[The usefulness of hormonal therapy in the treatment of prostatic cancer--clinical analysis of 160 cases over 12 years in the single institute].
At the Second Tokyo National Hospital, treatment of patients with prostatic cancer was carried out under the same protocol over 12 years. The mean age of the patients was 73.6 years, and 50% of them fell into the Stage D category. As the initial treatment, hormonal therapy consisting primarily of diethylstilbestrol diphosphate (DES-P) was given to 93.8% of the patients, and the effectiveness of the initial treatment was observed in 87.4% of them. The pre-treatment tumor marker value was high in 65.6% of the patients, and reverted to within normal limits after treatment in 51.3% of them. Relapse was observed in 15.0% of the patients. Side effects of hormonal therapy were observed in 20.7% of the patients, and the side effects resulted in death in 1.3% of them. Throughout the duration of the study, 34.4% of the patients resulted in death; 18.8% of these deaths related to cancer and 13.1% of them to other causes. The 5-year survival rate of all patients was 68.1%, and the 10-year survival rate was 52.7%. DES-P which is the primary drug in the protocol employed at our institution was well tolerated in the patients with minimal side effects when given appropriately and was believed to be an extremely effective drug in the treatment of prostatic cancer in Japan.


Consumer acceptance of an SMS-assisted smoking cessation intervention: a multicountry study.
This study assesses smokers' perceptions, motivations, and intentions towards using an SMS-assisted smoking cessation intervention in Australia, France, and Mexico through an extended technology acceptance model with mediating variables. Data was collected through online surveys. Results show that perceived usefulness and vicarious innovativeness predict use intentions for all three countries. Perceived ease of use is significant only for Mexico. Subjective norms are significant only for Mexico and Australia. Perceived monetary value and perceived annoyance are significant mediating variables for all three countries, whereas perceived enjoyment is significant only for Mexico and Australia. These results contribute to theory and practice.


[Vaccination against hepatitis B in France in 1996].
A national campain aimed at promoting immunization against hepatitis B was launched in 1994. Two years later, a survey was designed to estimate the situation of the hepatitis B vaccination in France. Around ninety per cent of physicians were hepatitis B vaccinated. The rate of vaccinated population among public hospitals personnel were more than 90% and lower in private hospitals (79%). A quarter of the general population was vaccinated and the higher rate (69%) was observed in the 13-20 years young people. Progressively the contribution of the physicians to the vaccination was increasing (89% in 1996). After a selective vaccination of risk groups and the instauration of the prevention of mother/infant transmission, the French programme was extended to cover adolescents and children. The success of the hepatitis B vaccination campain was obtained by the promotion message toward population and physicians.


Topographic analysis of the alpha-subunit of human follicle-stimulating hormone using site-specific antipeptide antisera.
Structure-function investigations were undertaken to increase understanding of the surface topology of the alpha-subunit of human FSH (hFSH). The objectives were to determine which sequences of the alpha-subunit of hFSH are surface-oriented (exposed to antibody) and to identify which of these surface-oriented sequences are in contact with the beta-subunit of hFSH in the alpha/beta heterodimer. Seven overlapping synthetic peptides spanning the primary structure of hFSH alpha were used for immunizing rabbits to generate site-specific antipeptide antisera. The antisera were characterized with respect to their reactivity to the seven synthetic peptides, as well as hFSH, hFSH alpha, hFSH beta, and hFSH alpha r/a (reduced and alkylated), using an enzyme-linked immunosorbent assay. All of the peptides successfully generated antipeptide antisera with titers that range from 1:1,600 to 1:80,000. Anti-1-15 bound exclusively to hFSH alpha. Anti-11-27 and anti-33-58 bound to hFSH alpha to a much greater extent than to hFSH. In contrast, anti-73-92 had only slightly higher binding to hFSH alpha than to hFSH. Anti-22-39, anti-51-65, and anti-61-78 all failed to bind to either hFSH or hFSH alpha. With the exception of anti-22-39, all of the remaining antisera bound to hFSH alpha r/a. None of the antisera bound to hFSH beta. These data strongly suggest the following. Sequences 1-15, 11-27, and 33-58 contain residues that are masked by hFSH beta and are thus in or near the alpha/beta-subunit interface. In addition, sequences 11-27 and 33-58 contain other distinct residues that are surface-oriented in the hFSH heterodimer. In contrast, sequence 73-92 appears to be surface-oriented in the hFSH heterodimer. Lastly, sequences 51-65 and 61-78 appear to be buried within the native alpha-subunit and, thus, are unable to interact with antibodies. These results agree with and extend previous findings and will prove useful to those currently investigating the surface topology and structure-function relationships of the glycoprotein hormones.


Burden of illness associated with sinusoidal obstruction syndrome/veno-occlusive disease in patients with hematopoietic stem cell transplantation.
Sinusoidal obstruction syndrome (SOS) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT) associated with significant morbidity and mortality. Healthcare utilization, costs, and mortality were assessed in HSCT patients diagnosed with SOS, with and without multi-organ dysfunction (MOD). This retrospective observational study identified real-world patients undergoing HSCT between January 1, 2009 and May 31, 2014 using the Premier Healthcare Database. In absence of a formal ICD-9-CM diagnostic code, SOS patients were identified using a pre-specified definition adapted from Baltimore and Seattle criteria and clinical practice. Severe SOS (SOS/MOD) and non-severe SOS (SOS/no-MOD) were classified according to clinical evidence for MOD in the database. Of the 5,418 patients with a discharge diagnosis of HSCT, 291 had SOS, with 134 categorized as SOS/MOD and 157 as SOS/no-MOD. The remaining 5,127 patients had HSCT without SOS. Overall SOS incidence was 5.4%, with 46% having evidence of MOD. Distribution of age, gender, and race were similar between the SOS cohorts and non-SOS patients. After controlling for hospital profile and admission characteristics, demographics, and clinical characteristics, the adjusted mean LOS was 31.0 days in SOS/MOD compared to 23.9 days in the non-SOS cohort (medians = 26.9 days vs 20.8 days, p < .001). The adjusted mean cost of SOS/MOD patients was $140,653, which was $41,702 higher than the non-SOS cohort (medians = $105,749 vs $74,395, p < .001). An almost 6-fold increased odds of inpatient mortality was associated with SOS/MOD compared to the non-SOS cohort (odds ratio = 5.88; 95% CI = 3.45-10.33). Limitations of retrospective observational studies apply, since the study was not randomized. Definition for SOS was based on ICD-9 diagnosis codes from a hospital administrative database and reliant on completeness and accuracy of coding. Analysis of real-world data shows that SOS/MOD is associated with significant increases in healthcare utilization, costs, and inpatient mortality.


Natural Products and Their Mimics as Targets of Opportunity for Discovery.
Diverse structural types of natural products and their mimics have served as targets of opportunity in our laboratory to inspire the discovery and development of new methods and strategies to assemble polyfunctional and polycyclic molecular architectures. Furthermore, our efforts toward identifying novel compounds having useful biological properties led to the creation of new targets, many of which posed synthetic challenges that required the invention of new methodology. In this Perspective, selected examples of how we have exploited a diverse range of natural products and their mimics to create, explore, and solve a variety of problems in chemistry and biology will be discussed. The journey was not without its twists and turns, but the unexpected often led to new revelations and insights. Indeed, in our recent excursion into applications of synthetic organic chemistry to neuroscience, avoiding the more-traveled paths was richly rewarding.


Ventricular fibrillation induced by high-output ICD shock: report of cases and review of literature.
This report highlights the importance of realising that even the modern-day implantable cardioverter defibrillators (ICDs) with R wave synchronised appropriate shocks have a potential proarrhythmic effect. We present two cases of ventricular fibrillation induction resulting from an appropriate ICD shock observed in two different patients at our institution. Such cases have not been reported before. We discuss the possible reasons for our observations and are also submitting a pertinent literature review with our reports.


Leriche Syndrome with Digital Gangrene: Is Aortic Bypass Grafting Safe in Intravenous Drug Abusers? A Case Report and Literature Review.
A 47-year-old male with Leriche syndrome presented with digital gangrene due to TASC II type-D occlusion of the distal aorta and common iliac arteries. Open revascularization was performed using a Dacron aorto-biiliac bypass graft; however, the postoperative course revealed a nondisclosed history of intravenous opioid abuse as he went into withdrawal psychosis. Our report highlights ways to mitigate infection risk associated with prosthetic aortic grafts in suspected or confirmed intravenous drug abusers. The literature review suggests alternative strategies like aortoiliac endarterectomy, total endovascular approach using non-covered stents, or a hybrid approach. The primary use of autologous venous grafts should be considered as a last resort so that the veins are retained for future use in case of graft infection. Patient factors like comorbidities, fitness to undergo surgery, anatomical extent of occlusion, and availability of facilities/expertise can further guide the management plan owing to a lack of evidence-based guidelines.


U.S. Survey of factors associated with adherence to standard of care in treating pregnant women with opioid use disorder.
Objective: To identify, factors associated with obstetricians' treatment recommendations for pregnant women with an opioid use disorder (PWOUD), and to determine the prevalence of physicians waivered for buprenorphine as a medication-assisted treatment (MAT).Methods: We conducted a structured online survey of a nationally representative sample of 565 obstetrical physicians, with a response rate of 38%. Logistic regression models were derived to identify factors that influence treatment recommendations for PWOUD. The Clopper-Pearson method was used to derive the confidence interval (CI) for the number of physicians waivered for buprenorphine.Results: Approximately 77% of respondents had provided care for a PWOUD within the last year. Physicians reported that at least 75% of their PWOUD received Medicaid for prenatal care. The most common opioids used at patient presentation were prescription opioids, with the second most common being methadone. A total of 14.0% had buprenorphine waivers (95% CI: 11.6-16.7%), and among those waivered, 47% prescribed buprenorphine to PWOUD. Factors associated with buprenorphine waiver encompass referrals to community support services. The three most prominent factors associated with adherence to standard of care were: type of opioid at presentation, patient's choice, and physician's experience. Type of opioid was associated with methadone presentation, socioeconomic status, shared decision making and practice setting. Patient's choice was associated with physician preparedness and practice duration. Physician's experience was associated with referral to recovery-oriented services.Conclusions: Novel interventions are needed to (1) promote office-based treatment for opioid use disorder through continuing medical education, (2) provide physicians with access to recovery-oriented resources and (3) increase patient autonomy in healthcare decision making. These proposed evidence-based interventions will promote best practices for women and their infants and greater accessibility to standard of care.


