Single-molecule measurement of elasticity of serine-, glutamate- and lysine-rich repeats of invertebrate connectin reveals that its elasticity is caused entropically by random coil structure.
Invertebrate connectin (I-connectin) is a 1960 kDa elastic protein linking the Z line to the tip of the myosin filament in the giant sarcomere of crayfish claw closer muscle (Fukuzawa et al., 2001 EMBO J 20: 4826-4835). I-Connectin can be extended up to 3.5 microns upon stretch of giant sarcomeres. There are several extensible regions in I-connectin: two long PEVK regions, one unique sequence region and Ser-, Glu- and Lys-rich 68 residue-repeats called SEK repeats. In the present study, the force measurement of the single recombinant SEK polypeptide containing biotinylated BDTC and GST tags at the N and C termini, respectively, were performed by intermolecular force microscopy (IFM), a refined AFM system. The force vs. extension curves were well fit to the wormlike chain (WLC) model and the obtained persistence length of 0.37 +/- 0.01 nm (n = 11) indicates that the SEK region is a random coil along its full length. This is the first observation of an entropic elasticity of a fully random coil region that contributes to the physiological function of I-connectin.


Open-Label Study of the Stability of Sublingual Nitroglycerin Tablets in Simulated Real-Life Conditions.
Contemporary practice favors refilling sublingual nitroglycerin (SL NTG) every 3 to 6 months. This recommendation is based on antiquated data that does not consider the reformulated tablet and the improved manufacturing process. Our objective was to investigate the stability of SL NTG over time using simulated real-life scenarios in comparison to controlled storage conditions. This was an open-label study of 100- and 25-count commercial SL NTG bottles stored in either controlled temperature and relative humidity conditions, or carried in a pocket or purse. SL NTG potency (chemical stability) was assessed using high performance liquid chromatography and physical stability was assessed by changes in tablet weights over time through the labeled expiration date. Both chemical and physical stability of SL NTG were affected by environmental and physical factors. High temperature storage resulted in the most rapid loss of potency. Tablets carried in a pant pocket lost potency faster than those carried in a purse. Potency was also dependent on headspace of the bottle. Tablets stored in the original bottle in a temperate environment could be expected to maintained potency for more than 2 years when carried in a purse, irrespective of package size. When carried in a pant pocket, potency of a 25-count bottle was maintained for 2 years, whereas potency of a 100-count bottle fell below acceptable limits at 12 months. In conclusion, since potency is dependent on temperature, headspace, and carrying practices, frequency of SL NTG refills should be based on individual patient behavior.


Effects of progestagens on follicular growth and oocyte developmental competence in FSH-treated ewes.
Previous research has reported evidence for negative effects of progestagens on follicular growth and oocyte competence. In the present study, negative effects of progestagens on follicular growth and oocyte developmental competence were assessed. During the breeding season, 20 Sarda ewes were treated with two doses of cloprostenol, 10 days apart, to assure the presence of a corpus luteum (CL). On day 5 after the second cloprostenol dose, 10 ewes were treated with a progestagen sponge while 10 females remained untreated. Starting on day 7 after the second cloprostenol dose, all the ewes were treated with 6 equal doses of 24 I.U. of FSH (Ovagen, ICP, NZ), every 12h. The number of follicles > or =2mm in diameter increased (P<0.0005) in all the ewes from 24 h before to 60 h after the first FSH dose (from 12.8+/-1.1 to 23.4+/-1.3 in treated and from 12+/-0.6 to 22+/-1.2 in untreated ewes, n.s.). There were no significant differences in follicle dynamics between groups, but concentrations of estradiol in control ewes were higher than in the progestagen group (P<0.05). Twelve hours after the last FSH dose, oocytes were collected by ovum pick-up. Recovery rates were lower for progestagen-treated ewes (71.1 versus 83%; P<0.001). After IVP procedure, cleavage rate was also lower in the progestagen group (39.1 versus 82.6%; P<0.001). Furthermore, blastocysts output revealed that oocyte developmental competence was lower in progestagen group (17.3 versus 30.4%; P=0.245), although differences were not significant. These results suggest deleterious effects from progestagen on oocyte developmental competence and set the basis for new protocols for in vitro embryo production.


First report of a blaNDM-resistant gene in a Klebsiella aerogenes clinical isolate from Brazil.
Carbapenemase-resistant enterobacteria that produce the bla NDM gene are found worldwide. However, this is the first report of blaNDM in Klebsiella aerogenes in Brazil. The identification of bacterial species was performed using anautomated system and confirmed by biochemical tests, 16S rRNA gene sequencing, and detection of resistance genes. The clinical isolate showed minimum inhibitory concentration resistance to meropenem and polymyxin B at 8mg/L and 4mg/L, respectively. Only the blaNDM gene was detected. The current report of the blaNDM gene in isolated MDR enterobacteria indicates that this gene can spread silently in a hospital setting.


A systematic review and meta-analysis of the efficacy and safety of hysteroscopic electric resection versus vaginal surgery in the treatment of uterine scar defects after cesarean section.
Cesarean sections are increasingly likely to be applied; however, uterine scar defects (USD) often remain after delivery. The two existing treatment methods, hysteroscopic electric resection and vaginal surgery, are still controversial in terms of efficacy and safety. So, this paper to compares the effectiveness and safety of hysteroscopic electric resection and vaginal surgery in the treatment of USD after cesarean section. We performed a related literature search from main databases. According to the PICOS principles inclusion criteria were adult female USD patients to evaluate the efficacy of hysteroscopic resection and vaginal surgery for the treatment of USD, outcome data could be extracted to compare the efficacy and safety of the two procedures. Subsequently, according to the titles, abstracts, and full texts of the retrieved articles, studies that did not meet the inclusion criteria were eliminated. The RevMan 5.20 software was used for meta-analysis and Cochrane Risk of Bias 2 (RoB 2.0) was used to assess the risk of bias. The effectiveness and safety of hysteroscopic resection and vaginal surgery in the treatment of USD patients after cesarean section were compared. Eight articles were finally included, with a total of 191 patients in the hysteroscopic electric resection group and 212 patients in the vaginal surgery group. Compared with hysteroscopic resection and vaginal surgery, there is less intraoperative blood loss [mean difference (MD) is -25.23, P<0.00001], shorter operation time (MD is -29.45, P<0.00001), and shorter hospital stay (MD is -1.87, P<0.00001), but menstrual improvement risk ratio (RR) is 0.71 (P=0.51) and diverticulum recovery RR is 0.60 (P=0.43) there were no significant differences. Hysteroscopic electric resection provides a more satisfactory outcome than vaginal surgery in terms of intraoperative blood loss, operation time, and hospital stay. However, the sample size of the study was not large enough and some studies had high risk of bias, more large-sample multi-center high quality studies are needed for further comprehensive comparative analysis.


Artificial neural network to predict the effect of obesity on the risk of tuberculosis infection.
Body weight has been implicated as a risk factor for latent tuberculosis infection (LTBI) and the active disease. This study aimed to develop artificial neural network (ANN) models for predicting LTBI from body weight and other host-related disease risk factors. We used datasets from participants of the US-National Health and Nutrition Examination Survey (NHANES; 2012; n=5,156; 514 with LTBI and 4,642 controls) to develop three ANNs employing body mass index (BMI, Network I), BMI and HbA1C (as a proxy for diabetes; Network II) and BMI, HbA1C and education (as a proxy for socioeconomic status; Network III). The models were trained on n=1018 age- and sex-matched subjects equally distributed between the control and LTBI groups. The endpoint was the prediction of LTBI. When data was adjusted for age, sex, diabetes and level of education, odds ratio (OR) and 95% confidence intervals (CI) for risk of LTBI with increased BMI was 0.85 (95%CI: 0.77 - 0.96, p=0.01). The three ANNs had a predictive accuracy varied from 75 to 80% with sensitivities ranged from 85% to 94% and specificities of approximately 70%. Areas under the receiver operating characteristic curve (AUC) were between 0.82 and 0.87. Optimal ANN performance was noted using BMI as a risk indicator. Body weight can be employed in developing artificial intelligence-based tool to predict LTBI. This can be useful in precise decision making in clinical and public health practices aiming to curb the burden of tuberculosis, e.g., in the management and monitoring of the tuberculosis prevention programs and to evaluate the impact of healthy weight on tuberculosis risk and burden.


Hydroxyl radical-induced degradation of fenuron in pulse and gamma radiolysis: kinetics and product analysis.
Radiolytic reactions of phenylureas were studied in detail with fenuron model compound in dilute aqueous solutions using pulse radiolysis for detection of the intermediates, gamma radiolysis with UV-Vis and HPLC-MS techniques for analysis of the final products. The kinetics of oxidation was followed by COD, TOC and toxicity measurements. During radiolysis of aerated solutions hydroxyl radical ((•)OH), eaq (-), H(•) and O2 (•-)/HO2 (•) reactive intermediates are produced, the degradation of solute takes place practically entirely through (•)OH reactions. Therefore, the product distribution is similar to the distributions reported in other advanced oxidation processes with (•)OH as main reactant. (•)OH mainly reacts with the aromatic ring, forming cyclohexadienyl radical as an intermediate. This radical in pulse radiolysis has a wide absorption band in the 310-390 nm wavelength range with a maximum at 350 nm. Cyclohexadienyl radical reacts with dissolved O2 with a rate coefficient of ∼ 4 × 10(8) mol(-1) dm(3) s(-1) forming peroxy radical. The latter may eliminate HO2 (•) giving phenols or undergoes fragmentation. The one-electron oxidant (•)OH on average induces more than two-electron oxidations. The toxicity first increases with absorbed dose, then decreases. This increase is partly due to phenols formed during the first degradation period.


Imaging of pediatric pelvic neoplasms.
Pediatric pelvic neoplasms, although relatively uncommon, are often difficult to evaluate and characterize with imaging, due to their overlapping appearances. This article discusses key clinical features and imaging findings that help limit the differential diagnosis of pediatric pelvic neoplasms. Testicular, ovarian, uterine, and bladder masses are included in addition to sacrococcygeal teratoma.


The augmin complex architecture reveals structural insights into microtubule branching.
In mitosis, the augmin complex binds to spindle microtubules to recruit the γ-tubulin ring complex (γ-TuRC), the principal microtubule nucleator, for the formation of branched microtubules. Our understanding of augmin-mediated microtubule branching is hampered by the lack of structural information on the augmin complex. Here, we elucidate the molecular architecture and conformational plasticity of the augmin complex using an integrative structural biology approach. The elongated structure of the augmin complex is characterised by extensive coiled-coil segments and comprises two structural elements with distinct but complementary functions in γ-TuRC and microtubule binding, linked by a flexible hinge. The augmin complex is recruited to microtubules via a composite microtubule binding site comprising a positively charged unordered extension and two calponin homology domains. Our study provides the structural basis for augmin function in branched microtubule formation, decisively fostering our understanding of spindle formation in mitosis.


