Pharmacological management of obstructive peripheral arterial disease: two case reports.
Peripheral artery disease (PAD), also abbreviated as LEAD or lower extremity artery disease, is an important predictor of cardiovascular morbidity and mortality. Rivaroxaban, a selective direct factor Xa inhibitor, is proposed as an additional pharmacologic option for managing this disease. Two patients presented with PAD and high-risk comorbidities. The first case showed how the evaluation of the cardiovascular risk guided the therapeutic management of the patient. The second case was about a patient diagnosed with LEAD who experienced worsening from exertional ischemia toward critical ischemia requiring amputation despite distal revascularization, and parenteral vasodilator therapy to relieve pain. This case suggested a comprehensive care management approach, adapted to PAD progression stages. The PAD management consists nowadays of optimizing the management of cardiovascular risk factors and disease progression. Diagnosis, treatment, monitoring, and patient education should be handled by a vascular specialist in a specialized care unit.


Major depressive disorder in hepatitis C: an open-label trial of escitalopram.
Depression is a common condition associated with hepatitis C and may be induced by interferon alfa, the primary treatment for hepatitis C. Depression is also a major barrier to the initiation of such treatment. This study examined the effect of escitalopram on measures of depression, quality of life, and tests of liver function in subjects with comorbid hepatitis C and depression. Subjects with DSM-IV major depressive disorder and hepatitis C were included in this open-label study. The recruitment period was from October 2002 through February 2004. Treatment status with regard to interferon therapy was neither an inclusion nor an exclusion criterion. Subjects received escitalopram for 8 weeks starting at 10 mg/day. Dosage adjustments up to 20 mg/day were made after week 4, as deemed clinically necessary. Scores on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and the Clinical Global Impressions-Severity of Illness scale (CGI-S) and results of liver function tests (AST, ALT, GGT) were obtained at baseline, 2 weeks, 4 weeks, and 8 weeks. Medical Outcomes Study Short Form Health Survey (SF-36) ratings and Hopkins Symptom Checklist-90-Revised (SCL-90-R) scores were obtained at baseline and week 8. Eighteen subjects (12 female, 6 male) participated in this study. The mean daily dose of escitalopram at endpoint was 12.78 mg. Mean HAM-D-17 scores decreased significantly with treatment (t = 8.535, df = 17, p < .0001). Statistically significant improvement was also demonstrated on many subscales of the SF-36, the SCL-90-R, and the CGI-S. Tests of liver function showed no significant changes. These results suggest that depression in patients with hepatitis C may be effectively and safely treated with escitalopram.


Metrorrhagia in a human immunodeficiency virus positive woman caused by cervical histoplasmosis.
In patients with AIDS, infection with Histoplasma capsulatum frequently results in disseminated disease. We discuss a 42-year old HIV-infected woman presenting with fever, weight loss, pulmonary infiltrates, diarrhea, and metrorrhagia. Biopsy of bone marrow and skin demonstrated H capsulatum. Necrotic lesions of the uterine cervix, initially thought to represent cervical carcinoma, proved to be because of disseminated histoplasmosis. Involvement of the female genital tract by histoplasmosis is exceedingly rare, with cervical disease not having been described previously.


Recent advances in therapeutic modalities and vaccines to counter COVID-19/SARS-CoV-2.
The novel coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has rapidly spread across the world. This resulted an alarming number of fatalities with millions of confirmed infected cases, pretending severe public health, economic, and social threats. There is no specific therapeutic drugs or licensed vaccines or treatments to fight against lethal COVID-19 infections. Given the significant threats of COVID-19, the global organizations are racing to identify epidemiological and pathogenic mechanisms of COVID-19 to find treatment regimens and effective therapeutic modalities for future prevention. Herein, we reviewed the therapeutic interventions and vaccines for COVID-19 based on the existing knowledge and understanding of similar coronaviruses, including MERS-CoV and SARS-CoV. The information constitutes a paramount intellectual basis to sustenance ongoing research for the discovery of vaccines and therapeutic agents. This review signifies the most available frontiers in the viral vaccine development approaches to counter the COVID-19/SARS-CoV-2.


Diagnosis of bacterial meningitis and septicemia by serum counterimmunoelectrophoresis.
We compare the results obtained by counterimmunoelectrophoresis in samples of serum and cerebrospinal fluid with microbiologic methods for 3,298 patients suspected of bacterial meningitis and/or septicemia at Instituto Adolfo Lutz, São Paulo, in a retrospective study of the period from July 1998 to July 1994. Of the 415 patients (12.6% of the total cases studied) who were positive by the serum test, only 249 (7.6% of the total cases studied) were also positive when cerebrospinal fluid was assayed. Thus, 40% of the positives (5.6% of the total) were identifiable by analysis of serum but not of cerebrospinal fluid. Neisseria meningitidis accounted for 77.7% (129) and Haemophilus influenzae for 22.3% (37) of the positive results obtained only when serum was examined. These data show that although sensitivity and specificity of serum counterimmunoelectrophoresis are relatively low compared to cerebrospinal fluid counterimmunoelectrophoresis, the serum test is necessary to complement cerebrospinal fluid counterimmunoelectrophoresis data.


[Features of cognitive audiory evoked potentials changes at participants of liquidation of chernobyl accident consequences the message II. the analysis of late component P300].
At 10 participants of liquidation of consequences of Chernobyl accident (middle age 50.5 +/- 4.0 years) and at 10 healthy persons (middle age 47.0 +/- 6.0 years) are performed complex neuropsychological examination and registration acoustical cognitive evoked potentials (EP) using odd-ball paradigms. Neuropsyhological research has revealed at liquidators disorders of the higher mental functions, such as aspontanity, decrease speech and a visual memory, and also deficit of higher motor functions. According to the analysis of amplitude-time characteristics of component P300 acoustical cognitive EP a decrease in amplitude of this component at liquidators in all areas of the brain, for both experimental situations for all stimulus in comparison with healthy persons the same age was revealed. At the analysis of latent period (LP) P300 at liquidators the most distinct increase was revealed in a situation of passive listening for all kinds of stimulus. The analysis of reactivity of LP in different experimental situations has shown that at healthy persons during passive listening had similar values for all kinds of stimulus, and an account situation the maximum values--for significant stimulus. For liquidators the type of reaction in the form of increase in LP values at the majority of stimulus in both experimental situations. The analysis of regional LP changes of component P300 has found out the maximum distinctions between groups in frontal area of the left hemisphere. Along with it at liquidators the type the reactions similar for all shown stimulus without dependence from their importance in comparison with norm is revealed "uneconomical, superfluous". It can testify about decreasing of attention and memory reserves and to promote disorder of the higher mental functions. The described of amplitude-time characteristics of component P300 of acoustical EP at liquidators EP can testify to delay of perception, processing and the information analysis in a combination to easing of inhibitory processes leading to the higher mental dysfunctions. The obtained data have similarity to people of old age, supporting a hypothesis about the accelerated ageing of a brain, and also about pathological development of processes of ageing as a result of influence of low doses of radiation.


