Use of the socio-ecological model to explore factors that influence the implementation of a diabetes structured education programme (EXTEND project) inLilongwe, Malawi and Maputo, Mozambique: a qualitative study.
Diabetes Self-Management Education and Support (DSMES) programmes are vital for type 2 diabetes mellitus (T2DM) management. However, they are limited in Sub-Saharan Africa (SSA). To address this gap, a DSMES, namedEXTEND was developed in Lilongwe (Malawi) and Maputo (Mozambique). This qualitative study aimed to explore factors that influence the implementation of DSMES in these settings. The Socio-ecological model was applied to explore factors influencing the implementation of DSMES in SSA. Data was analysed using the Framework method and constant comparative techniques. Sixty-six people participated in the study: people with T2DM who participated in the EXTEND programme; healthcare professionals (HCPs), EXTEND educators, EXTEND trainers, and stakeholders. Our findings indicate that there is a need to develop an integrated and dedicated diabetes services in SSA healthcare systems, incorporating culturally adapted DSMES and tailored diabetes training to all professions involved in diabetes management. Traditional media and the involvement of community leaders were proposed as important elements to help engage and promote DSMES programmes in local communities. During the design and implementation of DSMES, it is important to consider individual and societal barriers to self-care. Findings from this study suggest that multi-faceted factors play a significant role to the implementation of DSMES programmes in LICs. In the future, EXTEND could be incorporated in the development of diabetes training and dedicated diabetes services in SSA healthcare systems, acting as an educational tool for both people with T2DM and HCPs. This project was supported by the Medical Research Council GCRF NCDs Foundation Awards 2016 Development Pathway Funding.


[Dispersion pattern of saline indicator on canine left ventricle (author's transl)].
The cardiac output evaluation is usually realized through indicator dilution techniques and this principle was applied to ventricular volume measurements. However this approach has been criticized by several workers. Based on the recently developed association of indicator dilution method with intraventricular impedance recording to cardiac output determinations, the present investigation was designed to analize the dipersion pattern of saline solution within the ventricle. Three bipolar eletrodes were placed in different positions on the left ventricle in order to record the duration in seconds, for the saline to reach these positions. The detection of the saline was done through conductibility changes at the eletrodes ends. The results indicate a time duration smaller to the indicator dispersion than those of the diastole duration, simultaneously measured.


Barriers to Implementing a Reporting and Learning Patient Safety System: Pediatric Chiropractic Perspective.
A reporting and learning system is a method of monitoring the occurrence of incidents that affect patient safety. This cross-sectional survey asked pediatric chiropractors about factors that may limit their participation in such a system. The list of potential barriers for participation was developed using a systematic approach. All members of the 2 pediatric councils associated with US national chiropractic organizations were invited to complete the survey (N = 400). The cross-sectional survey was created using an online survey tool (REDCap) and sent directly to member emails addressed by the respective executive committees. Of the 400 potential respondents, 81 responded (20.3%). The most common limitations to participating were identified as time pressure (96%) and patient concerns (81%). Reporting and learning systems have been utilized to increase safety awareness in many high-risk industries. To be successful, future patient safety studies with pediatric chiropractors need to ensure these barriers are understood and addressed.


Multiresidue determination of pesticides in drinking and related waters by solid-phase extraction and liquid chromatography with ultraviolet detection: interlaboratory study.
As part of a project funded by the European Commission (EC) for the development and evaluation of multiresidue methods for analysis of drinking and related waters, 17 European laboratories evaluated a method using styrene-divinylbenzene copolymer solid-phase extraction followed by liquid chromatography with diode array detection. The main aim of the study was to evaluate whether the method meets the requirements of EC Drinking Water Directive 98/83 in terms of accuracy, precision, and detection limit for 21 pesticides according to the following requirements: limit of detection, < or =0.025 microg/L; accuracy expressed as recovery, between 75 and 125%; and precision expressed as repeatability relative standard deviation of the method, <12.5%, and as reproducibility relative standard deviation of the method, <25%. Analyses for unknown concentrations were performed with commercial bottled and tap waters. All laboratories were able to achieve detection limits of 0.01 microg/L for all pesticides except pirimicarb (0.02 microg/L). The criteria for repeatability were met for all compounds. Terbutryn in bottled water and carbendazim in tap water did not meet the criteria for reproducibility. In terms of accuracy, the method met the requirements for all pesticides in both matrixes, except for metamitron. However, several compounds (linuron, terbutryn, propazine, metobromuron, and isoproturon) showed recoveries slightly below 75%.


New ulcerative colitis model induced by sulfhydryl blockers in rats and the effects of antiinflammatory drugs on the colitis.
We tried to produce a new ulcerative colitis model in rats by topical administration of sulfhydryl blockers. After male SD rats were fasted for 24 hr, 100 microliters of 3% N-ethylmaleimide (NEM) or iodoacetamide (IA) was introduced into the colon via a Nelaton's catheter. Both NEM and IA caused severe diarrhea with rectal bleeding and decreased body weight for about 7 days. At autopsy, adhesions and dilatation of the colon and severe mucosal lesions were observed. Both the weight and myeloperoxidase activity of the colon increased markedly. Maximum changes were observed within 1-3 days followed by gradual recovery, but even on day 21, some abnormalities were still observed. The ulceration and inflammation of the colon were confirmed by histological studies. Antiinflammatory drugs such as indomethacin inhibited the inflammation of the colon by NEM, but aggravated the ulceration. These results revealed that sulfhydryl blockers instilled into the colon caused ulcerative colitis in the rat. This model may be useful in studies on the pathogenesis of ulcerative colitis and the evaluation of drugs for therapy. Furthermore, it was suggested that antiinflammatory drugs may delay the healing of colonic ulcers.


The Fire Within: NF-κB Involvement in Non-Small Cell Lung Cancer.
Thirty-four years since its discovery, NF-κB remains a transcription factor with great potential for cancer therapy. However, NF-κB-targeted therapies have yet to find a way to be clinically translatable. Here, we focus exclusively on the role of NF-κB in non-small cell lung cancer (NSCLC) and discuss its contributing effect on cancer hallmarks such as inflammation, proliferation, survival, apoptosis, angiogenesis, epithelial-mesenchymal transition, metastasis, stemness, metabolism, and therapy resistance. In addition, we present our current knowledge of the clinical significance of NF-κB and its involvement in the treatment of patients with NSCLC with chemotherapy, targeted therapies, and immunotherapy.


[Diagnosis and treatment of imported African schistosomiasis].
This paper summarizes the clinical diagnosis and treatment of imported African schistosomiasis, in order to make the therapeutic standards. Imported African schistosomiasis includes mainly schistosomiasis haematobia and schistosomiasis mansoni in China. In order to set up the operational standards, enhance diagnostic and cure rates, and reduce the complications, we review the related literature combined with our experience over years, and summarize, in this paper, the pathogenic mechanism, and key points of clinical diagnosis and treatment of schistosomiasis haematobia and schistosomiasis mansoni, so as to provide the reference for clinical doctors.


The E3 ubiquitin ligase Pellino3 protects against obesity-induced inflammation and insulin resistance.
Diet-induced obesity can induce low-level inflammation and insulin resistance. Interleukin-1β (IL-1β) is one of the key proinflammatory cytokines that contributes to the generation of insulin resistance and diabetes, but the mechanisms that regulate obesity-driven inflammation are ill defined. Here we found reduced expression of the E3 ubiquitin ligase Pellino3 in human abdominal adipose tissue from obese subjects and in adipose tissue of mice fed a high-fat diet and showing signs of insulin resistance. Pellino3-deficient mice demonstrated exacerbated high-fat-diet-induced inflammation, IL-1β expression, and insulin resistance. Mechanistically, Pellino3 negatively regulated TNF receptor associated 6 (TRAF6)-mediated ubiquitination and stabilization of hypoxia-inducible factor 1α (HIF1α), resulting in reduced HIF1α-induced expression of IL-1β. Our studies identify a regulatory mechanism controlling diet-induced insulin resistance by highlighting a critical role for Pellino3 in regulating IL-1β expression with implications for diseases like type 2 diabetes.


Asymmetric Synthesis of the Tricyclooctane Core of Trachylobane Natural Products and Related Terpenoids.
Enantioselective synthesis of a highly versatile building block en route to trachylobanes and related terpenoids is presented. The synthesis features diastereoselective Diels-Alder cycloaddition reaction, a cyclopropanation/homoquadricyclane rearrangement cascade, and palladium-catalyzed C-H acetoxylation. The targeted tricyclooctane was obtained in 20% yield over 8 steps and in 95% ee. The ketone and alcohol functional groups serve as handles for further elaboration.


Endothelin-1/Endothelin Receptor Type A-Angiopoietins/Tie-2 Pathway in Regulating the Cross Talk Between Glomerular Endothelial Cells and Podocytes in Trichloroethylene-Induced Renal Immune Injury.
This study aimed to investigate the mechanism in regulating the cross talk between glomerular endothelial cells and podocytes in "occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT)" patients. Totally 6 OMLDT patients, 18 controls, and 102 BALB/c female mice were involved in this study. Patient's serum endothelin-1 (ET-1), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), blood urea nitrogen (BUN), and podocalyxin (PCX) were detected. All the mice were used to establish the trichloroethylene (TCE) sensitized mouse model. Transmission electron microscope results were used to reflect renal glomerulus injury. Protein levels were detected by Western blot. Ang-1/Ang-2 gene level was reflected by RT-PCR. Cell apoptosis level was detected by using TUNEL assay kit. We found that in OMLDT patients, ET-1, Ang-2, BUN, and PCX were highly expressed but Ang-1 was inhibited. In TCE sensitized positive mouse, the downregulation of Ang-1, pTie-2 and the upregulation of Ang-2 were mediated by ET-1/ETAR but not ET-1/ETBR. The promotor of apoptosis proteins was downregulated and the inhibitor of apoptosis proteins was upregulated by treating with BQ123. ET-1/ETAR-Angs/Tie-2 pathway mediated the cross talk between glomerular endothelial cells and podocytes. BQ123 can alleviate glomerulus immune injury.