Dengue Fever in Italy: The "Eternal Return" of an Emerging Arboviral Disease.
Enhanced surveillance for dengue virus (DENV) infections in Italy has been implemented since 2012, with annual reports from the National Health Institute. In this study, we summarize available evidence on the epidemiology of officially notified DENV infections from 2010-2021. In total, 1043 DENV infection cases were diagnosed, and most of them occurred in travelers, with only 11 autochthonous cases. The annual incidence rates of DENV infections peaked during 2019 with 0.277 cases per 100,000 (95% confidence interval [95% CI] 0.187-0.267), (age-adjusted incidence rate: 0.328, 95% CI 0.314-0.314). Cases of DENV were clustered during the summer months of July (11.4%), August (19.3%), and September (12.7%). The areas characterized by higher notification rates were north-western (29.0%), and mostly north-eastern Italy (41.3%). The risk for DENV infection in travelers increased in the time period 2015-2019 (risk ratio [RR] 1.808, 95% CI 1.594-2.051) and even during 2020-2021 (RR 1.771, 95% CI 1.238-2.543). Higher risk for DENV was additionally reported in male subjects compared with females subjects, and aged 25 to 44 years, and in individuals from northern and central Italy compared to southern regions and islands. In a multivariable Poisson regression model, the increased number of travelers per 100 inhabitants (incidence rate ratio [IRR] 1.065, 95% CI 1.036-1.096), the incidence in other countries (IRR 1.323, 95% CI 1.165-1.481), the share of individuals aged 25 to 44 years (IRR 1.622, 95% CI 1.338-1.968), and foreign-born residents (IRR 2.717, 95% CI 1.555-3.881), were identified as effectors of annual incidence. In summary, although the circulation of DENV remains clustered among travelers, enhanced surveillance is vital for the early detection of human cases and the prompt implementation of response measures.


High rates of transitions to injecting drug use among Mexican American non-injecting heroin users in San Antonio, Texas (never and former injectors).
To assess the incidence and rate of transition to injecting among Mexican American noninjecting heroin users. In a prospective cohort study of street-recruited MA-NIU in San Antonio, Texas, 2002-2005, participants were administered structured interviews and tested for Human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). The analysis sample comprised former injection drug users (last injected >6 months ago, n=47) and those who had never injected drugs and tested HCV negative (n=219). A transition to injecting was defined as the first injection of illicit drugs since baseline interview. Transition rates were based on person-years at-risk (PYAR). Proportional hazards regression was used to estimate crude and adjusted (for significant differences between former and never injectors) hazard ratios and 95% confidence intervals of injecting history on transitioning to injecting. Sixty-three (24%) participants transitioned to injecting at a rate of 22.3/100 PYAR (95% CI: 17.2-28.2). Former-injectors were significantly more likely to transition than never injectors (43% or 20/47 vs. 20% or 43/219; p<0.001), and did so at a faster rate (40.4/100 PYAR, 95% CI: 24.6-60.0 vs. 18.5/100 PYAR, 95% CI: 13.4-24.4), with the crude HR=1.931 (95% CI: 1.116, 3.341) and adjusted HR=2.263 (95% CI: 1.192-4.294). The rate of transitioning to injecting was high and greater among former injectors. Of particular concern is the high rate of injecting initiation among never injectors. Future analyses will examine factors associated with injecting initiation, including individual susceptibility and behaviors, social networks, and the cultural and drug market context.


An analysis of pediatric blood cultures in the postpneumococcal conjugate vaccine era in a community hospital emergency department.
Blood cultures are commonly included in the evaluation of febrile children younger than 3 years without focal source of infection. Clinicians treat patients with a positive blood culture before final identification of the organism. Their treatment might include reevaluation in the emergency department (ED), additional tests, parenteral antibiotics, and hospital admission even for children who ultimately have false-positive (FP) blood cultures. The advent of pneumococcal conjugate vaccine (PCV) has made occult bacteremia less common, decreasing the likelihood that a positive blood culture result before final organism identification will be a true pathogen. This study will identify the characteristics of patients with FP blood cultures in the post-PCV era. Charts were reviewed of all children ages 1 to 36 months with a temperature of at least 38.08 degrees C who had a blood culture obtained in our community hospital ED from January 1997 to January 2005. Bacteria grew in 106 (3.5%) out of 2971 blood cultures. True positives (TPs), defined as true pathogens, had a prevalence of 0.7%, representing 19.8% of positives. FPs, defined as contaminants, occurred in 2.8% of cultures, representing 80.2% of positives. Patients with FP cultures had lower mean white blood cell (WBC) counts (10.51 x 10(9)/L vs. 16.95 x 10(9)/L; P = 0.0001) and lower mean presenting temperatures (38.8 degrees C vs. 39.4 degrees C; P = 0.005). FPs had longer time to positivity (34.6 vs. 17.7 hours; P = 0.001) than TPs. A culture with a Gram stain suggestive of a contaminant, time to positivity greater than 24 hours and a WBC of less than 15 x 10(9)/L had a PPV for an FP of 97%. When analysis was restricted to well-appearing children age 2 to 36 months with temperature of more than 39 degrees C without focal source of infection who were discharged from the ED, these three criteria had a PPV for an FP of 100%. In these highly febrile children, the FPs had significantly lower WBCs (9.14 x 10(9)/L vs. 22.84 x 10(9)/L; P = 0.0001) and longer time topositivity (33.4 vs. 19.8 hours; P = 0.007) than TPs. The likelihood of obtaining FP cultures increased after the introduction of PCV from 62.5% to 87.8% odds ratio, 4.3; 95%confidence internal, 1.44-13.38). In the post-PCV era, the majority of blood culture results will be FPs. FP cultures are predictable in febrile children with WBC counts less than 15.00 x 10(9)/L, time to positivity of more than 24 hours, and a Gram stain result suggestive of a contaminant. Prospective studies applying these criteria to the at-risk population for occult bacteremia are indicated.


Holistic dermatology: An evidence-based review of modifiable lifestyle factor associations with dermatologic disorders.
Holistic dermatology focuses on treating the human body as a whole and implementing lifestyle changes to enhance the treatment and prognosis of skin disease. Understanding the interplay between modifiable lifestyle factors and patients' dermatologic health will help physicians better inform patients on self-care methods to mitigate the burden of their skin disease(s). To review the current scientific literature on the relationship between modifiable lifestyle factors and the dermatologic outcome of skin disorders. A systematic literature search on PubMed, Cochrane, and Web of Science was conducted to identify research articles examining the relationship between dermatology and 6 major categories of modifiable lifestyle factors: diet, sleep, exercise, stress, alcohol, and smoking. A substantial amount of evidence supports the relationship between modifiable lifestyle factors and dermatologic outcomes. There were the most studies on diet, stress, alcohol, and smoking, but all lifestyle factors were supported by some degree of scientific evidence. All modifiable lifestyle factors explored in this review play a critical role in modulating the onset and progression of skin disease. We anticipate more research studies in the future and an increasing integration of holistic dermatology into patient care.


The effects of hedonically acceptable red pepper doses on thermogenesis and appetite.
Previous studies suggest consumption of red pepper (RP) promotes negative energy balance. However, the RP dose provided in these studies (up to 10 g/meal) usually exceeded the amount preferred by the general population in the United States (mean=~1 g/meal). The objective of this study was to evaluate the effects of hedonically acceptable RP doses served at a single meal in healthy, lean individuals on thermogenesis and appetite. Twenty-five men and women (aged 23.0 ± 0.5 years, BMI 22.6 ± 0.3 kg/m(2), 13 spicy food users and 12 non-users) participated in a randomized crossover trial during which they consumed a standardized quantity (1 g); their preferred quantity (regular spicy food users 1.8 ± 0.3 g/meal, non-users 0.3 ± 0.1 g/meal); or no RP. Energy expenditure, core body and skin temperature, and appetite were measured. Postprandial energy expenditure and core body temperature were greater, and skin temperature was lower, after test loads with 1 g RP than no RP. Respiratory quotient was lower after the preferred RP dose was ingested orally, compared to in capsule form. These findings suggest that RP's effects on energy balance stem from a combination of metabolic and sensory inputs, and that oral exposure is necessary to achieve RP's maximum benefits. Energy intake was lower after test loads with 1 g RP than no RP in non-users, but not in users. Preoccupation with food, and the desire to consume fatty, salty, and sweet foods were decreased more (or tended to be decreased more) in non-users than users after a 1 g RP test load, but did not vary after a test load with no RP. This suggests that individuals may become desensitized to the effects of RP with long-term spicy food intake.


Granulomas in acquired immunodeficiency syndrome-associated cutaneous Kaposi sarcoma: evidence for a role for Mycobacterium tuberculosis.
Co-lesional acquired immunodeficiency syndrome-associated cutaneous Kaposi sarcoma (AIDS-KS) and Mycobacterium tuberculosis-associated granulomatous inflammation are undocumented. Retrospective appraisal of skin biopsies with co-lesional AIDS-KS and microscopic tuberculosis (TB). Sixteen biopsies from nine males and seven females form the study cohort. Histological assessment confirmed nodular and plaque KS in 12 and 4 cases each, respectively. Necrotizing, non-necrotizing and a combination of necrotizing and non-necrotizing granulomatous inflammation were present in nine, two and five biopsies each, respectively. The identification of acid fast bacilli on Ziehl-Neelsen staining and M. tuberculosis on polymerase chain reaction confirmed co-lesional TB in 15/16 biopsies. Co-lesional AIDS-KS and lichen scrofulosorum, hitherto undocumented, were confirmed in one biopsy. The histopathological findings served as a marker of human immunodeficiency virus (HIV) infection, visceral TB, therapeutic noncompliance and multidrug resistant pulmonary TB in nine, eight, five and one patient, respectively. M. tuberculosis was cultured from sputum or nodal tissue of all patients. Granulomatous inflammation in KS requires optimal histopathological and molecular investigation to confirm an M. tuberculosis origin. The cutaneous co-lesional occurrence of AIDS-KS and microscopic TB may serve as the sentinel clue to HIV infection, systemic TB, therapeutic noncompliance or multidrug resistant TB.