Granulocyte-macrophage colony-stimulating factor (GM-CSF) in subjects with different stages of periodontitis according to the new classification.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional cytokine that regulates inflammatory responses in various autoimmune and inflammatory disorders. The purpose of this study was to analyze the gingival crevicular fluid (GCF) for GM-CSF, interleukin-1 beta (IL-1β), and macrophage inflammatory protein-1 alpha (MIP-1α) levels in patients with stage I, stage II, stage III, and stage IV periodontitis (SI-P, SII-P, SIII-P, and SIV-P). A total of 126 individuals were recruited for this study, including 21 periodontal healthy (PH), 21 gingivitis (G), 21 SI-P, 21 SII-P, 21 SIII-P, and 21 SIV-P patients. Plaque index (PI), gingival index (GI), presence of bleeding on probing (BOP), probing depth (PD), and attachment loss (AL) were used during the clinical periodontal assessment. GCF samples were obtained and analyzed by an enzyme-linked immunosorbent assay (ELISA). GCF GM-CSF, MIP-1α, and IL-1β were significantly higher in SII-P and SIII-P groups than in PH, G, and SI-P groups (p<0.05). There was no significant difference among the PH, G, and SI-P groups in IL-1β, GM-CSF, and MIP-1α levels (p>0.05). These results show that GM-CSF expression was increased in SII-P, SIII-P, and SIV-P. Furthermore, GM-CSF levels may have some potential to discriminate between early and advanced stages of periodontitis.


Small bowel allograft rejection detected by serum intestinal fatty acid-binding protein is reversible.
We hypothesized that, following experimental small bowel transplantation, immunosuppressive therapy initiated on the day of the initial rise in serum intestinal fatty acid-binding protein (I-FABP) would result in graft salvage. In previously published work, we showed that I-FABP was not detectable in the serum of isografted Lewis rats, but could be measured in the peripheral circulation during small bowel allograft rejection. A clinically useful method to monitor trans- planted allografts for rejection should detect the problem early in its evolution so that treatment to reverse the process would salvage a functional organ. Lewis rats served as recipients of LBNF1 out-of-continuity small bowel allografts and were studied in two groups: group I (control) received no immunosuppression and group II received cyclosporine (CsA, 15 mg/kg/d, p.o.) when I-FABP rose to > or = 80 ng/ml. Serum I-FABP was measured daily until the time of sacrifice. Full-thickness graft biopsies were obtained on postoperative days 3 (baseline), 6 or 7 (elevated I-FABP), 10, and 14 (sacrifice). Following transplantation baseline serum I-FABP (day 2 or 3) averaged < or = 10.0 ng/ml. I-FABP remained at baseline through day 5 (range 0-50 ng/ml) in all animals and then rose abruptly on either day 6 or 7 (range 86-150 ng/ml; P < 0.001 vs. baseline). Histology on day 6 or 7 revealed a mild-to-moderate cellular rejection. Cyclosporine therapy reversed the rejection reaction and restored the bowel to normal histology. Serum I-FABP returned to baseline. In untreated animals, serum I-FABP remained elevated for several days and then returned to baseline levels coincident with fulminant rejection and mucosal sloughing. I-FABP was released into the peripheral circulation early in the evolution of acute rejection in this model of small bowel transplantation. Immunosuppressive therapy initiated when elevated levels of I-FABP were detected in the serum resulted in graft salvage. Cyclosporine immunotherapy consistently reversed rejection in this model. This article represents the first report of salvage of small bowel allografts when immunosuppressive therapy was instituted prospectively on the basis of a serum marker. Immunoreactive I-FABP appears to hold significant potential as a biochemical screening tool for acute rejection occurring In small bowell allografts.


Determinants of chronic fatigue in disease-free breast cancer patients: a cross-sectional study.
Quality of life after cancer treatment becomes more important as the number of long-term survivors increases. This study aimed to investigate complaints of fatigue after treatment for breast cancer. The study patients were 150 women who had finished curative treatment for breast cancer by a mean of 29 months before commencement of this study. Measurements included computerised questionnaires and a daily Self-Observation List. Thirty-eight per cent of the sample were severely fatigued, compared with 11% in a matched sample of women without a history of cancer. No association was found between fatigue and former treatment. The 'severely fatigued disease-free breast cancer patient' scored more 'problematic' on psychological well-being, functional impairment, sleep disturbance, physical activity, social support, neuropsychological and social functioning compared with the 'non-severely fatigued disease-free breast cancer patient'. Furthermore, the severely fatigued patients had a lower sense of control with respect to their fatigue complaints and stronger breast cancer- and psychologically-related attributions with regard to the causes of fatigue compared with the non-severely fatigued patients. Regression analyses indicated that sleep disturbance, physical activity and causal attributions contributed significantly to the subjective experience of fatigue. Severe fatigue is a problem for almost 40% of the sample of breast cancer survivors. Severe fatigue is related to physical, psychological, social, cognitive and behavioural factors.


Bone maturation reflects the secular trend in growth.
The aim of this study was to compare a series of X-rays from the mid-1990s with another taken in the mid-1980s in order to test the possibility that environmental causes affect the skeletal maturation. The first group of subjects included a total of 1,057 girls and 1, 055 boys participating in a project for Japan and China health research in 1986. The second group of subjects included a total of 382 girls and 629 boys participating in a project for bone mineral density research in 1996. The skeletal maturity score using the Tanner-Whitehouse 2-RUS method was used as the fundamental datum. This score was used to represent each group. The Wilcoxon's rank sum test was applied to examine the significance of the difference between the 1986 and the 1996 groups. The 1996 children had not matured more than the 1986 children; children in both groups reached the given scores at almost the same ages. In girls, there was little difference between the groups at 7 years of age, but it declined from 8 years of age onward. Some apparent differences arose at ages 14 and 15, but ceased by age 16 in girls. In boys, no differences were found in those aged from 7 to 17 years, except for 12-year-olds. We did not detect much of a difference in bone maturation between the 1986 and 1996 groups of children, and no differences in height during the same period. Our findings suggest that bone maturation reflects the secular trend in growth.


[IIa/IIo conversion of RNA polymerase II during heat shock].
Heat-shock treatment of cells activates a protein kinase which phosphorylates a heptapeptide analogous to the repeated motif of the C-terminal domain (CTD) of the large subunit of RNA polymerase II from mammalian cells. This is corroborated with a modification of the large subunit of this enzyme during thermal stress in HeLa cells. We have observed a shift from the IIa form (unphosphorylated) to the IIo form (phosphorylated) with a higher apparent molecular weight, during a heat-shock at 44, 45 or 46 degrees C and by a chemical stress induced by sodium arsenite. RNA polymerase II hyperphosphorylation, together with the activation of the heat-shock transcription factor, might contribute to the onset of the preferential transcription of heat-shock genes.


