rescued by overexpression of YAP1. Taken together, our results demonstrated that JMJD1C controls the proliferation of EC via modulation of H3K9me2 activity, targeting the YAP1 gene expression and functions as a tumor suppressor in EC. This novel pathway may serve as a therapeutic target for EC patients.


Sperm chromatin accessibility's involvement in the intergenerational effects of stress hormone receptor activation.
Dexamethasone is a stress hormone receptor agonist used widely in clinics. We and others previously showed that paternal administration of dexamethasone in mice affects the phenotype of their offspring. The substrate of intergenerational transmission of environmentally induced effects often involves changes in sperm RNA, yet other epigenetic modifications in the germline can be affected and are also plausible candidates. First, we tested the involvement of altered sperm RNAs in the transmission of dexamethasone induced phenotypes across generations. We did this by injecting sperm RNA into naïve fertilized oocytes, before performing metabolic and behavioral phenotyping of the offspring. We observed phenotypic changes in discordance with those found in offspring generated by in vitro fertilization using sperm from dexamethasone exposed males. Second, we investigated the effect of dexamethasone on chromatin accessibility using ATAC sequencing and found significant changes at specific genomic features and gene regulatory loci. Employing q-RT-PCR, we show altered expression of a gene in the tissue of offspring affected by accessibility changes in sperm. Third, we establish a correlation between specific DNA modifications and stress hormone receptor activity as a likely contributing factor influencing sperm accessibility. Finally, we independently investigated this dependency by genetically reducing thymine-DNA glycosylase levels and observing concomitant changes at the level of chromatin accessibility and stress hormone receptor activity.


Effects of oxygen and carbogen breathing on choroidal hemodynamics in humans.
Previous studies in humans have demonstrated that oxygen (O2) reduces retinal vessel caliber and blood flow, whereas carbon dioxide (CO2) usually has opposite effects. The influence of O2 and CO2 on choroidal circulation is not fully understood, however. This study was conducted to determine the effects of systemic hyperoxia and hypercapnia on global choroidal hemodynamics, as evaluated by pulsatile ocular blood flow (POBF) tonography. In this experiment, 16 and 22 healthy volunteers breathed 100% O2 and carbogen, respectively. POBF and intraocular pressure (IOP) were measured twice with a UK OBF tonograph for each of the following conditions: in ambient room air breathing, after breathing pure O2 or carbogen through a face mask, and in ambient room air 10 minutes after mask removal. Heart rate (HR), hemoglobin oxygen saturation level (SaO2), and systemic arterial blood pressure (BP) were monitored throughout testing. The end-tidal CO2 (EtCO2) level and respiratory rate (RR) were also recorded during carbogen breathing. Results revealed that HR was reduced (P<0.004) and SaO2 was increased (P = 0.0001) by both oxygen and carbogen breathing. Systemic arterial BP remained stable throughout the experiment. EtCO2 was increased during carbogen breathing (P = 0.0001), whereas RR was reduced (P = 0.0175). IOP was significantly decreased during both phases of the experiment (P = 0.0001). Finally, POBF was not altered by pure O2 breathing, but it increased on average by 7.7% during carbogen breathing (P = 0.0222). The data obtained with POBF tonography indicate that the choroid reacts to increased blood CO2 concentration, but not to systemic hyperoxia, in a manner similar to that in retinal and brain vessels.


The National Kidney Foundation Dialysis Outcomes Quality Initiative.
Rigorously developed clinical practice guidelines have the potential to change practice patterns to obtain improved patient outcomes. Toward that end, in March 1995 the National Kidney Foundation initiated the Dialysis Outcomes Quality Initiative, a comprehensive effort to create literature-based clinical practice guidelines in nephrology. Independent interdisciplinary work groups reviewed the available body of scientific literature on the following topics: hemodialysis adequacy, peritoneal dialysis adequacy, vascular access, and anemia. More than 11,000 papers were identified; of these approximately 1500 were found to be relevant, requiring formal structured review. Work groups formulated draft guidelines with supporting rationales that included the evidentiary basis for the recommendations. The draft guidelines were subjected to an unprecedented three-stage review process that involved more than 50 organizations from the renal community, including end-stage renal disease networks, patients dialysis providers, managed care organizations, and government. The finalized guidelines were issued in September 1997. Planned guideline implementation activities will focus on achieving the following: cooperation from the renal community; education of patients, clinicians, policy makers, and dialysis providers; information system tools to facilitate adoption of the guidelines; and evaluation strategies to determine whether practice patterns and outcome goals are achieved.


Capture-mark-recapture to estimate the number of missed articles for systematic reviews in surgery.
Systematic reviews are an important knowledge synthesis tool, but with new literature available each day, reviewers must balance identifying all relevant literature against timely synthesis. This study tested capture-mark-recapture (CMR), an ecology-based technique, to estimate the total number of articles in the literature identified in a systematic review of adult trauma care quality indicators. The systematic review included 40 articles identified from online searches and citation references. The CMR model suggested that 3 (95% confidence interval [CI]: 0 to 6) articles were missed and the database search provided 93% (one-sided 95% CI: ≥83%) of known articles for inclusion in the systematic review. The search order used for identifying the articles was optimal among the 24 that could have been used. The CMR technique can be used in systematic reviews in surgery to estimate the closeness to capturing the total body of literature for a specific topic.


[Expanded access program in the United States and Alimta program for malignant mesothelioma patients].
In the United States, Expanded Access Program is allowed by FDA to facilitate the availability of promising new drugs to desperately ill patients as early in the drug development process as possible, before marketing begins, and to obtain additional data on the drug's safety and effectiveness. Eli Lilly conducted Alimta Expanded Access Programs for 1200 malignant mesothelioma patients with free of charge and obtained clinical efficacy and severe adverse events. The system development for Expanded Access Program should be discussed for future Japanese participation to this program.


The periodontal status of indirectly lead-exposed apprentices working in autorepair workshops.
The aim of this study was to evaluate the periodontal health status of lead-exposed apprentices and to search the correlation between clinical periodontal parameters and either blood lead or oxidative stress/damage indices in erythrocytes. Sixty male subjects were recruited for this study (30 apprentices and 30 controls). The periodontal health status was determined with gingival index, plaque index, gingival bleeding time index, probing depth, and clinical attachment level records. Additionally, blood lead level and indices of oxidative stress (glutathione peroxidase, superoxide dismutase), catalase activities and damage (malondialdehyde concentration) in erythrocytes were determined. The results showed that lead level was significantly higher in apprentices than in controls (P < 0.05). None of the clinical periodontal parameters and oxidative stress/damage indices were significantly different between the groups (P > 0.05). Significant correlation between plaque index and catalase, probing depth and superoxide dismutase, clinical attachment level and superoxide dismutase, and clinical attachment level and malondialdehyde in apprentices group (P < 0.05), and gingival bleeding time index and glutathione peroxidase in control group were found (P < 0.05). In multiple regression analysis, there were statistically significant associations between gingival index and working status, family income and either probing depth or clinical attachment level (P < 0.05). The results of this study showed significant association between the clinical periodontal parameters and oxidative stress/damage indices in apprentices indirectly exposed to low levels of lead.


Cathepsin D. Characteristics of immunoinhibition and the confirmation of a role in cartilage breakdown.
1. Antisera were raised against lysosomal cathepsin D of man, chicken and rabbit. 2. The antisera were found to be specific and potent inhibitors of cathepsin D activity. 3. The immunological nature of the inhibition was established. 4. The inhibitory effect was studied by varying pH, antiserum/enzyme ratio, time of incubation, concentration of components and order of mixing, and by using purified antibody and univalent antibody fragments. 5. The specificities of the antisera were examined with respect to other enzymes, isoenzymes of cathepsin D and cathepsin D from different organs. 6. The antisera prevented the action of cathepsin D on isolated proteoglycans and on cartilage. 7. The antisera produced up to 90% inhibition of the autolysis of cartilage from chicks and rabbits, indicating that cathepsin D is the enzyme mainly responsible for the breakdown of proteoglycans in this system.