Nutritional interventions for exercise-induced muscle damage: an umbrella review of systematic reviews and meta-analyses of randomized trials.
Several meta-analyses have been conducted on the effect of nutritional interventions on various factors related to muscle damage. However, the strength of the evidence and its clinical significance are unclear. This umbrella review aimed to provide an evidence-based overview of nutritional interventions for exercise-induced muscle damage (EIMD). PubMed, Scopus, and ISI Web of Science were systematically searched up to May 2022. Systematic reviews and meta-analyses of randomized controlled trials investigating nutritional interventions' effects on recovery following EIMD were included. The certainty of the evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Fifty-three randomized controlled trial meta-analyses were included, evaluating 24 nutritional interventions on 10 different outcomes. The results revealed a significant effect of hydroxymethylbutyrate (HMB) supplementation and l-carnitine supplementation for reducing postexercise creatine kinase; HMB supplementation for reducing lactate dehydrogenase; branched-chain amino acids and leaf extract supplementation for reducing the delayed onset of muscle soreness; and l-carnitine, curcumin, ginseng, polyphenols, and anthocyanins for reducing muscle soreness, all with moderate certainty of evidence. Supplementation with HMB, l-carnitine, branched-chain amino acids, curcumin, ginseng, leaf extract, polyphenols, and anthocyanins showed favorable effects on some EIMD-related outcomes. PROSPERO registration no. CRD42022352565.


A review of adverse effects of COVID-19 vaccines.
The COVID-19 pandemic has led to unanticipated pressures on all aspects of human life. Multiple approaches to eliciting protective immunity must be rapidly evaluated. Numerous efforts have been made to develop an effective vaccine for this novel coronavirus, resulting in a race for vaccine development. To combat COVID-19, all nations must focus their efforts on widespread vaccination with an effective and safe vaccine. Globally, concerns about potential long-term adverse effects of vaccines have led to some apprehension about vaccine use. A vaccine's adverse effect has an integral role in the public's confidence and vaccine uptake. This article reviews the current primary literature regarding adverse effects associated with different COVID-19 vaccines in use worldwide.


Cardiac allograft aortic dissection: successful repair using a composite valve graft and modified-Cabrol coronary reconstruction.
We report a 55-year-old man, the recipient of a cardiac allograft for ischemic cardiomyopathy 9 years earlier, who presented with progressive aortic root dilation, worsening aortic insufficiency, and an incidentally discovered chronic type A aortic dissection limited to the donor aorta. The patient was taken to the operating room, and the aortic dissection successfully repaired using standard reoperative techniques. This is the sixth case reported in the literature, and only the fourth survivor. To our knowledge, this case represents the first successful repair, of a limited aortic dissection of the donor aorta postcardiac transplantation, using a composite valve graft and modified-Cabrol coronary reconstruction.


Iron-based nanoparticles prepared from yerba mate extract. Synthesis, characterization and use on chromium removal.
Iron-based nanoparticles were synthesized by a rapid method at room temperature using yerba mate (YM) extracts with FeCl3 in different proportions. Materials prepared from green tea (GT) extracts were also synthesized for comparison. These materials were thoroughly characterized by chemical analyses, XRD, magnetization, SEM-EDS, TEM-SAED, FTIR, UV-Vis, Raman, Mössbauer and XANES spectroscopies, and BET area analysis. It was concluded that the products are nonmagnetic iron complexes of the components of the extracts. The applicability of the materials for Cr(VI) (300 μM) removal from aqueous solutions at pH 3 using two Cr(VI):Fe molar ratios (MR), 1:3 and 1:0.5, has been tested. At Cr(VI):Fe MR = 1:3, the best YM materials gave complete Cr(VI) removal after two minutes of contact, similar to that obtained with commercial nanoscale zerovalent iron (N25), with dissolved Fe(II), and with a likewise prepared GT material. At a lower Cr(VI):Fe MR (1:0.5), although Cr(VI) removal was not complete after 20 min of reaction, the YM nanoparticles were more efficient than N25, GT nanoparticles and Fe(II) in solution. The results suggest that an optimal Cr(VI):Fe MR ratio could be reached when using the new YM nanoparticles, able to achieve a complete Cr(VI) reduction, and leaving very low Cr and Fe concentrations in the treated solutions. The rapid preparation of the nanoparticles would allow their use in removal of pollutants in soils and groundwater by direct injection of the mixture of precursors.


Adolescent substance use disorders and comorbidity.
It is imperative to know what risk factors are more likely to appear during specific developmental stages so that identification and interventions can be used to decrease the risk for future SUD. Continued surveying of risk factors that can occur at any stage in childhood are important to ensure that other risk factors are anticipated and intervened upon as well. Multiple risk factors increase the magnitude of the risk for SUD, and therefore all risk factors should be detected to convert these to protective factors. Screening instruments that can assess risk factors found to increase the risk for substance abuse can be found in examples, such as the Drug Usage Screening Instrument [81] and the Problem-Oriented Screening Instrument for Teenagers. The detection of risk factors by primary care providers is becoming increasingly important. However, other professionals are beginning to recognize that early recognition and treatment can enable a youth to go on to a productive life in other arenas as well. Drug courts and diversion programs are beginning to treat first-time offenders and their families rather than taking the punitive approach. These have proven to be very successful. Primary care physicians also should become familiar with motivational enhancement therapy when confronting a youth with a suspected substance abuse problem [57]. This method has proven to be more effective in getting youth into treatment than the direct, confrontational style, which often puts the youth in a defensive mode. Motivational enhancement therapy includes interventions that are delivered in a neutral and empathetic way. The six components of motivational enhancement therapy (also called FRAMES) include: Feedback on personal impairment Emphasis on personal responsibility Clear advice to change Menu of alternative options Empathy as a counseling style Self-efficacy In this way, a clinician can elicit pros and cons, give advice, provide choices, practice empathy, clarify goals, and remove barriers. This technique allows youth to be less defensive and more proactive. Monti et al. [59] have demonstrated that this technique has been useful in getting youth into treatment. Primary care physicians can use instruments that will assess the possibility of both externalizing (e.g., ADHD) and internalizing (e.g., depression and anxiety) disorders. Examples of this type of instrument are the Auchenbach child behavior checklist, teacher report form, and youth self-report form, which survey symptoms for these disorders [1]. Social anxiety disorder can be detected by asking whether the prelatency child went into new situations willingly and tended to hang back or whether the child had difficulty separating from his or her parents. Other questions to ask are whether the child tended to isolate or was fearful of speaking in front of the class. Of course, any bruising or behavior that suggests exposure to adult-related sexual acts may cause concern for physical or sexual abuse and possible PTSD. However, interest in sex earlier than expected for the age of the child may also indicate the possibility of bipolar disorder. These children have many symptoms of ADHD with a high degree of irritability and may seem boastful or grandiose. They may be "daredevils" with no fear of dangerous consequences. Referral to a specialist is necessary to evaluate these children further. Because substance use at age 14 or 15 years can be predicted by academic and social behavior at ages 7 to 9 years, early detection of poor social skills and learning difficulties is essential [43]. Learning disorders can be uncovered by asking the school to do an evaluation. However, schools having economic problems may not be able to accommodate all requests. A parent may have to pay a private provider to complete this workup because insurance companies seldom pay for educational testing. Learning disorders may go undetected because many school systems opt to use a higher deviation from the full-scale IQ to detect learning problems. For instance, if a student has an IQ of 115, the standard nationally recommended deviation from this IQ to detect a learning disorder is 15. Therefore, any child who scores 100 or less on an achievement test should be considered to have a learning disorder. Some schools prefer to use a deviation of up to 23 so that learning disorders are not detected. Few schools screen for processing problems, including auditory and visual motor processing problems, processing speed, comprehension, and short-term and long-term memory problems. This is extremely important because ADHD can be confused with an auditory processing problem. Stimulants may help this condition, but accommodations must be made to ensure continued success. Early-intervention programs, such as Drug Abuse Resistance Education (DARE), proved to be ineffective because the programs did not target components that have been shown to predict future drug use [54]. One program that has targeted these components, normative beliefs, lifestyle-behavior incongruence, and commitment is the All Stars program [39,40]. A strong initial dosage with booster interventions for at least 2 years is also important [10]. Before a child is diagnosed with oppositional defiant disorder or conduct disorder, every effort should be made to detect any underlying psychiatric disorder that has not been treated and therefore may look like a conduct disorder (e.g., bipolar disorder). Proper psychopharmacologic interventions should be made for psychiatric disorders. If one drug has been ineffective, another untreated psychiatric disorder may be present, and it is always important to tease out what remaining symptoms are present after a therapeutic trial has been tried. It is important to form a team approach so that all risk factors can be approached. Members of the team often include a primary care physician, a child psychologist, the parents, the patient, a teacher, a school counselor, a child psychiatrist, and sometimes a pediatric neurologist. No one member of the treatment team can provide all of the necessary services to prevent the future risk for substance abuse.


In vitro evaluation of the hydraulic permeability of polysulfone dialysers.
An in vitro set-up has been designed to study the hydraulic permeability of hollow fiber dialysers. Forward and reverse dialysate ultrafiltration were determined using both sterile dialysers and samples with a protein layer settled on the membrane (Fresenius F6, F8, F60 and F80). The ultrafiltration coefficient KUF (ml/h.mmHg) was calculated as the ratio of volumetrical flow (QUF) and transmembrane pressure (TMP) measurements. The protein layer on the membrane was induced either by recirculating human plasma through the dialysers (in vitro) or by a standard hemodialysis session (in vivo). KUF is largely independent of TMP up to 600mmHg (low flux) and 60mmHg (high flux) for forward and reverse flow In sterile dialysers, backfiltration yields a significantly different KUF except for the F80. An in vitro induced protein layer on the membrane decreases KUF15-30% (forward) and 4-12% (backward) in low flux and 45-70% (forward) and 65-73% (backward) in high flux dialysers.


Particle-particle chemistry between micrometer-sized PbSO4 and CaCO3 particles in turbulent flow initiated by liquid water.
A mixture of natural and anthropogenic particles is ubiquitous in the troposphere and exerts an important influence on air quality. This work reports the study of mixing and heterogeneous chemistry of particles of natural-like mineral dust (CaCO(3)) and anthropogenic-like microparticle (PbSO(4)) in turbulent air flow under varying relative humidity. Sparse monolayers of laboratory-generated particles were collected on substrates using impaction. The grain size distribution and chemistry of micrometer-sized particles were determined as CaCO(3)-PbSO(4) internal and external mixtures by Raman imaging, scanning electron microscopy, and time-of-flight static secondary ionization mass spectrometry. The condensation of a thin water layer on mixed aggregates initiates the formation of complex internal mixtures of Pb(3)(CO(3))(2)(OH)(2), PbCO(3), CaSO(4)·2H(2)O, CaCO(3), and PbSO(4) fine particles. These heterogeneous chemistry processes which may occur in ambient air can increase dramatically the amounts of hazardous breathable particles.