Surface plasmon coupling in end-to-end linked gold nanorod dimers and trimers.
Colloidal gold nanorods were aligned end-to-end via dithiol coupling. The scattering properties of the resultant nanostructures were investigated at the single particle level by combining dark-field microscopy and high resolution scanning electron microscopy. The longitudinal surface plasmon resonance of end-to-end coupled Au nanorods exhibited a red-shift as the number of rods in the chain increased. The nanostructures exhibited polarization-dependent optical properties, due to selective excitation of collective bonding and anti-bonding modes. The surface plasmon peak energy was not strongly dependent on the angle of rod-sphere-rod trimers. The experimental scattering spectra were compared with the results obtained from theoretical calculations using the Finite Element Method (FEM) and found to be in good agreement.


Necrotizing enterocolitis (NEC)--mortality and long-term results.
From 1974-88 73 patients were treated for necrotizing enterocolitis (NEC) in the surgical department at the Children's Hospital of Cologne. 70% of these had other complaints and 77% were premature babies, of which 30% were small-for-dates. A greater than expected proportion of deaths occurred in babies not of low birth-weight: Of those above 2500 g 35% died and of those under 1500 g 20%. Initial signs and symptoms became apparent in 80% within the first two weeks. The most frequent signs were distended abdomen (81%), diffuse tenderness (46%), bloody stools (39%) and absent peristalsis (39%). Radiology showed edema of the bowel wall in 49%, free air in the abdomen in 38% and intestinal pneumatosis in 34%. It remains questionable whether peritoneal lavage could lead to earlier diagnosis and referral of the sick children to the hospital. The course of the disease was less severe when babies had received breast milk. Colon and distal ileum were involved most frequently. Laparotomy showed perforations of the bowel in 39 patients (64%), inflammatory alterations in 18 and necroses in 12. The survival rates improved within the period of 1974-88 from 64 to 79%. Thirty-two of the 51 survivors were available for follow-up: 9 patients (28%) had more than 4 stools/day, 8 (25%) were underweight, 8 (25%) suffered from food intolerance, 5 (16%) from diarrhoea, 4 (13%) from limited exercise tolerance. Physical retardation could only be seen in 3 children under the age of 2.


Impact of soil types and petroleum effluents on the earthworm, Eudrilus eugeniae.
Earthworm, Eudrilus eugeniae, exposed to different concentrations of dump-site soil and petroleum effluents exhibited different morbidity and mortality responses. Lake sediments caused varied fluctuations in weight over a 20 day exposure period. Colour changes and mortality up to 15% were observed in earthworms cultured in 100% lake sediment, while weight loss, coiling and sluggish movement were observed in 50% lake water. The effects of 100% dump-site soils were more pronounced as 40% death, swelling, body lesions, stiffening, coiling and low reproduction were recorded. Earthworms were useful as an organism in testing the toxicity of dump-site soils and effluent from a petroleum industry. Dump-site soils and soils polluted with petroleum effluent reduced populations of earthworms and this could subsequently affect other components of the ecosystems associated with earthworm activities.


CCL11, a novel mediator of inflammatory bone resorption.
Normal bone homeostasis, which is regulated by bone-resorbing osteoclasts and bone-forming osteoblasts is perturbed by inflammation. In chronic inflammatory disease with disturbed bone remodelling, e.g. rheumatoid arthritis, patients show increased serum levels of the chemokine eotaxin-1 (CCL11). Herein, we demonstrate an inflammatory driven expression of CCL11 in bone tissue and a novel role of CCL11 in osteoclast migration and resorption. Using an inflammatory bone lesion model and primary cell cultures, we discovered that osteoblasts express CCL11 in vivo and in vitro and that expression increased during inflammatory conditions. Osteoclasts did not express CCL11, but the high affinity receptor CCR3 was significantly upregulated during osteoclast differentiation and found to colocalise with CCL11. Exogenous CCL11 was internalised in osteoclast and stimulated the migration of pre-osteoclast and concomitant increase in bone resorption. Our data pinpoints that the CCL11/CCR3 pathway could be a new target for treatment of inflammatory bone resorption.


Substance use, sexual behaviour and prevention strategies of Vancouver gay and bisexual men who recently attended group sex events.
Group sex events are an epidemiologically important part of some gay and bisexual men's sexual culture in Canada. Associated with condomless anal intercourse and polysubstance use, such events have been cited as disproportionally contributing to HIV infection rates. We analysed questionnaire data from the Momentum Health Study in Vancouver, Canada, to understand substance use, sexual behaviour, psychosocial variables (Sexual Sensation Seeking, Sexual Escape Motivation, Treatment Optimism) and HIV prevention strategies (sero-sorting, strategic positioning, avoiding anal sex, disclosure, treatment as prevention) of men attending such events, which were defined as group (n ≥ 4 partners) sex parties, blackout events and darkrooms. Analysis by multivariable logistic regression compared men attending group sex events within the past six months (n = 180) with non-attendees (n = 539). Results showed that attendees reported: (1) significantly higher use of sex drugs and alcohol consumption, (2) higher scores on the Sexual Sensation Scale, more anal sex partners, greater odds of any condomless anal sex with sero-discordant partners and greater odds of reporting fisting and sex toy use and (3) different prevention practices that varied by HIV-serostatus. Findings are interpreted in light of the importance of pleasure, sociality and HIV/STI prevention strategies associated with group sex events. Findings contribute to the development of appropriate education and intervention for attendees.


Multidimensional Applications and Challenges of Riboswitches in Biosensing and Biotherapy.
Riboswitches have received significant attention over the last two decades for their multiple functionalities and great potential for applications in various fields. This article highlights and reviews the recent advances in biosensing and biotherapy. These fields involve a wide range of applications, such as food safety detection, environmental monitoring, metabolic engineering, live cell imaging, wearable biosensors, antibacterial drug targets, and gene therapy. The discovery, origin, and optimization of riboswitches are summarized to help readers better understand their multidimensional applications. Finally, this review discusses the multidimensional challenges and development of riboswitches in order to further expand their potential for novel applications.


Binding of Divalent Cations to Insulin: Capillary Electrophoresis and Molecular Simulations.
In the present study, we characterize the binding of divalent cations to insulin in aqueous salt solutions by means of capillary electrophoresis and molecular dynamics simulations. The results show a strong pH dependence. At low pH, at which all the carboxylate groups are protonated and the protein has an overall positive charge, all the cations exhibit only weak and rather unspecific interactions with insulin. In contrast, at close to neutral pH, when all the carboxylate groups are deprotonated and negatively charged, the charge-neutralizing effect of magnesium, calcium, and zinc, in particular, on the electrophoretic mobility of insulin is significant. This is also reflected in the results of molecular dynamics simulations showing accumulation of cations at the protein surface, which becomes smaller in magnitude upon effective inclusion of electronic polarization via charge rescaling.


Cost-effectiveness of treating wet age-related macular degeneration at the Kuopio University Hospital in Finland based on a two-eye Markov transition model.
Wet age-related macular degeneration (AMD) is the leading cause of blindness worldwide, which can be treated with regular intraocular anti-vascular endothelial growth factor (VEGF) injections. In this study, we wanted to evaluate whether less frequent injections of aflibercept would make it more cost-effective when compared with ranibizumab and low priced bevacizumab. We used a two-eye model to simulate the progression and the treatment of the disease. We selected an 8-year period, 3-month cycles and five health states based on the visual acuity of the better-seeing eye. The transition probabilities and utilities attached to the health states were gathered from previous studies. We conducted the analysis from the hospital perspective and we used the health care costs obtained from Kuopio University Hospital. The costs of intraocular adverse events were taken into account. The incremental cost-effectiveness ratio (ICER) with 3% discount rate (€/QALY) for aflibercept compared with monthly bevacizumab was 1 801 228 and when compared with ranibizumab given as needed, the ICER was minus 3 716 943. The sensitivity analysis showed that a change of 20% of the estimated model parameters or a longer follow-up period did not influence these conclusions. A two-eye Markov transition model was developed to analyse the cost-effectiveness of wet AMD treatment, as quality of life years (QALYs) are largely based on the visual acuity of the better-seeing eye. Monthly injected bevacizumab was the most cost-effective treatment and monthly ranibizumab the least effective.


Rare structural chromosomal abnormalities in prenatal diagnosis; clinical and cytogenetic findings on 10125 prenatal cases.
Objective: The aim of this study was presentation of the ultrasonographic findings and perinatal autopsy of cases with rare chromosomal abnormalities. A total of 10125 prenatal cases over 17 years including 8731 amniocentesis, 973 chorionic villus sampling, and 421 fetal blood sampling cases were evaluated for prenatal cytogenetic diagnosis. Conventional cytogenetic studies, fluorescence in situ hybridization studies, and Array-CGH analysis techniques were used for genetic analysis. A structural chromosomal abnormality was observed in 95 cases. The most frequently observed structural abnormalities were balanced translocations with a frequency of 53.7% (51 cases) followed by unbalanced translocations (16.8%), inversions (11.6%), supernumerary marker chromosomes (8.4%), duplications (4.2%), deletions and ring chromosomes (2.1%) and complex translocation (1.1%). Rare structural chromosomal abnormalities including de novo balanced translocations, unbalanced translocations, inversions, duplications, deletions, ring chromosomes, and supernumerary marker chromosomes were detected in 24 cases. The rate of rare chromosomal abnormalities varies from 2.4% (South East Ireland) to 12.9% (Northern England) in Europe with a total rate of 7.4/10 000 births. In our study, the overall rate of chromosomal abnormality in prenatal cytogenetic diagnosis was 3.7%, similar to South East Ireland. Ultrasonographic and perinatal autopsy findings of the cases with rare structural chromosomal abnormalities are important for proper genetic counseling for further similar cases.


Digital Forms of Dating Violence: What School Nurses Need to Know.
A substantial amount of U.S. teenagers experience physical or sexual abuse within their romantic relationship. With recent technological advances, teenage dating violence can also be perpetrated digitally by harassing or controlling a romantic partner through the Internet or mobile phone. School nurses are naturally positioned to act as first responders for victims of an abusive romantic relationship. As online and offline forms of dating violence are often intertwined, it is imperative that school nurses are able to identify different types of digital dating violence as this could signal the presence of offline forms of dating abuse. Therefore, being able to interpret potential warning signs could help school nurses to play an active role in prevention and intervention of different types of dating violence. In this article, we provide an overview of the recent research on the context and consequences of cyber dating abuse and outline several suggestions for prevention and intervention.