Protective effect of Crataegus oxyacantha against reperfusion arrhythmias after global no-flow ischemia in the rat heart.
The protective effect against reperfusion arrhythmias of a 3-month oral pretreatment with a dried extract of Crataegus oxyacantha (LI 132)(standardized to 2.2% flavonoids) was studied with the Langendorff heart of the rat after global no-flow ischemia. The heart was perfused with a modified Krebs-Henseleit solution in which the K+ content was reduced to 3.4 mmol/l in order to lower the fibrillation threshold. According to pilot experiments which considered various durations of global no-flow ischemia ranging from 10 to 20 minutes, two durations were chosen for the present study: 20 minutes (group 20) in which ventricular fibrillation (VF) was the predominant form of arrhythmias, and 18 minutes (group 18) in which the prevalence of VF was markedly lower despite the small difference in the duration of ischemia. Crataegus pretreatment significantly (p = 0.02) reduced the average prevalence of malignant arrhythmias (VF + Flutter) as observed during the 20-min-period of reperfusion as follows: group 20: from 89% (control, n = 9) to 51% (LI 132, n = 7), group 18: from 48% (control, n = 8) to 8% (LI 132, n = 8). In group 20, ventricular tachycardia (VT) could be observed only in the treated group, because of the predominance of VF in the control group. LI 132 pretreatment reduced the average prevalence of VT in group 18 in spite of the identical percentage of occurrence (6 out of 8 rats, with and without treatment) due to a shorter duration of the VT episodes. Thus, under the conditions of our experiments, effective prevention against reperfusion arrhythmias by Crataegus pretreatment was evident.


Meta-Analysis of Randomized Controlled Trials of the Effects of Tai Chi on Blood Pressure.
The purpose of this study was to investigate the influences of Tai Chi on blood pressure (BP) using the meta-analysis. This paper used 6 e-resource databases, and randomized controlled trials on the role of Tai Chi on blood pressure were retrieved. Besides, the meta-analysis was conducted according to the guidelines of the Moose-recommendations and applied with Review Manager 5.3, and the risk of bias assessment was performed with the Cochrane Collaboration's tool. The inclusion, data extraction, and risk of bias assessment were independently finished by two researchers. There are 24 trials meeting the criteria of inclusion and the results were reviewed. The meta-analysis indicates that, compared with no exercise, Tai Chi had the influence of lowering systolic blood pressure (mean difference = -6.07, 95%CI (-8.75, -3.39), P < 0.00001) and diastolic blood pressure (mean difference MD = -3.83, 95%CI (-4.97, -2.69), P < 0.00001). No significant discrepancies in all outcomes between Tai Chi and other aerobic exercises were discovered. Tai Chi can significantly reduce systolic and diastolic pressure than inactivity. However, Tai Chi does not show advantages in reducing blood pressure compared to other aerobic exercises. The trial is registered with CRD42020175306.


Induction of Rheb mRNA following middle cerebral artery occlusion in the rat.
Rheb is a recently identified member of the Ras super-family and is an immediate early gene that is rapidly and transiently induced in the hippocampal granule cells by NMDA-dependent synaptic activity in the long term potentiation paradigm. The close homologies with Ras and its rapid inducibility strongly suggest that Rheb shares many biochemical and signaling properties with Ras. The present study investigated the effect of middle cerebral artery (MCA) occlusion on the expression of Rheb mRNA in the rat brain. In situ hybridization autoradiography showed that Rheb mRNA was induced in the extensive regions of cerebral cortex and medial striatum surrounding the ischemic region and bilateral hippocampal formation following MCA occlusion. The induction of Rheb mRNA in the cingulate cortex persisted prominently at 24 h of MCA occlusion. Although the Rheb mRNA induction in the medial striatum and hippocampal formation decreased after 8h of occlusion, it still remained significant at 24h of occlusion. The data suggest the possibility that Ras signaling pathways can be implicated in the cerebral ischemia-elicited events through NMDA receptor activation.


[Toxoplasmosis of the brain as an example of the opportunistic invasion of the women HIV positive].
Most toxoplasmosis infections occur in the brain. Cerebral toxoplasmosis is a specially serious complication in patients with AIDS. Similarly to other opportunistic pathogens, Toxoplasma gondii causes rapidly progressive, and often fatal disease in immunosuppressed patients. The diagnosis is difficult, since no sensitive and specific non-invasive diagnostic tests exist. The subject of our study is a 27-old female initially diagnosed with metastasis in central nervous system.


Genome Engineering with TALE and CRISPR Systems in Neuroscience.
Recent advancement in genome engineering technology is changing the landscape of biological research and providing neuroscientists with an opportunity to develop new methodologies to ask critical research questions. This advancement is highlighted by the increased use of programmable DNA-binding agents (PDBAs) such as transcription activator-like effector (TALE) and RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated (Cas) systems. These PDBAs fused or co-expressed with various effector domains allow precise modification of genomic sequences and gene expression levels. These technologies mirror and extend beyond classic gene targeting methods contributing to the development of novel tools for basic and clinical neuroscience. In this Review, we discuss the recent development in genome engineering and potential applications of this technology in the field of neuroscience.


Total reconstruction of upper lip and columella with bipedicled depressor anguli oris island musculocutaneous flap.
The authors present the case report of a patient exhibiting upper lip deformity and total columella loss with cosmetic and functional impairment as a result of multiple previous facial carcinomata resections. Repair was achieved with bipedicled depressor anguli oris musculocutaneous island flap.


Clozapine and COVID-19: A Case Report and Clinical Considerations.
The emergence of coronavirus SARS-CoV-2, and the subsequent global epidemic of COVID-19, brought with it innumerable new clinical experiences across all medical specialties, and psychiatry is no exception. Individuals with serious mental illness, in particular schizophrenia and related disorders, may be especially susceptible to coronavirus infection given the overlapping risk factors of vulnerable sociodemographic status, increased challenges with quarantining requirements, and limited compliance with "respiratory etiquette." The case presented here describes a patient with schizophrenia who was being managed on clozapine and who developed symptomatic COVID-19 infection. Special care was taken to ensure that potential interactions between clozapine and the associated COVID-19 treatments were safe for the patient's mental and physical wellbeing. A 71-year-old schizophrenic Caucasian male is being managed with clozapine. While hospitalized, the patient was screened positive for COVID-19 and was admitted to the ICU due to his declining respiratory status. He was treated with both remdesivir and prednisone. He was able to fully recover from his COVID-19 infection. The authors review the clinical characteristics of the case, highlighting both the overlapping synergistic effects and antagonistic influences of clozapine therapy in combination with COVID-19 and its associated treatments. A review of the literature offers an opportunity to examine various frameworks for individualized clinical decision-making while making the case for greater epidemiologic research into the optimal management of individuals with a psychotic disorder who are diagnosed with COVID-19 infection.


A public/private partnership: the Royal Ottawa Hospital experience.
The last few years have seen some provincial governments introduce public/private partnerships (P3s) for the development and operation of healthcare facilities. One such case involves the redevelopment of the Royal Ottawa Hospital.


Effects of melatonin on spinal cord injury-induced oxidative damage in mice testis.
This study evaluated the effects of melatonin on spinal cord injury (SCI)-induced oxidative damage in testes. Adult male C57BL/6 mice were randomly divided into sham-, SCI- or melatonin (10 mg/kg, i.p.)-treated SCI groups. To induce SCI, a standard weight-drop method that induced a contusion injury at T10 was used. After 1 week, testicular blood flow velocity was measured using the Laser Doppler Line Scanner. Malondialdehyde (MDA), glutathione (GSH), oxidised glutathione (GSSG) and myeloperoxidase (MPO) were measured in testis homogenates. Microvascular permeability of the testes to Evan's Blue was examined by spectrophotometric and fluorescence microscopic quantitation. The tight junction protein zonula occludens-1 (ZO-1) and occludin in testes were assessed by immunoblot analysis. Melatonin increased the reduced blood flow and decreased SCI-induced permeability of capillaries. MDA levels and MPO activity were elevated in the SCI group compared with shams, which was reversed by melatonin. In contrast, SCI-induced reductions in GSH/GSSG ratio were restored by melatonin. Decreased expression of ZO-1 and occludin was observed, which was attenuated by melatonin. Overall, melatonin treatment protects the testes against oxidative stress damage caused by SCI.