Circulating apoptotic endothelial cells and apoptotic endothelial microparticles independently predict the presence of cardiac allograft vasculopathy.
Maintenance of endothelial homeostasis may prevent the development of cardiac allograft vasculopathy (CAV). This study investigated whether biomarkers related to endothelial injury and endothelial repair discriminate between CAV-negative and CAV-positive heart transplant recipients. CAV is the most important determinant of cardiac allograft survival and a major cause of death after heart transplantation. Fifty-two patients undergoing coronary angiography between 5 and 15 years after heart transplantation were recruited in this study. Flow cytometry was applied to quantify endothelial progenitor cells (EPCs), circulating endothelial cells (CECs), and endothelial microparticles. Cell culture was used for quantification of circulating EPC number and hematopoietic progenitor cell number and for analysis of EPC function. The EPC number and function did not differ between CAV-negative and CAV-positive patients. In univariable models, age, creatinine, steroid dose, granulocyte colony-forming units, apoptotic CECs, and apoptotic endothelial microparticles discriminated between CAV-positive and CAV-negative patients. The logistic regression model containing apoptotic CECs and apoptotic endothelial microparticles as independent predictors provided high discrimination between CAV-positive and CAV-negative patients (C-statistic 0.812; 95% confidence interval: 0.692 to 0.932). In a logistic regression model with age and creatinine as covariates, apoptotic CECs (p = 0.0112) and apoptotic endothelial microparticles (p = 0.0141) were independent predictors (C-statistic 0.855; 95% confidence interval: 0.756 to 0.953). These 2 biomarkers remained independent predictors when steroid dose was introduced in the model. The high discriminative ability of apoptotic CECs and apoptotic endothelial microparticles is a solid foundation for the development of clinical prediction models of CAV.


Out-of-Africa origin and dispersal-mediated diversification of the butterfly genus Junonia (Nymphalidae: Nymphalinae).
The relative importance of dispersal and vicariance in the diversification of taxa has been much debated. Within butterflies, a few studies published so far have demonstrated vicariant patterns at the global level. We studied the historical biogeography of the genus Junonia (Nymphalidae: Nymphalinae) at the intercontinental level based on a molecular phylogeny. The genus is distributed over all major biogeographical regions of the world except the Palaearctic. We found dispersal to be the dominant process in the diversification of the genus. The genus originated and started diversifying in Africa about 20 Ma and soon after dispersed into Asia possibly through the Arabian Peninsula. From Asia, there were dispersals into Africa and Australasia, all around 5 Ma. The origin of the New World species is ambiguous; the ancestral may have dispersed from Asia via the Beringian Strait or from Africa over the Atlantic, about 3 Ma. We found no evidence for vicariance at the intercontinental scale. We argue that dispersal is as important as vicariance, if not more, in the global diversification of butterflies.


GSH depletion and consequent AKT inhibition contribute to the Nrf2 knockdown-induced decrease in proliferation in glioblastoma U251 cells.
Nuclear factor erythroid 2-related factor 2 (Nrf2), a pivotal transcription regulator that controls the expression of numerous antioxidant and cytoprotective genes, was recently defined as a proto-oncogene. However, the role and mechanism of Nrf2 in glioma pathoetiology remain unclear. In the present study, we first evaluated the expression patterns of Nrf2 in normal human astrocytes and 3 glioblastoma (GBM) cell lines (U251, U87 and A172) and found that all 3 GBM cell lines overexpressed Nrf2, with the highest level observed in the U251 cells. We further assessed the biological effects of Nrf2 in U251 cells by specific knockdown of Nrf2 using lentivirus‑mediated RNA interference. We discovered that Nrf2 deficiency led to a decrease in U251 cell proliferation and caused intracellular redox imbalance [diminished glutathione (GSH) levels and increased reactive oxygen species (ROS) levels]. Both N-acetylcysteine and glutathione monoethyl ester (GMEE) supplementation completely eliminated the increased levels of ROS that were present in the Nrf2‑deficient U251 cells. However, only GMEE supplementation both reversed Nrf2 deficiency-induced cell growth arrest and restored intracellular GSH levels. Moreover, AKT and ERK1/2 signaling were both impaired in the Nrf2-knockdown U251 cells, but GMEE supplementation restored AKT signaling but not ERK1/2 signaling, and blocking AKT signaling with an AKT-specific inhibitor greatly diminished the GMEE-induced Nrf2-deficient cell proliferation. In conclusion, our findings revealed novel functions for Nrf2 in the regulation of redox status and cell proliferation, and that intracellular GSH levels and AKT signaling are required for this process, a new viewpoint by which to comprehend the role and underlying mechanism of Nrf2 in tumorigenesis.


[Rational diagnosis of anemias].
An algorithmic approach to the diagnosis of anemias is presented. It starts with history, physical examination, and a basic laboratory program including erythrocyte morphology. On the basis of the reticulocyte count and MCH-value anemias are divided into hypo- and hyperregenerative as well as micro-, normo-, or macrocytic forms. Within these groups it is easy to diagnose common anemias by only a few laboratory tests. Rare forms of anemia will be recognized as such and diagnosed by special investigations.


Social elements as mind.
The assumption that 'mind' is the product of individual development and that cognition and emotion must be sited in individual people has dominated psychology until recently. The new conception of a 'social construction of mind' is grounded in the idea that an interpersonal conversation is the fundamental psychological reality, and that individual minds are appropriations from it. Such a personal mind is created by making private what is originally and primarily public. This idea strikes at the Cartesian basis of both behaviourist and non-behaviourist psychology, suggesting a more complex multidimensional set of polar oppositions for defining the problems of scientific psychology. For example, perhaps knowledge should be studied as a collective resource rather than as individual beliefs. There is evidence from anthropology that even that intimate form of cognitive organization we call the 'self' may have social origins in favoured grammatical models and so may be expected to differ from one linguistic culture to another.


[Treatment of ischemic heart disease in the elderly. Comparison of diltiazem, verapamil and gallopamil].
The medical therapy of myocardial ischemia in elderly patients has not been well evaluated. We studied the age-related changes in 127 patients with proved coronary artery disease and stable effort angina the efficacy and the safety of diltiazem 120 mg tid, verapamil 120 mg tid and gallopamil 50 mg tid a medium term parallel, double blind cross-over placebo controlled study. All patients have been clinically and ergometrically evaluated. In middle-age patients diltiazem, verapamil and gallopamil induced a significant increasing of exercise duration and time to onset ST segment depression > or = 1 mm. In the elderly patients both verapamil and diltiazem as increased the exercise duration and ischemic threshold, while the diltiazem did not increased the exercise duration even if the time of onset ST segment depression > or = 1 mm is increased. At peak exercise the ST segment depression have been reduced both in middle-age and elderly patients after active drugs. Weekly angina and DNT consumption have been significantly reduced after diltiazem, verapamil and gallopamil in middle-age and elderly patients. Side effects have not been relevant even if gallopamil as a lower frequency of them in comparison to diltiazem and verapamil. No patients stopped the treatment because major side effects. Our experience suggests that diltiazem, verapamil and gallopamil have a similar efficacy and rare well tolerated. The choice of one instead of another must be suggested on the basis of side effects developing.


Natural killer cells and cytotoxic T cells induce DNA fragmentation in both human and murine target cells in vitro.
DNA fragmentation induced by cytolytic lymphocytes in human erythromyeloid cell line K562 and murine T lymphoma cell line YAC-1 was investigated by means of agarose gel electrophoresis. Murine natural killer (NK) and cytotoxic T (Tc) cells induced DNA fragmentation in YAC-1 cells, with the fragments being approximately multiples of 180 bp. More significantly, murine NK cells can induce a similar pattern of DNA fragmentation in human K562 cells. Therefore, cytolytic lymphocytes can induce apoptosis or programmed cell death in human target cells.


Transpleural vascularization of pulmonary arteries in fibrous mediastinitis. Report of a case.
Idiopathic granulomatous and fibrous mediastinitis is an uncommon disease, the manifestation of which depends upon the organs involved. In a case of a Moroccan the rather unique complication of pulmonary artery obstruction on one side resulted in the development of functional important anastomoses between the bronchial and pulmonary arteries and also between the intercostal and pulmonary arteries by way of transpleural vascularization as is clearly demonstrated by bronchial and intercostal arteriography.


The effect of metabolites of testosterone on the development of fertilizing ability by spermatozoa in the epididymis of castrated hamsters.
The effects of testosterone, 17beta-hydroxy-5alpha-androstane-3-one (5alpha-dihydrotestosterone; 5alpha-DHT), 5alpha-androstane-3alpha, 17beta-diol (3alpha-androstanediol; 3alpha-diol) and 5alpha-androstane-3beta, 17beta-diol (3beta-androstanediol; 3beta-diol) on the development of fertilizing ability by spermatozoa in the epididymis were compared in castrated hamsters. The left corpus epididymidis was ligated for 14 days in intact and castrated animals to prevent the in-flow of spermatozoa into the cauda epididymidis and the ductuli efferentes were bilaterally ligated. The fertilization rate of spermatozoa in the left cauda epididymidis of control animals decreased to 71.1% after 14 days whereas that of spermatozoa in the unobstructed right cauda epididymis remained at the control level of 100%. After castration, 50 mug testosterone, 25 mug 5alpha-DHT and only 9 mug 3alpha-diol/day were the minimal doses that facilitated normal development of fertilizing ability but 75 mug testosterone, 37.5 mug 5alpha-DHT and 12.5 mug 3alpha-diol/day were required to maintain sperm survival at the control level. However, 3beta-diol was ineffective for both sperm maturation and survival.


The reproducibility of cephalometric landmarks: an experimental study on skulls.
Few previous cephalometric studies have used dry skulls in order to eliminate the effects of the facial soft tissues. The aim of this study were to quantify the intra-examiner reproducibility of the commonly used cephalometric landmarks, angles and distances, using dry skulls and to compare these errors with previous error data obtained from normal cephalograms of living patients. Thirty skulls were mounted in a purpose-designed holder and repeat cephalograms of each skull were recorded and digitised. All measurements were made relative to an X-Y coordinate reference grid. Scattergrams were produced to show the characteristic distribution of the intra-examiner reproducibility errors for the landmarks, and the reproducibility of the angles and distances were tabulated. This data was compared with a related study that included the soft tissue profile. The standard deviations of the skeletal and dental angles and distances were greater in the presence of the soft tissues. These differences were up to four times larger for measurements including the location of Nasion (e.g. SNA, SNB and SNPg), which was the landmark location most affected by the presence of soft tissues, and for the distance: Incisal tip of Lower Incisor to Pogonion. Anterior Nasal Spine, in the horizontal plane, was also greatly affected by the presence of the soft tissues. By using dry skulls, the errors observed in this study may serve as standards for the rational interpretation of clinical cephalometric values.