Medical cardioversion of atrial fibrillation and flutter with class IC antiarrhythmic drugs in young patients with and without congenital heart disease.
The use of flecainide and propafenone for medical cardioversion of atrial fibrillation (AF) and atrial flutter/intra-atrial reentrant tachycardia (IART) is well-described in adults without congenital heart disease (CHD). Data are sparse regarding their use for the same purpose in adults with CHD and in adolescent patients with anatomically normal hearts and we sought to describe the use of class IC drugs in this population and identify factors associated with decreased likelihood of success. Single center retrospective cohort study of patients who received oral flecainide or propafenone for medical cardioversion of AF or IART from 2000 to 2022. The unit of analysis was each episode of AF/IART. We performed a time-to-sinus rhythm analysis using a Cox proportional hazards model clustering on the patient to identify factors associated with increased likelihood of success. We identified 45 episodes involving 41 patients. As only episodes of AF were successfully cardioverted with medical therapy, episodes of IART were excluded from our analyses. Use of flecainide was the only factor associated with increased likelihood of success. There was a statistically insignificant trend toward decreased likelihood of success in patients with CHD. Flecainide was more effective than propafenone. We did not detect a difference in rate of conversion to sinus rhythm between patients with and without CHD and were likely underpowered to do so, however, there was a trend toward decreased likelihood of success in patients with CHD. That said, medical therapy was effective in >50% of patients with CHD with AF.


Stress reduction in phase-separated, cross-linked networks: influence of phase structure and kinetics of reaction.
A mechanism for polymerization shrinkage and stress reduction was developed for heterogeneous networks formed via ambient, photo-initiated polymerization-induced phase separation (PIPS). The material system used consists of a bulk homopolymer matrix of triethylene glycol dimethacrylate (TEGDMA) modified with one of three non-reactive, linear prepolymers (poly-methyl, ethyl and butyl methacrylate). At higher prepolymer loading levels (10-20 wt%) an enhanced reduction in both shrinkage and polymerization stress is observed. The onset of gelation in these materials is delayed to a higher degree of methacrylate conversion (~15-25%), providing more time for phase structure evolution by thermodynamically driven monomer diffusion between immiscible phases prior to network macro-gelation. The resulting phase structure was probed by introducing a fluorescently tagged prepolymer into the matrix. The phase structure evolves from a dispersion of prepolymer at low loading levels to a fully co-continuous heterogeneous network at higher loadings. The bulk modulus in phase separated networks is equivalent or greater than that of poly(TEGDMA), despite a reduced polymerization rate and cross-link density in the prepolymer-rich domains.


Primary fallopian tube carcinoma: a case report.
Primary cancer of the fallopian tube is very rare and their preoperative diagnosis is difficult due to the lack of specific symptoms. We report a case in a patient aged 42 years, discovered after abdominopelvic mass. Total surgery was performed, followed by platinum-based chemotherapy. The authors report a review of the literature regarding the epidemiology, diagnosis, treatment and prognosis of this cancer.


Novel and recurrent genetic variants of VHL, SDHB, and RET genes in Chinese pheochromocytoma and paraganglioma patients.
Background: Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors arising from chromaffin cells in the adrenal medulla and extra-adrenal ganglia, respectively. The study was aimed to investigate the clinical and genetic characteristics of 22 individuals from six families. Methods: The medical records of six PPGL probands who presented to our hospital between 2016 and 2021 were retrospectively studied. DNA isolated from the probands was analyzed using whole exome sequencing. The identified genetic variants were confirmed by Sanger sequencing and undergone bioinformatic analysis. Results: Six different genetic variants in the six probands were identified, respectively, of which three were novel. A novel von Hippel-Lindau (VHL) variant, c.602T>C (p.L201P), in exon 3 was found. Two novel genetic variants in SDHB (succinate dehydrogenases subunit B), c.423 + 1 G>T and c.662A>G (p.D221G), were identified. Two recurrent genetic variants of VHL, c.C284G (p.P95R) and c.558_560AGAdel (p.186Edel), and one in RET (ret proto-oncogene), c.1901G>A (p.C634Y), were also found. The ClinVar accession number for the present variants are SCV002028348, and SCV002028352 to SCV002028361. Conclusion: Genetic variants in VHL, SDHB and RET were identified in Chinese PPGL patients, which contributed to the knowledge of the genetic etiology and clinical outcome of these tumors.


2-(2-Iodo-phen-yl)-1,2,3,4-tetra-hydro-isoquinoline-1-carbonitrile.
In the title compound, C(16)H(13)IN(2), the two benzene rings make a dihedral angle of 67.26 (5)°. The six-membered heterocycle of the tetra-hydro-isoquinoline unit adopts a half-chair conformation. In the crystal, adjacent mol-ecules are linked by pairs of weak inter-molecular C-H⋯N hydrogen bonds, forming inversion dimers. An intra-molecular C-H⋯I close contact is also observed.


Making Trauma Less Traumatic: Implementing Inpatient Pediatric Screening of Acute Stress Symptoms.
Pediatric patients hospitalized for physical injury and trauma are at increased risk of developing acute stress disorder. Routine identification and referral for treatment of patients with psychological sequelae of traumatic injury were added to the accreditation requirements of the American College of Surgeons for pediatric trauma centers in 2022. We aimed to use quality improvement methodology with iterative interventions to increase psychological screening consults for admitted pediatric trauma patients to 80% in 6 months. We planned a quality improvement intervention to increase identification of posttraumatic psychological symptoms in pediatric trauma patients. We created a Making Trauma Less Traumatic consultation service with a dedicated therapist to provide screening, treatment, and referral. Key interventions included education of key stakeholders and iterative improvements in consultation workflow. Our primary measure was frequency of eligible pediatric trauma patients who had consultation requests for posttrauma therapy during admission. We additionally monitored percent of patients with positive symptom screens and lost to follow-up. From September 2020 through November 2021, consults for eligible pediatric trauma patients improved from a baseline of 4.1% to a weekly mean of 100%. Of those screened, 32.7% had at least 1 symptom of acute stress. No families declined screening or therapy, though 29.5% were lost to intended follow-up. We present a successful model of implementing routine psychological screening of pediatric trauma patients utilizing a dedicated consultation service. A high number of admitted patients screened positive for symptoms during hospitalization. Families were accepting of the intervention though follow-up was challenging.


Elevated Glucose and Interleukin-1β Differentially Affect Retinal Microglial Cell Proliferation.
Diabetic retinopathy is considered a neurovascular disorder, hyperglycemia being considered the main risk factor for this pathology. Diabetic retinopathy also presents features of a low-grade chronic inflammatory disease, including increased levels of cytokines in the retina, such as interleukin-1 beta (IL-1β). However, how high glucose and IL-1β affect the different retinal cell types remains to be clarified. In retinal neural cell cultures, we found that IL-1β and IL-1RI are present in microglia, macroglia, and neurons. Exposure of retinal neural cell cultures to high glucose upregulated both mRNA and protein levels of IL-1β. High glucose decreased microglial and macroglial cell proliferation, whereas IL-1β increased their proliferation. Interestingly, under high glucose condition, although the number of microglial cells decreased, they showed a less ramified morphology, suggesting a more activated state, as supported by the upregulation of the levels of ED-1, a marker of microglia activation. In conclusion, IL-1β might play a key role in diabetic retinopathy, affecting microglial and macroglial cells and ultimately contributing to neural changes observed in diabetic patients. Particularly, since IL-1β has an important role in retinal microglia activation and proliferation under diabetes, limiting IL-1β-triggered inflammatory processes may provide a new therapeutic strategy to prevent the progression of diabetic retinopathy.


Diversity of the bacteria in the roots of sugarcane used to produce Wasanbon in Kagawa, Japan.
Soil bacteria are an important factor in the cycle of nutrients in soil, while root bacteria in the internal tissues of plants can promote plant growth. The aim of this research was to study the diversity of root bacteria of sugarcane grown in Kagawa, Japan. The sugarcane, derived from Saccharum sinense and grown only in this area, is used as a raw material for Wasanbon (a fine-grained Japanese sugar) and is characterized by thin stalks and a low sugar content. To determine its bacterial diversity, bacterial DNA was extracted from the soil and roots, and 16S rRNA genes were sequenced. A total of 1259 operational taxonomic units (OTUs) were detected in the root bacteria and 3894 OTUs in the soil bacteria. The α-diversity between the soil and root bacteria was significantly different. The most abundant class of root and soil bacteria was proteobacteria at more than 50 and 30%, respectively. The endophyte bacteria of rhizobium were also isolated and the nifH gene was detected. The relationship between the application of nitrogen-fixing bacteria and the production of Wasanbon should be studied.


Effect of Terminal Alkylation of Aryl and Heteroaryl Hydrazines in the Fischer Indole Synthesis.
The effect of alkylation on the terminal position of aryl and heteroaryl hydrazines in the Fischer indole synthesis was examined. Compared to their unalkylated counterparts, reactions using alkylated hydrazines provided indole products with higher yields and faster rates. The reactions can be conducted at lower temperatures and are compatible with acid-sensitive functionality. The terminally alkylated hydrazines were readily prepared by a new two-step sequence and held as stable hydrazinium salts. The mild formation of the salts along with the favorable Fischer indole reaction conditions highlights the potential of this approach in later-stage synthetic use.


Bayesian spatiotemporal analysis of zero-inflated biological population density data by a delta-normal spatiotemporal additive model.
We evaluate the spatiotemporal changes in the density of a particular species of crustacean known as deep-water rose shrimp, Parapenaeus longirostris, based on biological sample data collected during trawl surveys carried out from 1995 to 2006 as part of the international project MEDITS (MEDiterranean International Trawl Surveys). As is the case for many biological variables, density data are continuous and characterized by unusually large amounts of zeros, accompanied by a skewed distribution of the remaining values. Here we analyze the normalized density data by a Bayesian delta-normal semiparametric additive model including the effects of covariates, using penalized regression with low-rank thin-plate splines for nonlinear spatial and temporal effects. Modeling the zero and nonzero values by two joint processes, as we propose in this work, allows to obtain great flexibility and easily handling of complex likelihood functions, avoiding inaccurate statistical inferences due to misclassification of the high proportion of exact zeros in the model. Bayesian model estimation is obtained by Markov chain Monte Carlo simulations, suitably specifying the complex likelihood function of the zero-inflated density data. The study highlights relevant nonlinear spatial and temporal effects and the influence of the annual Mediterranean oscillations index and of the sea surface temperature on the distribution of the deep-water rose shrimp density.