Scorpion sting: a management problem.
Admissions for scorpion sting in 1 year and deaths resulting from scorpion sting over 3 years were analysed. Features that indicated the severity of the clinical condition were identified. Pulmonary oedema and shock were the usual causes of death. Poor management of fluid therapy was responsible for the frequently unsatisfactory resolution of envenoming, especially when purified human plasma was used. The role of the scorpion antivenom used is questioned and controversy regarding the most appropriate sedative to use in the management of scorpion sting is still not resolved. An in-depth study of these management issues is urgently required.


Early detection and screening for ovarian cancer: does physician specialty matter?
To examine physician factors associated with ovarian cancer screening. Postal questionnaires to Maryland primary care physicians. Bivariate tests for statistical significance used X-Square and Student's t tests. Multivariate analysis and logistic regression were used to analyze responses based on specialty type, gender, and work experience. Fifty-six percent of the 375 were male, 44%, females; 33%, OB/GYN; and 67%, family/internal medicine (FM/IM). The mean age was 47 and the mean number of years in practice was 16. OB/GYNs provided more ovarian cancer counseling, OR 2.64 (CI 1.55, 4.48) and were more likely to respond correctly to knowledge questions--i.e., reduction of ovarian cancer risk with oral contraceptive (OCP) use than IM/FM, OR 8.57 (CI 3.54, 20.8). Overall, there were few gender differences in approach to evaluation, but male physicians were less likely to be aware of the relationship of OCP use to ovarian cancer risk than females, OR 0.48 (CI 0.25, 0.91). IF/FM physicians were less likely to order CA-125 for patients (of any age) based upon symptoms of bloating or physical examination alone. OB/GYN physicians, OR 4.77 (2.73, 8.34) and physicians with > 15 years in practice, OR 2.79 (1.46, 5.35) attended more meetings on ovarian cancer than non OB/GYNs or those with less experience. Although 74% indicated access to the Internet, just 16% to 26% used the Internet for cancer information; OB/GYNs used the Internet less frequently than FM/IMs, OR 0.53 (0.28, 0.97). Specialty was more predictive of knowledge, approach to evaluation, and counseling than gender or experience.


WhiB4 Is Required for the Reactivation of Persistent Infection of Mycobacterium marinum in Zebrafish.
Granulomas are the pathological hallmark of tuberculosis (TB). In individuals with latent TB infection, Mycobacterium tuberculosis cells reside within granulomas in a nonreplicating dormant state, and a portion of them will develop active TB. Little is known on the bacterial mechanisms/factors involved in this process. In this study, we found that WhiB4, an oxygen sensor and a transcription factor, plays a critical role in disease progression and reactivation of Mycobacterium marinum (M. marinum) infection in zebrafish. We show that the whiB4::Tn mutant of M. marinum caused persistent infection in adult zebrafish, which is characterized by the lower but stable bacterial loads, constant number of nonnecrotized granulomas in fewer organs, and reduced inflammation compared to those of zebrafish infected with the wild-type bacteria or the complemented strain. The mutant bacteria in zebrafish were also less responsive to antibiotic treatments. Moreover, the whiB4::Tn mutant was defective in resuscitation from hypoxia-induced dormancy and the DosR regulon was dysregulated in the mutant. Taken together, our results suggest that WhiB4 is a major driver of reactivation from persistent infection. IMPORTANCE About one-quarter of the world's population has latent TB infection, and 5 to 10% of those individuals will fall ill with TB. Our finding suggests that WhiB4 is an attractive target for the development of novel therapeutics, which may help to prevent the reactivation of latent infection, thereby reducing the incidences of active TB.


A Systematic Review and Meta-analysis of Diabetes Associated Mortality in Patients with COVID-19.
Coronavirus disease 2019 (COVID-19) has been one of the deadliest pandemics in recent decade. The virus has specifically targeted the comorbid population in terms of mortality. The present systematic review and meta-analysis aimed to determine the overall mortality and diabetes-associated mortality in COVID-19 patients. To obtain the related data, six databases, including Pubmed, Embase, MEDLINE, Web of Science, Google Scholar, and DOAJ, were searched. The full-texts of articles presenting the data of COVID-19 mortality and diabetes-associated mortality were screened and retrieved. Statistical analysis was performed using the Stata (version 13). The odds ratio (OR) of mortality in diabetic patients was calculated with 95% confidence interval (CI). Random-effects model was used to synthesize data for the relevant outcomes. Heterogeneity was evaluated using I2 statistic. Forest plots visually showed the effect estimates of the included studies. We used funnel plots to evaluate potential publication bias. A two tailed P < 0.05 was considered as statistically significant. A total of 35 studies with 25,934 patients were finally included for meta-analysis. The pooled prevalence of diabetes mellitus in patients with COVID-19 was 16.8% (n = 4381). The overall mortality seen in all the studies was 12.81% (n = 3159), and diabetes-associated mortality was 22.14% (n = 970). The pooled analysis of included studies showed that diabetes mellitus had a significantly higher mortality rate (22.14% vs. 12.81%, P < 0.05) with higher odds of death (pooled OR 1.83, 95% CI: 1.61 - 2.05). The funnel plot was symmetric, thereby indicating a low risk of publication bias. In conclusion, the presence of diabetes was associated with a significantly increased risk of mortality in patients admitted to the hospital with COVID-19. Thus, this subpopulation must be continuously monitored for glycemic levels, coagulation abnormalities, and inflammatory surge.


[Treatment and outcome in small bowel cancer].
In adenocarcinoma of the small intestine, delays in diagnosis are frequent, and the majority of patients present with advanced- stage disease and either lymph node involvement or distant metastatic disease. Surgical resection is a mainstay in treatment of this disease, but the role of adjuvant therapy is unclear. Recent retrospective and prospective studies have helped to clarify the optimal chemotherapy approach for advanced small bowel adenocarcinoma. The combination of capecitabine and oxaliplatin is reportedly highly effective. Further clinical studies on this rare type of tumor are needed. This article reviews the focuses on recent advances in management. The 72nd Japanese Society for Cancer of the Colon and Rectum have conducted a retrospective review of Japanese patients with adenocarcinoma of the jejunum or ileum. The data indicated that although not statistically significant, there was a trend in median overall survival favoring the chemotherapy for advanced jejunal or ileal adenocarcinoma (17 months vs. 8 months, p=0.114).