Comparative evaluation of mutagenic, genotoxic, cytotoxic, and antimicrobial effects of flavour and fragrance aldehydes, ketones, oximes, and oxime ethers.
Despite the large number of odoriferous compounds available, new ones with interesting olfactory characteristics are desired due to their potentially high commercial value. Here, we report for the first time mutagenic, genotoxic, and cytotoxic effects, and antimicrobial properties of low-molecular fragrant oxime ethers, and we compare their properties with corresponding oximes and carbonyl compounds. 24 aldehydes, ketones, oximes, and oxime ethers were evaluated for mutagenic and cytotoxic effects in Ames (using Salmonella typhimurium strains TA 98 with genotype hisD3052, rfa, uvrB, pKM101, and TA100 with genotype hisG46, rfa, uvrB, pKM101, concentration range: 0.0781-40 mg/mL) and MTS (using HEK293T cell line concentration of tested substances: 0.025 mM) assays. Antimicrobial evaluation was carried out against Bacillus cereus (ATCC 10876), Staphylococcus aureus (ATCC 6538), Enterococcus hirae (ATCC 10541), Pseudomonas aeruginosa (ATCC 15442), Escherichia coli (ATCC 10536), Legionella pneumophila (ATCC 33152); Candida albicans (ATCC 10231) and Aspergillus brasiliensis (ATCC 16404) with concentration range of tested substances 9.375 - 2.400 mg/mL. Furthermore, 5 representatives of carbonyl compounds, oximes, and an oxime ether (stemone, buccoxime, citral, citral oxime, and propiophenone oxime O-ethyl ether) were evaluated for genotoxic properties in SOS-Chromotest (concentration range: 7.8·10-5 - 5·10-3 mg/mL). All of the tested compounds did not exhibit mutagenic, genotoxic, or cytotoxic effects. Oximes and oxime ethers showed relevant antimicrobial activity against pathogenic species (P. aeruginosa, S. aureus, E.coli, L. pneumophila, A. brasiliensis, C. albicans) in the MIC range 0.075 - 2.400 mg/mL compared to the common preservative methylparaben with the MIC range 0.400-3.600 mg/mL. Our study shows that oxime ethers have the potential to be used as fragrant agents in functional products.


Long non-coding RNA HOTTIP enhances IL-6 expression to potentiate immune escape of ovarian cancer cells by upregulating the expression of PD-L1 in neutrophils.
Long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP), has been demonstrated to be a vital biomarker when evaluating the prognosis of multiple cancers. Nevertheless, the potential function of HOTTIP in ovarian cancer (OC), a prevalent cancer among women worldwide, remains elusive. Hence, the current study aimed to elucidate the functional relevance of HOTTIP in the development of OC. Positive expression of PD-L1 and IL-6 was determined using immunohistochemical staining in the collected OC and normal tissues. The correlation of IL-6 and PD-L1 was analyzed using flow cytometry, Western blot analysis as well as Pearson's correlation coefficient. The interaction among HOTTIP, c-jun and IL-6 was investigated with the use of RIP, ChIP and dual luciferase reporter gene assays. Finally, the effects of HOTTIP on T cell proliferation and infiltration were identified through gain- and loss-of-function studies in vitro and in vivo. HOTTIP, IL-6 and PD-L1 were all highly expressed in OC tissues. A positive correlation was observed between IL-6 and PD-L1 and that between HOTTIP and IL-6 in OC tissues. HOTTIP was noted to promote the expression of IL-6 by binding to c-jun, which resulted in a promoted PD-L1 expression in neutrophils and immune escape while inhibiting T cell proliferation as well as tumor immunotherapy. Taken together, our study unveiled that HOTTIP could promote the secretion of IL-6, and consequently up-regulate the expression of PD-L1 in neutrophils, thus inhibiting the activity of T cells and ultimately accelerating immune escape of OC cells. Our study provides a potential therapeutic strategy by targeting HOTTIP in OC.


Building capacity for dementia care: training program to develop primary care memory clinics.
Currently, dementia care provided by family physicians is suboptimal and access to specialist resources is limited. With the aging population, there is a need for system-wide, programmatic interventions to improve the diagnosis and management of patients with memory difficulties. The development of primary care memory clinics addresses this need. The Memory Clinic Training Program aims to develop highly functioning interprofessional memory clinics that assist family physicians in providing improved care for patients with dementia and other forms of cognitive impairment. The interprofessional training program consists of a 2-day case-based workshop, 1 day of observership and clinical training at the Centre for Family Medicine Memory Clinic, and 2 days of on-site mentorship at each newly formed memory clinic. The Memory Clinic Training Program is an accredited, comprehensive program designed to assist family practice groups with developing primary care memory clinics. These clinics aim to transform the current limited practice capability of individual family physicians into a systematic, comprehensive, interprofessional health care service that improves capacity and quality of primary care for patients with cognitive impairment and dementia.


Risk of agranulocytosis and aplastic anemia in relation to history of infectious mononucleosis: a report from the international agranulocytosis and aplastic anemia study.
The general objective of this study was to evaluate the risks of agranulocytosis and aplastic anemia in relation to drug use. Other potential risk factors, including history of infectious mononucleosis, were also evaluated. In an international population-based case-control study, cases of agranulocytosis and aplastic anemia and controls, who were patients with selected diagnoses, were identified from the same hospitals. Information on drug use was obtained in a structured interview. Limited information on environmental exposures and on selected items of medical history, including infectious mononucleosis, was also recorded. The possible effects of these factors on the risk of the two blood dyscrasias were evaluated. Relative risks were estimated by stratified analysis and by multiple logistic regression. Among 319 cases of agranulocytosis, 12 patients (4%) gave a history of infectious mononucleosis at least 1 year previously; among 2180 controls the corresponding number was 11 (0.5%) (multivariate relative risk estimate, 6.2; 95% confidence interval, 2.3-17). A nonsignificant elevation in the relative risk was observed for aplastic anemia. The data suggest that infectious mononucleosis may confer a long-term increase in the risk of agranulocytosis. However, the association was an unexpected one, identified in the course of multiple comparisons, and it must be independently confirmed.


Evaluation of Mammogram Parties as an Effective Community Navigation Method.
Women of color do not have the same level of access to mammography services as their White counterparts, and this inequity may be one of the contributing factors to the documented racial disparity in breast cancer mortality in the US. The present study sought to assess the effectiveness of the mammogram party, a promising, but under-studied approach to increasing mammography uptake, particularly among under-served populations. The program targeted mammogram-eligible women in community settings on the west and southwest sides of Chicago, gathering basic demographic information, mammography history, and interest in assistance obtaining a mammogram. Women were navigated either through traditional one-on-one navigation or to a mammogram party. Seven outcome metrics were calculated for each type of navigation. We compared navigation outcomes for those who attended to those who did not attend a mammogram party using two-tailed t tests and chi-square tests. We found that the mammography completion rate for mammogram parties was comparable to that for standard one-on-one navigation (65.8 vs. 63.7%), which is more labor-intensive as evidenced by the number of contacts needed to successfully navigate a woman to mammography (10.9 vs. 15.0). Mammogram parties offer a unique opportunity for fellowship and support for clients who are particularly fearful of mammograms or identifying breast cancer. Programmatically, mammogram parties are an efficient way to complete several mammograms in 1 day. Having the option to both navigate women to mammogram parties or one-on-one navigation allows for more flexibility for scheduling and may ensure a completed a mammogram.


Toxic nephropathy: Adverse renal effects caused by drugs.
This is a brief overview of toxic nephropathy, which is an increasingly recognised problem with the continual introduction of new drugs and novel drug modalities, especially in oncology, and the risks associated with polypharmacy in many patients; although it is important to remember that it may not always be caused by a drug. It is also important to note that several possibly harmful drugs are now available without prescription ('over-the-counter') and can be purchased easily over the internet, including some poorly characterised herbal remedies. Knowing exactly what our patients are taking as medication is not always easy and patients often fail to mention drugs that may not have been prescribed by a doctor or recommended by a pharmacist. Moreover, patients with several comorbidities often require care from more than one doctor in other specialties, which can also lead to drug prescribing in isolation. This article will summarise some key aspects of drug nephrotoxicity and provide a few clinical pointers to consider, bearing in mind that there is rarely any antidote available, and effective treatment relies on early detection, prompt drug withdrawal, and supportive care. This short review is intended only as a primer to highlight some of the more practical aspects of toxic nephropathy; its content is based on a lecture delivered during the 2021 European Congress of Internal Medicine.


Scleractinian coral population size structures and growth rates indicate coral resilience on the fringing reefs of North Jamaica.
Coral reefs throughout the world are under severe challenges from many environmental factors. This paper quantifies the size structure of populations and the growth rates of corals from 2000 to 2008 to test whether the Discovery Bay coral colonies showed resilience in the face of multiple acute stressors of hurricanes and bleaching. There was a reduction in numbers of colonies in the smallest size class for all the species at all the sites in 2006, after the mass bleaching of 2005, with subsequent increases for all species at all sites in 2007 and 2008. Radial growth rates (mm yr(-1)) of non-branching corals and linear extension rates (mm yr(-1)) of branching corals calculated on an annual basis from 2000-2008 showed few significant differences either spatially or temporally. At Dairy Bull reef, live coral cover increased from 13+/-5% in 2006 to 20+/-9% in 2007 and 31+/-7% in 2008, while live Acropora species increased from 2+/-2% in 2006 to 10+/-4% in 2007 and 22+/-7% in 2008. These studies indicate good levels of coral resilience on the fringing reefs around Discovery Bay in Jamaica.


Correction to: User satisfaction with public oral health services in the Brazilian unified health system.
Following publication of the original article [1], the authors have reported that there is an error in Table 2 - Distribution of users concerning satisfaction with oral health services: the categories 'No' and 'Yes' should swap places.


[Schnitzler syndrome].
Schnitzler syndrome is a rare systemic inflammatory disease characterized by the presence of chronic urticarial skin rash and a monoclonal immunoglobulin M (IgM) gammopathy, combined with further, variable disease symptoms. The term refers to a young disease entity which has recently gained increasing acknowledgement and attention, also due to the availability of interleukin-1 (IL-1) blockade as an effective therapeutic option. Insights into the pathophysiology of the disease have resulted in the assumption of Schnitzler syndrome being a special form of an autoinflammatory disease with late onset or an acquired genesis. This article provides an overview on the clinical appearance, current knowledge of pathophysiology and available therapeutic options.