Field-caught permethrin-resistant Anopheles gambiae overexpress CYP6P3, a P450 that metabolises pyrethroids.
Insects exposed to pesticides undergo strong natural selection and have developed various adaptive mechanisms to survive. Resistance to pyrethroid insecticides in the malaria vector Anopheles gambiae is receiving increasing attention because it threatens the sustainability of malaria vector control programs in sub-Saharan Africa. An understanding of the molecular mechanisms conferring pyrethroid resistance gives insight into the processes of evolution of adaptive traits and facilitates the development of simple monitoring tools and novel strategies to restore the efficacy of insecticides. For this purpose, it is essential to understand which mechanisms are important in wild mosquitoes. Here, our aim was to identify enzymes that may be important in metabolic resistance to pyrethroids by measuring gene expression for over 250 genes potentially involved in metabolic resistance in phenotyped individuals from a highly resistant, wild A. gambiae population from Ghana. A cytochrome P450, CYP6P3, was significantly overexpressed in the survivors, and we show that the translated enzyme metabolises both alpha-cyano and non-alpha-cyano pyrethroids. This is the first study to demonstrate the capacity of a P450 identified in wild A. gambiae to metabolise insecticides. The findings add to the understanding of the genetic basis of insecticide resistance in wild mosquito populations.


Update on anti-phospholipid antibodies in SLE: the Hopkins' Lupus Cohort.
Anti-phospholipid antibodies are common in patients in the Hopkins' Lupus Cohort: 47% have anti-cardiolipin, 32.5% anti-beta(2)-glycoprotein I and 26% lupus anticoagulant (by dRVVT confirmatory testing). Systemic lupus erythematosus patients with the lupus anticoagulant at baseline have a 50% chance of a deep venous thrombosis/pulmonary embolus in the next 20 years. Anti-phospholipid antibodies differ in their association with thrombosis: the lupus anticoagulant is most strongly associated with arterial and venous thrombosis and is the only anti-phospholipid antibody associated with myocardial infarction. Anti-phospholipid antibodies are not associated with atherosclerosis.


Electrochemical control of the conductivity in an organic memristor: a time-resolved X-ray fluorescence study of ionic drift as a function of the applied voltage.
Grazing-incidence X-ray fluorescence measurements were applied for a time-resolved study of an organic memristor conductivity variation mechanism. A comparison of these results with electrical measurements has allowed us to conclude that the variation of the fluorescence intensity of Rb ions is directly connected to the ionic charge transferred between the conducting polymer and the solid electrolyte, which made up the device. In addition, the conductivity of the memristor was shown to be a function of the transferred ionic charge.


A case of acute anterolateral infarction complicated with "left posterior hemiblock".
A case of transient left posterior hemiblock and various intraventricular conduction disturbances associated with acute anterolateral infarction is reported. The earliest manifestation was an appearance of ventricular premature systoles originated in the area of the left posterior fascicle. On following recordings left posterior hemiblock with periods of high grade A-V block developed. A few minutes later regular alternation of left posterior hemiblock and left anterior hemiblock was recorded in the presence of 2:1 A-V block. The mechanism for such rare manifestation is analysed. After representing complete left bundle branch block, spontaneous recovery of normal conduction was obtained without any change in heart rate.


An Application of Keystone Perforator Island Flap for Closure of Lumbosacral Myelomeningocele Defects.
Myelomeningocele, also known as spina bifida, is the commonest form of neural tube defect in which both meninges and spinal cord herniate through a large vertebral defect. It may be located at any spinal level; however; lumbosacral involvement is most common. After birth, the closure of spinal lesion is preferably undertaken in the first 48 hours to minimize the risk of injury and central nervous system infection. Relatively small skin defects overlying the dural repair may be directly closed. However, larger defects require reconstructive closure. Numerous methods of reconstruction have been described, such as split skin graft, local flaps or lumbosacral fasciocutaneous flaps, muscle flaps using latissimus dorsi, gluteal or paraspinous muscles, and perforator flaps namely superior gluteal artery perforators, and dorsal intercostal artery perforator flaps. At Monash Health, Victoria, we have used the keystone perforator island flaps to reconstruct lumbosacral myelomeningocele defects on 5 newborns between January 2008 and January 2014. This article evaluates the short-term and long-term outcomes of these patients who were followed up for 10 to 66 months.


Clinical experience with recombinant somatropin: German collaborative study.
A multicentre trial with recombinant somatropin was initiated in West Germany in early 1986. Acceptance of patients to the study was determined according to criteria outlined in a detailed study protocol. A total of 62 patients with GH deficiency has now been treated with recombinant somatropin for a minimum of 12 months. Of these, 34 were previously untreated and 28 had previously received pituitary GH. Recombinant somatropin, 12 IU/m2/week, was administered subcutaneously, divided into six doses. Height velocities increased from 3.4 cm/year (pretreatment) to 10.4 cm/year in the previously untreated group, and from 6.0 cm/year during the last year on pituitary GH to 8.3 cm/year for the previously treated patients. Tolerance of recombinant somatropin was good, and no anti-GH antibodies were detected in any of the patients.


Are Non-intellectually Disabled Black Youth with ASD Less Impaired on Parent Report than Their White Peers?
There is a lack of research examining differences in functioning in autism spectrum disorder (ASD) across ethnicity, particularly among those without intellectual disability (ID). This study investigated ethnic differences in parent-reported impairment in executive function, adaptive behavior, and social-emotional functioning. White and Black youth (n = 64; ages 6-17) with ASD without ID were compared on each of these domains. Black youth had significantly lower levels of impairment on all three domains. Findings may reflect better daily functioning among Black youth with ASD and/or cultural differences in parent response to questionnaires. Regardless, these findings raise concern about the sensitivity of commonly used measures for Black children with ASD and the impact of culture on daily functioning and symptom manifestation.


Formation of silicate nanoscrolls through solvothermal treatment of layered octosilicate intercalated with organoammonium ions.
We report silicate nanoscrolls composed of only SiO4 tetrahedra with crystalline walls for the first time in this study. The procedure consists of the intercalation of layered octosilicate with dioctadecyldimethylammonium bromide ((C18)2DMABr) and the subsequent solvothermal treatment of the intercalated material in heptane. The walls of the obtained nanoscrolls are crystalline, which originates from layer crystallinity in the pristine silicate. The direction of rolling up is fixed at the a- or b-axis of the silicate based on the electron diffraction patterns of the nanoscrolls. Desorption of (C18)2DMABr, which is present in addition to (C18)2DMA cations, from the interlayer during solvothermal treatment is likely related to the nanoscrolling process. Although the yield of nanoscrolls is low, these findings will lead to the re-estimation of many layered silicates intercalated with long-chain alkylammonium compounds as precursors for silicate nanoscrolls with crystalline walls.


Free fatty acid receptors as therapeutic targets for the treatment of diabetes.
Nutrition regulates energy balance; however, dysfunction of energy balance can cause metabolic disorders, such as obesity and diabetes. Fatty acids are an essential energy source and signaling molecules that regulate various cellular processes and physiological functions. Recently, several orphan G protein-coupled receptors were identified as free fatty acid receptors (FFARs). GPR40/FFAR1 and GPR120/FFAR4 are activated by medium- and/or long-chain fatty acids, whereas GPR41/FFAR3 and GPR43/FFAR2 are activated by short-chain fatty acids. FFARs are regarded as targets for novel drugs to treat metabolic disorders, such as obesity and type 2 diabetes, because recent studies have showed that these receptors are involved in the energy metabolism in various tissues, including adipose, intestinal, and immune tissue. In this review, we summarize physiological roles of the FFARs, provide a comprehensive overview of energy regulation by FFARs, and discuss new prospects for treatment of metabolic disorders.


Kill kinetics of bacteria under fluctuating concentrations of various antibiotics. I. Description of the model.
Traditional antimicrobial susceptibility testing uses fixed concentrations of an antibiotic over 24 hours. In order to imitate conditions closer to the actual in vivo situation we developed a model which allows us to simulate serum and tissue concentrations observed under clinical conditions in vitro. Kill kinetics and regrowth pattern of various bacteria have been investigated under the influence of different antibiotics in this kinetic model.


Association between post-extubation upper airway obstruction symptoms and airway size measured by computed tomography: a single-center observational study.
Computed tomography (CT) is often performed to assess patients; however, little is known about how airway size measured by CT scan imaging might influence the occurrence of post-extubation upper airway obstruction. This study aimed to evaluate the association between airway size measured by CT and the incidence of post-extubation upper airway obstruction symptoms for each sex. This single-center observational study was conducted at a tertiary emergency medical center/severe trauma center with a 12-bed intensive care unit. We enrolled consecutive adult patients (aged ≥ 20 years), who were intubated in the emergency room, between January 2016 and March 2019. Patients who underwent a CT scan of the glottic region within three hours before and after intubation were included in the analysis. For each sex, we first divided the patients into two groups: those who had post-extubation stridor, hoarseness, or both and those who had no such symptoms. Then, we compared the two groups using the Mann-Whitney U test and Fisher's exact test. Univariate and multivariate logistic regression analyses were also performed. During the 39 months, 855 patients were enrolled in this study. A total of 217 patients underwent CT of the glottic region within three hours before and after intubation. Five patients had no records of symptoms after extubation. Thus, we analyzed data from 212 patients. This study included 144 males and 68 females. In female patients, the median [inter-quartile range] (average) of the transverse diameter of the glottis/endotracheal tube outer diameter (OD) ratio was smaller in patients with post-extubation upper airway obstruction symptoms than in patients without the symptoms (1.00 [1.00-1.00] (0.9572) vs. 1.00 [1.00-1.00] (1.00296), respectively; p = .013). Multivariate logistic regression analysis showed that the glottis/tube OD ratio < 1 was associated with the symptoms in females (odds ratio: 95% confidence interval, 5.68: 1.04-30.97). There was no relation between the airway sizes and the symptoms in male patients. In female patients, no gap between the endotracheal tube and the vocal codes or the glottic transverse diameter being smaller than the endotracheal tube OD on CT scan was associated with post-extubation upper airway obstruction symptoms.