Morphologic and Microvascular Differences Between Macular Neovascularization With and Without Subretinal Fibrosis.
To evaluate morphologic and microvascular differences between eyes with and without subretinal fibrosis (SF) caused by neovascular age-related macular degeneration (nAMD). Patients with nAMD with a minimum history of 12 months of anti-VEGF treatment were prospectively included in this cross-sectional study. Patients were imaged using standard imaging, swept-source optical coherence tomography angiography for quantitative microvascular analysis and polarization-sensitive OCT as an ancillary method for automated SF segmentation. The presence of reticular pseudodrusen, hyperreflective foci (HRF), and outer retinal tubulation (ORT) were also evaluated. Sixty eyes of 60 participants (37 female) with nAMD and a mean 3.1 (±2.7)-year history of anti-VEGF treatment were included, 20 (33%) of which were diagnosed with SF. Eyes with SF had a higher prevalence of ORT (P < 0.001) and a lower prevalence of HRF (P = 0.004) than eyes without SF. Fifty eyes were analyzed quantitatively for microvascular biomarkers. Eyes with SF had a larger greatest vascular caliber (P = 0.001) and greatest linear diameter (P = 0.042), a larger microvascular neovascularization (MNV) area (P = 0.026), larger vessel area (P = 0.037), higher number of vessel junctions (P = 0.025), longer total vessel length (P = 0.027), higher number of vessel endpoints (P = 0.007), and higher endpoint density (P = 0.047). This multimodal imaging approach demonstrated in vivo microvascular and morphological differences in eyes with and without SF. Eyes with SF tend to have larger MNV lesions with thicker vessels and are often associated with the presence of ORT. This study points out imaging biomarkers in patients with SF, which may help identifying high-risk patients.


Dumbbell-Shaped Ternary Transition-Metal (Cu, Ni, Co) Phosphate Bundles: A Promising Catalyst for the Oxygen Evolution Reaction.
Development of economical and high-performance electrocatalysts for the oxygen evolution reaction (OER) is of tremendous interest for future applications as sustainable energy materials. Here, a unique member of efficient OER electrocatalysts has been developed based upon structurally versatile dumbbell-shaped ternary transition-metal (Cu, Ni, Co) phosphates with a three-dimensional (3D) (Cu2(OH)(PO4)/Ni3(PO4)2·8H2O/Co3(PO4)2·8H2O) (CNCP) structure. This structure is prepared using a simple aqueous stepwise addition of metal ion source approach. Various structural investigations demonstrate highly crystalline nature of the composite structure. Apart from the unique structural aspect, it is important that the CNCP composite structure has proved to be an excellent electrocatalyst for OER performance in comparison with its binary or constituent phosphate under alkaline and neutral conditions. Notably, the CNCP electrocatalyst displays a much lower overpotential of 224 mV at a current density of 10 mA cm-2 and a lower Tafel slope of 53 mV dec-1 with high stability in alkaline medium. In addition, X-ray photoelectron spectroscopy analysis suggested that the activity and long-term durability for the OER of the ternary 3D metal phosphate are due to the presence of electrochemically dynamic constituents such as Ni and Co and their resulting synergistic effects, which was further supported by theoretical studies. Theoretical calculations also reveal that the incredible OER execution was ascribed to the electron redistribution set off in the presence of Ni and Cu and the most favorable interaction between the *OOH intermediate and the active sites of CNCP. This work may attract the attention of researchers to construct efficient 3D ternary metal phosphate catalysts for various applications in the field of electrochemistry.


Characterization of Methylobacterium strains isolated from the phyllosphere and description of Methylobacterium longum sp. nov.
Methylobacterium strains are abundantly found in the phyllosphere of plants. Morphological, physiological and chemotaxonomical properties of 12 previously isolated strains were analyzed in order to obtain a more detailed overview of the characteristics of phyllosphere colonizing Methylobacterium strains. All strains showed the typical properties of the genus Methylobacterium, including pink pigmentation, facultative methylotrophy, a fatty acid profile dominated by C18:1 ω7c, and a high G+C content of 65 mol % or more. However, some strains showed only weak growth on methanol and pigmentation varied from pale pink to red. Strains grew best under mesophilic, neutrophilic conditions and low salt (≤1%) concentrations, but variation was seen with respect to the temperature and pH range under which growth occurred. Likewise, differences were seen with respect to carbon source utilization. Some strains were versatile and utilized diverse organic acids, amino acids and sugars, while others could only metabolize a restricted number of organic acids. The strains that were most distinct from existing type strains based on 16S rRNA gene sequence analysis were selected for DNA-DNA hybridization experiments to analyze whether they are sufficiently different at the genomic level from existing type strains to justify their classification as new species. This resulted in the delineation of strain 440 and its description as Methylobacterium longum sp. nov. strain 440 (=DSM 23933(T) = CECT 7806(T)). A main characteristic of this species is the formation of relatively long rods compared to other Methylobacterium species.


The significance of preoperative shoulder arthrography in painful arc patients.
Preoperative shoulder arthrography was performed on 34 patients with painful arc syndromes. Rotator cuff rupture was diagnosed in 20 cases. Out of these the arthrography correctly showed rupture in 17 cases, while in one case rupture was not seen and two examinations were unsuccessful. Rotator cuff rupture was not found in 14 cases at operation. Of these, arthrography had been negative in eight cases and in six cases the rupture had merely been suspected. Sensitivity of shoulder arthrography in showing rotator cuff rupture was thus 85%, specificity 57% and accuracy 74%. The biceps tendon was intact in all cases with rotator cuff rupture. So-called "bicipital leakage" was seen in four cases, but its significance remains unclear.


Safety considerations in providing allergen immunotherapy in the office.
This review highlights the risks of allergy immunotherapy, methods to improve the quality and safety of allergy treatment, the current status of allergy quality metrics, and the future of quality measurement. In the current healthcare environment, the emphasis on outcomes measurement is increasing, and providers must be better equipped in the development, measurement, and reporting of safety and quality measures. Immunotherapy offers the only potential cure for allergic disease and asthma. Although well tolerated and effective, immunotherapy can be associated with serious consequence, including anaphylaxis and death. Many predisposing factors and errors that lead to serious systemic reactions are preventable, and the evaluation and implementation of quality measures are crucial to developing a safe immunotherapy practice. Although quality metrics for immunotherapy are in their infancy, they will become increasingly sophisticated, and providers will face increased pressure to deliver safe, high-quality, patient-centered, evidence-based, and efficient allergy care. The establishment of safety in the allergy office involves recognition of potential risk factors for anaphylaxis, the development and measurement of quality metrics, and changing systems-wide practices if needed. Quality improvement is a continuous process, and although national allergy-specific quality metrics do not yet exist, they are in development.


Modeling longitudinal changes in buprenorphine treatment outcome for opioid dependence.
The present analysis describes the longitudinal change in buprenorphine treatment outcome. It also examines several participant characteristics to predict response to buprenorphine. Participants (n=501, age>15 years) received buprenorphine/naloxone treatment for 4 weeks, and then were randomly assigned to undergo dose tapering over either 7 days or 28 days. An empirical model was developed to describe the longitudinal changes in treatment outcome. Several patient characteristics were also examined as possible factors influencing treatment outcome. We have developed a model that captures the general behavior of the longitudinal change in the probability of having an opioid-negative urine sample following buprenorphine treatment. The model captures both the initial increase (i. e., initial response) and the subsequent decrease (i. e., relapse to opioid) in the likelihood of providing an opioid-negative urine sample. Characteristics associated with successful buprenorphine treatment outcome include: having a negative urine test for drugs, having alcohol problems [assessed using alcohol domain of addiction severity index (ASI-alcohol)] at screening, being older, and receiving low cumulative buprenorphine dose. However, ASI-alcohol values were generally low which make the application of the proposed alcohol effect for patients with more severe alcohol problems questionable. A novel approach for analyzing buprenorphine treatment outcome is presented in this manuscript. This approach describes the longitudinal change in the probability of providing an opioid-free urine sample instead of considering opioid use outcome at a single time point. Additionally, this model successfully describes relapse to opioid. Finally, several patient characteristics are identified as predictors of treatment outcome.