Re-positioning faculty development as knowledge mobilization for health professions education.
Faculty development as knowledge mobilization offers a particularly fruitful and novel avenue for exploring the research-practice interface in health professions education. We use this 'eye opener' to build off this assertion to envision faculty development as an enterprise that provides a formal, recognized space for the sharing of research and practical knowledge among health professions educators. Faculty development's knowledge mobilizing strategies and outcomes, which draw upon varied sources of knowledge, make it a potentially effective knowledge mobilization vehicle.First, we explain our choice of the term knowledge mobilization over translation, in an attempt to resist the false dichotomy of 'knowledge user' and 'knowledge creator'. Second, we leverage the documented strengths of faculty development against the documented critiques of knowledge mobilization in the hopes of avoiding some of the pitfalls that have befallen previous attempts at closing knowing-doing gaps.Through faculty development, faculty are indeed educated, in the traditional sense, to acquire new knowledge and skill, but they are also socialized to go on to form the systems and structures of their workplaces, as leaders and workers. Therefore, faculty development can not only mobilize knowledge, but also create knowledge mobilizers. Achieving this vision of faculty development as knowledge mobilization requires an acceptance of multiple sources of knowledge, including practice-based knowledge, and of multiple purposes for education and faculty development, including professional socialization.


Integrative analysis prioritizes the relevant genes and risk factors for chronic venous disease.
Chronic venous disease (CVD) refers to a range of symptoms resulting from long-term morphological and functional abnormalities of the venous system. However, the mechanism of CVD development remains largely unknown. Here, we aim to provide more information on CVD pathogenesis, prevention strategies, and therapy development through the integrative analysis of large-scale genetic data. Genetic data were obtained from publicly accessible databases. We used different approaches, including Functional Mapping and Annotation, DEPICT, Sherlock, SMR/HEIDIS, DEPICT, and NetWAS to identify possible causal genes for CVD. Candidate genes were prioritized to further literature-based review. The differential expression of prioritized genes was validated by microarray from the Gene Expression Omnibus, a public genomics data repository and real-time quantitative polymerase chain reaction of varicose vein specimens. The causal relationships between risk factors and CVD were assessed using the two-sample Mendelian randomization approach. We identified 46 lead single-nucleotide polymorphisms and 26 plausible causal genes for CVD. Microarray data indicated differential expression of possible causal genes in CVD when compared with controls. The expression levels of WDR92, RSPO3, LIMA, ABCB10, DNAJC7, C1S, and CXCL1 were significantly downregulated (P < .05). PHLDA1 and SERPINE1 were significantly upregulated (P < .05). Dysregulated expression of WDR92, RSPO3, and CASZ1 was also found in varicose vein specimens by quantitative polymerase chain reaction. Two-sample Mendelian randomization suggested causative effects of body mass index (odds ratio [OR], 1.008; 95% confidence interval [CI], 1.005-1.010), standing height (OR, 1.009; 95% CI, 1.007-1.011), college degree (OR, 0.983; 95% CI, 0.991-0.976), insulin (OR, 0.858; 95% CI, 0.794-0.928), and metformin (OR, 0.944; 95% CI, 0.904-0.985) on CVD. Our study integrates genetic and gene expression data to make an effective risk gene prediction and etiological inferences for CVD. Prioritized candidate genes provide more insights into CVD pathogenesis, and the causative effects of risk factors on CVD that deserve further investigation.


Monoclonal Gammopathy of Renal Significance with Deposits of Peculiar Morphology and Injuries of Secondary Thrombotic Microangiopathy: A Case Report and Review of the Literature.
We present the case of an 82-year-old woman diagnosed with monoclonal gammopathy of renal significance (MGRS) with the presence of different and peculiar kidney lesions, who began treatment with bortezomib and dexamethasone, presenting during her evolution a relapse. Although the bone marrow biopsy in this case showed plasma cells as pathologic clone and there was also a reduction after chemotherapeutic treatment, rituximab was proposed as a second line. We suspected that the relapse was possibly due to another precursor as B-cell or lymphoplasmacytic cell clone. We review the literature and suggest that the treatment for MGRS should be patient-tailored, preferably by consulting a multidisciplinary team. Future research is needed to better understand the disease course and establish the efficacy and safety of the therapeutic approach for the relapse of MGRS.


Specific volumes of unsaturated phosphatidylcholines in the liquid crystalline lamellar phase.
The specific volumes of seven 1,2-diacyl-sn-glycero-3-phosphocholines with symmetric, unbranched acyl chains containing one, four, or six cis double bonds per chain, or with a saturated sn-1 chain and one, four, or six cis double bonds in the sn-2 chain were determined by the neutral buoyancy method. Experiments were conducted in the liquid crystalline lamellar phase over the temperature range from 5 to 35 degrees C. It is demonstrated that the molecular volume of phosphatidylcholines can be well approximated as the sum of a constant volume of the polar lipid head region and the temperature-dependent volumes of hydrocarbon chain CH2, CH, and terminal CH3 groups. A linear dependence of chain segment volumes on temperature was observed. A self-consistent set of partially temperature-dependent volumes is obtained that allows prediction of phosphatidylcholine molecular volumes within very tight error margins.


Metastatic carcinoma of prostate 23 years after radical prostatectomy.
Carcinoma of the prostate may present with metastatic disease many years after treatment. We present a patient with adenocarcinoma of the prostate, "cured" by radical perineal prostatectomy in 1962, with the first signs of metastases presenting in 1985. This emphasizes the importance of long-term follow-up of patients with prostate carcinoma.


Has the yolk an influence on the differentiation of embryonic Drosophila blastemas?
1. Anterior and posterior halves of 6 hour-old embryos were transplanted with or without their central egg yolk filling into the abdomens of adult females. 2. It was found that the yolk has no formative or nutritive influence on the differentiation which proceeds normally in the adult milieu.


Perisaccadic mislocalization without saccadic eye movements.
Despite frequent saccadic gaze shifts we perceive the surrounding visual world as stable. It has been proposed that the brain uses extraretinal eye position signals to cancel out saccade-induced retinal image motion. Nevertheless, stimuli flashed briefly around the onset of a saccade are grossly mislocalized, resulting in a shift and, under certain conditions, an additional compression of visual space. Perisaccadic mislocalization has been related to a spatio-temporal misalignment of an extraretinal eye position signal with the corresponding saccade. Here, we investigated perceptual mislocalization of human observers both in saccade and fixation conditions. In the latter conditions, the retinal stimulation during saccadic eye movements was simulated by a fast saccade-like shift of the stimulus display. We show that the spatio-temporal pattern of both the shift and compression components of perceptual mislocalization can be surprisingly similar before real and simulated saccades. Our findings suggest that the full pattern of perisaccadic mislocalization can also occur in conditions which are unlikely to involve changes of an extraretinal eye position signal. Instead, we suggest that, under the conditions of our experiments, the arising difficulty to establish a stable percept of a briefly flashed stimulus within a given visual reference frame yields mislocalizations before fast retinal image motion. The availability of visual references appears to exert a major influence on the relative contributions of shift and compression components to mislocalization across the visual field.


Evaluation of environmental parameters in the Espinar Puno stabilization lagoon.
The "Espinar" stabilization lagoon is a body of wastewater that is located in the district (region of Puno), which accumulates wastewater that comes from the population of the city of Puno-Peru. The present study was carried out in January and February of 2019 in affluent and effluent wastewater. The measures of pH, water temperature, total suspended solids, electrical conductivity and salinity were evaluated. The results showed that there are significant differences between the data of the affluent and effluent samples during the periods analyzed (Krustal Wallis). The median concentrations values of the effluent for the parameters of temperature (16.60 °C), salinity (0.67 mg/L), pH (7.70), total dissolved solids (669.00 ppm) and electrical conductivity (1463.07 μs/cm), they all show significant differences. Also, the removal efficiency was calculated by the total dissolved solids (TDS) and the positive removal of 7.80% of pollutant load was found. Although these results are within the established limits, the monitoring mechanisms must be established for an adequate control of the parameters evaluated and thus, there won't be a deterioration of the environment surrounding the lagoon.


Microwave and open vessel digestion methods for biochar.
Digestion of biomass derived carbonaceous materials such as biochar (BC) can be challenging due to their high chemical recalcitrance and vast variations in composition. Reports on the development of specific sample digestion methods for such materials remain inadequate and thus require considerable attention. Nine different carbonaceous materials; slow-pyrolyzed tea-waste and king coconut BC produced at 300 °C, 500 °C and 700 °C, sludge waste BC produced at 700 °C, wet fast-pyrolyzed Douglas-Fir BC and steam activated coconut shell BC have been tested to evaluate a relatively fast and convenient open-vessel digestion method using seven digestion reagents including nitric acid (NA), fuming nitric acid (FNA), sulfuric acid (SA), NA/SA, FNA/SA, NA/H2O2 and SA/H2O2 mixtures. From the tested digestion reagents, SA/H2O2 mixture dissolved low temperature produced BC (LTBC) within 2 h with occasional shaking and no external heating. Except peroxide mixtures, the other reagents were used to evaluate microwave digestion (MWD) efficiency. Nitric acid mixture was capable of only completely digesting LTBC in the MWD procedure whereas FNA, NA/SA and FNA/SA mixtures resulted in the successful dissolution of all tested carbonaceous materials. Amongst them, FNA provided the least matrix effect in the quantification of the four metals tested using flame atomic absorption spectrophotometry. Tested recoveries for FNA were satisfactory as well. It was concluded that FNA is a preferable reagent for microwave digestion of BC.


Immunohistochemical study of the postnatal development of pituitary thyrotrophs in the rat, with special reference to cluster formation.
The postnatal development of rat pituitary thyrotrophs was investigated immunohistochemically on days 1, 3, 5, 10, 15 and 25. Fetal thyrotrophs are strongly immunoreactive. In the postnatal period, however, weakly immunoreactive thyrotrophs increase in number to constitute clusters on days 3--5. The numbers and dimensions of the clusters reach a maximum on day 10. Thereafter the clusters break down to give rise to single, scattered neogenic thyrotrophs. Thyrotrophs in clusters on day 10 were investigated by electron microscopy in adjacent sections. They can be characterized as an immature type of basophil, according to the classification of Yoshimura et al. (1977): 1) Type I basophils, which are irregularly shaped with elongate processes, and characterized by rows of secretory granules about 100 nm in diameter. 2) Type I/II basophils, i.e., forms intermediate between Types I and II, containing less numerous secretory granules about 100--150 nm in diameter. Type II basophils which correspond to the classical thyrotrophs are not fully developed on day 10. Thus, most thyrotrophs develop from the clusters in the neonatal period. Such neogenic thyrotrophs retain the immature characteristics of Type I and I/II cells and may develop into Type II cells during subsequent maturation.