Changes in net ecosystem productivity of boreal black spruce stands in response to changes in temperature at diurnal and seasonal time scales.
Net ecosystem productivity (NEP) of boreal coniferous forests is believed to rise with climate warming, thereby offsetting some of the rise in atmospheric CO(2) concentration (C(a)) by which warming is caused. However, the response of conifer NEP to warming may vary seasonally, with rises in spring and declines in summer. To gain more insight into this response, we compared changes in CO(2) exchange measured by eddy covariance and simulated by the ecosystem process model ecosys under rising mean annual air temperatures (T(a)) during 2004-2006 at black spruce stands in Saskatchewan, Manitoba and Quebec. Hourly net CO(2) uptake was found to rise with warming at T(a) < 15 degrees C and to decline with warming at T(a) > 20 degrees C. As mean annual T(a) rose from 2004 to 2006, increases in net CO(2) uptake with warming at lower T(a) were greater than declines with warming at higher T(a) so that annual gross primary productivity and hence NEP increased. Increases in net CO(2) uptake measured at lower T(a) were explained in the model by earlier recovery of photosynthetic capacity in spring, and by increases in carboxylation activity, using parameters for the Arrhenius temperature functions of key carboxylation processes derived from independent experiments. Declines in net CO(2) uptake measured at higher T(a) were explained in the model by sharp declines in mid-afternoon canopy stomatal conductance (g(c)) under higher vapor pressure deficits (D). These declines were modeled from a hydraulic constraint to water uptake imposed by low axial conductivity of conifer roots and boles that forced declines in canopy water potential (psi(c)), and hence in g(c) under higher D when equilibrating water uptake with transpiration. In a model sensitivity study, the contrasting responses of net CO(2) uptake to specified rises in T(a) caused annual NEP of black spruce in the model to rise with increases in T(a) of up to 6 degrees C, but to decline with further increases at mid-continental sites with lower precipitation. However, these contrasting responses to warming also indicate that rises in NEP with climate warming would depend on the seasonality (spring versus summer) as well as the magnitude of rises in T(a).


Adherence to guidance for prioritizing higher risk groups for breast cancer screening during the COVID-19 pandemic in the Ontario Breast Screening Program: a descriptive study.
Breast cancer screening in Ontario, Canada, was deferred during the first wave of the COVID-19 pandemic, and a prioritization framework to resume services according to breast cancer risk was developed. The purpose of this study was to assess the impact of the pandemic within the Ontario Breast Screening Program (OBSP) by comparing total volumes of screening mammographic examinations and volumes of screening mammographic examinations with abnormal results before and during the pandemic, and to assess backlogs on the basis of adherence to the prioritization framework. A descriptive study was conducted among women aged 50 to 74 years at average risk and women aged 30 to 69 years at high risk, who participated in the OBSP. Percentage change was calculated by comparing observed monthly volumes of mammographic examinations from March 2020 to March 2021 with 2019 volumes and proportions by risk group. We plotted estimates of backlog volumes of mammographic examinations by risk group, comparing pandemic with prepandemic screening practices. Volumes of mammographic examinations with abnormal results were plotted by risk group. Volumes of mammographic examinations in the OBSP showed the largest declines in April and May 2020 (> 99% decrease) and returned to prepandemic levels as of March 2021, with an accumulated backlog of 340 876 examinations. As of March 2021, prioritization had reduced the backlog volumes of screens for participants at high risk for breast cancer by 96.5% (186 v. 5469 expected) and annual rescreens for participants at average risk for breast cancer by 13.5% (62 432 v. 72 202 expected); there was a minimal decline for initial screens. Conversely, the backlog increased by 7.6% for biennial rescreens (221 674 v. 206 079 expected). More than half (59.4%) of mammographic examinations with abnormal results were for participants in the higher risk groups. Prioritizing screening for those at higher risk for breast cancer may increase diagnostic yield and redirect resources to minimize potential long-term harms caused by the pandemic. This further supports the clinical utility of risk-stratified cancer screening.


Antiproliferative Activity and Cytotoxicity of Some Medicinal Wood-Destroying Mushrooms from Russia.
We analyzed the antiproliferative activity of 6 medicinal wood-destroying mushrooms (Fomes fomentarius, Fomitopsis pinicola, Trametes versicolor, Trichaptum biforme, Inonotus obliquus, and Coniophora puteana) that are common in deciduous and mixed coniferous forests in Central Russia. Morphological identification of strains collected from the wild was confirmed based on ribosomal DNA internal transcribed spacer phylogenetic analysis. We observed cytotoxic and cell growth-inhibitory effects of hot water extracts from mycelial biomass of 5 species-T. versicolor, C. puteana, F. fomentarius, F. pinicola, and I. obliquus-on leukemia cell lines (Jukart, K562, and THP-1); the effective extract concentrations were mostly less than 50 μg · mL-1. However, we observed no antiproliferative activity of dry biomass from methanol-chloroform (1:1) extracts of C. puteana and F. fomentarius. A chemosensitivity assay showed that the most effective polypore mushroom extract was the methanol extract of T. versicolor (strain It-1), which inhibited the growth of 6 various solid tumors (A-549 and SWi573 [lung], HBL-100 and T-47D [breast], HeLa [cervix], and WiDr [colon]) at concentrations below 45 μg · mL-1, with a concentration as low as 0.7-3.6 μg · mL-1 causing 50% reduction in the proliferation of cancer cells in lung and cervix tumors. Methanol extracts of F. pinicola and I. obliquus were less effective, with proliferation-inhibiting capacities at concentrations below 70 and 200 μg · mL-1, respectively. Thus, T. versicolor is a prospective candidate in the search for and production of new antiproliferative chemical compounds.


A case-referent study on acute myeloid leukemia, background radiation and exposure to solvents and other agents.
The effect of potential risk factors for acute myeloid leukemia was evaluated in a case-referent study encompassing 42 cases and 244 referents, all deceased. Information on exposure was obtained with questionnaires mailed to the next of kin. Particularly the effect of background radiation was evaluated, as assessed with a gamma radiation index weighing the time spent outdoors and indoors and considering the building material (stone, wood, etc.) in the homes and the workplaces of the subjects. Especially between the ages of 20 and 49 a, to some extent also between 50 and 69 a but not above 70, there seemed to be an effect from background radiation and a trend suggesting an exposure-effect relationship. There was also about a sixfold increase in the rate ratio with regard to solvent exposure, which also seemed to modify the effect of background radiation. Other exposures were associated with relatively modest increases in the rate ratios and/or very small numbers of exposed individuals. It would be worthwhile to undertake further cancer epidemiologic studies of background radiation in which effective study designs are applied and a variety of potential confounders and modifiers of effect are identified and accounted for.


Updates of cost of illness and quality of life estimates for use in economic evaluations of HIV prevention programs.
To allocate limited economic and other resources for HIV prevention and treatment for maximum benefit, health policy planners and decision makers require accurate, current estimates of the lifetime costs of HIV-related illness and the impact of therapy on the quality of life of HIV-infected persons. These data are central input parameters to the economic evaluation methodology known as cost-utility analysis. The estimates available in the literature are already outdated, and this paper presents updated estimates of the projected lifetime health care costs associated with HIV disease in the United States and the number of quality-adjusted life years (QALYs) lost to HIV in light of recent advancements in HIV diagnostics and therapeutics. Results indicate that the lifetime cost of HIV medical care has grown from about $55,000 U.S. to more than $155,000 U.S., while the number of QALYs lost per case of HIV infection has decreased from 9.26 to 7.10, when discounted at a 5% annual rate. When these figures are discounted instead at the newly recommended 3% rate, lifetime costs rise to more than $195,000 U.S. and lost QALYs increase to 11.23. The net effect of these increases in the medical costs of care and treatment saved by averting an HIV infection and in QALYs makes HIV prevention a relatively more cost-effective strategy than other, non-HIV health-related programs.


Diffuse Increased Sodium Fluoride Gastric Activity in a Patient With Hypercalcemia.
Increased extraosseous uptake of sodium fluoride can be visualized because of many different etiologies. A 62-year-old man with a history of osteoporosis had an F-sodium fluoride PET/CT scan for accessing chest pain caused by an accident. The images showed multiple fractures. Unexpectedly, diffuse activity was noted in the gastric wall, which was suggestive of possible hypercalcemia. The serum calcium level confirmed the patient had hypercalcemia.


Sub-micrometer four-point probe transport measurements on graphene.
Usually, electronic transport measurements on two-dimensional materials, such as graphene and transition metal dichalcogenides, require deposition of electrodes on top of the material, in, for instance, the form of a Hall bar device. In this work, we show that by making use of a collinear micro-four-point probe, electrical transport measurements on small flakes of graphene can be performed without having to fabricate electrodes on top of the flakes. Using probes with probe pitches down to sub-micrometer scale, we show back-gate tuned transport measurements in graphene on silicon oxide and on hexagonal boron nitride. The charge carrier mobilities and the minimum conductivity of graphene are in good agreement with conventional transport measurements. In addition, we assess the possible damage caused by landing these probes on graphene.


