"Less Than A Wife": A Study of Polycystic Ovary Syndrome Content in Teen and Women's Digital Magazines.
Polycystic ovary syndrome (PCOS) is a major public health problem that affects women's physical and mental health. According to the US National Institutes of Health Office of Disease Prevention, there is a need to improve public awareness of the syndrome among health care providers and the public. Women's magazines are a type of "edutainment" that publish health content in addition to beauty, fashion, and entertainment content. These media have the potential to expose primarily female readers to content on PCOS and influence readers' beliefs and attitudes about women with PCOS. The objective of this study was to explore how digital (online) teen and women's magazines portray women with PCOS. We used data from the Alliance for Audited Media to identify popular digital teen and women's magazines with circulation rates ≥1,000,001. We also included magazines with circulation rates 100,001-1,000,000 directed toward racial and ethnic minority readers. A search of magazine websites over a 1-month period in 2015 yielded 21 magazines (eg, Glamour, Cosmopolitan en Español, Essence, and O, The Oprah Magazine) and 170 articles containing "PCOS" and "polycystic ovary syndrome." Textual analysis using a grounded theory approach was used to identify themes. Articles depicted PCOS symptoms as a hindrance to women's social roles as wives and mothers and largely placed personal responsibility on women to improve their health. To a lesser extent, women were depicted as using their personal experience with PCOS to advocate for women's health. Experiences of Latina and African American women and adolescents with PCOS were absent from women's magazine articles. The findings can inform health education programs that teach women to be critical consumers of PCOS-related content in digital women's magazines. Future research on PCOS content in digital teen and women's magazines can help researchers, patients, and consumer groups engage with the media to increase public awareness of PCOS.


Facile Synthesis of Chiral Polymers with Defined Architecture via Cooperative Assembly of Confined Templates.
Herein is presented the synergistically self-assembled system as biomimetic polymerization media. This approach allows the facile synthesis of chiral amino acid-based polymers with high molecular weight and low dispersity inside of the bilayer of catanionic vesicles by using a conventional radical polymerization under moderate conditions.


A novel miniaturized electroanalytical device integrated with gas extraction for the voltammetric determination of sulfite in beverages.
Voltammetry and amperometry are inexpensive and high-performance analytical techniques. However, their lack of selectivity limits their use in complex matrices such as biological, environmental, and food samples. Therefore, voltammetric and amperometric analyses of these samples usually require time-consuming and laborious sample pretreatments. In this study, we present a simple and cost-effective approach to fabricate a miniaturized electrochemical cell that can be easily coupled to a head space-like gas extraction procedure in such a way the sample pretreatment and voltammetric detection are performed in a single step. As a proof of concept, we have used the proposed system to quantify sulfite in beverage samples after its conversion to SO2(g). Despite the simplicity and low cost of the proposed system, it provided good analytical performance and a limit of detection of 4.0 μmol L-1 was achieved after only 10 min of extraction. The proposed system is quite versatile since it can be applied to quantify any volatile electroactive species. Also, the proposed system provides a unique way to assess real-time extraction curves, which are essential to study and optimize new gas extraction procedures. Therefore, the approach described in this study could contribute to both applied and fundamental Analytical Chemistry.


Developmental progression in play behavior of children between nine and thirty months. I: Spontaneous play and imitation.
The developmental progression of play behavior was studied cross-sectionally in 85 children at eight age-levels between nine and 30 months. In a structured play situation, three major play patterns were distinguished: (1) exploratory play (at the end of the first year); (2) functional play (beginning of second year); and (3) representational play (after 15 months). Sequential play first occurred at 21 months. Play behavior with spatial characteristics was also observed: relational and container play between nine and 15 months, and understanding of spatial relationships, stacking and grouping between 18 and 24 months. There was a significant relationship between spontaneous and imitative play behavior; the greatest affect was displayed when the demonstrated behaviors matched the child's developmental level of play.


Treatment of hepatitis C after liver transplantation.
This article summarizes the current therapies, with particular emphasis on antiviral therapy. Because these alternatives have substantial limitations, pretransplant or early post-transplant recognition of patients with high risk of severe post-transplantation outcome is desirable to target these patients for intervention. Alternatively, the implementation of measures aimed at reducing or avoiding factors known to be associated with an aggressive recurrence is an additional strategy that needs to be explored.


Effect of diabetes mellitus on pancreatic exocrine secretion from isolated perfused pancreas in rats.
We studied pancreatic exocrine function in response to cerulein and carbamylcholine in isolated perfused pancreas obtained from control, streptozotocin-induced diabetic, and insulin-treated diabetic rats. The time course of pancreatic juice, protein, amylase, and trypsinogen secretion in response to cerulein or carbamylcholine in diabetic rats was similar to that in control rats. Basal as well as cerulein- or carbamylcholine-stimulated output of amylase from diabetic rat pancreas was significantly reduced, whereas that of trypsinogen was similar to the control. Amylase and trypsinogen outputs in response to 620 pM (1.0 ng/ml) cerulein from insulin-treated diabetic rat pancreas were significantly lower than those from control rat pancreas, although the pancreatic contents of these enzymes were similar to or greater than those in control rats. The dose-response curves of pancreatic juice, protein, amylase, and trypsinogen for cerulein and carbamylcholine were biphasic in both control and diabetic rats. The minimal and the maximal release in response to cerulein occurred with higher concentrations in diabetic rats compared with control rats. In contrast, the maximal responses were obtained with 1 microM carbamylcholine in control rats and with 0.1-1 microM carbamylcholine in diabetic rats. The present study demonstrates that the concentration of cerulein required to elicit maximal response was increased, whereas that to carbamylcholine was reduced in diabetic rat pancreas, and that the protein and enzyme outputs in response to cerulein were significantly reduced in insulin-treated diabetic rat pancreas despite restoration of the pancreatic enzyme contents to control levels.


Energy and macronutrient intakes in preschool children in urban areas of Ho Chi Minh City, Vietnam.
An increasing prevalence of overweight and obesity has been documented in preschool children in Ho Chi Minh City (HCMC), Vietnam. However, little is known about what preschool children in HCMC eat or how well their nutrient intake meets nutrient recommendations. This study aims to describe the energy and macronutrient intake and compare these nutrient intakes with the recommendations for Vietnamese children aged four to five years. The data comes from the baseline measurement of a one year follow-up study on obesity in 670 children attending kindergartens in HCMC. Dietary information for each child at the school and home settings was collected using Food Frequency Questionnaires (FFQs), by interviewing teachers and parents or main caregivers. The average energy and nutrient intake in a day was calculated. The proportion of children with energy intake from macronutrients meeting or exceeding the recommendations was estimated based on the 2006 recommended daily allowance (RDA) for Vietnamese children in this age group. The dietary intake of the participants contained more energy from protein and fat, particularly animal protein and fat, and less energy from carbohydrates, than the RDA. Most children (98.1%) had mean energy intake from protein greater than the recommended level of 15%, and no child obtained energy from animal fat that was in accordance with the recommendation of less than 30% of the total fat intake. Nearly one half of children (46.5%) consumed less than the advised range of mean energy intake from carbohydrate (60%-70%). In this preschool child population in HCMC, in which obesity is emerging as major public health problem, there is an imbalance in dietary intake. Healthy eating programs need to be developed as a part of an obesity prevention program for young children in HCMC.


Construction of IMMS Containing Multi-site Liposomes for Dynamic Monitoring of Blood CTC in Patients with Osimertinib-resistant Non-small-cell Lung Cancer and its Mechanism.
This article aims to establish a liquid biopsy system for gene detection of circulating tumor cells (CTC) in lung cancer, systematically analyze the significance of osimertinib resistance, and formulate an individualized diagnosis and treatment plan. Liposome-contained magnetic microspheres coated with Fe3O4 nanoparticles were synthesized by microemulsion, and the surface was modified with EGFR antibody to form EGFR/EpCAM multi-site liposome-contained immunomagnetic microspheres (IMMSs). The CTCs were isolated and identified from peripheral blood samples and the cell lines of lung cancer patients collected by the multi-site liposome-contained IMMSs. To investigate the effects of the order of use of IMMSs sequence at different sites on the sorting and trapping efficiency of non-small-cell lung cancer (NSCLC) cells . The preliminary verification of drug-resistant gene function and dynamic monitoring of CTCs in 20 patients with EGFR-positive NSCLC were screened and statistically analyzed before and after osimertinib treatment. Sensitivity analysis and drug resistance evaluation of oxitidine were detected in vitro. Results showed the prepared multi-site liposome-contained IMMSs had high stability and specificity. The number of CTCs in blood samples of the patients with NSCLC was detected, revealing high sorting efficiency, and positive sorting rate reaching more than 90%. We investigated the effect of osimertinib on the HER-2 expression on the EGFR-mutated NSCLC cells and found that osimertinib increased the expression of HER-2 on the cell surface of NSCLC cell lines., And further explored the therapeutic potential of osimertinib combined with T-DM1 at different dosing times. Our results demonstrate that the prepared multi-site liposome-contained IMMSs can efficiently isolate CTCs from the peripheral blood in lung cancer. Combined with the experimental data about osimertinib can be effectively identified, the resistant genes of NSCLC including EGFR, which will provide a new scientific basis for guiding clinical medication and formulating individualized treatment plans.


Bacteriophage control of Salmonella Typhimurium in milk.
This study was designed to evaluate the effect of bacteriophage P22 on the inhibition of growth of Salmonella Typhimurium. The P22 belongs to Podoviridae family consisting of a hexagonal head and short tail. The inhibitory effect of phage in milk was noticeable at the early storage period, showing more than 3 log reduction at 4 h and day 3. The pH values of milk treated with P22 were significantly decreased from 6.7 to 6.3 after 24 h incubation at 37 °C, while no significant changes in pH values were observed for the control and bacteriophage treatment throughout the storage at 4 °C for 12 days. The slight color changes were observed in the control and bacteriophage treatment throughout the storage at 4 °C for 12 days and 37 °C for 24 h. These results provide useful information for enhancing microbiological safety and quality of milk and designing effective bacteriophage-based control in food system.