[Methodologic approach to individual evaluation of the pharmacodynamic effects of single doses of hydralazine, endralazine, prazosine and propranolol in hypertension patients].
The possibility to apply impedance cardiography technique and individual statistical analysis based on Dixon's criterion to pharmacodynamic studies of single hydralazine ( apressine ), prazosine ( pratsiol ), endralazine ( mirethilan ), propranolol (obsidan) doses is discussed. 12 patients with essential hypertension, stage II were examined. Blood pressure was measured by the method of Korotkov , heart volume and total peripheral vascular resistance were determined by impedance cardiography. Apressin , mirethilan , pratsiol and obsidan doses were 50-100 mg, 5-15 mg, 2-5 mg and 80-120 mg, respectively. The drug effect was compared with that of placebo. Impedance cardiography in combination with the method of Korotkov were shown to be appropriate for recording qualitative alterations of hemodynamic parameters during pharmacodynamic studies of single apressine , mirethilan , pratsiol an obsidan doses. The data obtained allow objective individual assessment of single dose efficacy based on Dixon's criterion.


Structure-guided design of pyridoclax derivatives based on Noxa / Mcl-1 interaction mode.
Protein-protein interactions are attractive targets because they control numerous cellular processes. In oncology, apoptosis regulating Bcl-2 family proteins are of particular interest. Apoptotic cell death is controlled via PPIs between the anti-apoptotic proteins hydrophobic groove and the pro-apoptotic proteins BH3 domain. In ovarian carcinoma, it has been previously demonstrated that Bcl-xL and Mcl-1 cooperate to protect tumor cells against apoptosis. Moreover, Mcl-1 is a key regulator of cancer cell survival and is a known resistance factor to Bcl-2/Bcl-xL pharmacological inhibitors making it an attractive therapeutic target. Here, using a structure-guided design from the oligopyridine lead Pyridoclax based on Noxa/Mcl-1 interaction we identified a new derivative, active at lower concentration as compared to Pyridoclax. This new derivative selectively binds to the Mcl-1 hydrophobic groove and releases Bak and Bim from Mcl-1 to induce cell death and sensitize cancer cells to Bcl-2/Bcl-xL targeting strategies.


A novel framework of N-H...Br hydrogen bonds forming Br(4,4'-bipyridinium)(4) supramolecular synthons: bis(4,4'-bipyridinium) tris[tetrabromidoferrate(III)] bromide.
In the asymmetric unit of the title compound, (C(10)H(10)N(2))(2)[FeBr(4)](3)Br, the Fe atoms are in a distorted tetrahedral environment. The crystal structure contains a novel arrangement of Br(4,4'-bipyridinium)(4) supramolecular synthons assembled via short N-H...Br hydrogen bonds (H...Br = 2.55, 2.40, 2.38 and 2.55 A), where four cations surround one nonbonded bromide ion in a tetrahedral arrangement. These synthons are further connected by hydrogen bonds using the remaining terminal NH hydrogens in each cation and the Br(-) ions to form an adamantoid-like network and thus produce a three-dimensional supramolecular architecture with the [FeBr(4)](-) ions located in the cavities. The structure shows no significant intermolecular Br...Br, Br...aryl or aryl-aryl interactions.


Comparison of tryptic peptides of benzodiazepine binding proteins photolabeled with [3H]flunitrazepam or [3H]Ro 15-4513.
When rat brain membranes were incubated with the benzodiazepine agonist [3H]flunitrazepam or the partial inverse benzodiazepine agonist [3H]Ro 15-4513 in the presence of ultraviolet light one protein (P51) was specifically and irreversibly labeled in cerebellum and at least two proteins (P51 and P55) were labeled in hippocampus. After digestion of the membranes with trypsin, protein P51 was degraded into several peptides. When P51 was photolabeled with [3H]Ro 15-4513, four peptides with apparent molecular weights of 39,000, 29,000, 21,000, and 17,000 were observed. When P51 was labeled with [3H]flunitrazepam, only two peptides with apparent molecular weights of 39,000 and 25,000 were obtained. Protein P55 was only partially degraded by trypsin, and whether it was labeled with [3H]flunitrazepam or [3H]Ro 15-4513 it yielded the same two proteolytic peptides with apparent molecular weights of 42,000 and 45,000. These results support the existence of at least two different benzodiazepine receptor subtypes associated with proteins P51 and P55. The different receptors seem to be differentially protected against treatment with trypsin. In addition, these results indicate that in the benzodiazepine receptor subtype associated with P51 benzodiazepine agonists and partial inverse benzodiazepine agonists irreversibly bind to different parts of the molecule.


Preemptive renal transplantation: why not?
Dialysis has been the long-established initial choice of treatment for persons with end-stage renal disease. Transplantation before dialysis, or preemptive renal transplantation (PRT), has been controversial because of the paucity of clinical evidence that has clarified the benefits vs. risks of this approach. However, several recent observational analyses indicate that PRT is the optimal strategy to benefit patients requiring renal replacement therapy. This current review will discuss the advantages that are associated with PRT, and will summarize studies that have investigated the impact of the timing of transplantation on outcomes. We will also discuss the utility of PRT from various perspectives, and describe the challenges ahead in expanding the opportunity of PRT for more patients.


Empiric monotherapy versus combination therapy of nosocomial pneumonia in trauma patients.
Combination therapy for nosocomial pneumonia with a beta-lactam and aminoglycoside is widely accepted because of synergy and reduction of resistant bacteria. This prospective study of 109 trauma patients (94 blunt, 15 penetrating) with nosocomial pneumonia was performed in consecutive phases. In phase 1, patients were randomized to an anti-pseudomonal third-generation cephalosporin--cefoperazone or ceftazidime. Gentamicin was added to each regimen in phase 2. The mean age of the patients was 37 years, the mean ISS was 31, and there were no differences among the four treatment groups relative to associated injuries. Patients receiving monotherapy had a 56% cure rate compared with 31% for combination therapy (p < 0.04). Persistence rates were similar in these two groups (15% and 20%), but superinfection was significantly higher in the combination group (49% vs. 28%; p < 0.04). The predominant superinfecting organism was methicillin-resistant Staphylococcus aureus (MRSA). Nine patients died (5% monotherapy, 10% combination), and eight had a superinfection. We conclude that monotherapy had a higher cure rate than combination therapy for empiric therapy of pneumonia in our trauma patients. Combination therapy failed because of superinfection (primarily MRSA). Emergence of MRSA may be from host overgrowth or plasmid-mediated induction of resistance, possibly caused by gentamicin.


Quantitative electroencephalographic profiles for children with autistic spectrum disorder.
The present study examined quantitative electroencephalographic (QEEG) profile for children with autistic spectrum disorder (ASD). Five-minute QEEG data were obtained from 90 normal controls (NCs) and 66 children with ASD. Spectrum analyses revealed that ASD children showed significantly less relative alpha and more relative delta than NC. Specifically, 26% of ASD children and 2% of NCs showed 1.5 SDs of relative alpha below the normative mean. Children with this QEEG profile had 17 times the risk of having ASD than those without such a profile. Sensitivity and specificity of relative alpha were 91% and 73%, respectively. Split-half cross-validation yielded a sensitivity of 76%.


Intra-arterial chemotherapy plus BCG, a promising combination adjuvant treatment for high-risk NMIBC.
To develop a novel combination therapy for high-risk nonmuscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT), namely, intra-arterial chemotherapy (IAC) plus BCG immunotherapy, and to compare the feasibility and safety of the 2 therapies. A retrospective study was conducted on the data of 119 patients who were diagnosed with high-risk NMIBC and underwent TURBT in the past 5 years. Those who did not complete the treatment were excluded, and the remaining 98 patients were divided into 2 groups: both groups received intravesical BCG immunotherapy, while the BCG+IAC group received 4 courses of extra intra-arterial chemotherapy. Clinical and follow-up data were processed using statistical software. The recurrence rate was 22.2% in the BCG+IAC group and 35.8% in the BCG group, whereas the progression rates were 8.9% and 24.5%, respectively. In the Kaplan-Meier plot, a statistically significant difference was observed with respect to recurrence-free survival (p = 0.025), as well as the progression-free survival of the two groups was similar (p = 0.019). A total of 22.2% of the patients with adverse effects of IAC and 79.6% of patients suffered from adverse reactions to BCG immunotherapy, and most of the adverse effects were mild and tolerable. Univariate and multivariate analysis indicated that multifocal and treatment were independent risk factors for recurrence, while the history of recurrence and treatment were independent risk factors for progression. IAC could be a promising auxiliary treatment for BCG immunotherapy in decreasing the recurrence and progression rate of high-risk NMIBC with little additional toxicity.


Unveiling the Catalytic Role of B-Block Histidine in the N-S Acyl Shift Step of Protein Splicing.
Protein splicing is a post-translational modification that involves the excision of a segment denoted as "intein" and the joining of its two flanking segments. The process is autocatalytic, making inteins appealing for many applications in biotechnology, bioengineering, or medicine. The canonical mechanism of protein splicing is composed of four sequential steps, and is initialized by an N-S or N-O acyl shift to form a linear ester. It is well-established that a histidine, the most conserved amino acid in all inteins, catalyzes this initial step, even though its role remains to be understood. In this study, we combine molecular dynamics simulations and quantum mechanics/molecular mechanics (QM/MM) hybrid calculations to investigate the alternative reaction pathways proposed for the N-S acyl shift in Mycobacterium tuberculosis RecA intein. The results rule out the histidine acting as a base and activating the side chain of Cys1; instead, an aspartate performs this action. In the reaction mechanism proposed herein, denoted as the "Asp422 activated" mechanism, two sequential roles are attributed to the histidine: (i) ground-state destabilization by straining the scissile peptide bond and (ii) protonation of the leaving amide group. In summary, the study provides relevant data to understand the catalytic role of this histidine, and proposes a reaction pathway for the N-S acyl shift reaction in protein splicing that fits with the available experimental data.


Development of hepatitis C virus vaccine using hepatitis B core antigen as immuno-carrier.
To develop hepatitis C virus (HCV) vaccine using HBcAg as the immuno-carrier to express HCV T epitope and to investigate its immunogenicity in mice. We constructed the plasmid pTrc-core(NheI) using gene engineering technique, constructed the pcDNA3.1-core(NheI)-GFP plasmid with GFP as the reporter gene, and transfected them into Hela cells. The expression of GFP was observed under confocal microscopy and the feasibility of using HBcAg as an immuno-carrier vaccine was studied. pTrc-core gene with a synthetic T epitope antigen gene of HCV (35-44aa) was fused and expressed in the plasmid pTrc-core-HCV (T). For the fusion of the HBcAg-T protein, sucrose, density gradient centrifugation was used, and its molecular weight and purity were analyzed by SDS-PAGE. Then balb/c mice were immunized by the plasmid with the HBcAg (expressed by pTrc-core) protein as control. The tumor regression potential was investigated in mice and evaluated at appropriate time. After three times of immunization, the peripheral blood and spleen of vaccinated mice were collected. HBcAb was detected by ELISA, and nonspecific T lymphocyte proliferation and response of splenocytes were respectively examined by MTT assay. T cell subset of blood and spleen were detected by FACS. GFP was successfully expressed. Tumor regression trial showed that no tumor formation was found in the group receiving immunization, while tumor xenograft progression was not changed in the control group. Strong nonspecific lymphocyte proliferation response was induced. FACS also showed that the ratio of CD8+ T cells in the experimental group was higher than the controls, but the serum HBcAb in experimental group was similar to the control. HBcAg can be used as an immuno-carrier of vaccine, the fusion of HBcAg-T protein could induce stronger cellular immune responses and it might be a candidate for therapeutic vaccines specific for HCV.