Alteration of the disulfide-coupled folding pathway of BPTI by circular permutation.
The kinetics of disulfide-coupled folding and unfolding of four circularly permuted forms of bovine pancreatic trypsin inhibitor (BPTI) were studied and compared with previously published results for both wild-type BPTI and a cyclized form. Each of the permuted proteins was found to be less stable than either the wild-type or circular proteins, by 3-8 kcal/mole. These stability differences were used to estimate effective concentrations of the chain termini in the native proteins, which were 1 mM for the wild-type protein and 2.5 to 4000 M for the permuted forms. The circular permutations increased the rates of unfolding and caused a variety of effects on the kinetics of refolding. For two of the proteins, the rates of a direct disulfide-formation pathway were dramatically increased, making this process as fast or faster than the competing disulfide rearrangement mechanism that predominates in the folding of the wild-type protein. These two permutations break the covalent connectivity among the beta-strands of the native protein, and removal of these constraints appears to facilitate direct formation and reduction of nearby disulfides that are buried in the folded structure. The effects on folding kinetics and mechanism do not appear to be correlated with relative contact order, a measure of overall topological complexity. These observations are consistent with the results of other recent experimental and computational studies suggesting that circular permutation may generally influence folding mechanisms by favoring or disfavoring specific interactions that promote alternative pathways, rather than through effects on the overall topology of the native protein.


Studying Bacteriophage Efficacy Using a Zebrafish Model.
The rise of bacteria resistant to the antibiotics currently in use (multiple drug-resistant, MDR) is a serious problem for patients affected by infections. This situation is even more worrying in the case of chronic bacterial infections, such as those caused by Pseudomonas aeruginosa (Pa), in patients with cystic fibrosis (CF). As an alternative to antibiotic treatments, the use of bacteriophages (phages) to fight bacterial infections has gained increasing interest in the last few years. Phages are viruses that specifically infect and multiply within the bacteria without infecting eukaryotic cells. It is well assumed that phage therapy has a high bacterial specificity, which, unlike antibiotics, should limit the damage to the endogenous microbiome. In addition, phages can kill antibiotic-resistant bacteria and perform self-amplification at the site of the infection.The protocol detailed in this chapter describes how the antimicrobial effect of phages can be studied in vivo in the zebrafish (Danio rerio) model infected with Pa. The same procedure can be applied to test the effectiveness of several different phages killing other bacterial species and for the rapid preclinical testing of phages to be used as personalized medicine.


[Probability models of the spread of leukemias and lymphomas].
Probability models of horizontal dissemination of leukemia and lymphoma are considered. An analysis of the statistics on human and cattle morbidity in the Latvian SSR failed to establish any correlation between relevant indices for humans and cattle. Nor did it point to any evidence in support of the hypothesis on horizontal dissemination of hemablastosis in cattle under natural conditions.


[Mortality in an internal medicine department within a third-level hospital; twenty years experience].
To know and to analyze the main causes of death in an Internal Medicine Department (IM) and the mortality rate in such a Department. From 1977 to 1996, a total of 77,310 patients were attended in the service under analysis. There were a total of 4,720 deaths. Clinical and epidemiological variables were analyzed so do management parameters related to inpatient deaths. Global mortality rate was 6.1%; the number of admissions increased along the study, whereas mortality rate tended to decrease. Median age was 72.8 years in death patients, and this age tended to increase during the period of study. Women's age was greater than men's one. The causes of the demise were cardiovascular (stroke and cardiopathy), neoplasm and respiratory disease, in that order. Neoplastic diseases were the leading death cause in men as they were in patients younger than 65 years-old, and AIDS was the main reason of death in patients younger than 35 years. Finally, 28.7% who died had been inpatients for no more than 48 hours. We can conclude that deaths in our IM department affect, as a rule, elderly patients with cardiovascular or neoplastic disease. Moreover, AIDS has experienced an increasing frequency, so it had became the first cause of death in patients under the age of 35. The old age of patients who die in our service, the great percentage of early deaths and the fact that the motive was, in the majority of the patients, a terminal disease, support the idea that new social customs tend to remove illness and death from family home, approving demise as a hospital event.


Illuminating the oral microbiome and its host interactions: tools and approaches for molecular ecological studies.
A more comprehensive understanding of oral diseases like caries and periodontitis is dependent on an intimate understanding of the microbial ecological processes that are responsible for disease development. With this review, we provide a comprehensive overview of relevant molecular ecology techniques that have played critical roles in the current understanding of human oral biofilm development, interspecies interactions, and microbiome biogeography. The primary focus is on relevant technologies and examples available in the oral microbiology literature. However, most, if not all, of the described technologies should be readily adaptable for studies of microbiomes from other mucosal sites in the body. Therefore, this review is intended to serve as a reference guide used by microbiome researchers as they inevitably transition into molecular mechanistic studies of the many significant phenotypes observed clinically.


Structural transition in nanostructured Eu2O3 under high pressures.
We report here studies on the effect of high pressure on the structural properties of nano-sized Europium sesquioxide (Eu2O3) up to a pressure of about 16.4 GPa. At ambient conditions, the starting sample was found to be predominantly cubic type Eu2O3 or in Eu3+ state with a trace of Eu2+. The presence of Eu2+ state is assumed to be arising due to the non-stoichiometric Eu(1-x)O phase which is obtained from XPS studies by the deconvolution of the Eu 3d-core levels. The Raman studies at ambient show a strong peak at about 333 cm(-1), which is known to occur due to the Fg mode of cubic Eu2O3 and in a similar way, the XRD data shows major peaks corresponding to the cubic phase of Eu2O3. A Mao-Bell type diamond anvil cell (DAC) was used to generate high pressures for XRD and Raman spectroscopy studies. It was observed that the material undergoes a structural change from cubic to monoclinic structure with an on set transition pressure at around 2 GPa and completes at around 8 GPa. This has been inferred from the fact that above about 2.0 GPa pressure, Raman studies show the emergence of a new peak corresponding to the monoclinic phase which increases in intensity and shifts further with increase in pressure, while the XRD studies show that above about 2.0 GPa, the peaks corresponding to monoclinic phase emerge, which show a slight increase in preferred orientation as the pressure is increased. A detailed discussion has been provided to explain this fact.


A Compendium of Compounding Agents and Formulations, Part 1: Melatonin.
The lipophilic hormone melatonin is widely known as a sleep-inducing agent, but its dermal-healing effects remain underappreciated. Although numerous commercially manufactured products are prescribed to heal and protect the human skin, not all are effective, and not all patients can tolerate the combinations of drugs and excipients in those treatments (some of which, such as corticosteroids, produce adverse effects). In addition, required active ingredients may not be available in the doses or dosage forms needed. In such cases, a compounded preparation may provide an effective alternative, but finding formulations and information about which pharmaceuticals to compound as a sole treatment or in combination with other ingredients can require extensive research. To assist that effort, this series provides - in a quick-reference format - profiles of agents that can be effectively used in compounding and formulations that contain them. In this article, information about the healing and prophylactic effects of melatonin in various forms is presented, and 2 formulations for melatonin-containing compounds are provided.


Utilization of the Yellow Component of a Copper-Vapor Laser for Extending the Tuning Range of a Rhodamine 6G Dye Laser by Use of an Additional Dye in a Novel Coupled Resonator Scheme.
We demonstrate the use of both 510.6- and 578.2-nm components and the extension of the tuning range of a Rhodamine 6G dye laser in a novel coupled resonator scheme. Rhodamine 6G is pumped by 510.6-nm light in one resonator and Sulforhodamine B is pumped by 578.2 nm in the other. The spectral tuning range of 564-609 nm of the Rhodamine 6G laser is extended up to 640 nm. A two-mirror arrangement ensures continuous tuning across the spectral ranges of the two dyes by rotation of a single plane mirror.


Analog isolated electronic dynamometer based on a magnetoresistive current sensor.
In this work, an electronic system is presented to measure the force applied by a solenoid. The originality of the work is focused on the use of a magnetoresistive current sensor to provide the isolation barrier needed in the actual industrial plant where the solenoids are working. The design of the electronic system is presented as well as experimental measurements as a result of a calibration process showing a negligible hysteresis with that specific sensor. The magnetoresistive current sensor is used to develop transmission functions rather than playing its usual sensing roles.