Female social response to male sexual harassment in poeciliid fish: a comparison of six species.
Sexual harassment is common among poeciliid fish. In some fishes, males show a high frequency of sneak copulation; such sexual activity is costly to the females in terms of foraging efficiency. In mosquitofish (Gambusia holbrooki), when males are present, the distance between females tends to decrease, and this behavior has been interpreted as an adaptive strategy to dilute the costs of male sexual activity. In this study, the tendency to reduce distance in the presence of a male has been investigated in females of six poeciliid species (Girardinus metallicus, Girardinus falcatus, G. holbrooki, Poecilia reticulata, Xiphophorus hellerii, and Xiphophorus mayae) that exhibit different male mating strategies and different levels of sexual activity. Results revealed large interspecific differences in the pattern of female aggregation. Females of species with a high frequency of sneak copulations tended to reduce their social distance in the presence of a male. By contrast, species that rely mainly on courtship showed little or no variation in social distance. The proportion of sneak copulations predicts the degree of variation in female social response, but the amount of total sexual activity does not, suggesting that the change in females' social distance when a male is present may indeed serve to reduce the costs of male sexual harassment.


Relationship Among Corneal Stiffness, Thickness, and Biomechanical Parameters Measured by Corvis ST, Pentacam and ORA in Keratoconus.
To assess the relationship among corneal stiffness, thickness, and biomechanical parameters in keratoconus. The EENT Hospital of Fudan University, Shanghai, China. Comparative study. In this cross-sectional prospective study, 75 keratoconic eyes of 44 patients were recruited. Eyes were divided three groups according to the steepest K-readings (Kmax): mild (31 eyes; 42.1-54.5D); moderate (27 eyes, 55.0-61.6D); and severe (17 eyes, 65.2-94.5D). Thirty-one healthy subjects were recruited as the control group. All patients underwent Corvis ST, Pentacam and ORA examinations at the same time. Stiffness parameter A1 (SP-A1) and other dynamic parameters were assessed using the Corvis ST. Kmax and thinnest corneal thickness (TCT) was obtained using the Pentacam. Corneal resistance factor (CRF) and corneal hysteresis (CH) were measured using the ORA. Analysis of correlation was applied to investigate the association between variables. There was a decrease in SP-A1 in different stages of keratoconus compared with controls (P ≤ 0.001): with increasing severity, the value of SP-A1 became smaller (P < 0.05). A statistically significant linear relationship was noted between SP-A1 and TCT in each subgroup of keratoconus (P ≤ 0.001). In all three groups, SP-A1 was found to be positively correlated with first applanation time (P < 0.01), while negatively correlated with deformation amplitude (P < 0.05). Analysis of SP-A1 with regard to CRF and CH indicated statistically positive correlation in keratoconus (P < 0.05). Significant decreases in corneal stiffness were noted in kerotoconic eyes compared with normal eyes. The stiffness parameter could be a valuable clinical tool enables biomechanically track progression with keratoconus. Our study found that corneal thinning and biomechanical decreasing synchronize with one another throughout the progression of the keratoconus, and SP-A1 could be a potential biomarker evaluating disease progression.


Thoracoscopy: origins revisited.
The ways in which thoracoscopy has evolved wonderfully illustrate how a diagnostic and therapeutic technique can transcend a particular medical or surgical subspecialty. In this review, an in-depth history is provided to enable readers to better understand the nature of minimally invasive endoscopic pleural imaging techniques.


A new wine Torulaspora delbrueckii killer strain with broad antifungal activity and its toxin-encoding double-stranded RNA virus.
Wine Torulaspora delbrueckii strains producing a new killer toxin (Kbarr-1) were isolated and selected for wine making. They killed all the previously known Saccharomyces cerevisiae killer strains, in addition to other non-Saccharomyces yeasts. The Kbarr-1 phenotype is encoded by a medium-size 1.7 kb dsRNA, TdV-Mbarr-1, which seems to depend on a large-size 4.6 kb dsRNA virus (TdV-LAbarr) for stable maintenance and replication. The TdV-Mbarr-1 dsRNA was sequenced by new generation sequencing techniques. Its genome structure is similar to those of S. cerevisiae killer M dsRNAs, with a 5'-end coding region followed by an internal A-rich sequence and a 3'-end non-coding region. Mbarr-1 RNA positive strand carries cis acting signals at its 5' and 3' termini for transcription and replication respectively, similar to those RNAs of yeast killer viruses. The ORF at the 5' region codes for a putative preprotoxin with an N-terminal secretion signal, potential Kex2p/Kexlp processing sites, and N-glycosylation sites. No relevant sequence identity was found either between the full sequence of Mbarr-1 dsRNA and other yeast M dsRNAs, or between their respective toxin-encoded proteins. However, a relevant identity of TdV-Mbarr-1 RNA regions to the putative replication and packaging signals of most of the M-virus RNAs suggests that they are all evolutionarily related.


Robust prediction of mutation-induced protein stability change by property encoding of amino acids.
Current methods of predicting mutation-induced protein stability change are imprecise. Machine learning methods have been introduced for this prediction recently; however, the available experimental data used for training these predictors are biased. Abundant data are available for several frequently occurring amino acid substitutions, whereas only limited data have been accumulated for some other mutation types. Generally, current statistical models do not account for this bias toward the commoner amino acids during the encoding process and are thus less effective in making predictions on less frequently occurring mutations. In this paper, we propose a method based on support vector machines and property encoding of amino acids. The predictor we constructed outperforms other methods on the same data sets and is more robust with poor training data. The prediction accuracy for mutations with no training data exceeded 80%. This advantage is critical for practical application, where the prediction could be applied for any type of mutations. Further analysis demonstrates our model relies on biological significant features to make predictions. To overcome the drawbacks of classifying mutations into 'stabilizing' and 'destabilizing' ones, a three-class classification of mutations was also discussed, where our method obtained an overall accuracy of 79.1%.


A model of practice to address cultural competence in rehabilitation nursing.
A position statement developed by the Association of Rehabilitation Nurses (ARN), Appropriate Inclusion of Rehabilitation Nurses Wherever Rehabilitation is Provided, stated that nurses are an essential part of a client's rehabilitation because they provide holistic care and "attend to the full range of human experiences and responses to health and illness" (Association of Rehabilitation Nurses, 1996, p.1). Rehabilitation nurses must become strongly aware of the role that culture plays in this process. This article presents a conceptual model of practice with which to address cultural competence in rehabilitation nursing. The model's constructs of cultural awareness, cultural knowledge, cultural encounters, cultural skill, and cultural desire are discussed. Examples from the field of rehabilitation nursing are presented in the discussion of these constructs.


Impact of initial degree of coronary narrowing on left ventricular function in first myocardial infarction.
To determine whether the initial degree of coronary narrowing prior to a first myocardial infarction (MI) affects left ventricular function, we analyzed paired coronary angiograms and left ventriculography in 41 consecutive MI patients in whom coronary angiography was obtained before and after MI. Patients were divided into 2 groups according to coronary narrowing of the infarct culprit lesion at first angiogram; a significant narrowing group (group S, 15 patients) and a nonsignificant narrowing group (group N, 26 patients). Significant narrowing was defined as more than 75% stenosis of an infarct-related segment in the first angiography and nonsignificant narrowing was less than 50% narrowing. Clinical characteristics were similar in the two groups, with the exception of initial diameter stenosis. LV function was normal in both groups at initial examination. Group S patients had a higher prevalence of angina prior to MI (73% versus 23%; P = 0.001), good collateral development (73% versus 35%; P = 0.02), and non-Q MI (73% versus 27%; P = 0.004) than group N patients. RWM was also superior in group S compared with group N. The deterioration of global and infarction zone function was mild in group S compared with group N (group S; median EF -10%, RWM -0.27 SD/chord, group N; median EF -26%, RWM -1.62 SD/chord, P = 0.001). We conclude that deterioration of LV wall motion in patients with severe stenosis in their initial stenosis would be milder than in AMI that developed from a mild degree of stenosis.


In vivo knockdown of antisense non-coding mitochondrial RNAs by a lentiviral-encoded shRNA inhibits melanoma tumor growth and lung colonization.
The family of non-coding mitochondrial RNAs (ncmtRNA) is differentially expressed according to proliferative status. Normal proliferating cells express sense (SncmtRNA) and antisense ncmtRNAs (ASncmtRNAs), whereas tumor cells express SncmtRNA and downregulate ASncmtRNAs. Knockdown of ASncmtRNAs with oligonucleotides induces apoptotic cell death of tumor cells, leaving normal cells unaffected, suggesting a potential application for developing a novel cancer therapy. In this study, we knocked down the ASncmtRNAs in melanoma cell lines with a lentiviral-encoded shRNA approach. Transduction with lentiviral constructs targeted to the ASncmtRNAs induced apoptosis in murine B16F10 and human A375 melanoma cells in vitro and significantly retarded B16F10 primary tumor growth in vivo. Moreover, the treatment drastically reduced the number of lung metastatic foci in a tail vein injection assay, compared to controls. These results provide additional proof of concept to the knockdown of ncmtRNAs for cancer therapy and validate lentiviral-shRNA vectors for gene therapy.


Decomposition of hydrofluorocarbons in a dielectric-packed plasma reactor.
This study investigated the decomposition of hydrofluorocarbons (HFCs) having high global warming potentials by using a dielectric-packed-bed nonthermal plasma reactor with barium titanate beads as the packing material. The target HFCs were 1,1,1,2-tetrafluoroethane (HFC-134a) and 1,1-difluoroethene (HFC-132a). The effects of several parameters such as reaction temperature, oxygen content, and initial concentration on the HFC decomposition efficiency were evaluated. There was essentially no temperature dependence of the HFC decomposition efficiency in the range 150-250 degrees C. The optimum oxygen content for HFC decomposition was found to be about 0.5 vol %. Variations in the initial concentration did not affect the decomposition efficiency. The decomposition products were analyzed, and some decomposition pathways were elucidated. The energy requirements for the decomposition of HFC-134a and HFC-132a were found to be 0.038 and 0.062 mol MJ-1, respectively, based on the initial concentrations of 200 and 120 ppm (parts per million, volumetric).