Treatment of skin ulcers with cultured epidermal allografts.
Thirty-six skin ulcers in 23 patients were treated with cultured allogeneic epidermal sheets derived from neonatal foreskin. In 73% of ulcers, there was complete healing within 8 weeks, with a mean healing time of 3.3 weeks. In the other 27%, there was reduction in ulcer size of 35% to 93% by 8 weeks after grafting. In 30 painful ulcers, pain was markedly relieved within 24 hours of grafting. The healing pattern suggested that the cultured epidermal sheets acted by stimulation of host keratinocytes to divide and migrate rather than by permanent acceptance of the allograft. Of the 26 ulcers that healed within 8 weeks, 23 (88.5%) remained healed for follow-up periods of 10 to 18 months (mean 13.7 months), with an overall mean duration of healing of 13 months.


Percent free prostate-specific antigen is effective to predict prostate biopsy outcome in Chinese men with prostate-specific antigen between 10.1 and 20.0 ng ml(-1).
Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml-1 , however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA>4.0 ng ml-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 , respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 .


An exploration of Latino smokers and the use of pharmaceutical aids.
Latino smokers are less likely than white non-Latino smokers to use nicotine replacement therapy (NRT) or bupropion when trying to quit smoking. The current study explored sociocultural and psychosocial factors related to nonuse of smoking-cessation medications among Latino smokers. Structured discussions were held with six separate focus groups of current smokers (n =49) who self-identified as Latino, had attempted to quit in the past 12 months, and were aged 35 to 64 years. Participants were recruited from Latino-serving health clinics, community events, and community organizations. Session recordings were transcribed, and content analysis was used to organize themes into categories. Six thematic categories emerged across most or all discussion groups: (1) smoking is a weakness rather than an illness, (2) pharmaceuticals are generally avoided, (3) NRT is mistrusted, (4) bupropion is widely rejected, (5) views are mixed regarding ethnic dimensions of smoking and quitting, and (6) misconceptions are common regarding smoking and cessation. Cognitive reframing strategies should be developed and tested for Latino smokers who decline pharmacologic smoking-cessation assistance for reasons other than well-informed autonomous choice.


Potential years of life lost due to urogenital cancer in the United States: trends from 1972 to 2006 based on data from the SEER database.
Urogenital cancer is a major health problem in the United States. We assessed potential years of life lost secondary to genitourinary cancer in the United States from 1972 to 2006 using the SEER (Surveillance, Epidemiology and End Results) database. We report trends in potential years of life lost during the same period. Potential years of life lost were calculated to assess premature mortality trends for ureter, bladder, kidney and renal pelvis, penis, testis and prostate cancers. Calculations were based on SEER cancer mortality data. Potential years of life lost up to and including age 75 years were calculated by and across genders in 5-year increments between 1972 and 2006. A total of 7,733,235 potential years of life were lost in men and women. In each gender the greatest potential loss was for kidney and renal pelvis cancer related mortality. In each gender no improvement in the potential loss due to ureteral and bladder cancer related mortality was observed during 3 decades. In males the greatest decrease in potential years of life lost was for testicular cancer, followed by prostate cancer. There has been an increasing trend in potential years of life lost related to urogenital cancer during the last 35 years for males and females. This trend is mainly due to an increase in kidney cancer. The continued increase in potential years of life lost due to renal cancer and the lack of a decrease in the loss in those with bladder cancer should alert urologists and health care policy makers to deficient areas that most need to be addressed.


Stoichiometry and kinetics of the anaerobic ammonium oxidation (Anammox) with trace hydrazine addition.
Purpose of this study is to investigate the stoichiometry and kinetics of anaerobic ammonium oxidation (Anammox) with trace hydrazine addition. The stoichiometry was established based on the electron balance of Anammox process with trace N2H4 addition. The stoichiometric coefficients were determined by the proton consumption and the changes in substrates and products. It was found that trace N2H4 addition can increase the yield of Anammox bacteria (AnAOB) and reduce NO3(-) yield, which enhances the Anammox. Subsequently, kinetic model of Anammox with trace N2H4 addition was developed, and the parameters of the anaerobic degradation model of N2H4 were obtained for the first time. The maximum specific substrate utilization rate, half-saturation constant and inhibition constant of N2H4 were 25.09mgN/g VSS/d, 10.42mgN/L and 1393.88mgN/L, respectively. These kinetic parameters might provide important information for the engineering applications of Anammox with trace N2H4 addition.


Inhibitory effect of thalidomide on the growth, secretory function and angiogenesis of estrogen-induced prolactinoma in Fischer 344 rats.
The process of angiogenesis has been found to be essential for the development of estrogen-induced pituitary prolactinoma in Fischer 344 rats. Thalidomide [(alpha-(N-phthalimido)-glutarimide] is known to be a potent immunomodulatory drug with antiangiogenic properties, but its effect on lactotroph cell secretory function and pituitary prolactinoma formation has not been described yet. The purpose of this study was to examine the effects of thalidomide on secretion of prolactin (PRL) and vascular endothelial growth factor (VEGF), cell proliferation, apoptosis and angiogenesis within the anterior pituitary gland in long-term diethylstilboestrol (DES)-treated male F344 rats in vivo and in vitro. It was found that DES sharply increased serum PRL and VEGF levels. On the other hand, simultaneous treatment of F344 rats with thalidomide for the last 15 days of the experiment attenuated the stimulatory effect of DES on PRL and VEGF secretion. It also diminished prolactin cell proliferation evaluated as the number of proliferating cell nuclear antigen (PCNA)-positive stained cell nuclei and increased the number of apoptotic bodies determined by the terminal deoxynucleotidyl-mediated dUTP nick-end labeling (TUNEL) method in sections of the DES-induced pituitary prolactinoma. The density of pituitary microvessels evaluated by microscopic counting of CD-31-positive blood vessels was also diminished by the tested drug. In addition, thalidomide (10(-4) to 10(-6) M) inhibited cell proliferation, prolactin and VEGF secretion from rat pituitary prolactinoma cells cultured in vitro. In conclusion, our results provide strong evidence for the antiprolactin and antitumor activity of thalidomide in experimentally DES-induced pituitary adenoma.


Centrifugally spun alginate-poly(lactic acid) microbeads: A promising carrier for drug delivery and tissue engineering.
A facile and high yield centrifugal spinning technique known as Forcespinning® (FS) was used to develop unique microstructures consisting of PLA microbeads along alginate fibers. Morphological variation and structural features appeared in the field-emission scanning electron micrographs for the PLA-alginate composites and dried PLA-alginate films from precursor emulsions at constant PLA and varied alginate contents. Shrunk and deflated microbeads were observed for composites whilst spherical beads were evident for the PLA control. Furthermore, PLA was found surrounding the alginate when the alginate was present at 0.24 wt% or lower, while alginate (mushroom-like structures), were seen protruding through the PLA layer at ≥0.34 wt% alginate. Rheological characterization of the composite emulsions revealed that the filler (alginate) provided shear thinning properties including pseudoplasticity, desirable for printing and other related applications in contrast to the Newtonian flow shown by the PLA control. Along with infra-red spectroscopy, the nanocomposites were further characterized using thermal gravimetry and differential scanning calorimetry featuring reversible events influenced by heat capacity and irreversible kinetic/thermodynamic counterparts. The work provides a comprehensive investigation of biocompatible networks of PLA-alginate microbeads embedded in nano-sized fibers and the prospective application of these microbeads as a drug delivery system.


Prognostic Value of Coronary CTA in Stable Chest Pain: CAD-RADS, CAC, and Cardiovascular Events in PROMISE.
The purpose of this study was to compare Coronary Artery Disease Reporting and Data System (CAD-RADS) to traditional stenosis categories and the coronary artery calcium score (CACS) for predicting cardiovascular events in patients with stable chest pain and suspected coronary artery disease (CAD). The 2016 CAD-RADS has been established to standardize the reporting of CAD on coronary CT angiography (CTA). PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial participants' CTAs were assessed by a central CT core laboratory for CACS, traditional stenosis-based categories, and modified CAD-RADS grade including high-risk coronary plaque (HRP) features. Traditional stenosis categories and CAD-RADS grade were compared for the prediction of the composite endpoint of death, myocardial infarction, or hospitalization for unstable angina over a median follow-up of 25 months. Incremental prognostic value over traditional risk factors and CACS was assessed. In 3,840 eligible patients (mean age: 60.4 ± 8.2 years; 49% men), 3.0% (115) experienced events. CAD-RADS (concordance statistic [C-statistic] 0.747) had significantly higher discriminatory value than traditional stenosis-based assessments (C-statistic 0.698 to 0.717; all p for comparison ≤0.001). With no plaque (CAD-RADS 0) as the baseline, the hazard ratio (HR) for an event increased from 2.43 (95% confidence interval [CI]: 1.16 to 5.08) for CAD-RADS 1 to 21.84 (95% CI: 8.63 to 55.26) for CAD-RADS 4b and 5. In stepwise nested models, CAD-RADS added incremental prognostic value beyond ASCVD risk score and CACS (C-statistic 0.776 vs. 0.682; p < 0.001), and added incremental value persisted in all CACS strata. These data from a large representative contemporary cohort of patients undergoing coronary CTA for stable chest pain support the prognostic value of CAD-RADS as a standard reporting system for coronary CTA.


Evaluation of hiPSC-Derived Muscle Progenitor Cell Transplantation in a Mouse Duchenne Muscular Dystrophy Model.
For cell therapy toward Duchenne muscle dystrophy (DMD), muscle progenitor cells derived from human-induced pluripotent stem cell (hiPSC-MuPCs) are recognized as a good candidate, and currently, cell transplantation of hiPSC-MuPCs is being tested with several DMD animal models. In this article, we describe an efficient method to dissociate, purify by cell sorting, transplant, and evaluate the transplantation efficacy of hiPSC-MuPCs.


Endoscopic balloon sphincteroplasty for benign papillary stenosis--an alternative to surgical or endoscopic papillotomy?
Benign papillary stenosis is an uncommon but well recognised cause of recurrent biliary pain usually in post-cholecystectomy patients characterised by biliary dilatation without bile duct calculi or malignancy. Endoscopic or surgical papillotomy is the recommended treatment but may be associated with a higher complication rate than when performed for bile duct stones. We report 2 cases of papillary stenosis treated by endoscopic balloon dilatation or "sphincteroplasty", as a less traumatic intervention which improved biliary drainage and provided symptomatic relief. Our preliminary experience suggests more widespread evaluation of balloon sphincteroplasty should be considered for papillary stenosis.