Image-domain multimaterial decomposition for dual-energy computed tomography with nonconvex sparsity regularization.
Dual-energy computed tomography (CT) has the potential to decompose tissues into different materials. However, the classic direct inversion (DI) method for multimaterial decomposition (MMD) cannot accurately separate more than two basis materials due to the ill-posed problem and amplified image noise. We propose an integrated MMD method that addresses the piecewise smoothness and intrinsic sparsity property of the decomposition image. The proposed MMD was formulated as an optimization problem including a quadratic data fidelity term, an isotropic total variation term that encourages image smoothness, and a nonconvex penalty function that promotes decomposition image sparseness. The mass and volume conservation rule was formulated as the probability simplex constraint. An accelerated primal-dual splitting approach with line search was applied to solve the optimization problem. The proposed method with different penalty functions was compared against DI on a digital phantom, a Catphan® 600 phantom, a quantitative imaging phantom, and a pelvis patient. The proposed framework distinctly separated the CT image up to 12 basis materials plus air with high decomposition accuracy. The cross talks between two different materials are substantially reduced, as shown by the decreased nondiagonal elements of the normalized cross correlation (NCC) matrix. The mean square error of the measured electron densities was reduced by 72.6%. Across all datasets, the proposed method improved the average volume fraction accuracy from 61.2% to 99.9% and increased the diagonality of the NCC matrix from 0.73 to 0.96. Compared with DI, the proposed MMD framework improved decomposition accuracy and material separation.


Modifying the Dietary Carbohydrate-to-Protein Ratio Alters the Postprandial Macronutrient Oxidation Pattern in Liver of AMPK-Deficient Mice.
Background: Hepatic AMP-activated kinase (AMPK) activity is sensitive to the dietary carbohydrate-to-protein ratio. However, the role of AMPK in metabolic adaptations to variations in dietary macronutrients remains poorly understood.Objective: The objective of this study was to determine the role of hepatic AMPK in the adaptation of energy metabolism in response to modulation of the dietary carbohydrate-to-protein ratio.Methods: Male 7-wk-old wild-type (WT) and liver AMPK-deficient (knockout) mice were fed either a normal-protein and normal-carbohydrate diet (NP-NC; 14% protein, 76% carbohydrate on an energy basis), a low-protein and high-carbohydrate diet (LP-HC; 5% protein, 85% carbohydrate), or a high-protein and low-carbohydrate diet (HP-LC; 55% protein, 35% carbohydrate) for 3 wk. During this period, after an overnight fast, metabolic parameters were measured and indirect calorimetry was performed in mice during the first hours after refeeding a 1-g calibrated meal of their own diet in order to investigate lipid and carbohydrate metabolism.Results: Knockout mice fed an LP-HC or HP-LC meal exhibited 24% and 8% lower amplitudes in meal-induced carbohydrate and lipid oxidation changes. By contrast, knockout mice fed an NP-NC meal displayed normal carbohydrate and lipid oxidation profiles. These mice exhibited a transient increase in hepatic triglycerides and a decrease in hepatic glycogen. These changes were associated with a 650% higher secretion of fibroblast growth factor 21 (FGF21) 2 h after refeeding.Conclusions: The consequences of hepatic AMPK deletion depend on the dietary carbohydrate-to-protein ratio. In mice fed the NP-NC diet, deletion of AMPK in the liver led to an adaptation of liver metabolism resulting in increased secretion of FGF21. These changes possibly compensated for the absence of hepatic AMPK, as these mice exhibited normal postprandial changes in carbohydrate and lipid oxidation. By contrast, in mice fed the LP-HC and HP-LC diets, the lack of adjustment in liver metabolism in knockout mice resulted in a metabolic inflexibility, leading to a reduced amplitude of meal-induced changes in carbohydrate and lipid oxidation.


Fear of Movement in People With CRPS: A Psychometric Evaluation of the Tampa Scale-11 for Kinesiophobia.
People with complex regional pain syndrome (CRPS) commonly report a fear of movement that can worsen symptoms and increase disability. The Tampa Scale of Kinesiophobia (TSK) is used to evaluate fear of movement and (re)injury, but findings have been inconsistent in different populations. To evaluate the psychometric properties of the Persian version of TSK-11 in individuals with upper limb CRPS. Specifically, to determine whether the factor structure aligns with the original 2-factor model, consisting of "activity avoidance" and "somatic focus." People with CRPS (n=142, mean age=42, 54% female) completed the TSK. The psychometric testing included internal consistency, test-retest reliability (intraclass correlation coefficient), and convergent construct validity. Confirmatory and exploratory factor analyses were performed to evaluate the structural validity. The TSK-11 showed acceptable internal consistency (Cronbach alpha 0.93) and excellent test-retest reliability (intraclass correlation coefficient=0.93, 95% CI: 0.92-0.94). The Standard Error of Measurement and Minimal Detectable Change were 4.3 and 11.7, respectively. The results also demonstrated excellent criterion validity ( r =0.81). Confirmatory factor analysis demonstrated that the original 2-factor model did not fit. Exploratory factor analysis derived a 2-factor solution with different items. The factor structure accounted for 64.91% of the variance, and the internal consistency of the factors was acceptable (>0.90). Expert consensus suggested naming these 2 factors as fear avoidance and magnification and helplessness. The TSK-11 demonstrates excellent retest reliability in people with CRPS. The original 2-factor structure was not confirmed, and a new 2-factor structure of the TSK-11 was proposed consisting of subscales for Fear Avoidance Beliefs and Magnification/Helplessness. Given the overlap between these constructs and the construct of pain catastrophizing, further study is needed to clarify both measures' content validity and relative uniqueness.


Automated brain volumetrics in multiple sclerosis: a step closer to clinical application.
Whole brain volume (WBV) estimates in patients with multiple sclerosis (MS) correlate more robustly with clinical disability than traditional, lesion-based metrics. Numerous algorithms to measure WBV have been developed over the past two decades. We compare Structural Image Evaluation using Normalisation of Atrophy-Cross-sectional (SIENAX) to NeuroQuant and MSmetrix, for assessment of cross-sectional WBV in patients with MS. MRIs from 61 patients with relapsing-remitting MS and 2 patients with clinically isolated syndrome were analysed. WBV measurements were calculated using SIENAX, NeuroQuant and MSmetrix. Statistical agreement between the methods was evaluated using linear regression and Bland-Altman plots. Precision and accuracy of WBV measurement was calculated for (1) NeuroQuant versus SIENAX and (2) MSmetrix versus SIENAX. Precision (Pearson's r) of WBV estimation for NeuroQuant and MSmetrix versus SIENAX was 0.983 and 0.992, respectively. Accuracy (Cb) was 0.871 and 0.994, respectively. NeuroQuant and MSmetrix showed a 5.5% and 1.0% volume difference compared with SIENAX, respectively, that was consistent across low and high values. In the analysed population, NeuroQuant and MSmetrix both quantified cross-sectional WBV with comparable statistical agreement to SIENAX, a well-validated cross-sectional tool that has been used extensively in MS clinical studies.


The NaV1.7 Channel Subtype as an Antinociceptive Target for Spider Toxins in Adult Dorsal Root Ganglia Neurons.
Although necessary for human survival, pain may sometimes become pathologic if long-lasting and associated with alterations in its signaling pathway. Opioid painkillers are officially used to treat moderate to severe, and even mild, pain. However, the consequent strong and not so rare complications that occur, including addiction and overdose, combined with pain management costs, remain an important societal and economic concern. In this context, animal venom toxins represent an original source of antinociceptive peptides that mainly target ion channels (such as ASICs as well as TRP, CaV, KV and NaV channels) involved in pain transmission. The present review aims to highlight the NaV1.7 channel subtype as an antinociceptive target for spider toxins in adult dorsal root ganglia neurons. It will detail (i) the characteristics of these primary sensory neurons, the first ones in contact with pain stimulus and conveying the nociceptive message, (ii) the electrophysiological properties of the different NaV channel subtypes expressed in these neurons, with a particular attention on the NaV1.7 subtype, an antinociceptive target of choice that has been validated by human genetic evidence, and (iii) the features of spider venom toxins, shaped of inhibitory cysteine knot motif, that present high affinity for the NaV1.7 subtype associated with evidenced analgesic efficacy in animal models.