Outcome of twin pregnancies in North Jordan.
In a retrospective study we examined the outcome of twins delivered at Princess Badee'a Teaching Hospital from 1 January 1996 to 30 June 1999. The incidence of twin pregnancy was 1/86 with a gross perinatal mortality rate of 178 per 1000. Breech presentation was associated with the highest perinatal mortality rate (278 per 1000). One hundred and eighty-four out of the 386 twin pregnancies were preterm with the highest perinatal mortality rate (184 per 1000). The neonatal Mortality rate fell with increasing birthweight from 532 per 1000 at 1500 g to 16 per 1000 at 2500 g. Our results showed that the risk factors were mainly prematurity, low birthweight, pregnancy-induced hypertension, lack of proper antenatal care, birth asphyxia, and malpresentation.


[Tumor necrosis factor in sputa of patients with bronchial asthma on exacerbation].
TNF is a cytokine recently implicated as an important inflammatory mediator. TNF concentrations in sputa from 13 patients with bronchial asthma on exacerbation and 12 patients with chronic obstructive pulmonary disease were measured. After sonication, the sputa were centrifuged. The supernatants were assayed for the presence of TNF by use of an enzyme-linked immunosorbent assay. TNF was detected in all patients with bronchial asthma (1783 +/- 420 pg/ml), while low values of TNF were detected in only 5 of the 12 COPD patients. It is suggested that TNF is involved in airway inflammation in bronchial asthma.


Using Lean Process Improvement to Enhance Safety and Value in Orthopaedic Surgery: The Case of Spine Surgery.
Lean methodology was developed in the manufacturing industry to increase output and decrease costs. These labor organization methods have become the mainstay of major manufacturing companies worldwide. Lean methods involve continuous process improvement through the systematic elimination of waste, prevention of mistakes, and empowerment of workers to make changes. Because of the profit and productivity gains made in the manufacturing arena using lean methods, several healthcare organizations have adopted lean methodologies for patient care. Lean methods have now been implemented in many areas of health care. In orthopaedic surgery, lean methods have been applied to reduce complication rates and create a culture of continuous improvement. A step-by-step guide based on our experience can help surgeons use lean methods in practice. Surgeons and hospital centers well versed in lean methodology will be poised to reduce complications, improve patient outcomes, and optimize cost/benefit ratios for patient care.


A microfluidic DNA library preparation platform for next-generation sequencing.
Next-generation sequencing (NGS) is emerging as a powerful tool for elucidating genetic information for a wide range of applications. Unfortunately, the surging popularity of NGS has not yet been accompanied by an improvement in automated techniques for preparing formatted sequencing libraries. To address this challenge, we have developed a prototype microfluidic system for preparing sequencer-ready DNA libraries for analysis by Illumina sequencing. Our system combines droplet-based digital microfluidic (DMF) sample handling with peripheral modules to create a fully-integrated, sample-in library-out platform. In this report, we use our automated system to prepare NGS libraries from samples of human and bacterial genomic DNA. E. coli libraries prepared on-device from 5 ng of total DNA yielded excellent sequence coverage over the entire bacterial genome, with >99% alignment to the reference genome, even genome coverage, and good quality scores. Furthermore, we produced a de novo assembly on a previously unsequenced multi-drug resistant Klebsiella pneumoniae strain BAA-2146 (KpnNDM). The new method described here is fast, robust, scalable, and automated. Our device for library preparation will assist in the integration of NGS technology into a wide variety of laboratories, including small research laboratories and clinical laboratories.


Acute presentation of a solid pseudopapillary tumor of the pancreas.
We report a case of acute presentation of a solid pseudopapillary tumor of the pancreas in a young boy who had suffered a blunt abdominal trauma. Urgently performed CT examination and repeated ultrasound revealed a subhepatic mass, which gradually increased in size, but the imaging features were not specific enough to permit a precise diagnosis. Because signs of peritoneal irritation and increased circulatory instability gradually developed within the hours of observation, the decision was made to perform an urgent exploratory laparotomy. The exploration revealed a hematoperitoneum and a large hematoma-like subhepatic bleeding mass. Further exploration showed that this mass was a tumor arising from the head of the pancreas, which had ruptured on the surface. A curative pancreatoduodenectomy was performed. Pathohistological examination of the resected specimen revealed a solid pseudopapillary tumor of the pancreas, an extremely rare tumor predominantly occurring in adolescent girls and in young adult women. It has a favorable prognosis if resected radically. The boy in our report is feeling well 36 months after the operation.


catena-Poly[bis(μ-2,2'-bipyridin-6-olato)-κ³N,N':O;O:N,N'-dicopper(I,II) [[tetrafluoridoniobium(V)]-μ-oxido]].
A novel copper-niobium oxyfluoride, {[Cu₂(C₁₀H₇N₂O)₂][NbOF₄]}n, has been synthesized by a hydrothermal method and characterized by elemental analysis, EDS, IR, XPS and single-crystal X-ray diffraction. The structural unit consists of one C₂-symmetric [NbOF₄]⁻ anion and one centrosymmetric coordinated [Cu₂(obpy)₂]⁺ cation (obpy is 2,2'-bipyridin-6-olate). In the [NbOF₄]⁻ anion, each NbV metal centre is five-coordinated by four F atoms and one O atom in the first coordination shell, forming a square-pyramidal coordination geometry. These square pyramids are then further connected to each other via trans O atoms [Nb-O = 2.187 (3) Å], forming an infinite linear {[NbOF₄]⁻}n polyanion. In the coordinated [Cu₂(obpy)₂]⁺ cation, the oxidation state of each Cu site is disordered, which is confirmed by the XPS results. The disordered Cu sites are coordinated by two N atoms and one O atom from two different obpy ligands. The [NbOF₄]⁻ and [Cu₂(obpy)₂]⁺ units are assembled via weak C-H∙∙∙F hydrogen bonds, resulting in the formation of a three-dimensional supramolecular structure. π-π stacking interactions between the pyridine rings [centroid-centroid distance = 3.610 (2) Å] may further stabilize the crystal structure.


Introduction to international perspectives on therapeutic jurisprudence
Therapeutic Jurisprudence (TJ), a concept first conceived by law professors David Wexler (University of Puerto Rico and University of Arizona) and Bruce Winick (University of Miami) only a little more than a decade ago, has emerged as the leading conceptual perspective in the mental health law field. Indeed, a LEXIS search reveals well over 150 articles on, or citing to, therapeutic jurisprudence in American law review publications in the past decade (terms used were "therapeutic w/5 jurisprudence w/25 Wexler or Winick"). Copyright 1999 John Wiley & Sons, Ltd.