Altered striatal-opercular intrinsic connectivity reflects decreased aversion to losses in alcohol use disorder.
The persistence of addictive behaviours despite their adverse consequences highlights decreased punishment sensitivity as a facet of decision-making impairments in Alcohol Use Disorder (AUD). This attitude departs from the typical loss aversion (LA) pattern, i.e. the stronger sensitivity to negative than positive outcomes, previously associated with striatal and limbic-somatosensory responsiveness in healthy individuals. Consistent evidence highlights decreased LA as a marker of disease severity in AUD, but its neural bases remain largely unexplored. AUD-specific modulations of frontolateral activity by LA were previously related to the higher executive demands of anticipating losses than gains, but the relationship between LA and executive/working-memory performance in AUD is debated. Building on previous evidence of overlapping neural bases of LA during decision-making and at rest, we investigated a possible neural signature of altered LA in AUDs, and its connections with executive skills, in terms of complementary facets of resting-state functioning. In patients, smaller LA than controls, unrelated to executive performance, reflected reduced connectivity within striatal and medial temporal networks, and altered connectivity from these regions to the insular-opercular cortex. AUD-specific loss-related modulations of intrinsic connectivity thus involved structures previously associated both with drug-seeking and with coding the trade-off between appetitive and aversive motivational drives. These findings fit the hypothesis that altered striatal coding of choice-related incentive value, and interoceptive responsiveness to prospective outcomes, enhance neural sensitivity to drug-related stimuli in addictions. LA and its neural bases might prove useful markers of AUD severity and effectiveness of rehabilitation strategies targeting the salience of negative choice outcomes.


Effects of systemic clonidine on auditory event-related potentials in squirrel monkeys.
Event-related potential (ERP), electroencephalographic (EEG), and behavioral data were collected from squirrel monkeys (Saimiri sciureus) in a 90-10 auditory oddball paradigm. Background or target tones were presented once every 2 s, and responses to the targets were rewarded. ERPs were recorded from epidural electrodes following systemic administration of clonidine (0.1 mg/kg) or a saline placebo. EEG power spectral and behavioral performance were assessed simultaneously as indices of behavioral state. Clonidine significantly decreased the area and increased the latency of a P300-like potential. The amplitude and areas of the earlier P1, N1, and P2 components and a later slow wave-like potential were not reduced, nor were ther latencies altered. Clonidine produced increased EEG power in the alpha range (7.5-12 Hz) and decreased power in the upper beta range (20-40 Hz) but did not affect performance in the oddball task. Because two major effects of clonidine are to substantially reduce activity in the noradrenergic nucleus locus coeruleus (LC) and to reduce norepinephrine (NE) release from axons, the present results support the hypothesis that the LC and its efferent projection system are important in modulating the activity of P300-like potentials.


Bisphenol A alters sexual dimorphism and gene expression in marine medaka Oryzias melastigma.
Bisphenol A (BPA) is an endocrine disruptor that is present in freshwater and marine environments. However, conclusive evidence for the toxicity of chronic BPA exposure to marine fishes remains lacking. Therefore, we investigated the influence of BPA on male marine medaka (Oryzias melastigma). BPA exposure induced formation of testis-ova at 2610 µg/L, and male-type anal fins became more female type in a concentration-dependent manner. Some males with female-type anal fins had normal testes, indicating that anal fin shape is more sensitive to BPA. Gonadal soma-derived factor (gsdf) expression decreased after BPA exposure in the 746 and 2610 µg/L exposure groups, although the changes were not statistically significant. Additionally, liver vitellogenin (vtg) expression increased in a dose-dependent manner and was significantly higher in all exposure groups. vtg and gsdf are likely to be useful biomarkers for the impact of estrogenic endocrine disrupters in O. melastigma.


[Current role of lymph node dissection in renal cell carcinoma: review of the literature by the Oncology Committee of the French Association of Urology (CCAFU)].
Nowadays, most of renal cancers are incidental tumors less than 4 cm. Prevalence of lymph node involvement is low and does not require a systematic lymphadenectomy as described by Robson in the 1960s. Radiologic progress and particularly CT scan describe with high precision lymph node involvement in the initial work-up. In renal cancer with a high risk of recurrence, lymphadenectomy has a pronostic interest and therapeutic role in rare situations where lymph node involvement is isolated. In metastatic patients, the role of cytoreductive nephrectomy has to be assessed.


Core-shell structural nitrogen-doped carbon foam loaded with nano zero-valent iron for simultaneous remediation of Cd (II) and NAP in water and soil: Kinetics, mechanism, and environmental evaluation.
An economical, efficient, and environmentally friendly technology was developed for simultaneous remediation of heavy metals and polycyclic aromatic hydrocarbons (PAHs) in soil and water. In this study, using pinecones powder as the precursor, the core-shell structural nitrogen-doped carbon foam loaded with nano zero-valent iron (nZVI@NCF) was synthesized through Mannich reaction and high-temperature carbon reduction. The nZVI@NCF was applied as the adsorbent and catalyst to simultaneously remediate the composite pollutants of Cd (II) and naphthalene (NAP). Under the optimal conditions, the adsorption capacity of Cd (II) in water and soil were 13.9 mg·g-1 and 1.97 mg·g-1, respectively, and the adsorption process conformed to the pseudo-second-order kinetic model. The degradation rates of NAP in water (10 mg·L-1) reached almost 100% as well as it could reach 59.12% in soil (10 mg·kg-1). In addition, it was proved that the presence of NAP could compete with Cd (II) for the active sites on the surface of the material to inhibit the adsorption of Cd (II), while the co-existence of Cd (II) could improve the degradation of NAP by the nZVI@NCF/PMS system due to the nZVI-Cd bimetallic effect and the pro-oxidant effect of Cd (II) promoting the generation of ROS. The free radical quenching experiment revealed that the generated ·O2- was the main substance that mediated the redox of nZVI/Fe2+/Fe3+ to oxidative NAP during the degradation process. Furthermore, the results of the phytotoxicity test demonstrated that the nZVI@NCF/PMS system could effectively remediate the soil co-contaminated with Cd (II) and NAP as well as improve the soil environment quality. This research will provide new materials and potential technologies for the efficient treatment of the composite pollutants in the environment.


Facile fabrication of organic-inorganic hybrid beads by aminated alginate enabled gelation and biomimetic mineralization.
Inspired by biomineralization, design and preparation of biomimetic organic-inorganic composites have become a hot issue and a research frontier in many areas, including enzyme engineering. In this research, a unique and facile method for fabricating organic-inorganic hybrid beads is proposed. Modified alginate with a dual function of gelation and mineralization was synthesized for fabrication of hybrid carriers for enzyme immobilization. With the aid of EDC/NHS conjugation chemistry, the amine groups from diethylene triamine were grafted onto alginate in a controllable way. The resultant aminated alginate served manifold functions: forming a hydrogel via Ca(2+)-cross-linking, inducing the biomimetic silicification and manipulating the distribution of silica nanoparticles. Owing to the compact polymer network structure and the homogeneous silica nanoparticle dispersion, the as-prepared NH2-alginate/silica hybrid beads displayed superior swelling resistance and mechanical stability to pure alginate beads. The hybrid beads were subsequently utilized for encapsulation of yeast alcohol dehydrogenase (YADH). It was found that the thermal stability, pH tolerance and storage stability of the immobilized enzyme were all improved without significantly lowering the catalytic activity.


[Not all drugs are the same].
Drug use has changed dramatically in recent years. Classic drugs such as marijuana, heroin, and cocaine are being pushed progressively into the background. Consumer behavior has also changed and so-called designer drugs dominate the market. Designer drugs are synthetic or semi-synthetic drugs based on a well-known substance. Mostly amphetamine derivates, synthetic cannabinoids, and synthetic cathinone are used. Legal monitoring capabilities are limited, since these substances are so-called legal highs and are commercially available. A ban often follows a latency period. Estimating the risk is difficult, and the problem of intoxication increases. This overview presents the activity profiles and risks of classic and new drugs.


Accelerated atherosclerosis in the transplant recipient: role of hypertension.
An accelerated atherosclerosis may occur in the native arteries of a transplant recipient as well as in arteries of transplanted kidneys or hearts. The dominating cause of patient mortality are cardiovascular diseases, where ischaemic heart disease is predominant. The accelerated form of arteriosclerosis which takes place in transplanted kidneys and hearts, has a complex pathogenesis, which includes both immunological and nonimmunological factors. Hypertension is one such factor which has been claimed to be an independent risk factor of chronic renal transplant dysfunction, usually characterised by transplant arteriosclerosis. Whether a more intense treatment of hypertension or a more selective use of antihypertensive drugs would have a beneficial effect upon the progression rate of chronic rejection is still an open question.


Erratum: Migraine Aura, Transient Ischemic Attacks, Stroke, and Dying of the Brain Share the Same Key Pathophysiological Process in Neurons Driven by Gibbs-Donnan Forces, Namely Spreading Depolarization.
[This corrects the article DOI: 10.3389/fncel.2022.837650.].


hsp65 PCR-restriction analysis (PRA) with capillary electrophoresis for species identification and differentiation of Mycobacterium kansasii and Mycobacterium chelonae-Mycobacterium abscessus group.
The aim of the present study was to identify and differentiate Mycobacterium kansasii and Mycobacterium chelonae-Mycobacterium abscessus group strains isolated from clinical and environmental sources in different countries. PCR-restriction analysis of the hsp65 gene (PRA) with automated capillary electrophoresis was applied to the isolates previously identified by conventional biochemical testing and the molecular INNO-LiPA MYCOBACTERIA assay. PRA performed very well in comparison with the two other methods (96.4% concordance). Among 27 M. kansasii isolates, this method detected five genetic types, of which type 1 represented the most common clinical isolate, as it is worldwide. PRA differentiated 29 M. chelonae-M. abscessus group isolates into Mycobacterium immunogenum type 2 (n=13), M. chelonae (n=12), and M. abscessus types 1 (n=1) and 2 (n=1). M. immunogenum was the most frequent (69%) isolate from humans, but only one of 11 cases was clinically significant. M. chelonae was the most commonly (83%) recovered from water. PRA also identified two isolates with hsp65 alleles representing previously unreported patterns. PRA based on automated capillary electrophoresis is a rapid, simple, and reliable method for the identification and differentiation of both clinically relevant and environmental isolates of M. kansasii and M. chelonae-M. abscessus group.