Acute toxicity of lead particulates on pulmonary alveolar macrophages. Ultrastructural and microanalytical studies.
Although it is well established that respiratory uptake of lead-containing particles plays a substantial role in the epidemiology of plumbism, relatively little is known about the role of the pulmonary alveolar macrophage in lead poisoning. An in vitro system was designed to investigate the effects of lead oxide particles of respirable size on the rabbit alveolar macrophage. The studies were concerned with the intracellular solubility of PbO and Pb3O4 and changes in fine structure attributable to lead toxicity. The distribution of phagocytosed lead and its intracellular reprecipitation complexes was established by electron microprobe analysis and secondary ion mass spectroscopy in conjunction with transmission electron microscopy, scanning electron microscopy, scanning transmission electron microscopy, and backscatter imaging. It was found that Pb3O4, PbO and PbO-coated particles were ingested by the rabbit alveolar macrophages and that each of these lead oxide compounds produced similar damage to the fine structure of the cell. Swelling of the mitochondria, nuclear membrane, and endoplasmic reticulum was common, as well as were characteristic reprecipitation complexes of lead, phosphorous, and calcium within the nuclear heterochromatin and cytoplasm of the cell. The precipitation complexes were not seen in cells incubated with the particles if phagocytosis was blocked by 0.22-microns, membrane filters. It was concluded that phagocytosis of these lead oxide particles was necessary to produce the cytopathic changes. It is suggested that solubilization of lead from the ingested particles in phagosomes of macrophages results in the liberation of intracellular lead with the resultant formation of reprecipitation complexes.


Predictors of subgroups based on maximum drinks per occasion over six years for 833 adolescents and young adults in COGA.
A person's pattern of heavier drinking often changes over time, especially during the early drinking years, and reflects complex relationships among a wide range of characteristics. Optimal understanding of the predictors of drinking during times of change might come from studies of trajectories of alcohol intake rather than cross-sectional evaluations. The patterns of maximum drinks per occasion were evaluated every 2 years between the average ages of 18 and 24 years for 833 subjects from the Collaborative Study on the Genetics of Alcoholism. Latent class growth analysis identified latent classes for the trajectories of maximum drinks, and then logistic regression analyses highlighted variables that best predicted class membership. Four latent classes were found, including Class 1 (69%), with about 5 maximum drinks per occasion across time; Class 2 (15%), with about 9 drinks at baseline that increased to 18 across time; Class 3 (10%), who began with a maximum of 18 drinks per occasion but decreased to 9 over time; and Class 4 (6%), with a maximum of about 22 drinks across time. The most consistent predictors of higher drinking classes were female sex, a low baseline level of response to alcohol, externalizing characteristics, prior alcohol and tobacco use, and heavier drinking peers. Four trajectory classes were observed and were best predicted by a combination of items that reflected demography, substance use, level of response and externalizing phenotypes, and baseline environment and attitudes.


Hand hygiene practices of health care workers in long-term care facilities.
Little is known about hand hygiene practice in the long-term care setting. In this study, we observed 459 hand hygiene opportunities in 2 long-term care facilities in Hamilton, Ontario. Overall hand hygiene adherence was 14.7%, with a mean handwashing time of 15.9 seconds. Adherence varied by activity performed and the presence or absence of a sink.


Spiculous skeleton formation in the freshwater sponge Ephydatia fluviatilis under hypergravity conditions.
Successful dispersal of freshwater sponges depends on the formation of dormant sponge bodies (gemmules) under adverse conditions. Gemmule formation allows the sponge to overcome critical environmental conditions, for example, desiccation or freezing, and to re-establish as a fully developed sponge when conditions are more favorable. A key process in sponge development from hatched gemmules is the construction of the silica skeleton. Silica spicules form the structural support for the three-dimensional filtration system the sponge uses to filter food particles from ambient water. We studied the effect of different hypergravity forces (1, 2.5, 5, 10, and 20 × g for 48 h)-as measure for environmental stress-on the ability of developing sponges to set-up their spiculous skeleton. Additionally, we assessed whether the addition of nutrients (i.e., dissolved 13C- and 15N-labeled amino acids) compensates for this stress. Our results show that freshwater sponges can withstand prolonged periods of hypergravity exposure and successfully set-up their skeleton, even after 48 h under 20 × g. Developing sponges were found to take up and assimilate dissolved food before forming a functional filtering system. However, fed and non-fed sponges showed no differences in skeleton formation and relative surface area growth, suggesting that the gemmules' intrinsic energy fulfills the processes of skeleton construction. Additionally, non-fed sponges formed oscula significantly more often than fed sponges, especially under higher g-forces. This suggests that the eventual formation of a filtration system might be stimulated by food deprivation and environmentally stressful conditions. These findings indicate that the process of spiculous skeleton formation is energy-efficient and highly resilient. The uptake of dissolved food substances by freshwater sponges may contribute to the cycling of dissolved organic matter in freshwater ecosystems where sponges are abundant.


Efficacy and safety of pentoxifylline in geriatric patients with intermittent claudication.
The effects of pentoxifylline on intermittent claudication were evaluated at a dose of 1200 mg/day in an open-label twelve-week study on geriatric patients with chronic occlusive arterial disease (COAD). Standardized treadmill testing and clinical signs and symptoms of COAD were followed up before and during drug administration. Twenty-four subjects with a mean age of 73.5 years, capable of walking between 20 and 200 meters on the treadmill, were entered into the trial; 22 participated for eight weeks and 19 completed the study in terms of treadmill walking distance measurements at 12 weeks. The mean walking distance for all patients was increased 111% over baseline at week 12. Thirteen subjects were considered drug responders (greater than or equal to 50% increase in treadmill walking distance) and 9 were considered nonresponders (less than 50% increase). Improvements in clinical signs and symptoms of COAD were noted. Decreases in elevated systemic systolic pressures (but not diastolic) were unexpectedly observed in many drug responders. Seven of 19 males reported sexual function improvements while receiving pentoxifylline. Fourteen (58%) of the 24 subjects reported mild side effects of dyspepsia, nausea, vomiting, dizziness, headache, or insomnia; no subjects were withdrawn from the study because of side effects. In summary, pentoxifylline improved function and symptoms in 13 of 22 geriatric patients with intermittent claudication; the drug was safe and well tolerated at the usual dosage in this geriatric patient population.


Gracilaria gracilis (Gracilariales, Rhodophyta) from Dakhla (Southern Moroccan Atlantic Coast) as Source of Agar: Content, Chemical Characteristics, and Gelling Properties.
Agar is a sulfated polysaccharide extracted from certain marine red algae, and its gel properties depend on the seaweed source and extraction conditions. In the present study, the seaweed Gracilaria gracilis (Gracilariales, Rhodophyta) from Dakhla (Moroccan Atlantic Coast) was investigated for its agar content, structure, and gel properties. The agar yields of G. gracilis were 20.5% and 15.6% from alkaline pretreatment and native extraction, respectively. Agar with alkaline pretreatment showed a better gelling property supported by higher gel strength (377 g·cm-2), gelling (35.4 °C), and melting (82.1 °C) temperatures with a notable increase in 3,6-anhydro-galactose (11.85%) and decrease in sulphate (0.32%) contents. The sulfate falling subsequent to alkaline pretreatment was verified through FT-IR spectroscopy. The 13C NMR spectroscopy showed that alkaline-pretreated agar has a typical unsubstituted agar pattern. However, native agar had a partially methylated agarose structure. Overall, this study suggested the possibility of the exploitation of G. gracilis to produce a fine-quality agar. Yet, further investigation may need to determine the seasonal variability of this biopolymer according to the life cycle of G. gracilis.


Almond Skin Extracts and Chlorogenic Acid Delay Chronological Aging and Enhanced Oxidative Stress Response in Yeast.
Almond (Prunus dulcis (Mill.) D.A.Webb) is one of the largest nut crops in the world. Recently, phenolic compounds, mostly stored in almond skin, have been associated with much of the health-promoting behavior associated with their intake. The almond skin enriched fraction obtained from cold-pressed oil residues of the endemic Moroccan Beldi ecotypes is particularly rich in chlorogenic acid. In this study, both almond skin extract (AE) and chlorogenic acid (CHL) supplements, similar to traditional positive control resveratrol, significantly increased the chronological life-span of yeast compared to the untreated group. Our results showed that AE and CHL significantly reduced the production of reactive oxygen and nitrogen species (ROS/RNS), most likely due to their ability to maintain mitochondrial function during aging, as indicated by the maintenance of normal mitochondrial membrane potential in treated groups. This may be associated with the observed activation of the anti-oxidative stress response in treated yeast, which results in activation at both gene expression and enzymatic activity levels for SOD2 and SIR2, the latter being an upstream inducer of SOD2 expression. Interestingly, the differential gene expression induction of mitochondrial SOD2 gene at the expense of the cytosolic SOD1 gene confirms the key role of mitochondrial function in this regulation. Furthermore, AE and CHL have contributed to the survival of yeast under UV-C-induced oxidative stress, by reducing the development of ROS/RNS, resulting in a significant reduction in cellular oxidative damage, as evidenced by decreased membrane lipid peroxidation, protein carbonyl content and 8-oxo-guanine formation in DNA. Together, these results demonstrate the interest of AE and CHL as new regulators in the chronological life-span and control of the oxidative stress response of yeast.