The common MELAS mutation A3243G in mitochondrial DNA among young patients with an occipital brain infarct.
The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) may present with symptoms that resemble a stroke. The strokelike episodes most commonly involve the posterior part of the cerebrum. We identified retrospectively 38 patients with an occipital stroke between ages 18 to 45 years during a 19-year period in a hospital serving as the only neurologic center for a specific population. The common MELAS mutation at the base pair 3243 (A3243G) of the mitochondrial DNA (mtDNA) was analyzed in blood samples. We found four patients (10%) with a clinical or molecular diagnosis of a mitochondrial disorder. Two of the patients carried the A3243G mutation, suggesting frequencies of 6% among patients younger than 45 years of age and 14% among patients younger than 30 years for this mutation. Furthermore, we identified two patients with a clinically definite mitochondrial disorder, and sequencing of the 22 transfer RNA genes revealed the mtDNA mutation A12308G in one patient. Clinical evaluation revealed that occipital stroke was part of a more complex syndrome in these four patients. These population-based findings demonstrate that the A3243G mutation in the mtDNA, and mitochondrial disorders are not uncommon among young patients with occipital stroke.


Mechanical characterization of one-headed myosin-V using optical tweezers.
Class V myosin (myosin-V) is a cargo transporter that moves along an actin filament with large (approximately 36-nm) successive steps. It consists of two heads that each includes a motor domain and a long (23 nm) neck domain. One of the more popular models describing these steps, the hand-over-hand model, assumes the two-headed structure is imperative. However, we previously succeeded in observing successive large steps by one-headed myosin-V upon optimizing the angle of the acto-myosin interaction. In addition, it was reported that wild type myosin-VI and myosin-IX, both one-headed myosins, can also generate successive large steps. Here, we describe the mechanical properties (stepsize and stepping kinetics) of successive large steps by one-headed and two-headed myosin-Vs. This study shows that the stepsize and stepping kinetics of one-headed myosin-V are very similar to those of the two-headed one. However, there was a difference with regards to stability against load and the number of multisteps. One-headed myosin-V also showed unidirectional movement that like two-headed myosin-V required 3.5 k(B)T from ATP hydrolysis. This value is also similar to that of smooth muscle myosin-II, a non-processive motor, suggesting the myosin family uses a common mechanism for stepping regardless of the steps being processive or non-processive. In this present paper, we conclude that one-headed myosin-V can produce successive large steps without following the hand-over-hand mechanism.


Trends in hospital morbidity among adults in the region of Monastir (Tunisia) between 1996 and 2007.
To study trends of hospital morbidity among adults in the region of Monastir during a period of 12 years (1996 - 2007). We analyzed data from the morbidity database of the university hospital of Monastir (Tunisia) between 01/01/1996 and 31/12/2007. Data were drawn from the register of hospital morbidity implemented in the Department of Preventive Medicine and Epidemiology since 1995. The International Classification of Diseases (tenth revision) was used to identify and classify morbid conditions. During the study period, we collected 150749 admissions with male tendency (sex-ratio = 1.27). Among these admissions 24.4% were over than 64 years. Morbid conditions were dominated by Ischemic Heart diseases (4.24%) followed by cancers and diabetes mellitus (3.3% and 2.52% respectively). Chronological trends, using Spearman correlation rank test, showed that overall rate of chronic conditions increased significantly from 4.4% in 1996 to 9.1% in 2007 (r'= |0.88|, p-value < 0.001). In contrast, the rate of infectious and parasitic diseases decreased from 4.3% to 2.9% (r'= |0.98|, p-value < 0.001). Morbidity trends reflect the epidemiological transition of our country and call to a backing of the ambulatory system and the development of specific services able to decrease the needs of hospitalizations.


Natural orifice surgery (NOTES) and biliary disease, is there a role?
Natural orifice translumenal endoscopic surgery (NOTES) is a term coined by a joint group of surgeons and gastroenterologists organized by Society for American Gastrointestinal Endoscopic Surgeons (SAGES) and American Society of Gastroenterologists (ASGE) to describe the fusion of minimally invasive surgery and interventional endoscopy. Current literature and compiled personal experience in NOTES was reviewed to provide an expert opinion on the role of NOTES in HPB surgery. The majority of experience obtained to date has been in animal models. The few human cases and clinical trials that have been performed show excellent promising outcomes with minimal morbidity. The merger of interventional endoscopy and minimally invasive surgery is a natural progression as we continually push the envelope of minimally invasive surgery. Endoscopic retrograde cholangiopancreatography, biliary stents and endoscopic ultrasonography have forever changed treatment algorithms in HPB surgery. Advancement of minimally invasive surgery to include the liver resections, pancreatic resections and pseudocyst management has improved morbidity and become the standard of care in many cases. Continued development of natural orifice techniques may further alter the approaches to the biliary tract, liver and pancreas.


Apoptosis by a cytosolic extract from Fas-activated cells.
Fas is a type I membrane protein and its activation by binding of the Fas ligand or an agonistic anti-Fas antibody induces apoptosis in Fas-bearing cells. In this report we prepared lysates from cells treated with anti-Fas antibody. The lysates induced apoptotic morphological changes in nuclei from normal mouse liver, accompanied by DNA degradation. The apoptosis-inducing activity was quickly generated in cells by anti-Fas antibody and was found in the soluble cytosolic fraction. Induction of the activity in cells was inhibited by a tetrapeptide, acetyl-Tyr-Val-Ala-Asp-chloromethylketone, a specific inhibitor of interleukin-1 beta converting enzyme. Addition of COS cell lysates containing Bcl-2 to the assay significantly inhibited the apoptotic process, indicating that the in vitro process reflected apoptosis that occurs in intact cells.


Anxiety, anxiolytics and brain stimulation reinforcement.
The premise of this review is that neuronal substrates of anxiety are amenable to investigation using brain stimulation techniques. Anxiolytics such as meprobamate and the benzodiazepines may enhance intracranial self-stimulation (ICSS) behavior. Although demonstrated by numerous investigators, this effect shows considerable variability between and within laboratories. Some of this variability is explained by sedative/muscle relaxant effects, which are dissociable from drug-induced increases in ICSS and which may mask these increases. The anticonvulsant actions of anxiolytic drugs are unlikely to account for the increases in ICSS. Rather, anxiolytics appear to increase ICSS by attenuating concurrent aversive properties of stimulation. Consistent with this explanation, anxiolytic drugs attenuate escape from aversive dorsal tegmental stimulation. The neuronal substrates of this centrally mediated escape behavior differ from those mediating footshock-induced escape. Barbiturates also enhance ICSS, possibly due in part to an excitatory component that is not involved in benzodiazepine action. Inverse benzodiazepine agonists attenuate ICSS behavior in a manner that cannot be explained by nonspecific performance impairment. These substances, however, may not necessarily enhance stimulation-induced aversiveness. A strategy is proposed to integrate brain stimulation studies with molecular approaches to anxiety. Specifically, stimulation of sites associated with fear induction or fear reduction may selectively alter the release of endogeneous anxiogens or anxiolytic substances.


Transsphincteric repair of rectourethral fistulas following laparoscopic radical prostatectomy.
Rectourethral fistula is a serious complication following laparoscopic radical prostatectomy. We report our experience with a transsphincteric approach in the repair of this uncommon complication. The rectourethral fistula was repaired in a three-stage procedure comprising fecal diversion, transsphincteric repair of the fistula and, finally, closure of the stoma. Two patients with rectourethral fistulas underwent this procedure and the postoperative course was uneventful. In conclusion, a transsphincteric approach in the repair of rectourethral fistula by a three-stage procedure is safe and may be the treatment of choice.