Laparoscopically treated small bowel obstruction due to internal herniation through the broad ligament.
The authors reported a case of small bowel obstruction secondary to internal herniation through a defect of the broad ligament. This is a rare cause of small bowel obstruction. A 42 year-old woman without previous abdominal surgery presented with episodes of abdominal pain, nausea and vomiting. Due to rather unspecific and changing symptoms and the fact that objective findings were normal the patient was discharged and admitted a couple of times before a computed tomography-scan showed small bowel obstruction. Acute diagnostic laparoscopy showed internal herniation of a loop of small bowel trapped in a 2 cm defect in the right side of the broad ligament. The defect was gently expanded bluntly and it was then possible to retract the strangulated part of the small bowel which afterwards was vital. The defect was sutured laparoscopically. The postoperative recovery was uneventful. This case demonstrates that a preoperative diagnosis is difficult and a high index of suspicion is necessary to prevent diagnostic delay. Internal herniation through a defect in the broad ligament should be considered as a differential diagnosis in female patients presenting with symptoms of small bowel obstruction without a history of prior abdominal surgery, especially in parous women.


Four-week rapamycin treatment improves muscular dystrophy in a fukutin-deficient mouse model of dystroglycanopathy.
Secondary dystroglycanopathies are a subset of muscular dystrophy caused by abnormal glycosylation of α-dystroglycan (αDG). Loss of αDG functional glycosylation prevents it from binding to laminin and other extracellular matrix receptors, causing muscular dystrophy. Mutations in a number of genes, including FKTN (fukutin), disrupt αDG glycosylation. We analyzed conditional Fktn knockout (Fktn KO) muscle for levels of mTOR signaling pathway proteins by Western blot. Two cohorts of Myf5-cre/Fktn KO mice were treated with the mammalian target of rapamycin (mTOR) inhibitor rapamycin (RAPA) for 4 weeks and evaluated for changes in functional and histopathological features. Muscle from 17- to 25-week-old fukutin-deficient mice has activated mTOR signaling. However, in tamoxifen-inducible Fktn KO mice, factors related to Akt/mTOR signaling were unchanged before the onset of dystrophic pathology, suggesting that Akt/mTOR signaling pathway abnormalities occur after the onset of disease pathology and are not causative in early dystroglycanopathy development. To determine any pharmacological benefit of targeting mTOR signaling, we administered RAPA daily for 4 weeks to Myf5/Fktn KO mice to inhibit mTORC1. RAPA treatment reduced fibrosis, inflammation, activity-induced damage, and central nucleation, and increased muscle fiber size in Myf5/Fktn KO mice compared to controls. RAPA-treated KO mice also produced significantly higher torque at the conclusion of dosing. These findings validate a misregulation of mTOR signaling in dystrophic dystroglycanopathy skeletal muscle and suggest that such signaling molecules may be relevant targets to delay and/or reduce disease burden in dystrophic patients.


High-performance liquid chromatographic method for the determination of mangiferin in rat plasma and urine.
A reversed-phase high-performance liquid chromatography assay for mangiferin in rat plasma and urine was developed. Rutin was employed as an internal standard. The mobile phase consisted of acetonitrile-water (16:84, v/v) containing 3% acetic acid at a flow rate of 1 mL/min. Detection was at 257 and 365 nm for mangiferin in plasma and urine, respectively. The limit of quantitation (LOQ) of mangiferin was 0.6 microg/mL in plasma, and 0.48 microg/mL in urine. The standard curve was linear from 0.6 to 24 microg/mL in plasma, and 0.48 to 24 microg/mL in urine, both intra- and inter-day precision of the mangiferin were determined and their RSD did not exceed 10%. The method provides a technique for rapid analysis of mangiferin in rat plasma and urine, which can be used in pharmacokinetic studies.


Pharmacokinetics of vancomycin in patients with various degrees of renal function.
The pharmacokinetics of vancomycin were characterized in 56 patients with different degrees of renal function after an intravenous dose of 18.4 +/- 4.7 mg kg-1 (mean +/- standard deviation). Seven subjects had a creatinine clearance (CLCR) of greater than 60 ml min-1 (group I), 13 had a CLCR of 10 to 60 ml min-1 (group II), and 36 had a CLCR of less than 10 ml min-1 (group III). Serial serum samples (range, 3 to 8) were collected during the 168 h after drug administration. The serum concentration-time profile in all patients demonstrated monoexponential decay. The mean half-lives were 9.1, 32.3, and 146.7 h in groups I, II, and III, respectively. A significant decline in serum clearance (CLS) was also noted (62.7 to 28.3 to 4.87 ml min-1 in groups I, II, and III, respectively). The steady-state volume of distribution varied from 0.72 to 0.90 liter kg-1. There was no significant relationship between the steady-state volume of distribution and CLCR. The observed relationship between CLS and CLCR (CLS = 3.66 + 0.689 CLCR; r = 0.8807) can be utilized to devise dosage schedules for patients with any degree of renal impairment. This relationship was utilized to develop a nomogram for initial and maintenance dosing of vancomycin.


Characterization of murine B-cell epitopes on the Mycobacterium leprae proline-rich antigen by use of synthetic peptides.
Using synthetic peptides representing overlapping sequences of the 100-amino-acid-long N-terminal region of the proline-rich antigen of Mycobacterium leprae (PRA), we have mapped the epitopes in the primary structure of PRA recognized by four monoclonal antibodies. The M. leprae-specific monoclonal antibody F47-9 recognized the amino acid sequence LGSAYP (residues 34 to 39). Both monoclonal antibodies F67-1 and F67-5 recognized the sequence YPPP within the repeated sequence of PRA at four sites (residues 38 to 41, 50 to 53, 60 to 63, and 70 to 73). Monoclonal antibody F126-5 recognized the sequence SYPPP, also within the repeat, at three sites (residues 49 to 53, 59 to 63, and 69 to 73). All three epitopes appeared to be linear as far as can be determined by this approach.


A comparison of antioxidative capacities of fruit juices, drinks and nectars, as determined by EPR and UV-vis spectroscopies.
The differences in the Trolox Equivalent Antioxidant Capacity (TEAC) values at the same incubation time obtained by two different techniques: electron paramagnetic resonance (EPR) spectroscopy and ultraviolet visible (UV-vis) spectroscopy, which use the same antioxidant-free radical reaction mechanism, were determined for fruit juices, nectars and drinks. For this study, the stable free radical 1,1-Diphenyl-2-picryl-hydrazyl (DPPH(•)) was used. The antioxidant capacity was presented in Trolox Equivalents, e.g., μM trolox per 100 ml of sample. All of the studied fruit juices, drinks and nectars showed antioxidative properties. Dependencies between TEAC values and the percent fruit content and sample color were observed for the studied beverages. It was found that EPR spectroscopy is the more adequate method for determining TEAC values for these kinds of samples.


Effect of interface atomic structure on the electronic properties of nano-sized metal-oxide interfaces.
We report that the size dependence of electronic properties at nanosized metal-semiconducting oxide interfaces is significantly affected by the interface atomic structure. The properties of interfaces with two orientations are compared over size range of 20-200 nm. The difference in interface atomic structure leads to electronic structure differences that alter electron transfer paths. Specifically, interfaces with a higher concentration of undercoordinated Ti result in enhanced tunneling due to the presence of defect states or locally reduced tunnel barrier widths. This effect is superimposed on the mechanisms of size dependent properties at such small scales.


New directions in the design and evaluation of anti-cancer drugs.
The process of anti-cancer drug development undergoes continual change, responding to a variety of scientific and economic pressures. Institutional changes have resulted from the very success of drugs such as doxorubicin, which by their clinical success have greatly expanded the market and altered the economics of cancer chemotherapy, leading to a much greater involvement by the commercial pharmaceutical companies in basic drug design. Scientific changes have been driven by improved cell and molecular biological techniques, which have suggested new targets for therapy and have provided a much wider variety of laboratory biological test systems against which to evaluate new compounds. This review attempts to classify drugs in terms of the level of tumour cell selectivity (sub-cellular, cell kinetics, supra-cellular) which they possess. Seen from this perspective, the recent trend towards the development of non-myelosuppressive agents is more clearly defined as a move towards seeking selectivity at the sub- or supra-cellular levels, rather than at the traditional level of cell kinetics.


Effects of pulmonary x-irradiation and pulmonary tumor burden on hypoxia tolerance of mice.
Hypoxia tolerance was measured in female C3H mice which had been given single thoracic X-ray exposures or which were bearing pulmonary tumors. Thoracic X-ray exposures ranging from 500-1500 rad had no significant effect on hypoxic tolerance for up to 56 d following irradiation. The presence of pulmonary tumors from the Dunn osteosarcoma had no significant effect on hypoxic tolerance until a tumor burden of about 200 mm3 was reached. It is concluded that neither a pulmonary radiation history nor moderate lung tumor burdens militate against using reduced oxygen environments in radiotherapeutic regimens to treat pulmonary tumors.


Long-term followup of the artificial urinary sphincter.
The artificial urinary sphincter with a pressure regulating balloon was implanted in 30 patients. All implantations were done before September 1982, for a minimum followup of 1 year and an average followup of 3.7 years. Of the patients 21 (70 per cent) have a functioning sphincter: 17 are continent and 4 are slightly incontinent, requiring 1 pad per day. Failure was owing to erosion in 6 patients and infection of the device in 3. Critical factors for successful implantation include preoperative evaluation, cuff location and pressure, primary deactivation and postoperative care. Our experience supports the further use of this device in appropriate cases.