Intimate partner violence and condom use among women: does the information-motivation-behavioral skills model explain sexual risk behavior?
Intimate partner violence (IPV) undermines women's ability to enact safer sex and increases their vulnerability to HIV and other STDs. To better understand the relationship between IPV and sexual risk behavior, we investigated whether the Information-Motivation-Behavioral Skills (IMB) model differentially predicted risk behavior among women who had and had not recently experienced IPV. Data from 717 women who were recruited from a public health clinic showed that 18% reported IPV by a sexual partner in the past 3 months, 28% in the past year, and 57% lifetime. Women who experienced IPV in the last 3 months reported more episodes of unprotected sex and more episodes of unprotected sex with a steady partner in the past 3 months. Multi-group path analyses provided mixed evidence regarding the associations hypothesized by the IMB model; the strength of these associations varied as a function of IPV history. Thus, although information did not predict risk behavior for either group, motivation was associated with condom use only for women with no history of IPV. Behavioral skills were associated with more condom use for both groups. Overall, the IMB model is useful for predicting sexual risk behavior; however, for women with partner violence histories a broader model that includes other contextual factors may be needed. These findings can help to inform the development of more effective sexual risk reduction interventions.


Rigid ureteroscopic lithotripsy in the lateral decubitus position for upper urinary tract stones.
The current study aimed to assess a novel ureteroscopic technique developed for treating upper urinary calculi based on a specially designed lateral decubitus body position that could avoid stone loss by adjusting to the effects of gravity. This retrospective study examined patients with upper urinary calculi who were surgically treated from November 2008 to January 2020, using a new body position and a rigid ureteroscope. Clinical outcomes, stone-free rates, operative times and complications were evaluated, and factors that could influence treatment success were determined. In total, 1080 patients were included, and 1145 operations were performed. The maximum calculus diameters were 11.22 ± 5.01 mm. Operative times were 48.60 ± 27.44 min. A total of 1042 cases were successfully treated, with a stone-free rate of 91.00%. Multivariate analysis showed that female sex (OR = 2.135, 95% CI 1.332-3.422, P = 0.002), thin scope standby (OR = 1.643, 95% CI 1.074-2.514, P = 0.022), laser lithotripsy (OR = 5.087, 95% CI 2.400-10.785, P = 0.000) and stone size (OR = 0.946, 95% CI 0.912-0.981, P = 0.003) were independently associated with stone-free outcomes. In total, 2 ureteral perforations, 2 ureteric avulsions and 4 urosepsis cases were observed, but were all cured without sequelae. Ureteroscopic lithotripsy in the lateral decubitus position is a safe and effective technique for treating upper urinary tract calculi, especially upper ureteral calculi.


Chemically induced self-assembly of enzyme nanorings.
Continued exploration into the field of chemically induced dimerization (CID) has revealed a number of applications for its use in a broader context as a method of structural assembly (1-4). In particular, the use of CID technology to generate self-assembled (and selectively disassembled) protein toroids serves as a key advancement toward developing stable and controllable protein-based platforms. Such structures have broad application to the development of novel therapeutics, lab-on-a-chip technologies, and multi-enzyme assemblies (5, 6). This chapter describes a method of developing an enzymatically active protein nanostructure incorporating both a CID-based assembly region containing dihydrofolate reductase (DHFR) and an enzymatic region consisting of histidine triad nucleotide binding protein 1 (Hint1). Details of both the production and the characterization of this structure are provided.


Identification of known and novel nonpolar endocrine disruptors in human amniotic fluid.
Prenatal exposure to endocrine-disrupting compounds (EDCs) may contribute to endocrine-related diseases and disorders later in life. Nevertheless, data on in utero exposure to these compounds are still scarce. We investigated a wide range of known and novel nonpolar EDCs in full-term human amniotic fluid (AF), a representative matrix of direct fetal exposure. Gas chromatography high-resolution mass spectrometry (GC-HRMS) was used for the targeted and non-targeted analysis of chemicals present in nonpolar AF fractions with dioxin-like, (anti-)androgenic, and (anti-)estrogenic activity. The contribution of detected EDCs to the observed activity was determined based on their relative potencies. The multitude of features detected by non-targeted analysis was tentatively identified through spectra matching and data filtering, and further investigated using curated and freely available sources to predict endocrine activity. Prioritized suspects were purchased and their presence in AF was chemically and biologically confirmed with GC-HRMS and bioassay analysis. Targeted analysis revealed 42 known EDCs in AF including dioxins and furans, polybrominated diphenyl ethers, pesticides, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons. Only 30% of dioxin activity and <1% estrogenic and (anti-)androgenic activity was explained by the detected compounds. Non-targeted analysis revealed 14,110 features of which 3,243 matched with library spectra. Our data filtering strategy tentatively identified 121 compounds. Further data mining and in silico predictions revealed in total 69 suspected EDCs. We selected 14 chemicals for confirmation, of which 12 were biologically active and 9 were chemically confirmed in AF, including the plasticizer diphenyl isophthalate and industrial chemical p,p'-ditolylamine. This study reveals the presence of a wide variety of nonpolar EDCs in direct fetal environment and for the first time identifies novel EDCs in human AF. Further assessment of the source and extent of human fetal exposure to these compounds is warranted.


Identifying functional gene regulatory network phenotypes underlying single cell transcriptional variability.
Recent analysis of single-cell transcriptomic data has revealed a surprising organization of the transcriptional variability pervasive across individual neurons. In response to distinct combinations of synaptic input-type, a new organization of neuronal subtypes emerged based on transcriptional states that were aligned along a gradient of correlated gene expression. Individual neurons traverse across these transcriptional states in response to cellular inputs. However, the regulatory network interactions driving these changes remain unclear. Here we present a novel fuzzy logic-based approach to infer quantitative gene regulatory network models from highly variable single-cell gene expression data. Our approach involves developing an a priori regulatory network that is then trained against in vivo single-cell gene expression data in order to identify causal gene interactions and corresponding quantitative model parameters. Simulations of the inferred gene regulatory network response to experimentally observed stimuli levels mirrored the pattern and quantitative range of gene expression across individual neurons remarkably well. In addition, the network identification results revealed that distinct regulatory interactions, coupled with differences in the regulatory network stimuli, drive the variable gene expression patterns observed across the neuronal subtypes. We also identified a key difference between the neuronal subtype-specific networks with respect to negative feedback regulation, with the catecholaminergic subtype network lacking such interactions. Furthermore, by varying regulatory network stimuli over a wide range, we identified several cases in which divergent neuronal subtypes could be driven towards similar transcriptional states by distinct stimuli operating on subtype-specific regulatory networks. Based on these results, we conclude that heterogenous single-cell gene expression profiles should be interpreted through a regulatory network modeling perspective in order to separate the contributions of network interactions from those of cellular inputs.


Comparative effects of forskolin and isoproterenol on the cyclic AMP content of human adipocytes.
Alterations in adipocyte cyclic AMP concentrations in response to 100 microM forskolin and 10 microM isoproterenol over a 4 hour period were found to be similar; with each agent, a peak response was noted within 30 minutes. In general, the greater the magnitude of peak response, the more rapid the decline of cyclic AMP concentration during the ensuing 3 1/2 hours. Alpha-2 adrenergic activation, achieved with 10 microM clonidine or 10 microM epinephrine, substantially reduced the cyclic AMP concentrations in cells stimulated by 100 microM forskolin or 10 microM isoproterenol. Isoproterenol-stimulated cells appeared to be more sensitive to alpha adrenergic inhibition than did forskolin-stimulated cells. Cells preincubated for 3 hours with 100 microM forskolin were markedly less responsive to a second exposure to the diterpine. Cells exposed to forskolin for 3 hours also had a reduced response when incubated with isoproterenol; thus, desensitization to forskolin appears to be heterologous. Forskolin desensitization did not appear to be dependent on cellular ATP depletion since cells mildly stimulated during preincubation were as severely desensitized as those adipocytes strongly stimulated. Maximum desensitization required a preincubation time of 1-2 hours with either isoproterenol or forskolin.


Simultaneous measurement of tadehaginoside and its principal metabolite in rats by HPLC-MS/MS and its application in pharmacokinetics and tissue distribution study.
Tadehaginoside, an active ingredient isolated from Tadehagi triquetrum (Linn.) Ohashi (Leguminosae), exhibited various biological activities. However, the pharmacokinetics and tissue distribution which affect tadehaginoside's therapeutic actions and application remain elusive. To clarify the metabolism of tadehaginoside in vivo. The pharmacokinetics and tissue distribution of tadehaginoside and its metabolite p-hydroxycinnamic acid (HYD) were investigated using LC-MS/MS. Pharmacokinetic parameters were determined in 10 Sprague-Dawley rats divided into two groups, the intravenous group (5 mg/kg) and the oral group (25 mg/kg). For the tissue-distribution study, 20 rats were intravenously given tadehaginoside (5 mg/kg) before the experiment (n = 4). Biological samples were collected before drug administration (control group) and after drug administration. The linearity, accuracy, precision, stability, recovery and matrix effect of the method were well-validated and the results satisfied the requirements of biological sample measurement. Treatment with tadehaginoside via intragastric and intravenous administration, the calculated Cmax in rats was 6.01 ± 2.14 ng/mL and 109.77 ± 4.29 ng/mL, and Tmax was 0.025 ± 0.08 h and 0.08 h, respectively. The results indicated that the quick absorption of tadehaginoside was observed following intravenous administration, and tadehaginoside in plasma of rats with intragastric administration showed relatively low concentration may be due to the formation of its metabolite. Tissue-distribution study indicated that kidney and spleen were the major distribution organs for tadehaginoside in rats and there was no long-term accumulation in most tissues. These results could provide clues for exploring the bioactivity of tadehaginoside based on its pharmacokinetic characteristics.


Relation of platelet phospholipids to diabetic control.
In the present study we investigated platelet phospholipid concentration in diabetic patients in various conditions of metabolic control. We found an increase in total phospholipid concentration as well as in phosphatidylserine and phosphatidylethanolamine, the most pronounced changes being observed in poorly controlled patients. We discuss our findings in relation to the metabolic control of the disease and the high incidence of atherosclerotic lesions in these patients.