Bacteria cellulose framework-supported solid composite polymer electrolytes for ambient-temperature lithium metal batteries.
Composite polymer electrolyte (CPE) films with high room temperature ionic conductivity are urgently needed for the practical application of high-safety solid-state batteries (SSBs). Here, a flexible polymer-polymer CPE thin film reinforced by a three-dimensional (3D) bacterial cellulose (BC) framework derived from natural BC hydrogel was prepared via thein situphoto-polymerization method. The BC film was utilized as the supporting matrix to ensure high flexibility and mechanical strength. The BC-CPE attained a high room temperature ionic conductivity of 1.3 × 10-4S cm-1. The Li∣BC-CPE∣Li symmetric cell manifested stable cycles of more than 1200 h. The LCO∣BC-CPE∣Li full cell attained an initial discharge specific capacity of 128.7 mAh g-1with 82.6% discharge capacity retention after 150 cycles at 0.2 C under room temperature. The proposed polymer-polymer CPE configuration represents a promising route for manufacturing environmental SSBs, especially since cellulose biomaterials are abundant in nature.


Attribution of blame in incest.
This study was designed to identify the empirical structure of attitudes relating to attribution of blame in incest. A second purpose was to determine how variables such as gender, physically abused status, and sexually abused status influence the attribution of blame in incest. A sample of 201 male and 211 female college students was administered the Jackson Incest Blame Scale. Four factors emerged from the factor analysis of the total sample supporting the hypothesis that attribution of blame in incest is a multidimensional construct including victim, offender, situational, and societal factors. A difference in the level of victim blame was found between male and female samples. Results are discussed with regard to their implications for further research and training. Other potential uses of the Jackson Incest Blame Scale are suggested.


Extracorporeal ureteral tailoring during HIDES laparoscopic robotic-assisted ureteral reimplantation for megaureter.
Although laparoscopic robotic-assisted intracorporeal ureteral tailoring is feasible and several authors have reported doing it, it adds a level of complexity to the surgery that many robotic surgeons are uncomfortable with. Also, some techniques for tailoring the ureter, like the one described by Ossandon, would be very difficult to perform intracorporeally or violate principles of hidden incision endoscopic surgery (HIDES) by adding extra ports in visible locations. Extracorporeal ureteral tapering is performed by extracting the ureter through a 10-mm step trocar placed in the midline at the level of the biking line. Once the ureter is tapered and a stent has been secured, the 10-mm trocar is replaced and the rest of the reimplant is performed in a way very similar to when performing a robotic apendicovesicostomy. Extracorporeal ureteral tailoring can be added to the bag of tricks that robotic surgeons can resort to when faced with the situation of a dilated ureter without compromising cosmesis.


Long-term application of fertilizer and manures affect P fractions in Mollisol.
Application of phosphorus (P), a major plant nutrient, as fertilizer is critical to maintain P level for crop production and yield in most cultivated soils. While, it may impact the dynamics, limited studies have examined the long-term effects of fertilization on P fractions in a soil profile in Mollisol. A long-term field experiment was conducted at the State Key Experimental Station of Agroecology of the Chinese Academy of Sciences in Hailun county, Heilongjiang Province, China. A sequential fractionation procedure was used to determine the effect of fertilizer (types) treatments including no fertilizer (CK), chemical fertilizer (NPK), chemical fertilizer plus straw (NPK + S) and pig manure (OM) on fractions of P and their distribution within 0-100 cm soil profiles. Unlike CK treatment, the long-term application of fertilizers increased the concentration and accumulation of total and available P in 0-20 and 0-40 cm soil depths than deeper soils, respectively. The phosphorus activity coefficient (PAC) ranged from 1.5 to 13.8% within 0-100 cm soil depth. The largest PAC value was observed under OM treatment at 0-40 cm soil depth and under NPK + S treatment at 40-100 cm soil depth. The Ca2-P and Ca8-P concentrations increased significantly by 0.5-7.5 times and 0.5-10.4 times, respectively in OM treatment with the largest value in 0-40 cm soil depth over CK treatment. The Al-P concentration under NPK + S and OM treatments increased throughout the soil profile. The OM treatment increased all Po concentrations in the 0-40 cm soil depth, while NPK and NPK + S treatments increased labile organic P, moderately labile organic P, and highly stable organic P in the 0-20 cm soil depth. Thus, the application of fertilizer and straw, or organic manure may enhance inorganic and organic P pool in a Mollisol in Northeast China. Thus, organic manure application in the subsoil as a potential P source and their impact should be considered in developing management practices and policies regarding nutrient management.


Insulin as a factor of increased androgen production in women with obesity and polycystic ovaries.
To evaluate the possible role of moderate hyperinsulinemia on abnormal androgen secretion, we examined 4 age and weight-matched groups of obese subjects: 2 groups of women with normal menses whose fasting insulin (IRI) levels were less than or equal to 20 microU/ml (OB-I) or greater than or equal to 40 microU/ml (OB-I) and 2 groups of women with polycystic ovaries who were similarly grouped. All subjects underwent an oral glucose tolerance test, blood sex hormone determination and multiple LH determinations. Compared to OB, OB-PCO women showed significantly higher values of LH, androgen and estrogen concentrations. OB-I and OB-II showed similar hormonal patterns. On the contrary, OB-PCO-II presented significantly (p less than 0.05) higher androstenedione concentrations (348.7 +/- 129.9 ng/dl) (m +/- SD) than OB-PCO-I women (237.0 +/- 73.7 ng/dl). These differences were evident despite similar plasma LH concentrations. In conclusion, these results suggest that insulin may be a factor amplifying LH-dependent androgen secretion in hyperandrogenized women with obesity and PCO.


pH in the endosome. Measurements during pinocytosis and receptor-mediated endocytosis.
By fluorescence spectroscopy, the average pH within endocytic compartments was determined during endocytosis of fluorescein conjugates by macrophages and hepatocytes. In mouse macrophages and hepatocytes fluorescein conjugates taken up either in the fluid phase or by binding to cell surface receptors were rapidly transferred to an acidic compartment (pH 5-5.5). The half-time for this process was generally less than 4 min. The pH within yeast-containing phagosomes was also rapidly reduced to similar levels, following a unique and transient increase. In each case, the acid endosomal compartments involved probably do not contain lysosomal enzymes. When fluorescein conjugates of asialoglycoproteins were internalised by hepatocytes at 20 degrees C, no proteolysis occurred within the acidic endosome until the temperature was raised. Fluorescein conjugates of concanavalin A (conA) and polylysine were relatively more slowly internalised by macrophages. The half-times for uptake, estimated by fluorescence change, were comparable with the turnover time for bulk plasma membrane. The relatively high average pH experienced by these conjugates indicated that a small proportion of these non-specific cell-surface labels was always in contact with the extracellular medium.


Large variation in management of talar osteochondral lesions among foot and ankle surgeons: results from an international survey.
Surgeons management of osteochondral lesions of the talus (OLT) may be different to the published guidelines because not all treatment recommendations are feasible in every country. This study aimed to assess how OLT are managed worldwide by foot and ankle surgeons. A web-based survey was distributed to the members of 21 local and international scientific societies focused on foot and ankle or sports medicine surgery. Answers with a prevalence greater than 75% of respondents were considered a "main tendency", whereas where prevalence exceeded 50% of respondents they were considered a "tendency". A total of 1804 surgeons from 79 different countries returned the survey. The responses to 19 of 28 questions (68%) regarding management and treatment of OLT achieved a main tendency (> 75%) or a tendency (> 50%). Symptoms reported to be most suspicious for OLT were pain on weight-bearing (WB) and after activity (83%), deep localization of the pain (62%), and any history of trauma (55%). 89% of surgeons routinely obtain an MRI, 72% routinely get WB radiographs, and 50% perform a CT scan. When treated surgically, OLTs are managed in isolation by only 7% of surgeons, and combined with ligament repair or reconstruction by 79%; 67% report simultaneous excision of soft-tissue or bony impingements (64%). For lesions less than 10-15 mm in diameter, bone marrow stimulation (BMS) represents the first choice of treatment for 78% of surgeons (main tendency). No other treatment was recorded as a tendency. For lesions greater than 15 mm in diameter no tendencies were recorded. The BMS represented the most preferred treatment being the first choice of treatment for 41% of surgeons. OLT depth had little influence on treatment choice: 71% of surgeons treating small lesions and 69% treating large lesions would choose the same treatment regardless of whether the lesion had a depth lesser or greater than 5 mm. The management of OLT by foot and ankle surgeons from around the world remains extremely varied. The main clinical relevance of this study is that it provides updated information with regard to the management of OLT internationally, which could be used by surgeons worldwide in their decision-making and to inform the patient about available surgical options. Level IV.


PTH induces modification of transductive events in otosclerotic bone cell cultures.
We studied the effect of PTH (10-100 nM) on transductive mechanisms (adenylate cyclase activity, Ca2+ metabolism, IP3 levels) in cell cultures derived from normal and otosclerotic human bone fragments. The cultured cells were osteoblast-like but with calcitonin-receptors still present and with PTH receptors coupled with the adenylate cyclase system. The results showed that PTH activated adenylate cyclase and increased the intracellular Ca2+ levels with qualitative and quantitative differences between the two cellular populations. In particular, otosclerotic cells responded less to hormone stimulation, which is in accord with the current hypothesis of a desensitization of the receptor/enzyme complex associated with the pathological status.


Psychosocial and metabolic function by smoking status in individuals with binge eating disorder and obesity.
Individuals with binge eating disorder (BED) report smoking to control appetite and weight. Smoking in BED is associated with increased risk for comorbid psychiatric disorders, but its impact on psychosocial functioning and metabolic function has not been evaluated. Participants were 429 treatment-seeking adults (72.4% women; mean age 46.2±11.0years old) with BED comorbid with obesity. Participants were categorized into current smokers (n=66), former smokers (n=145), and never smokers (n=218). Smoking status was unrelated to most historical eating/weight variables and to current eating disorder psychopathology. Smoking status was associated with psychiatric, psychosocial, and metabolic functioning. Compared with never smokers, current smokers were more likely to meet lifetime diagnostic criteria for alcohol (OR=5.51 [95% CI=2.46-12.33]) and substance use disorders (OR=7.05 [95% CI=3.37-14.72]), poorer current physical quality of life, and increased risk for metabolic syndrome (OR=1.80 [95% CI=0.97-3.35]) and related metabolic risks (reduced HDL, elevated total cholesterol). On the other hand, the odds of meeting criteria for lifetime psychiatric comorbidity or metabolic abnormalities were not significantly greater in former smokers, relative to never smokers. Our findings suggest the importance of promoting smoking cessation in treatment-seeking patients with BED and obesity for its potential long-term implications for psychiatric and metabolic functioning.