Effects of alternating cycle lengths on refractoriness of the His-Purkinje system.
The effects of alternating cycle lengths (bigeminal rhythm) on His-Purkinje system refractoriness were studied in 14 patients using His bundle and right bundle recordings. Programmed atrial stimulation at constant cycle length (method I) was scanned using the atrial extrastimulus technique (A2) and compared with an atrial cycle length of identical duration coupled to A2 on alternate beats (method II). The results showed that (a) despite shorter cycle length of the His-Purkinje system with method II due to effect of A2 on atrioventricular nodal conduction (699 +/- 90 vs. 743 +/- 87 ms, P less than 0.001), the relative refractory period of the His-Purkinje system was always longer with method II (463 +/- 52 vs. 440 +/- 43 ms, P less than 0.001). A similar increase also occurred in effective refractory period of the His-Purkinje system; (b) while functional right bundle branch block occurred in eight patients and functional left bundle branch block in two patients with method I, functional right bundle branch block occurred in all 14 patients and left bundle branch block in seven patients with method II; (c) in two patients where both functional right and left bundle branch block occurred with method I this never was manifest at identical degree of abbreviation of His-Purkinje system cycle length but was manifest at identical abbreviation in each of seven patients with method II; (d) site of conduction delay and/or block during functional right bundle branch block was always proximal, i.e., between the His bundle and right bundle recordings with both methods. During method II this resulted in shortening of the subsequent right bundle cycle length relative to the subsequent His bundle (and of necessity left bundle) cycle length. The finding of increased His-Purkinje system refractoriness despite shorter preceding cycle length of the His-Purkinje system during atrial bigeminy has never been previously described and suggests that classical concepts of His-Purkinje system behavior may require revision in this setting. Secondly, during atrial bigeminy the occurrence of alternating functional bundle branch block cannot be accounted for solely by the degree of abbreviation of His-Purkinje system cycle length, but may be explained by a relative shortening of the next ipsilateral bundle branch cycle length in the bundle manifesting block.


Repeated botulinum toxin injection for idiopathic overactive bladder: will chemodenervation become a long-term solution?
Botulinum toxin A (BTX-A) has emerged as a novel treatment option for idiopathic overactive bladder (OAB) refractory to antimuscarinic agents. The clinical needs of refractory OAB patients have been recently met by sacral neuromodulation and augmentation enterocystoplasty. Important features of BTX-A should include safety, efficacy, and ease of delivery during long-term repeated usage. This article reviews the role of repeated BTX-A injections in the treatment of idiopathic OAB.


Gene-Wise Burden of Coding Variants Correlates to Noncoding Pharmacogenetic Risk Variants.
Genetic variability can modulate individual drug responses. A significant portion of pharmacogenetic variants reside in the noncoding genome yet it is unclear if the noncoding variants directly influence protein function and expression or are present on a haplotype including a functionally relevant genetic variation (synthetic association). Gene-wise variant burden (GVB) is a gene-level measure of deleteriousness, reflecting the cumulative effects of deleterious coding variants, predicted in silico. To test potential associations between noncoding and coding pharmacogenetic variants, we computed a drug-level GVB for 5099 drugs from DrugBank for 2504 genomes of the 1000 Genomes Project and evaluated the correlation between the long-known noncoding variant-drug associations in PharmGKB, with functionally relevant rare and common coding variants aggregated into GVBs. We obtained the area under the receiver operating characteristics curve (AUC) by comparing the drug-level GVB ranks against the corresponding pharmacogenetic variants-drug associations in PharmGKB. We obtained high overall AUCs (0.710 ± 0.022-0.734 ± 0.018) for six different methods (i.e., SIFT, MutationTaster, Polyphen-2 HVAR, Polyphen-2 HDIV, phyloP, and GERP++), and further improved the ethnicity-specific validations (0.759 ± 0.066-0.791 ± 0.078). These results suggest that a significant portion of the long-known noncoding variant-drug associations can be explained as synthetic associations with rare and common coding variants burden of the corresponding pharmacogenes.


Predictors of urgency in a pediatric psychiatric emergency service.
To test the hypothesis that youth present to a psychiatric emergency service (PES) at least 25% of the time for nonurgent reasons, to examine the demographic characteristics that distinguish urgent from nonurgent visits, and to develop a model to predict urgency. Psychiatric emergency visits of all patients under 18 years from July 1, 1997, through June 30, 1998, were ed and coded as to level of urgency using Rosenn's classification system. Age, gender, ethnicity, arrival status, social service involvement, violence, substance abuse, and diagnosis were examined with respect to urgency in bivariate and multivariable analyses. Forty percent of visits to the PES were not urgent. Demographic factors distinguished urgent from nonurgent visits. Independent predictors of urgency for the entire sample were age, diagnosis, arrival status, social service involvement, and violence. Only violence remained an independent predictor of urgency for the attention-deficit/hyperactivity disorder subgroup. A large percentage of pediatric visits to the PES were for nonurgent reasons. This suggests that there are considerable unmet mental health needs of children and adolescents. These findings can be applied to improve and design appropriate services.


Imunofan-RDKVYR Peptide-Stimulates Skin Cell Proliferation and Promotes Tissue Repair.
Regeneration and wound healing are vital to tissue homeostasis and organism survival. One of the biggest challenges of today's science and medicine is finding methods and factors to stimulate these processes in the human body. Effective solutions to promote regenerative responses will accelerate advances in tissue engineering, regenerative medicine, transplantology, and a number of other clinical specialties. In this study, we assessed the potential efficacy of a synthetic hexapeptide, RDKVYR, for the stimulation of tissue repair and wound healing. The hexapeptide is marketed under the name "Imunofan" (IM) as an immunostimulant. IM displayed stability in aqueous solutions, while in plasma it was rapidly bound by albumins. Structural analyses demonstrated the conformational flexibility of the peptide. Tests in human fibroblast and keratinocyte cell lines showed that IM exerted a statistically significant (p < 0.05) pro-proliferative activity (30-40% and 20-50% increase in proliferation of fibroblast and keratinocytes, respectively), revealed no cytotoxicity over a vast range of concentrations (p < 0.05), and had no allergic properties. IM was found to induce significant transcriptional responses, such as enhanced activity of genes involved in active DNA demethylation (p < 0.05) in fibroblasts and activation of genes involved in immune responses, migration, and chemotaxis in adipose-derived stem cells derived from surgery donors. Experiments in a model of ear pinna injury in mice indicated that IM moderately promoted tissue repair (8% in BALB/c and 36% in C57BL/6 in comparison to control).


Routine full blood counts as indicators of acute viral infections.
Over a period of three weeks about 9000 full blood counts were analysed on the Technicon H6000 automated haematology machine. From these, 62 patients were identified who had abnormally high numbers of large unstained white cells; these patients were followed up for evidence of viral infection. Seventeen were either lost to follow up or in chronic renal failure; of the remaining 45 patients, 40 had viral infections, 26 of which were due to Epstein-Barr virus. In the presence of a raised number of large unstained white cells, an IgM test for Epstein-Barr virus is recommended, followed by routine serology when necessary.


Will LHINs ever become the "eyes and ears" of the Health Minister for local community wisdom?
This commentary reflects on the intent of the legislation establishing the Local Health Integration Networks (LHINs) and comments on the performance gap between the vision for what could have been and the actual performance. A nine-point action plan to restore the LHINs' potential role as a positive force for health system integration and transformation at the local level is provided.


Establishment of a cell line persistently infected with chronic wasting disease prions.
Elk prion protein (PrP(C)) has been confirmed to be capable of rendering rabbit epithelial RK13 cells permissive to temporal infection by chronic wasting disease (CWD) prions. The present study satisfactorily generated persistently CWD prion-affected RK13 cells (RKC1-11) using elk PrP(C) expressing cells (elkRK13) that were generated via the lentiviral expression system with high efficiency. The elkRK13 cells have been shown to be permissive to accumulation of abnormal isoforms of prion protein (PrP(Sc)) resulting from CWD prions up to 97 serial passages thus far. This novel prion-affected cell line will help facilitate investigation of the molecular basis of CWD prion pathogenesis and confirmation of CWD prion infectivity in vitro.


[2018 update on chronic graft-versus-host disease].
Chronic graft-versus-host disease (GVHD) occurs in 30-40% of patients who undergo allogeneic hematopoietic cell transplantation. The symptoms of chronic GVHD resemble those of autoimmune diseases, and many sites, including the eyes, mouth, skin, gastrointestinal tract, liver, lungs, joints, and fascia, can be affected. Severe chronic GVHD increases patients' mortality and decreases their quality of life. The 2014 National Institutes of Health (NIH) Consensus has proposed a three-step model for classification of the mechanisms of chronic GVHD: early acute inflammation, chronic inflammation with dysregulated immunity, and tissue fibrosis. Many drugs targeting specific biological pathways for treating chronic GVHD are under development. The NIH Consensus has also clarified objective response measures, optimal endpoints, and clinical trial designs to be used for drug approval. More than 30 novel drugs for GVHD treatment are currently being tested in over 80 clinical trials worldwide.


Boys, girls and shuttling of SRY and SOX9.
In the mammalian embryo, SRY and SOX9 are key Sertoli cell proteins that drive the development of the bipotential gonad into a testes rather than an ovary, leading ultimately to the male phenotype. Clinical SRY and SOX9 mutations causing disorders of sex development (DSD) highlight defective protein-protein interactions between SRY or SOX9, and carrier proteins required for nuclear import (importin-b and calmodulin) and nuclear export (CRM-1). The fine balance between import and export determines the levels of transcriptionally active SRY and SOX9 in the nucleus. Recently, post-translational modifications of SRY and SOX9 have been identified which affect nuclear transport. It is therefore timely that the consequences of sex-reversal mutation upon nuclear transport be reviewed. SRY and SOX9 mutations in DSD have uncovered regulatory sites for sumoylation, ubiquitination, acetylation and phosphorylation, many of which are essential for their transport and sex determining functions.


Continuation of outpatient buprenorphine therapy after dispensing Buprenorphine-Naloxone from the emergency department.
Patients with opioid use disorder (OUD) are frequently seen in the ED for opioid-related reasons, which creates an opportunity for ED providers to discuss medications for OUD with their patients. Buprenorphine is a partial mu-opioid agonist that is FDA approved to treat OUD and may be initiated in the ED. Traditionally, buprenorphine therapy was initiated under healthcare provider observation; however, other strategies such as at-home induction have also emerged. This was a retrospective descriptive analysis of patients aged 18 years or older who received a take-home supply of buprenorphine-naloxone from an urban, academic ED between March 2018 and March 2020. The primary outcome was the proportion of patients who filled a prescription for buprenorphine at three months after index ED visit. The proportion of patients that filled a prescription for buprenorphine at six months was also evaluated. The primary safety endpoint was the proportion of patients with return ED visit within six months related to opioid overdose. There were 242 patient records reviewed with 155 patients included in final analysis. Seventy (45.2%) patients filled buprenorphine prescriptions at three months, with 64 (41.3%) who filled buprenorphine prescriptions at six months. Seventeen (11%) patients had a return ED visit related to opioid overdose within six months. Dispensing buprenorphine take-home kits from the ED resulted in continuation of outpatient buprenorphine in almost 50% of patients. Further studies are warranted to define the role of ED-dispensed buprenorphine.