Lithium di silicate ceramic surface treated with Er,Cr:YSGG and other conditioning regimes bonded to orthodontic bracket.
To assess bond integrity and modes of failure of metallic brackets to lithium disilicate ceramics (LDC) conditioned with Er,Cr:YSGG laser (ECL). Sixty LDC were arbitrarily allocated into six groups (n = 15) according to the type of ceramic surface conditioning treatment. Group 1 surface treated with silane (S) only, group 2 surface etched with hydrofluoric acid (HF)+ S, group 3 surface conditioned with HF+ ultrasonic bath (UB)+ S, group 4 sand blasting (SB) of glass ceramic surface with 50 µm Al2O3, group 5 surface conditioned with self-etch ceramic primer (SECP) and in group 6 surface treated with ECL + S. After conditioning, the specimens were positioned in a universal testing device for shear bond strength (SBS) testing. Adhesive Remnant Index (ARI) was used to determine sites of bond failure. Among experimental groups analysis of variance (ANOVA) and Tukey multiple comparison test was used at a significance level of (p < 0.05). The highest SBS values were observed in group 3 HF+ UB + S (18.21 ± 1.241) and the lowest SBS values were displayed group 1 surface treated with S only (5.21 ± 0.23). Specimens surface conditioned in group 2 with HF+ S (17.85 ± 1.25), group 3 HF+ UB + S (18.21 ± 1.241) and group 6 ECL + S (17.09 ± 1.114) unveiled comparable SBS values (p > 0.05). LDC conditioned with ECL at (4.5 W and 30 Hz) has a potential to be used in clinical settings alternate to HF acid.


Plasma cortisol is associated with cerebral hypometabolism across the Alzheimer's disease spectrum.
Hypothalamic-pituitary-adrenal dysregulation is proposed as a risk factor for Alzheimer's disease (AD). This study assessed cross-sectional relationships between cortisol and neuroimaging biomarkers of brain structure and glucose metabolism across the AD spectrum. Participants with normal cognition, mild cognitive impairment, and AD were selected from the Alzheimer's Disease Neuroimaging Initiative databank, based on baseline measures of plasma cortisol, gray matter volume (n = 556), and cerebral glucose metabolism (n = 288). Relationships between plasma cortisol and the neuroimaging biomarkers were assessed. Across the entire cohort, higher plasma cortisol levels were associated with lower glucose metabolism in lateral and medial parietal regions. Higher plasma cortisol was also related to lower gray matter volume in temporal-parietal-occipital regions and in the hippocampus. There were no significant group differences in these relationships with adjustment for covariates. Our results demonstrate that hypothalamic-pituitary-adrenal axis activation is related to glucose hypometabolism within posterior cortical regions vulnerable to AD pathology. This regional pattern appears to be distinct from cortisol-related associations with brain structure. Future studies should delineate pathophysiological mechanisms underlying these effects.


Source identification and hazardous risk delineation of heavy metal contamination in Yanqi basin, northwest China.
A total of 469 surface soil samples were collected from the Yanqi basin in northwest China and evaluated for levels of ten heavy metals. Multivariate statistical analyses were used to study sources of and map the spatial distribution of heavy metals, as well as determine the relationship between land use types and soil source materials. It was found that: (1) the average amounts of ten heavy metals in the Yanqi basin were all below the national soil environmental quality standards of China (GB15618-1998), but the average amount of Cd, Hg, Mn, Ni, Pb, and Zn all exceeded the heavy metal background levels of soil in Xinjiang, China and exhibited accumulation. The ten heavy metals analyzed in this study can be categorized into four principal components as follows: Principal component 1 was Co, Cr, Mn, Ni, and Zn, and principal component 3 was As and Cu. Both of these originated from a natural geological background. Principal component 2 consisted of Cd and Pb and originated from industrial, agricultural and transportation influences. Principal component 4 consisted of Hg and was due to industrial influences. Our study found that Pb and Zn were a large part in the principal components 1 and 3 and were influenced by a combination of geologic background and human activity. (2) Heavy metals Cd and Hg were at high levels in construction land and farmland, while Co, Cr, Cu, Mn, and Ni were significantly higher in lacustrine deposits than in sandy shale from weathered material, coarse crystalline rock weathered material, and diluvial material. The land use types correlated significantly with the accumulation of Cd and Hg, and the soil parent material was the major factor for the accumulation of As, Co, Cr, Cu, Mn, and Ni. (3) The single element, element integration and the corresponding principal component presented similar spatial patterns of hazardous risk. Following comprehensive assessment of all elements, the high risk regions were found to be located in densely-populated urban areas and western parts of the study area. This was attributed to the higher geological background in the western part and strong human influence in the central part. Research shows that Cd, Hg, Pb, and Zn were locally enriched in the basin and this warrants increased attention.


Validation of the 4DSQ somatization subscale in the occupational health care setting as a screener.
Somatoform disorders (physical symptoms without medical explanation that cause dysfunction) are prevalent in the occupational health (OH) care setting and are associated with functional impairment and absenteeism. Availability of psychometric instruments aimed at assessing somatoform disorders is limited. In the OH setting, so far only the Patient-Health-Questionnaire 15 has been validated as screener for somatoform disorder, and has been shown to have moderate validity. The Four-Dimensional Symptom Questionnaire (4DSQ) is frequently used in the OH setting but the Somatization subscale is not validated yet. The aim of this study is to validate the 4DSQ Somatization subscale as screener for DSM-IV somatoform disorder in the OH setting by using the MINI interview as gold standard. Employees absent from work due to physical symptoms, for a period longer than 6 weeks and shorter than 2 years, were asked to participate in this study. They filled out the 4DSQ and underwent a MINI interview by telephone for DSM-IV classification. Specificity and sensitivity scores were calculated for all possible cut-off scores and a receiver operator curve was computed for the Somatization subscale. 95 % confidence intervals (95 % CIs) were calculated for sensitivity and specificity. The Somatization subscale of the 4DSQ has an optimal cut point of 9, with specificity and sensitivity equal to 64.3 % [95 % CI (53.6; 73.7 %)] and 60.9 % [95 % CI (40.8; 77.8 %)], respectively. Receiver operator curves showed an area under the curve equal to 0.61 [SE = 0.07; 95 % CI (0.48; 0.75)] for the Somatization subscale of the 4DSQ. The 4DSQ Somatization subscale is a questionnaire of moderate sensitivity and specificity.


Peptide transporter 2 (PEPT2) expression in brain protects against 5-aminolevulinic acid neurotoxicity.
The proton-coupled oligopeptide transporter PEPT2 (or SLC15A2) is the major protein involved in the reclamation of peptide-bound amino acids and peptide-like drugs in kidney. PEPT2 is also important in effluxing peptides and peptidomimetics from CSF at the choroid plexus, thereby limiting their exposure in brain. In this study, we report a neuroprotective role for PEPT2 in modulating the toxicity of a heme precursor, 5-aminolevulinic acid (5-ALA). Our findings demonstrate that in PEPT2-deficient mice, 5-ALA administration results in reduced survivability, a worsening of neuromuscular dysfunction, and CSF concentrations of substrate that are 8-30 times higher than that in wild-type control animals. The ability of PEPT2 to limit 5-ALA exposure in CSF suggests that it may also have relevance as a secondary genetic modifier of conditions (such as acute hepatic porphyrias and lead poisoning) in which 5-ALA metabolism is altered and in which 5-ALA toxicity is important.


Drug-induced tendinopathy: from physiology to clinical applications.
Drug-induced tendon toxicity is rare but often underestimated. To date, four main drug classes have been incriminated in tendinopathies. Quinolones and long-term glucocorticoids are the most widely known, but statins and aromatase inhibitors can also induce tendon damage. The specific pathophysiological mechanisms responsible for drug-induced tendinopathies remain unknown. Proven risk factors have been identified, such as age older than 60 years, pre-existing tendinopathy, and potentiation of toxic effects when several drug classes are used in combination. Mean time to symptom onset varies from a few days with quinolones to several months with statins and several years for long-term glucocorticoid therapy. The most common sites of involvement are the lower limb tendons, most notably the body of the Achilles tendon. The first part of this review discusses tendon anatomy and the pathophysiology and radiological manifestations of tendinopathies. The second part provides details on the main characteristics of each of the drugs classes associated with tendon toxicity.


Is 'informed consent' an 'understood consent' in hematopoietic cell transplantation?
Hematopoietic cell transplantation (HCT) is a complex and highly specialized medical treatment that is associated with significant risks, including death. Furthermore, transplantation is offered to patients who often have no other curative treatment alternatives. The routine-consent process for HCT typically occurs before HCT and is influenced by many factors related to patients, physicians and the transplant per se. These factors can impede the consent process and subsequently result in a failure of proper engagement in and an understanding of the procedure with resultant adverse consequences influencing patients and even the patient-physician relationship. We contend that informed consent is a dynamic and ongoing process and that better patient education can assist in the decision making, fulfill the ethical principle of respect for autonomy and engage the patient to maximize compliance and adherence to therapy. This manuscript reviews the key literature pertaining to the decision-making and consent process in HCT and proposes guidelines for improving the consent process. Strategies for improving patient comprehension, engagement and enhancing consent forms are discussed.


Temperature-induced structural changes in the myosin thick filament of skinned rabbit psoas muscle.
By using synchrotron radiation and an imaging plate for recording diffraction patterns, we have obtained high-resolution x-ray patterns from relaxed rabbit psoas muscle at temperatures ranging from 1 degree C to 30 degrees C. This allowed us to obtain intensity profiles of the first six myosin layer lines and apply a model-building approach for structural analysis. At temperatures 20 degrees C and higher, the layer lines are sharp with clearly defined maxima. Modeling based on the data obtained at 20 degrees C reveals that the average center of the cross-bridges is at 135 A from the center of the thick filament and both of the myosin heads appear to wrap around the backbone. At 10 degrees C and lower, the layer lines become very weak and diffuse scattering increases considerably. At 4 degrees C, the peak of the first layer line shifts toward the meridian from 0.0047 to 0.0038 A(-1) and decreases in intensity approximately by a factor of four compared to that at 20 degrees C, although the intensities of higher-order layer lines remain approximately 10-15% of the first layer line. Our modeling suggests that as the temperature is lowered from 20 degrees C to 4 degrees C the center of cross-bridges extends radially away from the center of the filament (135 A to 175 A). Furthermore, the fraction of helically ordered cross-bridges decreases at least by a factor of two, while the isotropic disorder (the temperature factor) remains approximately unchanged. Our results on the order/disordering effects of temperature are in general agreement with earlier results of Wray [Wray, J. 1987. Structure of relaxed myosin filaments in relation to nucleotide state in vertebrate skeletal muscle. J. Muscle Res. Cell Motil. 8:62a (Abstr.)] and Lowy et al. (Lowy, J., D. Popp, and A. A. Stewart. 1991. X-ray studies of order-disorder transitions in the myosin heads of skinned rabbit psoas muscles. Biophys. J. 60:812-824). and support Poulsen and Lowy's hypothesis of coexistence of ordered and disordered cross-bridge populations in muscle (Poulsen, F. R., and J. Lowy. 1983. Small angle scattering from myosin heads in relaxed and rigor frog skeletal muscle. Nature (Lond.). 303:146-152.). However, our results added new insights into the disordered population. Present modeling together with data analysis (Xu, S., S. Malinchik, Th. Kraft, B. Brenner, and L. C. Yu. 1997. X-ray diffraction studies of cross-bridges weakly bound to actin in relaxed skinned fibers of rabbit psoas muscle. Biophys. J. 73:000-000) indicate that in a relaxed muscle, cross-bridges are distributed in three populations: those that are ordered on the thick filament helix and those that are disordered; and within the disordered population, some cross-bridges are detached and some are weakly attached to actin. One critical conclusion of the present study is that the apparent order <--> disorder transition as a function of temperature is not due to an increase/decrease in thermal motion (temperature factor) for the entire population, but a redistribution of cross-bridges among the three populations. Changing the temperature leads to a change in the fraction of cross-bridges located on the helix, while changing the ionic strength at a given temperature affects the disordered population leading to a change in the relative fraction of cross-bridges detached from and weakly attached to actin. Since the redistribution is reversible, we suggest that there is an equilibrium among the three populations of cross-bridges.