[Nutrition and health--potential health benefits and risks of vegetarianism and limited consumption of meat in the Netherlands].
In the latest Dutch national food consumption survey (1998) just over 1% of subjects (about 150,000 persons) claimed to be vegetarians; however, a much larger group (6% or approximately 1 million persons) ate meat < or = once a week. Vegetarianism can be subdivided into lacto-vegetarianism (a diet without meat and fish) and veganism (a diet without any animal foods whatsoever, including dairy products and eggs). A recent meta-analysis showed that vegetarians had a lower mortality from ischaemic heart disease than omniovorous subjects; however, cancer mortality and total mortality did not differ. Although a high consumption of red meat, which is rich in haeme iron and saturated fat, may increase the risk of cardiovascular disease and some types of cancer, this does not apply to white meat and fish. In fact, the most important protective effect would seem to be derived from the consumption of unrefined vegetable products (whole-grain cereals, vegetables, fruits, nuts and legumes) and fish. In other words, a prudent, omnivorous diet with moderate amounts of animal products, in which red meat is partly replaced by white meat and fish (especially fatty fish), together with the consumption of ample amounts of unrefined vegetable products, is thought to be just as protective as a vegetarian diet. On the other hand, the omission of meat and fish from the diet increases the risk of nutritional deficiencies. A vegan diet, in particular, leads to a strongly increased risk of deficiencies of vitamin B12, vitamin B2 and several minerals, such as calcium, iron and zinc. However, even a lacto-vegetarian diet produces an increased risk of deficiencies of vitamin B12 and possibly certain minerals, such as iron. Data from the latest Dutch food consumption survey suggest that 5-10% of all inhabitants of the Netherlands (up to 1 million persons) actually have a vitamin B12 intake below recommended daily levels. In medical practice, the possibility of vitamin B12 deficiency in subjects consuming meat or fish < or = once a week deserves serious consideration. In case of doubt, evaluation is indicated using sensitive and specific deficiency markers such as the levels of methylmalonic acid in plasma or urine. Alternative dietary sources of vitamin B12 instead of meat are fish (especially fatty fish is a good source of vitamin B12), or a vitamin-B12-supplement.


New evaluated radioxenon decay data and its implications in nuclear explosion monitoring.
This work presents the last updated evaluations of the nuclear and decay data of the four radioxenon isotopes of interest for the Comprehensive Nuclear-Test-Ban Treaty (CTBT): Xe-131 m, Xe-133, Xe-133 m and Xe-135. This includes the most recent measured values on the half-lives, gamma emission probabilities (Pγ) and internal conversion coefficients (ICC). The evaluation procedure has been made within the Decay Data Evaluation Project (DDEP) framework and using the latest available versions of nuclear and atomic data evaluation software tools and compilations. The consistency of the evaluations was confirmed by the very close result between the total available energy calculated with the present evaluated data and the tabulated Q-value. The article also analyzes the implications on the variation of the activity ratio calculations from radioxenon monitoring facilities depending on the nuclear database of reference.


Automated Fetal Head Detection and Circumference Estimation from Free-Hand Ultrasound Sweeps Using Deep Learning in Resource-Limited Countries.
Ultrasound imaging remains out of reach for most pregnant women in developing countries because it requires a trained sonographer to acquire and interpret the images. We address this problem by presenting a system that can automatically estimate the fetal head circumference (HC) from data obtained with use of the obstetric sweep protocol (OSP). The OSP consists of multiple pre-defined sweeps with the ultrasound transducer over the abdomen of the pregnant woman. The OSP can be taught within a day to any health care worker without prior knowledge of ultrasound. An experienced sonographer acquired both the standard plane-to obtain the reference HC-and the OSP from 183 pregnant women in St. Luke's Hospital, Wolisso, Ethiopia. The OSP data, which will most likely not contain the standard plane, was used to automatically estimate HC using two fully convolutional neural networks. First, a VGG-Net-inspired network was trained to automatically detect the frames that contained the fetal head. Second, a U-net-inspired network was trained to automatically measure the HC for all frames in which the first network detected a fetal head. The HC was estimated from these frame measurements, and the curve of Hadlock was used to determine gestational age (GA). The results indicated that most automatically estimated GAs fell within the P2.5-P97.5 interval of the Hadlock curve compared with the GAs obtained from the reference HC, so it is possible to automatically estimate GA from OSP data. Our method therefore has potential application for providing maternal care in resource-constrained countries.


Pellucid marginal corneal degeneration.
Pellucid marginal degeneration of the cornea is a bilateral, clear, inferior, peripheral corneal-thinning disorder. Protrusion of the cornea occurs above a band of thinning, which is located 1 to 2 mm from the limbus and measures 1 to 2 mm in width. American ophthalmologists are generally not familiar with the condition because most of the literature concerning pellucid degeneration is European. Four cases are described. This condition is differentiated from other noninflammatory cornel-thinning disorders such as keratoconus, keratoglobus, keratotorus, and posterior keratoconus. It is also differentiated from peripheral corneal disorders associated with inflammation such as Terrien's peripheral corneal degeneration, Mooren's ulcers, and ulcers from connective tissue disease.


Serotype b of Aggregatibacter actinomycetemcomitans triggers pro-inflammatory responses and amyloid beta secretion in hippocampal cells: a novel link between periodontitis and Alzheimer´s disease?
Introduction: Previous reports have proposed that Periodontal disease (PDis) predisposes to Alzheimer's disease (AD), both highly prevalent pathologies among the elderly. The bacteria Aggregatibacter actinomycetemcomitans (Aa), associated with the most aggressive forms of PDis, are classified in different serotypes with distinct virulence according to the antigenicity of their lipopolysaccharide (LPS). Methods: Here, we determined the effects of purified LPS, from serotypes a, b or c of Aa, on primary cultures of microglia or mixed hippocampal cells. Results: We found that both culture types exhibited higher levels of inflammatory cytokines (IL-1β, IL-6 and TNFα) when treated with serotype b-LPS, compared with controls, as quantified by qPCR and/or ELISA. Also, cultures treated with serotype a-LPS displayed increased mRNA levels of the modulatory cytokines IL-4 and IL-10. Mixed hippocampal cultures treated with serotype b-LPS exhibited severe neuronal morphological changes and displayed increased levels of secreted Aβ1-42 peptide. These results indicate that LPS from different Aa serotypes triggers discriminatory immune responses, which differentially affect primary hippocampal cells. Conclusion: Altogether, our results show that treatment with serotype b-LPS triggers the secretion of proinflammatory cytokines by microglia, induces neurite shrinking, and increases the extracellular Aβ1-42 levels, all features strongly associated with the etiology of AD.


[Characteristics of patients with alcohol- or drug problems in medical practices "addiction" in Mecklenburg-Vorpommern].
The pilot scheme "Medical practices with emphasis on addiction" examines one approach in the outpatient treatment of patients with addiction. Nine medical practices in Mecklenburg-West Pomerania participate in this project, and the goal is to lower the threshold for the utilisation of help and to provide a long-term relationship between the patient and the physician. Results of the first survey of patients and physicians are presented as part of the scientific evaluation of the entire project. Data of 876 patients was assessed. There is data about the severity of alcohol dependence (SESA), about negative consequences of drinking and about utilisation of help for n = 627 patients. These were compared with a sample of n = 153 subjects with a diagnosis of alcohol dependence from a population-based survey. Medical doctors provided information on the duration and quality of patient contact, current drug consumption and content of treatment for n = 472 patients. Of all patients, 51 % were treated for more than 3 years in the respective practice. Among the patients, 45 % were current drug users, further help was recommended for 77 %. In comparison with the reference group, patients with a diagnosis of alcohol dependence in those practices were more severely dependent, reported more problems concerning health, work, or finances and utilised addiction-specific help more often. The medical practices under examination undertake the task to provide long-term support for patients with addiction diagnoses and encourage patients to utilize more help from further sources. Their patients with alcohol diagnoses differ substantially from persons in the general population with regard to severity of dependence and related problems. This justifies an intensive medical and psychosocial support by specialised practitioners.