Adolescent idiopathic scoliosis: radiologic decision-making.
Adolescent onset of severe idiopathic scoliosis has traditionally been evaluated using standing posteroanterior radiographs of the full spine to assess lateral curvature with the Cobb method. The most tilted vertebral bodies above and below the apex of the spinal curve are used to create intersecting lines that give the curve degree. This definition is controversial, and patients do not exhibit clinically significant respiratory symptoms with idiopathic scoliosis until their curves are 60 to 100 degrees. There is no difference in the prevalence of back pain or mortality between patients with untreated adolescent idiopathic scoliosis and the general population. Therefore, many patients referred to physicians for evaluation of scoliosis do not need radiographic evaluation, back examinations, or treatment. Consensus recommendations for population screening, evaluation, and treatment of this disorder by medical organizations vary widely. Recent studies cast doubt on the clinical value of school-based screening programs.


Antibody-dependent lysis of tumor cells in vivo. I. Early lysis of tumor cells.
Possible mechanisms of in vivo killing of tumor cells by antibody (Ab) were explored in a model in which Ab suppresses tumor growth in mice. A proportion of tumor cells injected into the peritoneal cavities of complement-deficient A/J mice was lysed within 30 minutes in the presence of anti-tumor cell Ab as demonstrated by the release of 51Cr in vivo. Experiments in which [125I]5-iodo-2'-deoxyuridine-labeled tumor cells were used showed that most tumor cells did not leave the injection site and that lysis occurred inside the peritoneal cavity. In addition, a proportion of the remaining sensitized tumor cells was significantly damaged, as shown by their decreased resistance to osmotic lysis. Morphologic studies ruled out phagocytosis of tumor cells as a mechanism of major significance. Tumor cell damage but not tumor cell lysis could also be induced in vitro with Ab and normal peritoneal cells. These results provided direct evidence of primary cytolysis induced by Ab in vivo, though other concomitant cytotoxic mechanisms may also take place in this model.


Antidepressant Effect of Intracerebroventricularly Administered Deltorphin Analogs in the Mouse Tail Suspension Test.
Several studies have proposed δ opioid receptors as influential targets for developing novel antidepressants. Deltorphin (DLT) and deltorphin II (DLT-II) have high affinity and selectivity for δ opioid receptors; thus, it is likely that DLT analogs possess antidepressant-like effects. Based on this, we evaluated the effects of four DLT analogs (DLT-related synthetic peptides) on immobility behavior in the tail suspension test. Intracerebroventricular administration of DLT or [N-isobutyl-Gly6]DLT in mice significantly decreased immobile behavior. However, administration of DLT did not affect locomotor activity, whereas that of [N-isobutyl-Gly6]DLT significantly increased locomotion in mice. The effect of the shortened immobility time following DLT administration was counteracted by the administration of the selective δ1 opioid receptor antagonist 7-benzylidenenaltrexone, but not by the selective δ2 opioid receptor antagonist naltriben. These findings suggest that DLT has an antidepressant-like effect by activating the central δ1 opioid receptor in mice.


Ribosomes and translation in plant developmental control.
Ribosomes play a basic housekeeping role in global translation. However, a number of ribosomal-protein-defective mutants show common and rare developmental phenotypes including growth defects, changes in leaf development, and auxin-related phenotypes. This suggests that translational regulation may be occurring during development. In addition, proteomic and bioinformatic analyses have demonstrated a high heterogeneity in ribosome composition. Although this might be a sign of unequal roles of individual ribosomal proteins, it does not explain every ribosomal-protein-defective phenotype. Moreover, comprehensive interpretations concerning the relationship between ribosomal-protein-defective phenotypes and molecular changes in ribosome status are lacking. In this review, we address these phenotypes based on three models, ribosome insufficiency, heterogeneity, and aberrancy, to consider how ribosomes play developmental roles. We propose that the three models are not mutually exclusive, and ribosomal-protein-defective phenotypes can be explained with one or more of these models. The three models with reference to genetic, biochemical, and bioinformatic knowledge will serve as a foundation for future studies of translational regulation.


Out of mind, out of sight: perceptual consequences of memory suppression.
In the present study, the effect of memory suppression on subsequent perceptual processing of visual objects was examined within a modified think/no-think paradigm. Suppressing memories of visual objects significantly impaired subsequent perceptual identification of those objects when they were briefly encountered (Experiment 1) and when they were presented in noise (Experiment 2), relative to performance on baseline items for which participants did not undergo suppression training. However, in Experiment 3, when perceptual identification was performed on mirror-reversed images of to-be-suppressed objects, no impairment was observed. These findings, analogous to those showing forgetting of suppressed words in long-term memory, suggest that suppressing memories of visual objects might be mediated by direct inhibition of perceptual representations, which, in turn, impairs later perception of them. This study provides strong support for the role of inhibitory mechanisms in memory control and suggests a tight link between higher-order cognitive operations and perceptual processing.


Pancreatic cancer stem cells: new insight into a stubborn disease.
Resistance to conventional therapy and early distant metastasis contribute to the unsatisfactory prognosis of patients with pancreatic cancer. The concept of cancer stem cells (CSCs) brings new insights into cancer biology and therapy. Many studies have confirmed the important role of these stem cells in carcinogenesis and the development of hematopoietic and solid cancers. Recent studies have shown that CSCs regulate aggressive behavior, recurrence, and drug resistance in pancreatic cancer. Here, we review recent advances in pancreatic cancer stem cells (PCSCs) research. Particular attention is paid to the regulation mechanisms of pancreatic cancer stem cell functions, such as stemness-related signaling pathways, microRNAs, the epithelial-mesenchymal transition (EMT), and the tumor microenvironment, and the development of novel PCSCs targeted therapy. We seek to further understand PCSCs and explore potential therapeutic targets for pancreatic cancer.


The significance of CD5+ B cells in rheumatic diseases.
The presence of autoantibodies in rheumatoid arthritis (RA) and primary Sjögren' syndrome (SS) is a feature of these diseases. Because of the probable role of autoantibodies in the pathogenesis of RA and primary SS, the study of the origin and regulation of B lymphocytes producing autoantibodies is of special importance. In mice, B lymphocytes can be divided into two populations of distinct lineages, the conventional bone marrow-derived B subset and the self-renewing peripheral subset. B lymphocytes of the latter express an antigen initially described as T cell specific, the Ly-1 or CD5 antigen. In human, such CD5+B cells are found in foetal lymphoid tissue but their frequency diminishes in adult life. We have found a significant increase in CD5+B cells in the peripheral blood of patients with RA and primary SS, and a small family study of relatives of two RA patients suggests that such 'high phenotype' could be a genetic trait. Furthermore, CD5+B cells appear enriched in autoantibody-producing cells since they produce IgM-rheumatoid and other autoantibodies when suitably activated in vitro. Our current hypothesis is that persistence of high numbers of CD5+B cells in adulthood may predispose to chronic inflammatory arthritis due to the reactivity of the antigen receptor of these cells with a variety of autoantigens in the joint. Such reactivity would allow an autoimmune reactions causing the perpetuation of chronic inflammation at the disease site.


No evidence of effectiveness of mirror therapy early after stroke: an assessor-blinded randomized controlled trial.
The aim of this study was to investigate the efficacy of mirror therapy on upper-limb recovery in early post-stroke patients. Assessor-blinded randomized controlled trial. Inpatient rehabilitation clinic. A total of 40 patients with upper-limb impairment due to a first-ever ischaemic or haemorrhagic stroke, within four weeks from the cerebrovascular accident. The intervention group received mirror therapy, while the control group received sham therapy. During mirror therapy, patients' sound hand was reflected by a mirror. During sham therapy, an opaque surface replaced the mirror-reflecting surface. Both the mirror therapy and sham therapy groups practised their sound hand with exercises, ranging from the simple elbow flexion-extension to complex tasks (e.g. reaching and grasping). Mirror therapy and sham therapy were added to conventional rehabilitation. Primary outcome includes Fugl-Meyer upper extremity scale. Secondary outcomes include action research arm test (ARAT) and functional independence measure (FIM) scale. Outcomes were measured at the beginning (T0) and end (T1) of the treatment. At baseline, both groups (sham therapy vs. mirror therapy; mean (SD)) were comparable for Fugl-Meyer (30.9 (23.9) vs. 28.5 (21.8)), ARAT (25.1 (25.5) vs. 23.5 (24)) and FIM (71.0 (20.6) vs. 72.9 (17.8)) scores. At the end of the treatment, both groups significantly improved in the Fugl-Meyer (40.6 (21.3) vs. 38.3 (23.4)), ARAT (31.9 (23.0) vs. 30 (24.1)) and FIM (100.3 (21.9) vs. 99.4 (22.6)) scores. However, at T1, no significant difference was observed between the sham therapy and mirror therapy groups, neither for the Fugl-Meyer, nor for ARAT and FIM scores. Compared with sham therapy, mirror therapy did not add additional benefit to upper-limb recovery early after stroke.


Herpes simplex virus type 1 pathogenicity in mice expressed by lytic infection in pre-B and B cells.
The outcome of herpes simplex virus type 1 (HSV-1) infection in human or in the murine model can be influenced by host immunocompetency. We postulate in this work that HSV-1 infection alters bone marrow B lymphopoiesis in genetically determined susceptible mice. To verify this hypothesis, resistant C57BL/6 or susceptible A/J adult mice were intraperitoneally infected with HSV-1 (McIntyre strain). At various postinfection times, spleen and bone marrow were collected from both infected mouse strains. B lineage cell subpopulations were identified by double immunofluorescence assays using mAbs to terminal deoxynucleotidyl transferase (TdT), 220-kDa surface membrane glycoprotein (detected by mAb 14.8), and cytoplasmic (c mu) or surface (s mu) IgM chains. Results revealed a decrease in both percentage and absolute number of splenic B (c mu+, s mu+) cells and bone marrow pre-B (c mu+, s mu-) and B cells isolated only from susceptible A/J mice. No effect was observed on pro-B (14.8+, c mu-) or TdT+ precursor cells from both mouse strains. Intracellular viral proteins were detected in pre-B and B cells in in vivo-infected susceptible A/J mice. In vitro studies also revealed that virus-induced cell lysis occurred in purified splenic and bone marrow pre-B or B cells derived only from susceptible A/J mice. Viral tropism for pre-B and B cells represents another immunodeficiency mechanism involved in the genetic sensitivity to HSV-1.