Body mass index and susceptibility to knee osteoarthritis: a systematic review and meta-analysis.
Excess bodyweight, expressed as increased body mass index, is associated with osteoarthritis risk, especially in weight bearing joints. However, the strength of the association was inconsistent. The study was conducted to quantitatively assess the association between body mass index and the risk of knee osteoarthritis and investigate the difference of the strength stratified by sex, study type and osteoarthritis definition. We used published guidelines of the Meta-analysis of Observational Studies in Epidemiology Group (MOOSE) to perform the meta-analysis. The search strategy employed included computerized bibliographic searches of MEDLINE, PubMed, EMBASE, The Cochran Library and references of published manuscripts. Study-specific incremental estimates were standardized to determine the risk of knee osteoarthritis associated with a 5 kg/m(2) increase in BMI. Twenty-one studies were included in the study. The results showed that body mass index was significantly positive associated with osteoarthritis risk in knee site. A 5-unit increase in body mass index was associated with an 35% increased risk of knee osteoarthritis (RR: 1.35; 95%CI: 1.21, 1.51). Magnitude of the association was significantly stronger in women than that in men with significant difference (men, RR: 1.22; 95%CI: 1.19, 1.25; women, RR: 1.38; 95%CI: 1.23, 1.54; p=0.04). The summary effect size was 1.25(95%CI: 1.18, 1.32) in case-control studies and 1.37 (95%CI: 1.19, 1.56) in cohort studies (p=0.28). Body mass index was positively associated with knee osteoarthritis defined by radiography and/or clinical symptom (RR: 1.25, 95%CI: 1.17, 1.35) and clinical surgery (RR: 1.54, 95%CI: 1.29, 1.83). The latter tended to be stronger than the former (p<0.01). Increased body mass index contribute to a substantially increased risk of knee OA. The magnitude of the association varies by sex and OA definition.


Engineering [Ln(DPA)3] 3- binding sites in proteins: a widely applicable method for tagging proteins with lanthanide ions.
Paramagnetic relaxation enhancements from unpaired electrons observed in nuclear magnetic resonance (NMR) spectra present powerful long-range distance restraints. The most frequently used paramagnetic tags, however, are tethered to the protein via disulfide bonds, requiring proteins with single cysteine residues for covalent attachment. Here we present a straightforward strategy to tag proteins site-specifically with paramagnetic lanthanides without a tether and independent of cysteine residues. It relies on preferential binding of the complex between three dipicolinic acid molecules (DPA) and a lanthanide ion (Ln(3+)), [Ln(DPA)(3)](3-), to a pair of positively charged amino acids whose charges are not compensated by negatively charged residues nearby. This situation rarely occurs in wild-type proteins, allowing the creation of specific binding sites simply by introduction of positively charged residues that are positioned far from glutamate or aspartate residues. The concept is demonstrated with the hnRNPLL RRM1 domain. In addition, we show that histidine- and arginine-tags present binding sites for [Ln(DPA)(3)](3-).


Sequences which flank an 11p deletion observed in an hepatocellular carcinoma map to 11p13.
There is considerable interest in the 11p13 region because of its involvement in Wilms tumor, sporadic aniridia, and other congenital abnormalities. Cloned DNA sequences from this region might be useful in understanding the chromosomal abnormalities which lead to such disorders. However, few such markers exist. Using somatic cell hybrids which contain defined 11p deletions, two cloned DNA sequences which flank a deletion generated in an hepatocellular carcinoma (as a consequence of hepatitis B virus integration) were mapped to 11p13. Thus both ends of the deletion observed in an hepatocellular carcinoma are within 11p13.


Effects of metformin on peripheral insulin sensitivity and intracellular lipid contents in muscle and liver of overweight Japanese subjects.
Recent studies suggest that insulin resistance is associated with increased intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) contents. While metformin improves insulin resistance mainly in liver, its effects on IHL and IMCL have not been clarified yet. The aim of this study was to investigate the effects of low-dose metformin (750 mg/day) on peripheral insulin sensitivity, IHL and IMCL. Before and 3 months after low-dose metformin therapy, eight overweight/obese Japanese subjects [body mass index (BMI) >25 kg/m2] were studied with blood sampling, measurement of IHL and IMCL by 1H magnetic resonance spectroscopy and glucose infusion rate (GIR) during euglycaemic-hyperinsulinaemic clamp as an index of peripheral insulin sensitivity. A 3-month low-dose metformin therapy did not alter body weight, total body fat, fat distribution or physical activity level but increased GIR by 31% (from 6.24 +/- 0.86 to 7.82 +/- 0.82 mg/kg/min, p < 0.01). Although metformin treatment did not alter IMCL (from 4.1 +/- 1.0 to 4.2 +/- 0.9, not significant), it decreased IHL by 21% (from 15.9 +/- 2.8 to 11.8 +/- 2.2%, p < 0.05). A 3-month low-dose metformin treatment improved peripheral insulin sensitivity and reduced IHL, without significantly changing BMI, adiposity or IMCL.


Accuracy and precision of apparent diffusion coefficient measurements on a 1.5 T MR-Linac in central nervous system tumour patients.
MRI linear accelerators (MR-Linacs) may allow treatment adaptation to be guided by quantitative MRI including diffusion-weighted imaging (DWI). The aim of this study was to evaluate the accuracy and precision of apparent diffusion coefficient (ADC) measurements from DWI on a 1.5 T MR-Linac in patients with central nervous system (CNS) tumours through comparison with a diagnostic scanner. CNS patients were treated using a 1.5 T Elekta Unity MR-Linac. DWI was acquired during MR-Linac treatment and on a Philips Ingenia 1.5 T. The agreement between the two scanners on median ADC over the gross tumour/clinical target volumes (GTV/CTV) and in brain regions (white/grey matter, cerebrospinal fluid (CSF)) was computed. Repeated scans were used to estimate ADC repeatability. Daily changes in ADC over the GTV of high-grade gliomas were characterized from MR-Linac scans. DWI from 59 patients was analyzed. MR-Linac ADC measurements showed a small bias relative to Ingenia measurements in white matter, grey matter, GTV, and CTV (bias: -0.05 ± 0.03, -0.08 ± 0.05, -0.1 ± 0.1, -0.08 ± 0.07 μm2/ms). ADC differed substantially in CSF (bias: -0.5 ± 0.3 μm2/ms). The repeatability of MR-Linac ADC over white/grey matter was similar to previous reports (coefficients of variation for median ADC: 1.4%/1.8%). MR-Linac ADC changes in the GTV were detectable. It is possible to obtain ADC measurements in the brain on a 1.5 T MR-Linac that are comparable to those of diagnostic-quality scanners. This technical validation study adds to the foundation for future studies that will correlate brain tumour ADC with clinical outcomes.


Subtyping of substance use disorders in a high-risk welfare-to-work sample: a latent class analysis.
The goals of this study were (a) to investigate the existence of substance abuse/dependence subtypes in a diverse low-income welfare to work sample and (b) to explore subtype differences in rates of comorbid psychiatric and medical conditions. Data for all demographic and clinical variables were extracted from deidentified case records of 4,977 clients enrolled in a comprehensive case management program for welfare recipients with substance use disorders. Latent class analysis supported a five-class model made up of a multiple abuse/dependence class (n = 1,133), a cocaine/alcohol class (n = 2,120), an opioids class (n = 1,346), a cannabis class (n = 362), and a small polysubstance/none primary class (n = 16). Post hoc chi-square analyses revealed several between-class differences, perhaps reflecting differing levels of severity and service needs. All five classes were characterized by high rates of medical and psychiatric comorbidity.


Contribution of DNA methylation to the risk of hepatitis C virus-associated hepatocellular carcinoma: A meta-analysis.
DNA methylation is a crucial epigenetic modification in hepatocellular carcinoma (HCC), and hepatitis C virus (HCV) can induce hepatocarcinogenesis. Nevertheless, the interaction mechanism between DNA methylation and HCV infection in HCC is still ambiguous. In this study, we performed a comprehensive meta-analysis to assess the contribution of DNA methylation in HCV-associated HCC. After four steps of literature screening, we finally obtained 33 qualified case-control studies for this meta-analysis. These studies consisted of 587 HCV-positive cancer tissues and 326 HCV-negative cancer tissues. Our results revealed that four genes (p16, GSTP1, APC, and RUNX3) were more hypermethylated in the HCV-positive liver cancer tissues than in the HCV-negative liver cancer tissues. In addition, the p16 gene was more hypermethylated in the HCV-positive paracancerous tissues than in the HCV-negative paracancerous tissues. Subgroup meta-analysis by geographical populations showed that p16 methylation was significantly higher in HCV-positive cancerous tissues from Japanese and Chinese. Besides, p16 methylation was significantly higher among patients (> 60 years) but not among the others (≤ 60 years). However, there was no obvious association between DNA methylation and other clinicopathological characteristics, including gender, tumor size, differentiation, and clinical stage. Our study suggested that DNA methylation could become potential biomarkers for HCV-associated HCC. DNA methylation contributed to the risk of HCV-associated HCC.


Randomized Controlled Trials 6: Determining the Sample Size and Power for Clinical Trials and Cohort Studies.
Performing well-powered, randomized, controlled trials is of fundamental importance in clinical research. The goal of sample size calculations is to assure that statistical power is sufficiently high when the probability of falsely rejecting a true null hypothesis (type I error) is kept acceptably small. This chapter overviews the fundamental of sample size calculation for standard types of outcomes for 2-group studies. It also considers (1) the problem of determining the size of the treatment effect that a study should be designed to detect, (2) modifications to sample size calculations to account for loss to follow-up and nonadherence, (3) options that can be used when initial calculations indicate that the feasible sample size is insufficient to provide adequate power, (4) implications of using multiple primary end points. In addition, a discussion of cluster randomized trials is provided. Sample size estimates for longitudinal cohort studies must take account of confounding by baseline factors.