Cometary science. 67P/Churyumov-Gerasimenko, a Jupiter family comet with a high D/H ratio.
The provenance of water and organic compounds on Earth and other terrestrial planets has been discussed for a long time without reaching a consensus. One of the best means to distinguish between different scenarios is by determining the deuterium-to-hydrogen (D/H) ratios in the reservoirs for comets and Earth's oceans. Here, we report the direct in situ measurement of the D/H ratio in the Jupiter family comet 67P/Churyumov-Gerasimenko by the ROSINA mass spectrometer aboard the European Space Agency's Rosetta spacecraft, which is found to be (5.3 ± 0.7) × 10(-4)—that is, approximately three times the terrestrial value. Previous cometary measurements and our new finding suggest a wide range of D/H ratios in the water within Jupiter family objects and preclude the idea that this reservoir is solely composed of Earth ocean-like water.


Erectile dysfunction in men under 40: etiology and treatment choice.
We undertook a retrospective review of 100 impotent men under age 40 to determine the underlying etiologic factors in the group and to evaluate the role of surgery in their care. Although patients ranged in age from 18 to 40 (mean--32.2 years), the number of patients increased steadily with advancing years. The majority of patients (72) had vasculogenic impotence (arteriogenic--15, venogenic--46, mixed--11), followed by psychogenic (13), neurogenic (12) and other causes (4). The differential diagnosis did not correlate with age. Contributing factors were present in 76%, trauma and substance abuse being most common. Essentially equal numbers of patients were treated surgically (40) and with intracavernous injection of vasoactive agents (39). Considerably fewer had a vacuum constriction device (5), oral medication (5), psychotherapy (4), other therapy (4), and none (3). The majority of patients referred to our tertiary urologic practice for treatment of vasculogenic impotence were sent by other urologists. Although the referral source did not appear to influence the choice of treatment, it probably has accounted for the preponderance of vasculogenic impotence in this series.


Geometric and Electronic Effects in the Binding Affinity of Imidazole-Based N-Heterocyclic Carbenes to Cu(100)- and Ag(100)-Based Pd and Pt Single-Atom Alloy Surfaces.
We have conducted nonlocal periodic density functional theory (DFT) calculations of N-heterocyclic carbenes (NHCs) adsorbed to Pd/Cu(100), Pt/Cu(100), Pd/Ag(100), and Pt/Ag(100) single atom alloys (SAAs) utilizing the nonlocal optPBE-vdW functional. NHCs with electron donating groups (EDGs) are predicted to bind more strongly to the SAA surface compared to NHCs functionalized with electron withdrawing groups (EWGs). Our calculations show that NHCs typically bind to SAA geometries containing a small space between the heteroatom sites for the SAAs considered. Generally, this pattern is predicted to persist for a single NHCs or for a pair of NHCs bound to the SAA surfaces. Approximate linear relationships between NMR-based parameters and NHC-SAA binding energies are uncovered. We predict that the binding of NHCs to SAA surfaces is composition-dependent and heteroatom geometry dependent.


Bronchoscopic Cryotherapy. Clinical Applications of the Cryoprobe, Cryospray, and Cryoadhesion.
Cryotherapy is an evolving therapeutic and diagnostic tool used during bronchoscopy. Through rapid freeze-thaw cycles, cryotherapy causes cell death and tissue necrosis or tissue adherence that can be used via the flexible or rigid bronchoscope. This extreme cold can be used through the working channel of the bronchoscope via a specialized cryoprobe or directly with the use of spray cryotherapy. These properties allow for multiple bronchoscopic techniques, each with its own equipment and procedural, safety, and efficacy considerations. Bronchoscopic cryotherapy can be used in a variety of clinical scenarios, including the treatment of malignant and benign central airway obstruction and low-grade airway malignancy, foreign body removal or cryoextraction, endobronchial biopsy, and transbronchial biopsy. The bulk of the experience with bronchoscopic cryotherapy consists of uncontrolled case series of malignant central airway obstruction. There are also controlled data supporting the use of cryoadhesion for endobronchial biopsies, albeit with an increased risk of controllable bleeding. The use of cryoadhesion for transbronchial biopsies is an active area of investigation with limited controlled data. In addition, there are promising future directions using bronchoscopic cryotherapy, including chemosensitizing malignancy with cryotherapy and capitalizing on the synergy between cryotherapy and radiation.


Pulmonary papillary adenoma: a case report and review of the literature.
Pulmonary papillary adenomas are rare neoplasms that predominantly occur in the periphery of the lung. We describe a 24-year-old male with a 6.0-cm spherical mass found incidentally at the periphery of the left upper lobe by imaging. Enucleation of the neoplasm was performed with intraoperative frozen section analysis. The tumor histologically showed papillary proliferations containing fibrovascular cores lined by a single layer of tumor cells that lacked atypia, mitoses, or necrosis. The histologic features were consistent with a pulmonary papillary adenoma. Pulmonary papillary adenoma was previously considered to be a benign entity. However, because of its invasive growth pattern, it has been suggested that this neoplasm has intermediate malignant potential. The clinicopathologic features and differential diagnosis of this unusual neoplasm is discussed with a review of the English literature.


The Common Mechanisms of Sarcopenia and NAFLD.
Current studies have shown that sarcopenia and nonalcoholic fatty liver disease (NAFLD) have similar pathophysiological profiles. The cooccurrence of sarcopenia and NAFLD has been observed in elderly patients. The actions of these conditions are linked, and their treatments are similar. Therefore, studies should be conducted on NAFLD-sarcopenia rather than on NAFLD or sarcopenia.


Adjuvant chemotherapy in a unique population of patients with gastric cancer undergoing surgery.
Total gastrectomy with D2 dissection theoretically removes the gross primary tumor with its potential route of dissemination, that is locoregional lymph nodes. Complementary therapy for the control of systemic microscopic disease should be taken into consideration in patients whom surgery with curative intent was performed. Twenty-eight patients with moderately differentiated, locally advanced gastric carcinoma underwent total gastrectomy with D2 lymph node dissection. The operative mortality rate was 0% in this series. Fifteen patients received six courses of adjuvant 5-FU + leucovorin in doses of 425 mg/m2/d and 20 mg/m2/d respectively in five-day cycles month ly. The remaining 13 patients constituted the control (surgery only) group. The mean disease-free and overall survival rates were 41 and 48 months (p: 0.78) and 42 and 53 months (p: 0.43) in the control and chemotherapy groups, respectively. The odds ratio for crude mortality was 0.7. Although statistical significance has not been achieved in this study, a trend toward adjuvant chemotherapy has emerged in that unique group of patients with moderately differentiated (intestinal type) adenocarcinoma of the stomach undergoing curative surgery.


Matrix-assisted laser desorption/ionization capabilities in the study of non-enzymatic protein glycation.
Matrix-assisted laser desorption/ionization mass spectrometry has been successfully applied in the study of non-enzymatic glycation of different proteins. In the case of bovine serum albumin, glycated by in vitro experiments performed under pseudophysiological conditions, a clear increase in molecular weight is observed with respect to both glucose concentrations and incubation time. The in vitro glycation of ribonuclease with glucose and fructose shows some peculiar differences either in terms of the number of condensed sugar molecules or in terms of the reaction kinetics. The same approach, applied to plasma proteins of healthy and diabetic subjects, provides evidence for the occurrence of glycation of human serum albumin for the latter subjects.


Chemical and thyroid hormone profile of the bone marrow interstitial fluid in hematologic disorders and patients without primary hematologic disorders.
Bone marrow interstitial fluid (BMIF) has not been well characterized. BMIF was isolated from 60 patients including plasma cell dyscrasias (PCD, n = 33), other primary hematologic disorders (OHD, n = 15), and patients with secondary or nonhemtologic disorders (NHD, n = 12) and analyzed for an array of chemical constituents. These included total cholesterol, glucose, phosphate, creatinine, urea, total protein, albumin, globulins, total bilirubin, aspartate aminotransferase, lactate dehydrogenase, sodium, osmolarity, free triiodothyronine (free T3), total triiodothyronine (total T3), and free tetraiodothyronine (free T4). Levels of BMIF components were compared between patient groups and to plasma levels. Compared with plasma, total cholesterol, total protein, total bilirubin, sodium, and calculated osmolarity were lower in BMIF in all groups (P < 0.05). Calculated globulins and aspartate aminotransferase were lower in BMIF of PCD patients and patients with NHD. Albumin was lower in BMIF of patients with PCD and patients with OHD. Lastly, free T4 was significantly higher in BMIF of patients with PCD and patients with OHD. Similar results were demonstrated in a separate analysis performed in patients with multiple myeloma. To conclude, the chemical and thyroid hormone composition of BMIF differs significantly from plasma in several key constituents.


The Cyberbullying Picture Series (CyPicS): Developed for Use in Cyberbullying and Cyberbystander Research.
While research has examined bystander responses in a traditional sense, there is a dearth of research regarding responses of cyberbystanders in a real-time situation, such as observing a cyberbullying scenario. This article describes a novel protocol designed to develop a series of images to be used to undertake research that aims to examine cyberbystander responses. A total of 24 scenarios (12 negative (cyberbullying) and 12 neutral) were created by the researchers and designed to mimic the way such scenarios would appear on a social networking site. The negative (cyberbullying) stimuli were rated in terms of level of severity, and the scenarios were compared to a selection of images from the International Affective Picture System using the Self-Assessment Manikin. These stimuli were compiled to form the Cyberbullying Picture Series (CyPicS). Through the development of the CyPicS, this protocol will aid future researchers in examining responses to real-life scenarios, as it is the first of its kind to develop these scenarios and test and evaluate them. CyPicS will provide researchers with the means to systematically evaluate responses to validated, real-life cyberbullying scenarios. More specifically, future researchers can utilize CyPicS to investigate how cyberbystanders respond when observing cyberbullying stimuli compared to neutral stimuli, as well as to measure and understand reactions or perceptions of cyberbullying. CyPicS can be used in any form of cyberbullying research (including electroencephalography and eye-tracking studies, psychological research, and functional magnetic resonance imaging studies) that may utilize bystander reactions and behaviors. Findings from research that utilizes CyPicS will greatly increase our understanding of bystander responses, and with variations in study design, researchers can further examine past or future associations with cyber-victim/bully status and mental health outcomes.


Novel targets and derived small molecule inhibitors in multiple myeloma.
Recent research advances have defined a key role of the bone marrow (BM) in multiple myeloma (MM) pathogenesis thereby leading to new treatment paradigms, which aim to target both the tumor cell as well as its BM microenvironment. The incorporation of thalidomide, bortezomib, and lenalidomide into conventional cytotoxic and transplantation regimens in relapsed and refractory, but also in newly diagnosed MM has changed treatment options during the last decade. However, MM remains still incurable. Ongoing translational research aims to identify additional therapeutic targets and to design derived agents, predominantly small molecule inhibitors, with higher potency and less toxicity to further improve MM patient outcome and to overcome drug resistance.