Developments and new vistas in the field of melanocortins.
Melanocortins play a fundamental role in several basic functions of the organism (sexual activity, feeding, inflammation and immune responses, pain sensitivity, response to stressful situations, motivation, attention, learning, and memory). Moreover, a large body of animal data, some of which were also confirmed in humans, unequivocally show that melanocortins also have impressive therapeutic effects in several pathological conditions that are the leading cause of mortality and disability worldwide (hemorrhagic, or anyway hypovolemic, shock; septic shock; respiratory arrest; cardiac arrest; ischemia- and ischemia/reperfusion-induced damage of the brain, heart, intestine, and other organs; traumatic injury of brain, spinal cord, and peripheral nerves; neuropathic pain; toxic neuropathies; gouty arthritis; etc.). Recent data obtained in animal models seem to moreover confirm previous hypotheses and preliminary data concerning the neurotrophic activity of melanocortins in neurodegenerative diseases, in particular Alzheimer's disease. Our aim was (i) to critically reconsider the established extrahormonal effects of melanocortins (on sexual activity, feeding, inflammation, tissue hypoperfusion, and traumatic damage of central and peripheral nervous system) at the light of recent findings, (ii) to review the most recent advancements, particularly on the effects of melanocortins in models of neurodegenerative diseases, (iii) to discuss the reasons that support the introduction into clinical practice of melanocortins as life-saving agents in shock conditions and that suggest to verify in clinical setting the impressive results steadily obtained with melanocortins in different animal models of tissue ischemia and ischemia/reperfusion, and finally, (iv) to mention the advisable developments, particularly in terms of selectivity of action and of effects.


[Association of health literacy and physical sub-health among Chinese middle school students].
To examine the association between health literacy( HL) and physical sub-health in middle school students. From November 2015 to January 2016, a multi-stage convenient cluster sampling method was adopted to conduct a questionnaire survey among 22 628 middle school students from grade 7 to grade12 in Shenyang, Bengbu, Xinxiang, Ulanqab, Chongqing and Yangjiang, among whom10 990( 48. 6%) were boys and 11 638( 51. 4%) were girls. The Chinese Adolescent Interactive Health Literacy Questionnaire( CAIHLQ), the Multidimensional Sub-health Questionnaire of Adolescents( MSQA) and demographic variables were used to measure the Chinese middle school students ' HL and physical sub-health. The detection rate of physical sub-health was 30. 1%( 6822/22628). High school students reported more physical sub-health than junior school students. The detection rate of physical sub-health in developed area, being only children, resident students, with low socio-economic status was significantly higher detection rate of sub-health than their peers( P< 0. 001). The scores of CAIHLQ was( 104. 06 ± 18. 68). Students who were boys, junior school students, urban residence, only children in family, non-resident students, higher parental education level and lower family income had significantly higher HL scores than the correspnding other students( χ~2= 44. 62, 455. 21, 133. 54, 35. 04, 326. 06, 272. 09, 366. 19 and 572. 35, P < 0. 001). Multiple Logistic regression analysis showed that moderate or low level of overall HL and six dimensions increase the risk of physical sub-health. School type, whether it is an economically developed area, whether it is an only child, whether it lives in the school on the study day, and selfassessment of family economic conditions affecting physical sub-health, lower HL may increase the risk of physical subhealth among middle school students.


Does intravenous sildenafil clinically ameliorate pulmonary hypertension during perioperative management of congenital heart diseases in children? - a prospective randomized study.
Pulmonary hypertension (PHT), if present, can be a significant cause of increased morbidity and mortality in children undergoing surgery for congenital heart diseases (CHD). Various techniques and drugs have been used perioperatively to alleviate the effects of PHT. Intravenous (IV) sildenafil is one of them and not many studies validate its clinical use. To compare perioperative PaO 2 - FiO 2 ratio peak filling rate (PFR), systolic pulmonary artery pressure (PAP) - systolic aortic pressure (AoP) ratio, extubation time, and Intensive Care Unit (ICU) stay between two groups of children when one of them is administered IV sildenafil perioperatively during surgery for CHDs. Patients with ventricular septal defects and proven PHT, <14 years of age, all American Society of Anesthesiologists physical status III, undergoing cardiac surgery, were enrolled into two groups - Group S (IV sildenafil) and Group C (control) - over a period of 14 months, starting from October 2013. Independent t-test and Mann-Whitney U-test were used to compare the various parameters between two groups. PFR was higher throughout, perioperatively, in Group S. PAP/AoP was 0.3 and 0.4 in Group S and Group C, respectively. In Group S, mean group extubation time was 7 ± 7.34 h, whereas in Group C it was 22.1 ± 10.6. Postoperative ICU stay in Group S and Group C were 42.3 ± 8.8 h and 64.4 ± 15.9 h, respectively. IV sildenafil, when used perioperatively, in children with CHD having PHT undergoing corrective surgery, improves not only PaO 2 - FiO 2 ratio and PAP - AoP ratio but also reduces extubation time and postoperative ICU stay.


Visualization of Order Set Creation and Usage Patterns in Early Implementation Phases of an Electronic Health Record.
Robust order set catalogs are considered to be a vital part of a computerized physician order entry (CPOE) implementation. Tools and processes for building, localizing, and maintaining these content sets in a centralized repository are important in facilitating the knowledge management lifecycle. Collectively, these order sets represent a significant investment of effort and expertise in capturing and distributing best clinical practice throughout an enterprise. In order to address an important gap of understanding how order sets are both created and used in practice in a current EHR installation, we have developed tools to analyze how order sets are used and customized in clinical practice. In this paper, we present the capabilities of these tools. We further characterize early development patterns in our enterprise order set catalog in early phases of a system-wide vendor EHR rollout. We present data that show how personalized order sets (favorites) are authored and then used in clinical practice. We anticipate that this type of utility will provide useful insight and feedback for those tasked with content governance and maintenance in CPOE systems.


Effect of acetyl-L-carnitine treatment on brain ribonucleic acid levels in methylazoxymethanol-microencephalic rats.
The effects of methylazoxymethanol acetate (MAM) administered on the 15th gestational day, and of acetyl-L-carnitine treatment, on rat brain total and ribosomal RNA levels, were studied. In the brain of MAM-treated rats both total and ribosomal RNA concentrations were significantly reduced. Acetyl-L-carnitine treatment restored total and ribosomal RNA levels. The frontal cortex and the hippocampus were the brain areas most sensitive to acetyl-L-carnitine administration. Histochemical demonstration of tissue stores of nucleic acids showed that the loss of RNA induced by MAM occurs primarily within the cytoplasm of nerve cells in various telencephalic areas. Neuronal cytoplasmatic RNA is also sensitive to acetyl-L-carnitine treatment.


TGF-β based risk model to predict the prognosis and immune features in glioblastoma.
Transforming growth factor-β (TGF-β) is a multifunctional cytokine with an important role in tissue development and tumorigenesis. TGF-β can inhibit the function of many immune cells, prevent T cells from penetrating into the tumor center, so that the tumor cells escape from immune surveillance and lead to low sensitivity to immunotherapy. However, its potential roles in predicting clinical prognosis and tumor microenvironment (TME) immune features need to be deeply investigated in glioblastoma (GBM). The TCGA-GBM dataset was obtained from the Cancer Genome Atlas, and the validation dataset was downloaded from Gene Expression Omnibus. Firstly, differentially expressed TGF-β genes (DEGs) were screened between GBM and normal samples. Then, univariate and multivariate Cox analyses were used to identify prognostic genes and develop the TGF-β risk model. Subsequently, the roles of TGF-β risk score in predicting clinical prognosis and immune characteristics were investigated. The TGF-β risk score signature with an independent prognostic value was successfully developed. The TGF-β risk score was positively correlated with the infiltration levels of tumor-infiltrating immune cells, and the activities of anticancer immunity steps. In addition, the TGF-β risk score was positively related to the expression of immune checkpoints. Besides, the high score indicated higher sensitivity to immune checkpoint inhibitors. We first developed and validated a TGF-β risk signature that could predict the clinical prognosis and TME immune features for GBM. In addition, the TGF-β signature could guide a more personalized therapeutic approach for GBM.


Effects of hydroxytyrosol-enriched sunflower oil consumption on CVD risk factors.
Inclusion of biophenols in traditional foods transforms them into functional foods that may help to decrease CVD risk. The aim of the present study was to determine whether the consumption of hydroxytyrosol-enriched sunflower oil (HSO) improves certain CVD biomarker values. A total of twenty-two healthy volunteers participated in a cross-over study involving two 3-week periods, separated by a 2-week washout period, in which volunteers consumed 800-1275 μg/d [corrected] of either HSO (45-50 mg/d of hydroxytyrosol) or non-enriched (control) sunflower oil. Total cholesterol, LDL-cholesterol, HDL-cholesterol, arylesterase activity, oxidised LDL and soluble vascular cell adhesion molecule (sVCAM-1) levels were measured in the plasma obtained at the beginning and at the end of each treatment period. The HSO group displayed a significantly higher level (P < 0·01) of arylesterase activity and significantly lower levels of oxidised LDL and sVCAM-1 (both P < 0·05) than the control group. These results suggest that HSO may help prevent CVD.


Prognostic value of cytologic examination of peritoneal washings in patients with endometrial carcinoma.
Peritoneal pelvic washings from 54 women with pathologic stage I endometrial carcinoma were evaluated in a blind retrospective fashion for the concentration of malignant cells present. None of the 42 patients with normal washings developed recurrence after a median disease-free survival of 36 months. Of the 12 patients with adenocarcinoma in the washings, 4 had high concentrations of malignant cells (greater than 1000 cells/100 ml sample), and all 4 died as a consequence of carcinoma within two years. The remaining eight patients had lower concentrations of malignant cells in the washings (less than 1000 cells/100 ml sample), and six of these patients had no evidence of disease after 37 to 64 months. Cox's nonparametric statistical model showed that increasing concentrations of adenocarcinoma cells in washings significantly shortened the time to recurrence of disease. The abundance of malignant cells has prognostic importance in identifying those patients with pathologic stage I disease who may require more aggressive therapy.