Improving the Surgeon's participation in research: is It a problem of training or priority?
Although numerous important contributions have originated from basic science research performed by surgeons, it seems that such dedicated work is becoming increasingly difficult to accomplish. What are the reasons for this change and what improvements can be made? This study aims to characterize the basic research training and careers of senior academic surgeons to assess and devise strategies for sustaining productive and quality surgical research. A 25-item survey was sent to 850 senior-level members of academic societies, including the Association of Academic Surgeons, Society of University Surgeons, and American Surgical Association. It addressed each surgeon's clinical and research training and career, as well as opinions concerning surgical research. Three hundred seventy-seven (44%) surveys were received. Mean age was 64 years, and 73% were full professors. Seventy-two percent of respondents performed basic science research during training, and for 71% of this group, research was a significant reason for choosing a clinical specialty. Ninety-one percent performed research in the same specialty area during and after training. Of those who performed research during training, a full 99% continued to perform research on completion of training. However, 38% stopped performing basic research by age 39. Seventeen and twenty-three percent stopped basic research between 40 and 49 and between 50 and 59 years of age, respectively. The most common factors causing them to stop were increased clinical load (40%) and increased administrative duties (38%). For respondents who had stopped research prior to age 40, 73% cited increased clinical load as the primary reason. Eighty-five percent felt a dedicated research period should be included in surgery training. Most respondents had participated in basic research during training, and continued similar research after training. However, an overwhelming clinical practice at the junior faculty level seemed to hinder research. We conclude: (1) the majority consensus is that research training is integral to the development of academic surgeons; (2) such research training opportunities appear adequate; however, (3) faculty performing research, particularly at the junior level, need to be better protected from other academic duties, such as clinical practice and administration. The challenge to the leadership of academic surgery will be to enhance such research productivity in the context of increasing academic demands.


Time Course of Calcium Concentrations and Risk Factors for Hypocalcemia in Patients Receiving Denosumab for the Treatment of Bone Metastases From Cancer.
Severe hypocalcemia sometimes develops during denosumab treatment for bone metastases from cancer and is, therefore, an important issue. However, limited information is available on the risk factors for hypocalcemia and the appropriate interval for monitoring serum calcium concentration. The present study aimed to identify the risk factors for grade ≥2 hypocalcemia and to investigate the time course of serum calcium concentrations in patients receiving denosumab for bone metastases from cancer. The medical records of 66 cancer patients treated with denosumab between April 2012 and August 2013 were retrospectively reviewed. Of the 66 enrolled patients, 11, 5, and 1 developed grade 1, 2, and 3 hypocalcemia, respectively. All 4 patients with a baseline estimated glomerular filtration rate (eGFR) of <30 mL/min developed hypocalcemia. Hypocalcemia occurred in only 20%, 24%, and 15% of patients with an eGFR of 30 to 59, 60 to 89, and ≥90 mL/min, respectively. Multivariate logistic regression analysis revealed that lower eGFR values (odds ratio, 1.72 per 10 mL/min decrease, P = 0.02) were significantly associated with grade ≥2 hypocalcemia. In 11 patients who developed hypocalcemia during the first treatment course, the mean calcium concentrations decreased from 9.8 mg/dL at baseline to 8.4 mg/dL during the first week and reached a nadir of 8.1 mg/dL during the second week. Our results support more frequent monitoring of serum calcium concentrations at baseline and during the first 2 weeks of treatment in patients receiving denosumab, especially those with an eGFR <30 mL/min.


Diagnosing chronic pelvic pain of bladder origin.
Recent data show that in the significant majority of gynecologic patients, chronic pelvic pain (CPP) has its origin in the bladder in the chronic disease process known as interstitial cystitis (IC). IC can produce pain that is perceived in any location or locations in the pelvis in any combination, with or without urinary frequency/urgency. Until recently, the diagnosis of IC was complicated by the variable clinical presentation of the disease and a lack of diagnostic tools. With recent advances in the understanding of the disease, IC's distinctive symptom complex has become well known, and new diagnostic tools are available. Gynecologists can now test CPP patients for the presence of IC using a simple questionnaire, the Pelvic Pain and Urgency/Frequency (PUF) Patient Symptom Scale, and a minimally invasive, office-based procedure, the potassium sensitivity test (PST). Along with a careful history attuned to the characteristic clinical presentation of IC, the PUF Scale and PST can help the gynecologist establish the diagnosis and offer appropriate treatment promptly. IC can be treated very successfully in the majority of cases.


Identification of binding domains of the growth hormone-releasing hormone receptor by analysis of mutant and chimeric receptor proteins.
The hypothalamic peptide GH-releasing hormone (GHRH) stimulates the release of GH from the pituitary through binding and activation of the GHRH receptor, which belongs to the family of G protein-coupled receptors. The objective of this study was to identify regions of the receptor critical for interaction with the ligand by expressing and analyzing truncated and chimeric epitope-tagged GHRH receptors. Two truncated receptors, GHRHdeltaN, in which part of the N-terminal domain between the putative signal sequence and the first transmembrane domain was deleted, and GHRHdeltaC, which was truncated downstream of the first intracellular loop, were generated. Both the receptors were deficient in ligand binding, indicating that neither the N-terminal extracellular domain (N terminus) nor the membrane-spanning domains with the associated extracellular loops (C terminus) are alone sufficient for interaction with GHRH. In subsequent studies, chimeric proteins between the receptors for GHRH and vasoactive intestinal peptide (VIP) or secretin were generated, using the predicted start of the first transmembrane domain as the junction for the exchange of the N terminus between receptors. The chimeras having the N terminus of the GHRH receptor and the C terminus of either the VIP or secretin receptor (GNVC and GNSC) did not bind GHRH or activate adenylate cyclase after GHRH treatment. The reciprocal chimeras having the N terminus of either the VIP or secretin receptors and the C terminus of the GHRH receptor (VNGC and SNGC) bound GHRH and stimulated cAMP accumulation after GHRH treatment. These results suggest that although the N-terminal extracellular domain is essential for ligand binding, the transmembrane domains and associated extracellular loop regions of the GHRH receptor provide critical information necessary for specific interaction with GHRH.


Aberrant Levels of Hematopoietic/Neuronal Growth and Differentiation Factors in Euthyroid Women at Risk for Autoimmune Thyroid Disease.
Subjects at risk for major mood disorders have a higher risk to develop autoimmune thyroid disease (AITD) and vice-versa, implying a shared pathogenesis. In mood disorder patients, an abnormal profile of hematopoietic/neuronal growth factors is observed, suggesting that growth/differentiation abnormalities of these cell lineages may predispose to mood disorders. The first objective of our study was to investigate whether an aberrant profile of these hematopoietic/neuronal growth factors is also detectable in subjects at risk for AITD. A second objective was to study the inter relationship of these factors with previously determined and published growth factors/cytokines in the same subjects. We studied 64 TPO-Ab-negative females with at least 1 first- or second-degree relative with AITD, 32 of whom did and 32 who did not seroconvert to TPO-Ab positivity in 5-year follow-up. Subjects were compared with 32 healthy controls (HCs). We measured serum levels of brain-derived neurotrophic factor (BDNF), Stem Cell Factor (SCF), Insulin-like Growth Factor-Binding Protein 2 (IGFBP-2), Epidermal Growth Factor (EGF) and IL-7 at baseline. BDNF was significantly lower (8.2 vs 18.9 ng/ml, P<0.001), while EGF (506.9 vs 307.6 pg/ml, P = 0.003) and IGFBP-2 (388.3 vs 188.5 ng/ml, P = 0.028) were significantly higher in relatives than in HCs. Relatives who seroconverted in the next 5 years had significantly higher levels of SCF than non-seroconverters (26.5 vs 16.7 pg/ml, P = 0.017). In a cluster analysis with the previously published growth factors/cytokines SCF clustered together with IL-1β, IL-6 and CCL-3, of which high levels also preceded seroconversion. Relatives of AITD patients show aberrant serum levels of 4 hematopoietic/neuronal growth factors similar to the aberrancies found in mood disorder patients, suggesting that shared growth and differentiation defects in both the hematopoietic and neuronal system may underlie thyroid autoimmunity and mood disorders. A distinct pattern of four inter correlating immune factors in the relatives preceded TPO-Ab seroconversion in the next 5 years.


A transgene insertional mutation at an imprinted locus in the mouse genome.
Genetic imprinting in mice results in functional differences in the oocyte and spermatocyte genomes, as evidenced by both genetic and pronuclear transfer experiments. To gain insights into the molecular mechanisms involved in the imprinting process, researchers have studied methylation phenotypes and expression of hemizygous transgenes associated with parental origin. In this report, we describe a transgenic mouse lineage in which expression of both the transgene and an endogenous gene at the insertion site are determined by the parent of origin. The mutation caused by transgene insertion shows variable expressivity and incomplete penetrance in addition to a modified dominant pattern of inheritance.