The sensitivity and specificity of 18F-FDG PET/CT in spinal leptomeningeal metastases: the synergistic effect of the 18F-FDG PET-CT to gadolinium-enhanced MRI.
Magnetic resonance imaging (MRI) plays an important role in the diagnosis of leptomeningeal metastases (LM); however, some sub-centimeter lesions may be missed. Positron emission tomography/computed tomography (PET/CT) has a high sensitivity and may play a synergistic role with MRI in diagnosing spinal LM (SLM). We aimed to retrospectively evaluate the detection of SLM with 18F-fluorodeoxyglucose PET/CT (18F-FDG PET/CT) compared to that of whole spinal cord MRI in a single center. Patients with SLM who had undergone 18F-FDG PET/CT and MRI were enrolled. 18F-FDG PET/CT imaging findings were independently reviewed by 2 nuclear medicine physicians. 18F-FDG PET/CT findings of SLMs were described. A consistency test was conducted to assess the patient-based diagnostic results obtained by the 2 physicians. Patient-based sensitivity, accuracy, and specificity in diagnosing SLM between 18F-FDG PET/CT and MRI of the whole spinal cord were compared using the chi-square or Fisher's exact test. A P value of <0.05 was considered statistically significant. The receiver operating characteristic (ROC) curve was obtained to assess the diagnostic performance of maximum standardized uptake value (SUVmax) to diagnose SLM. A total of 16 patients with SLM were included in this study from October 2010 to April 2022. The primary tumor involved the lungs, liver, ovaries, prostate, esophagus, and unknown primary site. The mean age of patients, including 13 males and 3 females, was 57.8±11.2 (range, 34-73) years. Of 16 patients with SLM, 10 had nodular diseases, 2 had linear diseases, and 4 had mixed diseases. The kappa value of the consistency test of the 2 radiologists' diagnostic results was 0.765. The patient-based sensitivity, specificity, and accuracy of 18F-FDG PET/CT in diagnosing SLM were 87.5%, 89.2%, and 88.7%, respectively and those of whole spinal cord MRI were 75.0%, 100.0%, and 92.5%, respectively. There were no significant differences in sensitivity, specificity, and accuracy between the 2 methods, with P values of 0.654, 0.115, and 0.506, respectively. However, more nodular diseases were observed on PET/CT. The area under the ROC curve (AUC) for the prediction of SLM by SUVmax was 0.907 [95% confidence interval (CI): 0.831-0.983]. When SUVmax ≥2.45, the Youden index was the largest, and the sensitivity and specificity were 89.3% and 75.7%, respectively. 18F-FDG PET/CT is a good choice of imaging modality for assessing SLM. In the diagnosis of SLMs, PET/CT and enhanced MRI can play a better synergistic role.


Electrochemical properties of poly(3,4-ethylenedioxythiophene) nanofiber non-woven web formed by electrospinning.
Electrically conducting nano (micro) poly(3,4-ethylenedioxythiophene) (PEDOT) fiber non-woven web was fabricated using the electrospinning technique by applying high voltage of 10 to 30 kV to the electrospinning solution. To investigate the effects of various conditions on formation and properties of PEDOT fiber non-woven web, we changed the solvent or other components and their concentrations. We used 1-propanol or 1-butanol as a solvent and poly(vinyl pyrrolidone) (PVP) as a matrix polymer to prepare the electrospinning solution. The electrical conductivity of the electro-spun PEDOT non-woven web was as high as 7.5 S/cm when 1-propanol was used as the solvent. Electrochemical capacitor was assembled using one pair of the PEDOT non-woven webs as the electrodes by a simple stack method, where metal plates were used as current collectors. We observed the electrochemical charge and discharge behavior of the capacitor, confirming that the PEDOT non-woven web can be used as the electrode for flexible electrochemical capacitor.


Distinct HbA1c trajectories in a type 2 diabetes cohort.
The aim of this study was to identify subgroups of type 2 diabetes mellitus patients with distinct hemoglobin A1c (HbA1c) trajectories. Subgroup characteristics were determined and the prevalence of microvascular complications over time was investigated. Data from a cohort of 5,423 type 2 diabetes patients from a managed primary care system were used [mean follow-up 5.7 years (range 2-9 years)]. Latent class growth modeling was used to identify subgroups of patients with distinct HbA1c trajectories. Multinomial logistic regression analyses were conducted to determine which characteristics were associated with different classes. Four subgroups were identified. The first and largest subgroup (83 %) maintained good glycemic control over time (HbA1c ≤53 mmol/mol), the second subgroup (8 %) initially showed severe hyperglycemia, but reached the recommended HbA1c target within 2 years. Patients within this subgroup had significantly higher baseline HbA1c levels but were otherwise similar to the good glycemic control group. The third subgroup (5 %) showed hyperglycemia and a delayed response without reaching the recommended HbA1c target. The fourth subgroup (3.0 %) showed deteriorating hyperglycemia over time. Patients within the last two subgroups were significantly younger, had higher HbA1c levels and a longer diabetes duration at baseline. These subgroups also showed a higher prevalence of retinopathy and microalbuminuria. Four subgroups with distinct HbA1c trajectories were identified. More than 90 % reached and maintained good glycemic control (subgroup one and two). Patients within the two subgroups that showed a more unfavorable course of glycemic control were younger, had higher HbA1c levels and a longer diabetes duration at baseline.


Antistress effects of Kampo medicine "Yokukansan" via regulation of orexin secretion.
Various stressors induce stress responses through the hypothalamic-pituitary-adrenal and the sympathetic-adrenal-medullary axes, which are regulated, in part, by orexin. For example, secretion of orexin in the hypothalamus is increased in rats exposed to the stress of social isolation for 1 week. In this study, the antistress effects of Kampo medicine Yokukansan (YKS) via the regulation of orexin secretion were investigated using a rat model. The administration of 300 mg/kg per day of YKS to rats for 1 week significantly decreased the plasma orexin levels compared with non-treated rats, whereas the administration of 1,000 mg/kg of YKS had no effect on orexin levels. Therefore, 300 mg/kg of YKS was an effective dose for controlling orexin secretion. Subsequently, rats were divided into group-housed control (Con), individually housed stress (Stress), and individually housed YKS (300 mg/kg)-treated stress (Stress + YKS) groups. After 1 week, a resident-intruder aggression test was performed, and the plasma levels of orexin and corticosterone were measured. In the Stress group, aggressive behavior and the levels of corticosterone and orexin significantly increased compared with the Con group; however, these effects were inhibited in the Stress + YKS group. Further, an orexin receptor antagonist (TCS 1102; 10 mg/kg) was intraperitoneally administered to rats exposed to isolation stress to determine whether orexin was involved in stress responses. Under these conditions, aggressive behavior and the level of corticosterone significantly decreased compared with the Stress group. These results suggest that orexin is involved in the control of stress response and that YKS exerts an antistress effect via the regulation of orexin secretion.


Practice Variation in Utilization of Flap or Graft Reconstruction Among Veterans Affairs Surgeons After Extirpation of Keratinocyte Carcinoma on the Nose.
Practice variation has been well documented across the US health care system but has not been explored in reconstructive surgical choice after keratinocyte carcinoma (KC) extirpation. Assess practice variation in utilization of complex (flap or graft) reconstruction after excision of KC on the nose among a multidisciplinary group of reconstructive surgeons (Mohs micrographic and plastic surgery). A randomly selected subset of surgically treated, routine, primary, invasive KCs on the nose between 2000 to 2012 at the Veterans Affairs (VA)-Boston Healthcare System were assessed. Patient factors, tumor factors, and individual surgeons with sufficient case volume were fit to a multivariate logistic regression model to assess between-surgeon differences in the odds of performing a complex reconstruction. Ten surgeons met the case volume threshold for analysis, encompassing 338 KC on the nose excised and reconstructed from 2000 to 2012. After adjusting for patient age, tumor diameter, and location, 6 surgeons performed significantly more complex reconstructions than the reference surgeon, and the case-adjusted predicted probability of complex reconstruction ranged from 7% to 99% (p ≤ .0001). Marked practice variation in reconstruction choice exists among surgeons after extirpation of KC on the nose at one VA health care system. High-quality comparative studies regarding optimal nasal reconstruction after extirpation of KC are needed.


Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloblastic leukemia (AML): A single center experience.
We retrospectively analyzed the impact of pre- and post-transplant variables on the outcome of transplanta¬tion in 145 consecutive patients with acute myeloblastic leukemia (AML) allografted from their HLA-identical siblings in our single center cohort. The stem cell source used was bone marrow (BM) (36.6%) or peripheral blood (PB) (63.4%). Both neutrophil and platelet engraftments were observed on the median 14th day. Engraftment was faster in the PB group than in the BM group (p<0.0001). Severe acute graft versus host disease (aGvHD) was observed in 27.9% of the patients while chronic (c)GvHD developed in 61.2%. The use of PB was associated with more severe aGvHD. Estimated leukemia-free survival (LFS) and overall survival (OS) at 10 years were 43.4%±5.2% and 52.7%±4.6%, respectively. Both in univariate and multivariate analyses for LFS and OS, remission status at transplant and the presence of aGvHD were independent risk factors.


p53/58 binds COPI and is required for selective transport through the early secretory pathway.
p53/58 is a transmembrane protein that continuously recycles between the ER and pre-Golgi intermediates composed of vesicular-tubular clusters (VTCs) found in the cell periphery and at the cis face of the Golgi complex. We have generated an antibody that uniquely recognizes the p53/58 cytoplasmic tail. Here we present evidence that this antibody arrests the anterograde transport of vesicular stomatitis virus glycoprotein and leads to the accumulation of p58 in pre-Golgi intermediates. Consistent with a role for the KKXX retrieval motif found at the cytoplasmic carboxyl terminus of p53/58 in retrograde traffic, inhibition of transport through VTCs correlates with the ability of the antibody to block recruitment of COPI coats to the p53/58 cytoplasmic tail and to p53/58-containing membranes. We suggest that p53/58 function may be required for the coupled exchange of COPII for COPI coats during segregation of anterograde and retrograde transported proteins.