Virtual reality digital surgical planning for jaw reconstruction: a usability study.
Digital surgical planning (DSP) has revolutionized the preparation and execution of the management of complex head and neck pathologies. The addition of virtual reality (VR) allows the surgeon to have a three-dimensional experience with six degrees of freedom for visualizing and manipulating objects. This pilot study describes the participants experience with the first head and neck reconstructive VR-DSP platform. An original VR-DSP platform has been developed for planning the ablation and reconstruction of head and neck pathologies. A prospective trial utilizing this platform involving reconstructive surgeons was performed. Participants conducted a simulated VR-DSP planning session, pre- and post-questionnaire as well as audio recordings allowing for qualitative analysis. Thirteen consultant reconstructive surgeons representing three surgical backgrounds with varied experience were recruited. The majority of surgeons had no previous experience with VR. Based on the system usability score, the VR-DSP platform was found to have above average usability. The qualitative analysis demonstrated the majority had a positive experience. Participants identified some perceived barriers to implementing the VR-DSP platform. Virtual reality-digital surgical planning is usable and acceptable to reconstructive surgeons. Surgeons were able to perform the steps in an efficient time despite limited experience. The addition of VR offers additional benefits to current VSP platforms. Based on the results of this pilot study, it is likely that VR-DSP will be of benefit to the reconstructive surgeon.


Functional characterization of a Flavonol 3-O-rhamnosyltransferase and two UDP-rhamnose synthases from Hypericum monogynum.
Rhamnosyltransferase (RT) and rhamnose synthase (Rhs) are the key enzymes that are responsible for the biosynthesis of rhamnosides and UDP-l-rhamnose (UDP-Rha) in plants, respectively. How to discover such enzymes efficiently for use is still a problem to be solved. Here, we identified HmF3RT, HmRhs1, and HmRhs2 from Hypericum monogynum, which is abundant in flavonol rhamnosides, with the help of a full-length and high throughput transcriptome sequencing platform. HmF3RT could regiospecifically transfer the rhamnose moiety of UDP-Rha onto the 3-OH position of flavonols and has weakly catalytic for UDP-xylose (UDP-Xyl) and UDP-glucose (UDP-Glc). HmF3RT showed well quercetin substrate affinity and high catalytic efficiency with Km of 5.14 μM and kcat/Km of 2.21 × 105 S-1 M-1, respectively. Docking, dynamic simulation, and mutagenesis studies revealed that V129, D372, and N373 are critical residues for the activity and sugar donor recognition of HmF3RT, mutant V129A, and V129T greatly enhance the conversion rate of catalytic flavonol glucosides. HmRhs1 and HmRhs2 convert UDP-Glc to UDP-Rha, which could be further used by HmF3RT. The HmF3RT and HmRhs1 co-expressed strain RTS1 could produce quercetin 3-O-rhamnoside (quercitrin), kaempferol 3-O-rhamnoside (afzelin), and myricetin 3-O-rhamnoside (myricitrin) at yields of 85.1, 110.7, and 77.6 mg L-1, respectively. It would provide a valuable reference for establishing a better and more efficient biocatalyst for preparing bioactive flavonol rhamnosides by identifying HmF3RT and HmRhs.


The genotypes and virulence attributes of C. albicans isolates from oral leukoplakia.
There is a debate as to whether some types of oral leucoplakias (OL) are caused by Candida species, and whether they contribute to the malignant transformation, associated with a minority of such lesions. As no detailed population analysis of yeast isolates from OL is available, we evaluated the virulence attributes, and genotypes of 35 C. albicans from OL, and compared their genotypes with 18 oral isolates from healthy individuals. The virulence traits evaluated were esterase, phospholipase, proteinase, haemolysin and coagulase production, and phenotypic switching activity, and yeast adherence and biofilm formation. DNA from OL and control yeasts were evaluated for A, B or C genotype status. Phospholipase, proteinase, and coagulase activity and biofilm formation was observed in 80%, 66%, 97 % and 77 % of the isolates, respectively. Phenotypic switching was detected in 8.6%, while heamolytic, and esterase activity and adherence were noted in all isolates. The genotype A was predominant amongst both the OL and control groups. Due to the small sample size of our study a larger investigation to define the role of candidal virulent attributes in the pathogenicity of OL is warranted, and the current data should serve as a basis until then.


Self-healing traumatic bone cysts.
The etiology and pathogenesis of traumatic bone cyst are still far from being conclusively established with multiple theories, names, and forms of management being proposed and used. The rarity of these lesions in the older age groups suggests that self-healing can occur. This article presents two well-documented cases of what clinically and radiographically were consistent with so-called "traumatic bone cyst" of the mandible, which have appeared to heal without surgical intervention, thus providing additional information to our understanding of the biologic nature of this entity. Case 1 involved a 14-year-old boy with a lesion of the anterior left mandible that was monitored for 7 years and 5 months. Case 2 involved a 19-year-old female patient with a lesion of the right mandible that was monitored for 2 years and 9 months. In both cases, intraosseous biopsy or other surgical procedures were not undertaken. By the time both patients approached age 22, their lesions had resolved and the trabecular bone pattern radiographically approached normal.


Childhood hemolytic uremic syndrome in Argentina: long-term follow-up and prognostic features.
From January 1968 to December 1984, 312 infants and children with hemolytic uremic syndrome were admitted to our unit; 8 patients died (2.5%) during the acute phase; 118 children were followed as outpatients at yearly intervals for at least 10 years (mean follow-up 13 years, range 10-19.8 years). Four evolution patterns at the end of the follow-up were defined: group 1, complete recovery, 74 (62.7%); group 2, proteinuria with/without hypertension, 21 (17.7%); group 3, reduced creatinine clearance, often in conjunction with proteinuria and hypertension, 19 (16.1%); group 4, end-stage renal failure, 4 (3.4%). We investigated the association between several variables of the acute stage and the long-term evolution. Most non-anuric patients recovered completely (92.5%), while 38.4% of those with 1-10 days and 69.2% of those with 11 or more days of anuria had chronic renal sequelae. Similar results were found when analyzing the requirement for peritoneal dialysis. Of the patients with proteinuria at the 1-year control, 86% had renal abnormalities at the end of the follow-up. In our experience, although the final outcome was not predictable in every instance, the severity of acute renal failure-as determined by the days of anuria- and the presence of proteinuria 1 year after the acute phase were the most useful prognostic indicators.


Late recurrence of giant-cell tumor of bone: pharmacoangiographic evaluation.
Late recurrence (more than five years) of benign giant-cell tumor of bone is uncommon. Two patients were evaluated by angiography, including injection of vasoactive drugs, because of osteolytic lesions developing six and seven years after primary operation for benign giant-cell tumor. Angiography established a probable recurrence in both cases. Angiography also permitted accurate evaluation of tumor extension, facilitating pre-operative planning. Giant-cell tumors are predominantly hypervascular lesions. Angiographic evaluation is therefore recommended when a recurrent lesion is suspected.


Egg quality, hatchability, gosling quality, and amino acid profile in albumen and newly-hatched goslings' serum as affected by egg storage.
In modern poultry husbandry, storing fertilized eggs is a common measure to cope with the variable demands of the market and the maximum hatching capacity of the hatchery. However, this measure is harmful to the hatchability of eggs and the quality of newly hatched birds. Knowledge about the effects of storing fertilized eggs on the performance of goslings is still limited. The objective of this study was to investigate the effects of storing fertilized eggs on egg quality, hatchability, gosling quality, hatching weight, post-hatching growth performance, and amino acid profile in albumen and newly hatched goslings' serum. A total of 1,080 fertilized goose eggs (Jilin White goose) with a similar egg weight (126.56 ± 0.66 g) were used in this study. All eggs were distributed into 3 groups with 24 replicates per group and 15 eggs per replicate. The differences between groups were the storage duration of eggs (0, 7, or 14 d). We found that the Haugh unit, yolk weight, and eggshell weight decreased linearly, whereas the albumen pH increased linearly, with storage duration. Prolonging storage duration had negative effects on hatchability, hatching weight, post-hatching growth performance parameters, and gosling quality in a time-dependent manner. The analysis of the amino acid profile in albumen and newly-hatched goslings' serum showed that the amino acid content increased linearly with storage duration. Additionally, eggs stored for 14 d had the worst performance for all measured parameters. Therefore, we concluded that the storage of fertilized eggs negatively affects egg quality and post-hatching gosling quality. To produce high-quality goslings, it is necessary to shorten the storage duration for fertilized eggs.


Purification and properties of midgut alpha-amylase isolated from Morimus funereus (Coleoptera: Cerambycidae) larvae.
Using soluble starch as a substrate five isoforms of alpha-amylase were identified in a crude extract of Morimus funereus larvae. The main alpha-amylase (termed AMF-3) was purified by gel filtration chromatography and anion exchange chromatography to obtain a single band on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Its enzymatic purity was confirmed by an in-gel activity assay after SDS-PAGE. The purity of AMF-3 was increased 112-fold with a 15.4% yield. AMF-3 had apparent molecular masses of 33 and 31 kDa when analysed using SDS-PAGE and Superdex 75 FPLC gel filtration chromatography, respectively and a calculated isoelectric point of 3.2. Purified AMF-3 showed maximal activity at pH 5.2 and had an optimum activity temperature of 45 degrees C. AMF-3 retained over 90% of its maximum activity at temperatures from 45 to 60 degrees C. AMF-3 exhibited a high affinity towards soluble starch with a K(m) value of 0.43 mg/mL. Maximal AMF-3 activity was achieved in the presence of 0.1 mM CaCl(2), while at higher concentrations its activity decreased. AMF-3 activity increased with increasing NaCl concentration. AMF-3 activity was significantly inhibited by alpha-amylase wheat inhibitor. Using a number of raw starch substrates maximum AMF-3 activity was achieved with horse-radish starch, in contrast to undetectable activity towards potato starch.


An in vitro demonstration of oestrogenicity with potential for exploitation as a quantitative assay for oestrogenic potency.
The pre-implantation embryo of the mouse undergoes a histochemically detectable change in the properties of its trophoblastic cell-surface coat in the immediate pre-implantation period. This change is oestrogen-dependent in vivo and can be induced in vitro in a concentration-dependent manner by oestradiol-17 beta. There is evidence that this coat change is of functional importance in the process of implantation, and its demonstration is of potential value as the basis of an in vitro assay of oestrogenicity.