The acute muscular response to two distinct blood flow restriction protocols.
The purpose of this study was to determine acute physiological and perceptual responses to two commonly implemented blood flow restriction protocols. Using a within-subject design, 15 participants (age ∼25) performed four sets of unilateral elbow flexion with each arm. One arm exercised using a 3-cm elastic cuff inflated to 160 mmHg, whereas the other arm exercised using a 5-cm nylon cuff inflated to 40% of the individual's arterial occlusion pressure. While both protocols elicited increases in acute muscle thickness [pre: 4.5 (0.2) cm, post: 5.0 (0.2) cm; p < 0.001] and electromyography amplitude [first 3 reps: 55 ( 5 ) %MVC; last 3 reps: 87 ( 10 ) %MVC], there were no differences between conditions. Both protocols produced decreases in post-exercise strength (pre: 70 Nm, post: 51 Nm; p < 0.001) with no difference between conditions. The nylon protocol resulted in more repetitions during sets 2 [13 ( 2 ) vs. 9 ( 4 ); p = 0.001] and 3 [10 ( 2 ) vs. 7 ( 4 ); p = 0.05], while producing lower levels of discomfort following each set (average 3 vs. 4; p < 0.05). In conclusion, both protocols produced similar acute responses thought to be important for promoting muscle growth. However, the use of arbitrary pressures may place some individuals under complete arterial occlusion which may increase the potential risk of an adverse event.


Aqueous stem bark extract of Stereospermum kunthianum (Cham, Sandrine Petit) protects against generalized seizures in pentylenetetrazole and electro-convulsive models in rodents.
Stereospermum kunthianum, Cham Sandrine Petit (Bignoniaceae) known in English as pink jacaranda is used in traditional medicine to treat an array of ailments including febrile convulsions in infants and young children by the rural dwellers in Nigeria. This study examined the anticonvulsant activity of its aqueous stem bark extract (100 - 400mg/kg) against maximal electroshock and pentylenetetrazole-induced seizures in rodents. Phenobarbitone and ethosuximide were used as reference anticonvulsant drugs for comparison. Stereospermum kunthianum extract (200 - 400mg/kg, i.p.) remarkably protected (76.9% and 84.6 % respectively) the rats against electroshock-induced seizures. However, the extract (200- 400mg/kg) when administered orally showed a comparatively less effect (33.3% and 55.6% respectively) to the intraperitoneally administered extract in the maximal electroshock test. The extract (100-400mg/kg, i.p.) significantly delayed (p<0.05) the onset of pentylenetetrazole-induced clonic seizures but only slightly prolonged the time of death of the mice. Although the findings in the present study do not provide conclusive evidence, it appears that the aqueous stem bark extract of Stereospermum kunthianum produces its antiseizure effect by enhancing GABAergic neurotransmission and/or action in the brain. The results indicate that the aqueous extract possesses anticonvulsant activity in rodents and therefore tend to suggest that the shrub may be used as a natural supplementary remedy in the management, control and/or treatment of childhood convulsions. It can be concluded that the aqueous stem bark extract possesses anticonvulsant activity and therefore lend pharmacological credence to the traditionally claimed use in the treatment of childhood convulsions.


[Electron microscopic and mass spectrometric studies of lymphedema pathogenesis aspects].
A comprehensive examination was made, which included histological, electron microscopic and chromatographic mass spectrometric studies of biological specimens obtained from 18 patients with leg lymphedema. The development of lymphedema was found to accompanied by the specific connective tissue structure being formed along with the presence of low-differentiated and necrotic areas associated with the cytopathology of blood and lymph vessels and impaired microcirculation. The connective tissue areas under study were demonstrated to have a pronounced antigenicity and aggressive properties against other tissues and structures. The morphological changes revealed are directly related to the impaired metabolism of protein, fatty acids, and complex polysaccharides.


Prolongation of liver allograft survival by donor-specific soluble transplantation antigens and antigen-antibody complexes.
Soluble transplantation antigens were prepared from chacma baboon spleen cell membranes by a modified 3 M KCl technique. The extracts were soluble according to usually accepted criteria. Molecular weight was 37,700 daltons. Antigenicity was confirmed by inhibition of cytotoxicity of alloantibody. The antigens stimulated sensitized lymphocytes in culture but failed to stimulate unsensitized lymphocytes. Antigen-antibody complexes were assembled in vitro in the regions of equivalence and marked antigen excess. Administration of a single dose of soluble donor antigen at the time of orthotopic liver allotransplantation prolonged graft survival significantly. Concomitant administration of a polyspecific alloantibody, previously shown to prolong baboon liver allograft survival, abrogated the graft prolongation produced by the antigen or antibody given alone. When the administration of the soluble antigen was preceded by a dose of cyclophosphamide (20 mg/kg), graft prolongation was slightly curtailed. Antecedent administration of azathioprine and prednisolone for 3 days seemed to render the antigen immunogenic in that liver allograft rejection was accelerated. Antigen-antibody complexes at equivalence prolonged liver allograft survival beyond that seen with antigen alone, but complexes in marked antigen excess were immunogenic, inasmuch as graft survival was not prolonged and the histological features were those of accelerated rejection.


Exposure-response relationship of ramucirumab in RANGE, a randomized phase III trial in advanced urothelial carcinoma refractory to platinum therapy.
Patients with advanced urothelial carcinoma (UC) who progress after platinum-based chemotherapy have a poor prognosis, and there is a medical need to improve current treatment options. Ramucirumab plus docetaxel significantly improved progression-free survival but not overall survival (OS) in platinum-refractory advanced UC (RANGE trial; NCT02426125). Here, we report the exposure-response (ER) of ramucirumab plus docetaxel using data from the RANGE trial. Pharmacokinetic (PK) samples were collected (cycle 1-3, 5, 9 [day 1] and 30 days from treatment discontinuation), and PK data were analysed using population PK (popPK) analysis. The minimum ramucirumab concentration after first dose administration (Cmin,1 , or trough concentration immediately prior to the second dose) was derived by popPK analysis and used as the exposure parameter for ER analysis. Cox proportional hazards regression models and matched case-control analyses were used to evaluate the relationship between Cmin,1 and OS. The Cmin,1 relationship with safety was assessed descriptively. Several poor prognostic factors (ECOG 1, haemoglobin concentration <100 g/L, presence of liver metastases) appeared more frequently in the lower exposure quartiles, suggesting a possible disease-PK interaction. A significant association was identified between Cmin,1 and OS (P = .0108). Higher exposure quartiles were associated with longer survival and smaller hazard ratios compared to placebo. No new exposure-safety trends were observed within the exposure range (ramucirumab 10 mg/kg once every 3 weeks). This prespecified ER analyses suggests a positive relationship between efficacy and ramucirumab exposure, with an imbalance associated with disease prognostic factors. Further investigation may elucidate a possible disease-PK relationship.


A filtering method to generate high quality short reads using illumina paired-end technology.
Consensus between independent reads improves the accuracy of genome and transcriptome analyses, however lack of consensus between very similar sequences in metagenomic studies can and often does represent natural variation of biological significance. The common use of machine-assigned quality scores on next generation platforms does not necessarily correlate with accuracy. Here, we describe using the overlap of paired-end, short sequence reads to identify error-prone reads in marker gene analyses and their contribution to spurious OTUs following clustering analysis using QIIME. Our approach can also reduce error in shotgun sequencing data generated from libraries with small, tightly constrained insert sizes. The open-source implementation of this algorithm in Python programming language with user instructions can be obtained from https://github.com/meren/illumina-utils.


Detection of Dental Apical Lesions Using CNNs on Periapical Radiograph.
Apical lesions, the general term for chronic infectious diseases, are very common dental diseases in modern life, and are caused by various factors. The current prevailing endodontic treatment makes use of X-ray photography taken from patients where the lesion area is marked manually, which is therefore time consuming. Additionally, for some images the significant details might not be recognizable due to the different shooting angles or doses. To make the diagnosis process shorter and efficient, repetitive tasks should be performed automatically to allow the dentists to focus more on the technical and medical diagnosis, such as treatment, tooth cleaning, or medical communication. To realize the automatic diagnosis, this article proposes and establishes a lesion area analysis model based on convolutional neural networks (CNN). For establishing a standardized database for clinical application, the Institutional Review Board (IRB) with application number 202002030B0 has been approved with the database established by dentists who provided the practical clinical data. In this study, the image data is preprocessed by a Gaussian high-pass filter. Then, an iterative thresholding is applied to slice the X-ray image into several individual tooth sample images. The collection of individual tooth images that comprises the image database are used as input into the CNN migration learning model for training. Seventy percent (70%) of the image database is used for training and validating the model while the remaining 30% is used for testing and estimating the accuracy of the model. The practical diagnosis accuracy of the proposed CNN model is 92.5%. The proposed model successfully facilitated the automatic diagnosis of the apical lesion.