The regeneration of organogenesis.
We would like to welcome our readers to the regenerated Organogenesis and to share with you the reasoning behind the refocusing of this journal toward the development of tissues and organs as a future means to improve the health of patients.


Effects of monetary reserves and rate of gain on human risky choice under budget constraints.
The energy-budget rule is an optimal foraging model that predicts that choice should be risk averse when net gains plus reserves meet energy requirements (positive energy-budget conditions) and risk prone when net gains plus reserves fall below requirements (negative energy-budget conditions). Studies have shown that the energy-budget rule provides a good description of risky choice in humans when choice is studied under economic conditions (i.e., earnings budgets) that simulate positive and negative energy budgets. In previous human studies, earnings budgets were manipulated by varying earnings requirements, but in most nonhuman studies, energy budgets have been manipulated by varying reserves and/or mean rates of reinforcement. The present study therefore investigated choice in humans between certain and variable monetary outcomes when earnings budgets were manipulated by varying monetary reserves and mean rates of monetary gain. Consistent with the energy-budget rule, choice tended to be risk averse under positive-budget conditions and risk neutral or risk prone under negative-budget conditions. Sequential choices were also well described by a dynamic optimization model, especially when expected earnings for optimal choices were high. These results replicate and extend the results of prior experiments in showing that humans' choices are generally consistent with the predictions of the energy-budget rule when studied under conditions analogous to those used in nonhuman energy-budget studies, and that choice patterns tend to maximize reinforcement.


Free testosterone concentration in serum: elevation is the hallmark of hirsutism.
A simple, reliable procedure for quantitating the concentration of free (not protein bound and thus biologically active) testosterone in serum has been applied to normal and hirsute patients. Each of 32 hirsute women studied had a significantly elevated level of free testosterone (that is, more than two standard deviations above the mean of that found in normal women), although half of them had a total serum testosterone level within normal limits. Suppression of free testosterone to within normal limits could be accomplished by dexamethasone alone in 47 per cent of the hirsute group. In the remainder of the hirsute group, suppression of free testosterone to within normal limits could be accomplished by addition of Enovid-E. Use of free serum testosterone concentration is clearly superior to the use of total serum testosterone concentration for the identification and rational therapy of simple hirsutism.


Two-dimensional intravascular ultrasound: technical development and initial clinical experience.
This article reviews the development and current status of catheter-based, intravascular ultrasound imaging. The first section provides an introduction to some of the general technical issues encountered in the design of the catheter imaging systems and compares the potential merits of the multiple-element versus the mechanical approach. The second section of the article reviews the data from early studies correlating the intravascular ultrasound images with histologic sections (in vitro) and angiography (in vivo). The article concludes with a discussion of potential clinical applications and future technical developments.


Lung cancer screening eligibility and use with low-dose computed tomography: Results from the 2018 Behavioral Risk Factor Surveillance System cross-sectional survey.
In randomized controlled trials, lung cancer screening with low-dose chest computed tomography (LCS) has been reported to reduce lung cancer mortality. Although initial studies suggested that only approximately 5% of eligible patients have undergone LCS, recent studies have indicated that use of LCS may be increasing nationwide. The objective of the current study was to estimate recent LCS use using cross-sectional survey data from the 2018 Behavioral Risk Factor Surveillance System (BRFSS) survey. The BRFSS is a nationally representative, cross-sectional telephone survey of adults in the United States (response rate of approximately 50%). The 2018 BRFSS survey included questions regarding LCS eligibility and use in 8 states. The primary outcome was the percentage of participants (aged 55-79 years with a smoking history of >30 pack-years) who reported undergoing LCS. Logistic regression analyses evaluated the association between LCS use and sociodemographic characteristics, adjusted for potential confounders and accounting for complex survey design elements. A total of 26,910 participants were included, 9.9% of whom were eligible for LCS (95% CI, 8.8%-10.6%). Of the eligible patients, 19.2% reported undergoing LCS (95% CI, 14.0%-24.4%). Approximately 16.4% of current smokers were eligible for LCS (95% CI, 14.2%-18.6%). In our multiple variable analyses of eligible patients, age, sex, marital status, current smoking status, and race were not found to be associated with statistically significant differences in reported LCS (P > .05). Retired patients, patients with personal physicians, and patients who did not complete a high school education were more likely to report receiving LCS (P < .05). Compared with previously published studies, the results of the current study suggested that LCS use is increasing. However, LCS use remains low (19%) among eligible participants.


Relationship between diastolic ventricular dysfunction and subclinical sleep-disordered breathing in atrial fibrillation ablation candidates.
Sleep-disordered breathing (SDB) is recognized as a primary factor or mediator of atrial fibrillation (AF). We hypothesized that the severity of SDB among AF ablation candidates would be associated with left ventricular diastolic dysfunction (LVDD) even for subclinical SDB. A total of 246 patients hospitalized for initial pulmonary vein isolation (PVI) were analyzed. Known SDB cases were excluded. We measured the oxygen desaturation index (ODI) by pulse oximetry overnight as an indicator of SDB, and classified SDB severity by 3 % ODI as normal (ODI < 5 events/h), mild (ODI ≤ 5 to <15 events/h), or moderate-to-severe (ODI ≥15 events/h). The LVDD was assessed by echocardiography using combined categories with tissue Doppler imaging and left atrial (LA) volume measurement. Among the participants, 42 patients (17.1 %) had LVDD. The prevalence of LVDD increased with the SDB severity from 8.6 % (normal) to 12.7 % (mild) to 40.0 % (moderate-to-severe SDB) (p < 0.0001). In the multivariate logistic regression analysis, the odds ratio of having LVDD in the moderate-to-severe SDB group (ODI ≥ 15) vs. normal group (ODI < 5) was 5.96 (95 % CI, 2.10-19.00, P = 0.006). The presence of moderate-to-severe SDB in AF ablation candidates adversely affected LV diastolic function even during a subclinical state of SDB.


Modeling characterization of the vertical and temporal variability of environmental DNA in the mesopelagic ocean.
Increasingly, researchers are using innovative methods to census marine life, including identification of environmental DNA (eDNA) left behind by organisms in the water column. However, little is understood about how eDNA is distributed in the ocean, given that organisms are mobile and that physical and biological processes can transport eDNA after release from a host. Particularly in the vast mesopelagic ocean where many species vertically migrate hundreds of meters diurnally, it is important to link the location at which eDNA was shed by a host organism to the location at which eDNA was collected in a water sample. Here, we present a one-dimensional mechanistic model to simulate the eDNA vertical distribution after its release and to compare the impact of key biological and physical parameters on the eDNA vertical and temporal distribution. The modeled vertical eDNA profiles allow us to quantify spatial and temporal variability in eDNA concentration and to identify the most important parameters to consider when interpreting eDNA signals. We find that the vertical displacement by advection, dispersion, and settling has limited influence on the eDNA distribution, and the depth at which eDNA is found is generally within tens of meters of the depth at which the eDNA was originally shed from the organism. Thus, using information about representative vertical migration patterns, eDNA concentration variability can be used to answer ecological questions about migrating organisms such as what depths species can be found in the daytime and nighttime and what percentage of individuals within a species diurnally migrate. These findings are critical both to advance the understanding of the vertical distribution of eDNA in the water column and to link eDNA detection to organism presence in the mesopelagic ocean as well as other aquatic environments.


HPLC-fluorescence determination of unconjugated estrogens in pharmaceuticals.
A fluorimetric liquid chromatographic method (lambda(ex) = 280 nm; lambda(em) = 312 nm) was developed for measurements of unconjugated estrogens (estradiol and estriol) in pharmaceutical dosage forms using a reversed-phase column with water acetonitrile at different composition as mobile phase. The in vitro release profiles of three different estradiol transdermal therapeutic systems were determined through a medical-grade silicone rubber subdermal implant material membrane, using a modified Franz diffusion apparatus at 37 degrees C in presence of PEG 400. The HPLC method possesses advantages of rapidity, simplicity and accuracy.


Neonatal cerebral blood flow velocity measurement.
This article discusses the background, methodology, previous clinical studies, and the clinical role and limitations of the noninvasive Doppler technique in the assessment of the cerebral circulation of the newborn infant.


Regioselective synthesis of dispiro[1H-indene-2,3'-pyrrolidine-2',3''-[3H]indole]-1,2''(1''H)-diones of potential anti-tumor properties.
1,3-Dipolar cycloaddition reaction of 2-(arylmethylene)-2,3-dihydro-1H-inden-1-ones 1a-g with non-stabilized azomethine ylides, generated in situ via decarboxylative condensation of isatins 2a,b and sarcosine (3) afforded dispiro[1H-indene-2,3'-pyrrolidine-2',3''-[3H]indole]-1,2''(1''H)-diones 4a-n and not the isomeric forms dispiro[1H-indene-2,4'-pyrrolidine-2',3''-[3H]indole]-1,2''(1''H)-diones 5 in a highly regioselective manner. Anti-tumor activity screening for the synthesized compounds (4c,d,i-l) at a dose of 10 microM utilizing 56 different human tumor cell lines representing, leukemia, melanoma and cancers of the lung, colon, brain, ovary, breast, prostate and kidney was carried out. All the tested compounds exhibit promising anti-tumor activity against SK-MEL-2 (melanoma) cell line. Anti-inflammatory activity of the prepared compounds was determined in vivo by the acute carrageenan-induced paw oedema in rats. Many of the prepared compounds exhibit considerable anti-inflammatory properties "at a dose of 50 mg/kg body weight", especially 4a and 4m which reveal remarkable activities relative to indomethacin which was used as a reference standard in this study.


Docking Complete: A Step Further toward the Holy Grail of γδ T Cell Biology.
The direct ligands recognized by γδ T cell receptors (γδ TCRs) remain uncertain and controversial. In a study appearing in this issue, Willcox et al. use surface plasmon resonance and isothermal titration calorimetry to demonstrate that B7-like molecule BTNL3 makes physical contact with V4γ-bearing TCRs on γδ T cells.