Development of Action Threshold to Manage Common Leaf Spot and Black Seed Disease of Strawberry Caused by Mycosphaerella fragariae.
The fungus Mycosphaerella fragariae is responsible for two strawberry diseases: common leaf spot (CLS) and black seed disease (BSD). In June-bearing strawberry plantings, CLS influences vigor, yield, and winter survival. During production years, BSD causes black lesions around strawberry seeds, reducing the market value of the berries. The objective of this study was to characterize the relationships between CLS and BSD and to develop action thresholds for the management of BSD. Data on the number of lesions per leaf, number of black seeds per berry, and percentage of diseased berries were collected at two experimental and six commercial sites from 2000 to 2011, corresponding to 50 farm-years. First, logistic regression was used to model the relationship between BSD occurrence in its binary data form and the number of lesions per leaf assessed at 7, 14, 21, and 28 days before 10% bloom. Second, linear regression was used to model the relationship between BSD severity, BSD incidence, and number of lesions per leaf assessed at 7, 14, 21, and 28 days before 10% bloom. Resulting action thresholds of 15, 25, or 33 lesions per leaf at 21, 14, or 7 days before 10% bloom, respectively, were compared with the recommended practice at three commercial sites in 2014, 2015, and 2016. The percentage of diseased berries was significantly (P = 0.0016; least significant difference = 7.140) higher in the sections of the fields that were not managed for BSD, with an average of 15.22% diseased berries, in comparison with 3.22 and 2.44% diseased berries in sections managed according to the recommendations and the thresholds, respectively. Overall, 40% less fungicide was used when the thresholds were applied. Hence, these thresholds can be used as an additional decision tool to optimize fungicide applications during the prebloom period.


A truncating mutation in Alzheimer's disease inactivates neuroligin-1 synaptic function.
Neuroligins (NLs) are cell-adhesion proteins that regulate synapse formation and function. Neuroligin 1 (NL1) promotes the formation of glutamatergic synapses and mediates long-term potentiation in mouse models. Thus, altered NL1 function could mediate the synaptic and memory deficits associated with Alzheimer's disease (AD). Here, we describe a frameshift mutation, c.875_876insTT, in the neuroligin 1 gene (NLGN1) in a patient with AD and familial history of AD. The insertion generates a premature stop codon in the extracellular domain of NL1 (p.Thr271fs). Expression of mutant NL1 shows accumulation of truncated NL1 proteins in the endoplasmic reticulum. In hippocampal neurons, the p.Thr271fs mutation abolishes the ability of NL1 to promote the formation of glutamatergic synapses. Our data support a role for inactivating mutations in NLGN1 in AD. Previous studies have reported rare mutations in X-linked NLGNL3 and NLGNL4 genes in patients with autism, which result in the inactivation of the mutant alleles. Therefore, together with a role in neurodevelopmental disorders, altered NL function could underlie the molecular mechanisms associated with brain diseases in the elderly.


Puerperal endometritis and intrauterine adhesions.
The role of puerperal endometritis in intrauterine adhesion formation was studied by hysterography in 171 women who had cesarean sections. Of 28 patients who developed significant endometritis, only one developed intracervical adhesions. In the control group of 143 cases, there was also only one such case. Endometritis alone apparently does not play a significant role in intrauterine and endocervical adhesion formation. The possible role of placental fibroblasts in preventing endometrial regeneration is discussed.


IL6-174G/C polymorphism and fracture risk.
Several studies have examined the associations of polymorphism in interleukin-6 (IL6) with fracture risk. However, the results were conflicting. Thus, a meta-analysis was conducted to determine the relationship between IL6-174C/G polymorphism and risk of fracture. Databases including PubMed, EMBASE, Wanfang were searched. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using random-effects models. Six studies were included in this meta-analysis. IL6-174C/G polymorphism was associated with a significantly increased risk of fracture (OR=1.32; 95% CI, 1.10-1.58; I(2) =11%; Figure 1). In the subgroup analysis according to gender, women (RR=1.26; 95% CI, 1.09-1.46; I(2) =0%) was significantly associated with risk of fracture. In the age subgroup analysis, old population (RR=1.27; 95% CI, 1.11-1.48; I(2) =0%) showed increased fracture risk. However, young population did show increased risk of fracture (RR=1.95; 95% CI, 0.70-5.47; I(2) =51%). Postmenopausal women also showed an increased fracture risks (RR=1.24; 95% CI, 1.08-1.44; I(2) =0%). This meta-analysis suggested that IL6-174C/G polymorphism contributed the development of fracture.


Asymmetric construction of phosphono dihydropyranones from α-ketophosphonates enabled by Pd/chiral isothiourea relay catalysis.
A highly enantio- and diastereoselective approach has been developed for the synthesis of chiral phosphono dihydropyranones. This approach is enabled by Pd/chiral isothiourea relay catalysis under mild reaction conditions, starting from readily available benzyl bromides, CO, and α-ketophosphonates. The cascade reaction involves the generation of a ketene intermediate from Pd-catalyzed carbonylation of benzyl bromide and subsequent chiral Lewis base catalyzed formal [4 + 2] reaction. Phosphono lactone products can also be transformed to chiral 1,5-diester products in good yield and high stereoselectivity.


Culture of Safety Quality Improvement Project: Longitudinal AHRQ Survey Results From a Family Medicine Residency Program.
This project analyzed the culture of safety quality improvement at the Family Medicine Center (FMC). The Agency for Healthcare Research and Quality (AHRQ) Culture of Safety Survey was used as a benchmark for internal and external comparison. The AHRQ Culture of Safety Survey was administered to health care staff in 2015, 2017, and 2019, respectively, at the Family Medicine Center. Baseline perceptions of safety and quality were established using the data from the AHRQ Culture of Safety Survey in 2015. We performed multiple large-scope quality improvement projects that focused on identified deficiencies. The changes in perception were monitored over time every 2 years. We analyzed the results using the Kruskal-Wallace test (P=.05). The AHRQ Culture of Safety Survey showed statistically significant improvement in patient centeredness, effectiveness, timeliness, efficiency, equitableness, and overall patient safety from 2015 to 2019. Some inconsistencies were seen between different sections of responses, likely due to wording interpretations by the participants. Overall, the AHRQ Culture of Safety Survey is an effective way to help monitor employee perception of multiple domains that lead to a safe and effective clinical environment as compared to other practices across the country. Clinic-wide implementation of quality and patient care strategies resulted in significant improvements in nearly every category of the survey.


Impact of systemic lupus erythematosus on maternal and fetal outcomes following pregnancy: A meta-analysis of studies published between years 2001-2016.
Previous research has already shown systemic lupus erythematosus (SLE) to have severe consequences on pregnancy outcomes. However, insufficient number of participants, which were mainly limited to one particular region, limited outcomes analyzed and lack of evidence based analysis to support systematic reviews of the literature were the limitations observed. Therefore, by improving these limitations, we aimed to systematically show the impact of SLE on maternal and fetal outcomes following pregnancy. The Cochrane Database of Randomized Controlled Trials, EMBASE and Medline databases were carefully searched for appropriately relevant English language studies comparing maternal and/or fetal outcomes (endpoints) in pregnant women with and without SLE. With the presence of discontinuous data, risk ratios (RR) and 95% confidence intervals (CI) were calculated and the final analysis was carried out by RevMan 5.3 software. Eleven studies with a total number of 529,778 participants were included. This current analysis showed cesarean operation to be significantly higher in patients with SLE (RR: 1.85, 95% CI: 1.63-2.10; P = 0.00001). Pre-eclampsia and hypertension also significantly affected women with SLE, (RR: 1.91, 95% CI: 1.44-2.53; P = 0.00001) and (RR: 1.99, 95% CI: 1.54-2.56; P = 0.00001) respectively. In addition, spontaneous abortion, thromboembolic disease, and post-partum infection were also significantly higher in the SLE subgroup (RR: 1.51, 95% CI: 1.26-1.82; P = 0.0001), (RR: 11.29, 95% CI: 6.05-21.07; P = 0.00001) and (RR: 4.35, 95% CI: 2.69-7.03; P = 0.00001) respectively. Live birth significantly favored infants who were born from mothers without SLE (RR: 1.38, 95% CI: 1.14-1.67; P = 0.001). Significantly higher premature birth and infants classified as 'small for gestational age' were associated with SLE, (RR: 3.05, 95% CI: 2.56-3.63; P = 0.00001) and (RR: 1.69, 95% CI: 1.53-1.88; P = 0.00001) respectively. In addition, SLE was significantly associated with increased number of infants that required neonatal intensive care unit and infants with congenital defects (RR: 2.76, 95% CI: 2.27-3.35; P = 0.00001) and (RR: 2.63, 95% CI: 1.93-3.58; P = 0.00001) respectively. This meta-analysis has shown SLE to indeed have a high impact on maternal and fetal outcomes following pregnancy. Therefore, special treatments and care should be allocated to those women in order to manage adverse outcomes that might follow, and to improve successful normal delivery, term infants and to reduce congenital abnormalities in infants who were born from mothers with SLE.


Intravesical drug delivery for dysfunctional bladder.
The bladder is a hollow organ that can be treated locally by transurethral catheter for intravesical drug instillation or cystoscopy for intravesical drug injection. With advancing technology, local organ-specific therapy and drug delivery is of expanding interest for treating dysfunctional bladder, including interstitial cystitis/bladder pain syndrome, overactive bladder and sterile hemorrhagic cystitis after chemotherapy or pelvic radiation. Intravesical therapy has shown varying degrees of efficacy and safety in treating interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with new modalities being developed. Intravesical (regional) therapy has several advantages than oral (systemic) therapy, including high local concentration and less systemic toxicity. In recent years, intravesical delivery of biotechnological products including neurotoxins and immunosuppressive agents, and delivery platform including liposomes has shown promise for lower urinary tract symptoms. This review considers the current status of intravesical therapy in dysfunctional bladder including interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with special attention to lipid based novel drug-delivery.


Incidental Findings in Small Field of View Cone-beam Computed Tomography Scans.
The use of cone-beam computed tomography (CBCT) in endodontics has increased in recent years. In clinical application of small field of view (FOV) CBCTs, these scans are not reviewed routinely by a radiologist. Studies of large FOV CBCT scans show the prevalence of incidental findings to be greater than 90%. The purpose of this study was to evaluate the prevalence of missed findings by endodontic residents as compared with a radiologist on small FOV CBCT scans. Two hundred three small FOV CBCTs obtained for endodontic purposes were analyzed by an endodontic resident and a medical radiologist. The reported findings of each practitioner were compared to evaluate for missed incidental findings by the endodontic resident. The radiologist reported abnormalities in 176 of the 203 subjects (87%), with a total of 310 abnormalities reported. The endodontic resident reported abnormalities in 102 of the 203 subjects (50%), with a total of 126 abnormalities reported. The percentage of scans with any abnormality reported by the radiologist was significantly greater than the endodontic resident (P < .001). There was no significant difference between jaw locations in percentage of missed findings for the 3 most common types of finding-rarefying osteitis, sinusitis/mucosal lining thickening, and excess restorative material in the periapical area. Rarefying osteitis was missed significantly less than the other 2 types of findings (P < .001). A radiologist is significantly more likely to identify incidental findings in small FOV CBCT scans than an endodontic resident. Scan location had no significant association with the rate of missed findings.