RNA-Seq unveiled section-specific host response to lack of gut microbiota in mouse intestine.
To identify host responses induced by commensal microbiota in intestine, transcriptomes of four sections of the intestine were compared between germ-free (GF) mice and conventional (CV) controls using RNA-Seq. Cuffdiff revealed that jejunum had the highest number of differentially expressed genes (over 2000) between CV and GF mice, followed by large intestine (LI), duodenum, and ileum. Gene set association analysis identified section-specific alterations in pathways associated with the absence of commensal microbiota. For example, in GF mice, cytochrome P450 (Cyp)-mediated xenobiotic metabolism was preferably down-regulated in duodenum and ileum, whereas intermediary metabolism pathways such as protein digestion and amino acid metabolism were preferably up-regulated in duodenum, jejunum, and LI. In GF mice, carboxypeptidase A1 (Cpa1), which is important for protein digestion, was the top most up-regulated gene within the entire transcriptome in duodenum (53-fold) and LI (142-fold). Conversely, fatty acid binding protein 6 (Fabp6/Ibabp), which is important for bile acid intestinal reabsorption, was the top most down-regulated gene in jejunum (358-fold), and the drug-metabolizing enzyme Cyp1a1 was the top most down-regulated gene in ileum (40-fold). Section-specific host transcriptomic response to the absence of intestinal microbiota was also observed for other important physiological pathways such as cell junction, the absorption of small molecules, bile acid homeostasis, and immune response. In conclusion, the present study has revealed section-specific host gene transcriptional alterations in GF mice, highlighting the importance of intestinal microbiota in facilitating the physiological and drug responses of the host intestine.


Should we be Afraid of Immune Check Point Inhibitors in Cancer Patients with Pre-Existing Rheumatic Diseases? Immunotherapy in Pre-Existing Rheumatic Diseases.
Cancer immunotherapy is rapidly expanding but its clinical efficacy is hampered by immune related adverse events (ir-AE). There is a concern regarding patients with pre-existing auto-immune diseases (PAD) undergoing immunotherapy. An electronic search was performed (Medline) to identify cases of patients with PAD treated with immune checkpoint inhibitors (ICI). Published data are rather limited but continue to emerge. Patients with PAD exhibit a high risk of PAD flare and/or de novo ir-AE. In most cases PAD flares and de novo irAEs were not severe and could be managed effectively with standard treatment. This risk in patients with PAD appears acceptable, and therefore, these patients could receive immunotherapy under close monitoring. Collaboration of oncologists and rheumatologists for the management of these patients is crucial.


Epithelial carcinoma of the nasal fossa.
Epithelial carcinoma of the nasal cavity and vestibule occurs relatively rarely and is primarily treated with surgical excision, radiation therapy, or a combination of these two treatment modalities. This review describes the treatment methods and results of patients seen at the Indiana University School of Medicine from 1963 through 1983 in the Departments of Radiation Oncology and Otolaryngology. Using the medical records of 34 patients, this retrospective study reviews the clinical significance of histology, anatomical location of primary tumors, and therapeutic results, including the pattern of treatment failures of primary tumors. The results of radiation therapy alone compare favorably with the results of surgery alone. A review of the literature and this study indicate that patients receiving a combination of surgery and irradiation face a better prognosis than those who experience surgery or irradiation alone.


Exploring the multi-gene regulatory molecular mechanism of Saudi Arabian flora against epilepsy based on data mining, network pharmacology and docking analysis.
Epilepsy is a chronic neurological disorder marked by recurrent seizures, significantly affecting the population in Saudi Arabia across all age demographics. The global prevalence of active epilepsy is around 6.38/1,000 persons and in the Arabian region, the median prevalence of active epilepsy is 4.4/1,000 persons. However, over 75% of individuals are untreated. Consequently, the development of therapeutic strategies with increased efficacy and safety profiles is essential to improve the survival rate among epilepsy patients. The current study integrates network pharmacology along with Bioinformatics approaches to explore the potential molecular mechanisms of local flora of Saudi Arabia including Solanum incanum, Abrus precatorius, Withania somnifera, and Azadirachta indica in epilepsy treatment. In the preliminary phase, data related to the bioactive components of the local plants and the associated target genes of both these plants and epilepsy were gathered from scientific literature and open-source databases. This data was then analyzed to identify common targets between the plants and ovarian cancer. Based on these common targets, a protein-protein interaction (PPI) network was constructed utilizing the STRING database, which was subsequently incorporated into the Cytoscape software for identification of hub genes based on their degree of connectivity. Lastly, an interplay network depicting the associations between the compounds and the overlapping genes was formulated via Cytoscape, to study the potential network pharmacology implications of these active compounds in relation to ovarian cancer. Following that, a compound-target protein-pathway network was constructed which uncovered that namely abrectorin, genistin, (+)-catechin, precatorine, (+)-ascorbic acid, licoflavanone, skrofulein, stigmasterone, 5,7-Dihydroxy-4'-methoxy-8,3'-di-C-prenylflavanone could potentially be used as antagonists for the therapeutic management of epilepsy by targeting TNF and TP53 proteins. Furthermore, the implementation of molecular docking reinforces the binding affinity of the compound, indicating a robust stability of the forecasted compounds at the docked site. This research lays both a theoretical and experimental groundwork for more profound investigations and establishes a practical method for the strategic employment of active compounds in the development of anti-epileptic therapeutics.


Adult brain tumors in Sub-Saharan Africa: A scoping review.
Sub-Saharan African (SSA) neuro-oncologists report high workloads and challenges in delivering evidence-based care; however, these reports contrast with modeled estimates of adult neuro-oncology disease burden in the region. This scoping review aimed to better understand the reasons for this discrepancy by mapping out the SSA adult brain tumor landscape based on published literature. Systematic searches were conducted in OVID Medline, Global Index Medicus, African Journals Online, Google Scholar, and faculty of medicine libraries from database inception to May 31, 2021. The results were summarized quantitatively and narratively. English and French peer-reviewed articles were included (title, abstract, and full text). Of the 819 records identified, 119 articles by 24 SSA countries (42.9%) were included in the final review. Odeku published the first article in 1967, and nine of the ten most prolific years were in the 21st century. The greatest contributing region was Western Africa (n = 58, 48.7%) led by Nigeria (n = 37, 31.1%). Central Africa had fewer articles published later than the other SSA regions (P = .61). Most studies were nonrandomized (n = 75, 63.0%) and meningiomas (n = 50, 42.0%) were the most common brain tumors reported. Less than 30 studies reported on adjuvant treatment or patient outcomes. Most publications were hospital-based, and there was significant heterogeneity in the quality of evidence and reporting. This study highlights the need for rapid and sustainable investments and brain tumor research capacity in SSA.


The costs of a national health information network.
The use of information technology may result in a safer and more efficient health care system. However, consensus does not exist about the structure or costs of a national health information network (NHIN). To describe the potential structure and estimate the costs of an NHIN. Cost estimates of an NHIN model developed by an expert panel. U.S. health care system. An expert panel estimated the existing and the expected prevalence in 5 years of critical information technology functionalities. They then developed a model of an achievable NHIN by defining key providers, functionalities, and interoperability functions. By using these data and published cost estimates, the authors determined the cost of achieving this model NHIN in 5 years given the current state of information technology infrastructure. To achieve an NHIN would cost 156 billion dollars in capital investment over 5 years and 48 billion dollars in annual operating costs. Approximately two thirds of the capital costs would be required for acquiring functionalities and one third for interoperability. Ongoing costs would be more evenly divided between functionality and interoperability. If the current trajectory continues, the health care system will spend 24 billion dollars on functionalities over the next 5 years or about one quarter of the cost for functionalities of a model NHIN. Because of a lack of primary data, the authors relied on expert estimates. While an NHIN will be expensive, 156 billion dollars is equivalent to 2% of annual health care spending for 5 years. Assessments such as this one may assist policymakers in determining the level of investment that the United States should make in an NHIN.


Sleeve gastrectomy versus Roux-en-Y Gastric Bypass for remission of type 2 diabetes mellitus at 1, 3 and 5 years: a systematic review and meta-analysis.
Sleeve gastrectomy (SG) and Roux-en-Y Gastric Bypass (RYGB) are the two procedures used in the management of patient with obesity and type 2 diabetes mellitus (T2DM); however, it is still unclear which of the two is more efficient in the remission of type-2 diabetes mellitus. The aim of this study was to analyze the efficiency of RYGB and SG in the remission of type-2 diabetes mellitus after 1, 3 and 5 years of surgery. Three databases (i.e., PubMed, Scopus, Central and Web of Science) were searched. All randomized control trial studies with at least 12-year follow-up were selected with type-2 diabetes mellitus in patients undergoing Roux-en-Y Gastric Bypass or sleeve gastrectomy. The broad and the narrow criteria were lined with individual patients reported, being analyzed and pooled using the random-effects model. The 15 selected articles, including 707 obese type 2 diabetes patients, met the eligibility criteria for this meta-analysis. RYGB when compared with SG shows increased broad remissions (RR=1.43, 95% CI: 1.13-1.80; P=0.003) and narrow remissions (RR=1.32, 95% CI: 1.15-1.58; P=0.003) after one year of surgery, and broad remissions 5 years after surgery (RR=1.58, 95% CI: 0.97-2.56; P=0.06). No significant difference was identified between the two groups in broad and narrow remissions 3 years after surgery and narrow remissions 5 years after surgery. Our results suggest that RYGB was more effective in the remission of type-2 diabetes mellitus at 1 year and 5 years considering the broad and narrow criteria, while there was no difference found 3 years after surgery.


Isolation of drugs from blood by column chromatography on Amberlite XAD-2.
An investigation was carried out on the isolation of 28 drugs from blood by column chromatography on Amberlite XAD-2. The following substances were added to postmortem blood specimens at concentrations generally of 1--10 microgram/ml: barbital, heptabarbital, hexobarbital, pentobarbital, phenobarbital, phenylbutazone, monocrotophos, amidopyrine, carbromal, diazepam, meprobamate, methaqualone, nitrazepam, phenazetin, chlorpromazine, dibenzepin, diphenhydramine, haloperidol, imipramine, mescaline, methadone, morphine, pentazocine, pethidine, tilidine, triflupromazine, verapamil, N-propylajmalinium bitartrate. The samples were purified by column chromatography on Amberlite XAD-2 and simple solvent extraction and subsequently quantitated by gas chromatography. By systematic variation of the conditions for adsorption of the drugs and desorption from the resin, revoveries of more than 80% after XAD-2 column chromatography could be achieved for most drugs. Thereby it was demonstrated, that in cases of fatal poisoning or emergencies this procedure is a valuable tool for forensic and clinical toxicologists who have to find out the toxic agent by chemical analysis of the blood.


Comparative analysis of human microglial models for studies of HIV replication and pathogenesis.
HIV associated neurocognitive disorders cause significant morbidity and mortality despite the advent of highly active antiretroviral therapy. A deeper understanding of fundamental mechanisms underlying HIV infection and pathogenesis in the central nervous system is warranted. Microglia are resident myeloid cells of the brain that are readily infected by HIV and may constitute a CNS reservoir. We evaluated two microglial model cell lines (C20, HMC3) and two sources of primary cell-derived microglia (monocyte-derived microglia [MMG] and induced pluripotent stem cell-derived microglia [iPSC-MG]) as potential model systems for studying HIV-microglia interactions. All four microglial model cells expressed typical myeloid markers with the exception of low or absent CD45 and CD11b expression by C20 and HMC3, and all four expressed the microglia-specific markers P2RY12 and TMEM119. Marked differences were observed upon gene expression profiling, however, indicating that MMG and iPSC-MG cluster closely together with primary human microglial cells, while C20 and HMC3 were similar to each other but very different from primary microglia. Expression of HIV-relevant genes also revealed important differences, with iPSC-MG and MMG expressing relevant genes at levels more closely resembling primary microglia. iPSC-MG and MMG were readily infected with R5-tropic HIV, while C20 and HMC3 lack CD4 and require pseudotyping for infection. Despite many similarities, HIV replication dynamics and HIV-1 particle capture by Siglec-1 differed markedly between the MMG and iPSC-MG. MMG and iPSC-MG appear to be viable microglial models that are susceptible to HIV infection and bear more similarities to authentic microglia than two transformed microglia cell lines. The observed differences in HIV replication and particle capture between MMG and iPSC-MG warrant further study.


A pilot clinical study of complex rhegmatogenous retinal detachment treatment via foldable capsular buckle scleral buckling.
To evaluate the feasibility of and identify problems in treating complex rhegmatogenous retinal detachment using foldable capsular buckle scleral buckling. This prospective clinical study enrolled five patients with complex rhegmatogenous retinal detachment treated with foldable capsular buckle scleral buckling at the 988th Hospital of People's Liberation Army Joint Logistic Force, China. During the 24-week follow-up period, the patients underwent measurements of their best-corrected visual acuity, slit-lamp examination, indirect ophthalmoscopy, and visual field testing. Additionally, B-ultrasound and fundus photography of the patients' retinal reattachments helped evaluate the treatment's post-surgery efficacy. We determined the safety of foldable capsular buckle scleral buckling based on infection, eye pain, diplopia, elevated intraocular pressure, and other postoperative severe complications. All five patients' complex rhegmatogenous retinal detachments were successfully treated and evaluated via B-ultrasound and fundus photography after surgery. Visual acuity was enhanced in four patients 24 weeks after surgery, while the remaining patients developed diplopia after surgery. No other complications were observed. This pilot study preliminarily determined that foldable capsular buckle scleral buckling is feasible for efficient and safe treatment of complex rhegmatogenous retinal detachment. These results support this surgery as a potential and novel alternative to current extraocular procedures for treating complex rhegmatogenous retinal detachment. The prospective observational clinical study protocol was approved by the Institutional Review Board and Ethics Committee and registered at the clinical research center in the 988th Hospital of People's Liberation Army Joint Logistic Force, China (9,882,019,000).


Long-term follow-up and exploration of the mechanism of stromal vascular fraction gel in chronic wounds.
Chronic refractory wounds easily relapse and seriously affect the patients' quality of life. Previous studies have shown that stromal vascular fraction gel (SVF-gel) significantly promotes the early healing of chronic wounds; however, the mechanisms of SVF-gel function per se remain unclear, and a long-term follow-up is lacking. This study aims to explore the mechanisms of SVF-gel promoting the healing of chronic wounds and follow up the long-term efficacy of SVF-gel. Autologous SVF-gel transplantation was performed in 20 patients with chronic wounds (from March 2016 to September 2019), and the size of the wound before and after SVF-gel transplantation was observed. The conditioned medium (CM) was harvested from SVF-gel under serum-free, serum-deprivation and 10% fetal bovine serum (FBS) microenvironment in vitro, respectively. The concentration of the growth factors in the two kinds of gel-CM was tested, and their effects on the proliferation and migration of human dermal fibroblasts (HDFs) were detected. All patients had 100% wound closure eventually, and the average time to complete closure was 28.3 ± 9.7 days. The time of follow-up ranged from 2 to 6 years, and there was no wound recurrence. Interestingly, the concentrations of epidermal growth factor and transforming growth factor β1 of the CM were higher in serum-free and serum-deprivation condition than in 10% FBS microenvironment (p < 0.05). Correspondingly, the proliferation and migration ability of HDFs treated with gel-CM from serum-free condition were stronger than those treated with gel-CM from serum-deprivation (2% FBS) or 10% FBS microenvironment (p < 0.05). These results indicate that it is safe, effective, and lasting in effect to treat chronic wounds with SVF-gel and mechanisms of action that include secreting various cytokines and promoting cell proliferation and migration ability. Chinese Clinical Trail Registry, ChiCTR2000034624. Registered 12 July 2020-Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=56058.


Improving electricity production in tubular microbial fuel cells through optimizing the anolyte flow with spiral spacers.
The use of spiral spacers to create a helical flow for improving electricity generation in microbial fuel cells (MFCs) was investigated in both laboratory and on-site tests. The lab tests found that the MFC with the spiral spacers produced more electricity than the one without the spiral spacers at different recirculation rates or organic loading rates, likely due to the improved transport/distribution of ions and electron mediators instead of the substrates because the organic removal efficiency was not obviously affected by the presence of the spiral spacers. The energy production in the MFC with the spiral spacers reached 0.071 or 0.073 kWh/kg COD in either vertical or horizontal installment. The examination of the MFCs installed in an aeration tank of a municipal wastewater treatment plant confirmed the advantage of using the spiral spacers. Those results demonstrate that spiral spacers could be an effective approach to improve energy production in MFCs.


Screening, assessment and management of type 2 diabetes mellitus in children and adolescents: Australasian Paediatric Endocrine Group guidelines.
The incidence of type 2 diabetes mellitus has increased in children and adolescents due largely to the obesity epidemic, particularly in high risk ethnic groups. β-Cell function declines faster and diabetes complications develop earlier in paediatric type 2 diabetes compared with adult-onset type 2 diabetes. There are no consensus guidelines in Australasia for assessment and management of type 2 diabetes in paediatric populations and health professionals have had to refer to adult guidelines. Recent international paediatric guidelines did not address adaptations to care for patients from Indigenous backgrounds. This guideline provides advice on paediatric type 2 diabetes in relation to screening, diagnosis, diabetes education, monitoring including targets, multicomponent healthy lifestyle, pharmacotherapy, assessment and management of complications and comorbidities, and transition. There is also a dedicated section on considerations of care for children and adolescents from Indigenous background in Australia and New Zealand. Published international guidelines currently exist, but the challenges and specifics to care for children and adolescents with type 2 diabetes which should apply to Australasia have not been addressed to date. These include: recommendations regarding care of children and adolescents from Indigenous backgrounds in Australia and New Zealand including screening and management; tighter diabetes targets (glycated haemoglobin, ≤ 48 mmol/mol [≤ 6.5%]) for all children and adolescents; considering the use of newer medications approved for adults with type 2 diabetes under the guidance of a paediatric endocrinologist; and the need to transition adolescents with type 2 diabetes to a diabetes multidisciplinary care team including an adult endocrinologist for their ongoing care.


Bone marrow transplantation.
Bone marrow transplantations have a definite role in treatment of leukemias and lymphomas. In acute myeloid leukemia and CML an allogeneic transplant using an HLA identical donor certainly provides a far superior survival than chemotherapy. Patients with Ph' chromosome need to be transplanted in first remission if a suitable donor is available. In recurrent lymphomas the best results are achieved if the patient is transplanted in complete remission. Transplantation done using minor mismatched family donors or unrelated donors are still considered experimental and more data is needed before final recommendations can be made. Availability of supportive services is an absolute must prior to establishing transplant program. Selection of patients for transplantation should be done after carefully reviewing the indications and discussing with the family the emotional, financial and physical burden of the procedure. For selected indications in leukemias and lymphomas, BMT may be the only viable treatment option and therefore must be considered.


Characterization of a new hemoglobin variant: Hb Badalona (beta31[B13]Leu-->Val).
Hemoglobin (Hb) Badalona was identified in a 35-year-old Spanish female and two other family members. All affected subjects presented erythrocytosis and increased oxygen affinity (P(50): 21 mmHg). Hemoglobinopathy was not detected with electrophoretic methods. It was, however, separated and quantified by cation exchange and reverse-phase high-performance liquid chromatography. Hb Badalona accounted for 35% of the total Hb. No significant clinical symptoms were found to be related to this hemoglobinopathy. This is the first case of a Leu-->Val replacement at position beta31(B13) reported in the world literature.


Internet-administered, low-intensity cognitive behavioral therapy for parents of children treated for cancer: A feasibility trial (ENGAGE).
Parents of children treated for cancer may experience mental health difficulties, such as depression and anxiety. There is a lack of evidence-based psychological interventions for parents, with psychological support needs unmet. An internet-administered, guided, low-intensity cognitive behavioral therapy-based (LICBT) self-help intervention may provide a solution. The feasibility and acceptability of such an intervention was examined using a single-arm feasibility trial (ENGAGE). Primary objectives examined: (1) estimates of recruitment and retention rates; (2) feasibility and acceptability of data collection instruments and procedures; and (3) intervention feasibility and acceptability. Clinical outcomes were collected at baseline, post-treatment (12 weeks), and follow-up (6 months). The following progression criteria were met: sample size was exceeded within 5 months, with 11.0% enrolled of total population invited, study dropout rate was 24.0%, intervention dropout was 23.6%, missing data remained at ≤10% per measure, and no substantial negative consequences related to participation were reported. Intervention adherence was slightly lower than progression criteria (47.9%). Findings suggest an internet-administered, guided, LICBT self-help intervention may represent a feasible and acceptable solution for parents of children treated for cancer. With minor study protocol and intervention modifications, progression to a pilot randomized controlled trial (RCT) and subsequent superiority RCT is warranted.


Calcium/Calmodulin-Dependent Protein Kinase IV (CaMKIV) Mediates Acute Skeletal Muscle Inflammatory Response.
The objective of this study is to investigate the role of Calmodulin-dependent protein kinase IV (CaMKIV) in Cardiotoxin (CTX)-induced mice muscle inflammation. CTX injection i.m. was performed to induce B6 mice acute tibialis anterior (TA) muscle injury. The mice were then injected i.p. with the recombinant CaMKIV protein or its antagonist KN-93. Immunoblotting was used to assess Calmodulin (CaM) and CaMKIV levels. Immunofluorescence was used to detect intramuscular infiltration or major histocompatibility complex (MHC)-I expression in damaged muscle. The extent of infiltration was evaluated by fluorescent intensity analysis. Cytokines/chemokines levels were determined by qPCR. CaMKIV gene knockdown in C2C12 cells was performed in order to evaluate the effects of CaMKIV on immuno-behavior of muscle cells. CTX administration induced a strong up-regulation of CaM and p-CaMKIV levels in infiltrated mononuclear cells and regenerated myofibers. In vivo adding of the recombinant CaMKIV protein enhanced intramuscular infiltration of monocytes/macrophages in damaged muscle and increased the number of proinflammatory Ly-6C+F4/80+ macrophage cells. CaMKIV protein treatment induced a striking up-regulation of mRNA levels of IL-1, IL-6, MCP-1, and MCP-3 in CD45+ cells sorted from damaged muscle; increased the infiltration of CD8+ T cells; and induced the up-regulation of MHC-I in partial regenerated myofibers, which was rarely observed in muscle damage alone. Additionally, CaMKIV protein treatment diminished the regulatory T cells (Tregs) number and led to the damaged TA muscle repair delay. In vitro CaMKIV gene knockdown reversed IFN-γ-induced up-regulation of MHC-I/II and TLR3 in the differentiated C2C12 myotubes. CaMKIV can act as an immunostimulation molecule and enhances the acute muscle inflammatory responses.


Risk of all-cause mortality, recurrent myocardial infarction, and heart failure hospitalization associated with smoking status following myocardial infarction with left ventricular dysfunction.
Patients with left ventricular (LV) systolic dysfunction after myocardial infarction (MI) are at particularly high risk for recurrent adverse outcomes. The magnitude of the decrease in risk associated with smoking cessation after MI has not been well described in patients with LV dysfunction after MI. We aimed to quantify the risk decrease associated with smoking cessation in subjects with LV dysfunction after MI. The Survival and Ventricular Enlargement (SAVE) trial randomized 2,231 subjects with LV dysfunction 3 to 16 days after MI. Smoking status was assessed at randomization and at regular intervals during a median follow-up of 42 months. Propensity score-adjusted Cox proportional hazard models were used to quantify the decrease in risk of all-cause mortality, death or recurrent MI, and death or heart failure (HF) hospitalization associated with smoking cessation. In baseline smokers who survived to 6 months without interval events, smoking cessation at 6-month follow-up was associated with a significantly lower adjusted risk of all-cause mortality (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.31 to 0.91), death or recurrent MI (HR 0.68, 95% CI 0.47 to 0.99), and death or HF hospitalization (HR 0.65, 95% CI 0.46 to 0.92). In conclusion, in patients with LV dysfunction after MI, smoking cessation is associated with a 40% lower hazard of all-cause mortality and a 30% lower hazard of death or recurrent MI or death or HF hospitalization. These findings indicate that smoking cessation is beneficial after high-risk MI and highlight the importance of smoking cessation as a therapeutic target in patients with LV dysfunction after MI.


Antihypertensive beta blocking action as related to renin and age: a pharmacologic tool to identify pathogenetic mechanisms in essential hypertension.
Three hundred fifteen patients with essential hypertension were classified according to low (18 percent), normal (59 percent) or high (23 percent) renin-sodium index. The proportion of patients with low renin hypertension progressively increased with increasing age and blood pressure, there being no difference between the sexes. Two high renin groups emerged: a younger group with early moderate hypertension, and an older group with severe hypertension consequent to possibly ischemic renal disease. Long-term beta blocking monotherapy in 137 patients resulted in a reduction of idastolic pressure to 95 mm Hg or less in 65 percent: 85 percent in those with high and 73 percent in those with normal renin activity; pressure was reduced to this level in only 1 of 24 patients (4 percent) with a low renin index. Antihypertensive efficacy was also related to age, since diastolic pressure was normalized in 80 percent of patients under age 40 years, in 50 percent of those aged 40 to 60 years, but in only 20 percent of those over age 60 years. Age may heolp in patient selection but is no substitute for the more reliable renin index, especially in patients over age 40 years, or with high pressure. Using studiew with propranolol as a standard, similar renin responses were obtained with two cardioselective beta1 type blocking drugs, atenolol and metoprolol, as well as with two nonselective beta2+1 receptor antagonists, LL21945 exhibiting prolonged receptor affinity and oxprenolol in slow release form. These long-acting drugs, which proved effective in single daily doses, could be of value in improving patient compliance...


Epstein-Barr virus DNA in nasopharyngeal carcinomas from Chinese patients in Hong Kong.
To investigate the presence of Epstein-Barr virus (EBV) in cases of nasopharyngeal carcinoma (NPC) in Chinese patients living in Hong Kong. Nasopharyngeal biopsy specimens, formalin fixed and paraffin wax embedded, from 24 patients, eight with undifferentiated nasopharyngeal carcinoma, eight with well differentiated squamous carcinoma, and eight showing normal tissue histology, were analysed for the presence of Epstein-Barr virus (EBV) DNA by slot-blot hybridisation on extracted unamplified DNA, and also after amplification of EBV specific sequences by the polymerase chain reaction (PCR). DNA slot-blot analysis showed viral DNA in all the undifferentiated, five of the well differentiated tumours, and none of the normal biopsy specimens. PCR studies confirmed positivity in the eight undifferentiated tumours, but six of the well differentiated tumours and three of the normal biopsy specimens showed viral DNA by this method, illustrating its greater sensitivity. EBV genome is present in appreciable copy number in most cases of well differentiated NPC in Chinese patients in Hong Kong.


Ocular involvement in Mycoplasma induced rash and mucositis: A systematic review of the literature.
Mycoplasma pneumoniae induced rash and mucositis (MIRM) is a relatively newly identified clinical entity which is characterized by mucocutaneous manifestations in the setting of Mycoplasma infection. Though a clinically distinct disease, MIRM exists on a diagnostic continuum with entities including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and the recently described reactive infectious mucocutaneous eruption (RIME). In this systematic review, we discuss published findings on the epidemiology, clinical manifestations, diagnosis, and management of MIRM, with an emphasis on ocular disease. Lastly, we discuss some of the most recent developments and challenges in characterizing MIRM with respect to the related diagnosis of RIME.


Midbrain dopamine neurons arbiter OCD-like behavior.
The neurobiological understanding of obsessive-compulsive disorder (OCD) includes dysregulated frontostriatal circuitry and altered monoamine transmission. Repetitive stereotyped behavior (e.g., grooming), a featured symptom in OCD, has been proposed to be associated with perturbed dopamine (DA) signaling. However, the precise brain circuits participating in DA's control over this behavioral phenotype remain elusive. Here, we identified that DA neurons in substantia nigra pars compacta (SNc) orchestrate ventromedial striatum (VMS) microcircuits as well as lateral orbitofrontal cortex (lOFC) during self-grooming behavior. SNc-VMS and SNc-lOFC dopaminergic projections modulate grooming behaviors and striatal microcircuit function differentially. Specifically, the activity of the SNc-VMS pathway promotes grooming via D1 receptors, whereas the activity of the SNc-lOFC pathway suppresses grooming via D2 receptors. SNc DA neuron activity thus controls the OCD-like behaviors via both striatal and cortical projections as dual gating. These results support both pharmacological and brain-stimulation treatments for OCD.


Identification of a target gene for the bE-bW homeodomain protein complex in Ustilago maydis.
In the phytopathogenic fungus Ustilago maydis, sexual and pathogenic development are controlled by the multiallelic b mating type locus. The b locus encodes a pair of unrelated homeodomain proteins termed bE and bW that form a heterodimeric complex when both proteins originate from different alleles. The heterodimer is presumed to be the central regulator for pathogenicity genes. Here, we show that a translational fusion protein comprising specific domains of bE1 and bW2 remains biologically active and binds to a sequence motif in the promoter of lga2, a gene located in the a mating type locus. This b binding sequence 1 (bbs1) is also recognized by the native bE1-bW2 heterodimer in vivo and mediates the b-dependent regulation of the lga2 gene. Our data demonstrate that the bE-bW heterodimer can act as a positive transcriptional regulator.


Inverted mucoepidermoid papillomas of the epibulbar conjunctiva.
Juxtalimbal epibulbar inverted papillomas that were locally excised without recurrence developed in two women, aged 42 and 51 at the time of initial presentation. There is only one previous report of this unusual conjunctival neoplasm, which documented involvement of the plical, caruncular, or tarsal conjunctiva. The tumor grew by acanthosis of the surface nonkeratinizing squamous epithelium, with invagination into the underlying connective tissue in the absence of inflammation or a tendency toward keratinization. The initial invaginations may be cystic in character, but solid lobules secondarily originated from their walls to push into the connective tissue. Mucus-producing goblet cells were scattered throughout the lesions; highly distinctive eosinophilic globoid bodies, probably reflecting inspissated mucoid material, were found in the walls of the cysts and entrapped within their secretions. Conjunctival inverted papilloma does not exhibit locally aggressive behavior, does not involve extensive segments of the conjunctival epithelium, and does not display diffuse spread or multicentricity. The authors therefore believe that it should be clearly separated from inverted squamous (Schneiderian) papillomas of the nasal cavity and sinuses.