[Methods of the demonstration of the lymphatic vessels].
The methodological tools for the study of the lymphatic vascular system are reviewed. The use of intraparenchymal and retrograde injection techniques often results in poorly reliable specimens, whereas direct injections allow an accurate topographical study of superficial and deep lymphatic vessels. The results obtained by the following methods are discussed: 1) Gerota's method (modified by Ottaviani, 1954) which can be carried out by glass needles and syringes and a mass of Prussian blue; 2) polymers injection as Geon, Rhodopas AX, "Mercox" methyl-methacrylate and Neoprene 842 A. Especially the last yields three-dimensional casts which are matchless in elegance and definition of the relationship between lymphatic and blood vessels; 3) three-dimensional models from serial ultrathin sections, which represent a fundamental tool in order to go through the processes of transendothelial transport; 4) in vivo cinematography documents the lymph pulsed flow, the contractile activity of superficial lymphatic collectors and the play of their valves.


Rapidly Progressive Right Atrial Angiosarcoma with Atrial Perforation.
Cardiac angiosarcomas are highly aggressive, extremely rare malignancies with a poor prognosis. We report the case of a 39-year-old woman presenting with a right atrial angiosarcoma with perforation of the right atrium. There is almost always a diagnostic lag for cardiac angiosarcoma, leading to a poor prognosis. Cardiovascular sarcoma is one of the most invasive malignant tumors. Radical resection surgery as the core of comprehensive treatment presently is the best treatment plan.


Paraxial mesoderm organoids model development of human somites.
During the development of the vertebrate embryo, segmented structures called somites are periodically formed from the presomitic mesoderm (PSM) and give rise to the vertebral column. While somite formation has been studied in several animal models, it is less clear how well this process is conserved in humans. Recent progress has made it possible to study aspects of human paraxial mesoderm (PM) development such as the human segmentation clock in vitro using human pluripotent stem cells (hPSCs); however, somite formation has not been observed in these monolayer cultures. Here, we describe the generation of human PM organoids from hPSCs (termed Somitoids), which recapitulate the molecular, morphological, and functional features of PM development, including formation of somite-like structures in vitro. Using a quantitative image-based screen, we identify critical parameters such as initial cell number and signaling modulations that reproducibly yielded formation of somite-like structures in our organoid system. In addition, using single-cell RNA-sequencing and 3D imaging, we show that PM organoids both transcriptionally and morphologically resemble their in vivo counterparts and can be differentiated into somite derivatives. Our organoid system is reproducible and scalable, allowing for the systematic and quantitative analysis of human spine development and disease in vitro.


Examination of tyrosine/adenine stacking interactions in protein complexes.
The π-stacking interactions between tyrosine amino acid side chains and adenine-bearing ligands are examined. Crystalline protein structures from the protein data bank (PDB) exhibiting face-to-face tyrosine/adenine arrangements were used to construct 20 unique 4-methylphenol/N9-methyladenine (p-cresol/9MeA) model systems. Full geometry optimization of the 20 crystal structures with the M06-2X density functional theory method identified 11 unique low-energy conformations. CCSD(T) complete basis set (CBS) limit interaction energies were estimated for all of the structures to determine the magnitude of the interaction between the two ring systems. CCSD(T) computations with double-ζ basis sets (e.g., 6-31G*(0.25) and aug-cc-pVDZ) indicate that the MP2 method overbinds by as much as 3.07 kcal mol(-1) for the crystal structures and 3.90 kcal mol(-1) for the optimized structures. In the 20 crystal structures, the estimated CCSD(T) CBS limit interaction energy ranges from -4.00 to -6.83 kcal mol(-1), with an average interaction energy of -5.47 kcal mol(-1), values remarkably similar to the corresponding data for phenylalanine/adenine stacking interactions. Geometry optimization significantly increases the interaction energies of the p-cresol/9MeA model systems. The average estimated CCSD(T) CBS limit interaction energy of the 11 optimized structures is 3.23 kcal mol(-1) larger than that for the 20 crystal structures.


Intensive home health care in the United States. Financing as technology.
This paper assesses the impact of mechanisms for financing intensive home health care services in the United States on their utilization. As lengths of stay have decreased in response to prospective payment methods for hospitals, demand has increased for intensive and complex services provided to patients in the home. Third-party payers, however, are willing to satisfy only some of this potential demand that their reimbursement policies have generated. It is the policies of payers rather than the safety and effectiveness of devices and procedures that are the major constraints on the expansion of intensive home health care. We describe the effects of these policies on who receives intensive home health care services, who provides them, what services are provided, how their quality is monitored, and what they cost.


Determination of macrocyclic lactone drug residues in animal muscle by liquid chromatography/tandem mass spectrometry.
A robust, credible, and practical multiresidue method based on liquid chromatography/tandem/mass spectrometry (LC/MS/MS) was developed for the simultaneous determination of 9 macrocyclic lactone drugs (abamectin B1a, doramectin, erythromycin, ivermectin B1a, josamycin, kitasamycin, roxithromycin, tilmicosin, and tylosin A) in bovine, porcine, chicken, and sheep muscles. The drugs were extracted with acetonitrile, and the extracts were defatted with n-hexane and further cleaned up on a C18 solid-phase extraction cartridge. LC/MS/MS data acquisition was achieved by using the multiple-reaction monitoring (MRM) mode, i.e., 2 transitions, to provide a high degree of sensitivity and repeatability. Matrix-matched standard calibration curves were used to achieve the best accuracy of the method by compensating for the matrix effect. The calibration graphs were linear (r > 0.998) from 10 to 1000 ng/mL for erythromycin, josamycin, kitasamycin, roxithromycin, tilmicosin, and tylosin, and from 5 to 250 ng/mL for abamectin, doramectin, and ivermectin. The average recoveries of the 9 drugs were between 64.5 and 105%, calculated by using matrix-matched calibration, with relative standard deviation values ranging from 1.6 to 14%. The limits of detection were 0.1 microg/kg for erythromycin, josamycin, roxithromycin, and tylosin; 0.2 microg/kg for tilmicosin and kitasamycin; and 0.5 microg/kg for abamectin, doramectin, and ivermectin. For confirmation, the MRM ratios for the 9 drug residues in the samples and the solvent were evaluated and found to be within the ratio criteria set by the guidelines of the European Union.


The Ecological Dynamics Framework: An Innovative Approach to Performance in Extreme Environments: A Narrative Review.
(1) Background: Uncertainty in extreme sports performance environments, such as climbing, provides considerable psycho-emotional and physiological demands, notably due to the many different environments in which climbing can be performed. This variety of environments, conditions of practice and engagement would challenge the acquisition of perceptual-motor skills; (2) Methods: To better understand how perceptual-motor skills are controlled and acquired in climbing, we proposed a narrative review anchored in the ecological dynamics theoretical framework and showed how this theoretical framework would support a nonlinear pedagogy to skill acquisition and to design safe learning and training situations that are representative of extreme performance contexts; (3) Results: We explained three theoretical pillars and we provide examples for design intervention following nonlinear pedagogy, notably (i) to set a constraint-led approach (in particular task constraint), (ii) to implement conditions of practice (constant vs. variable, imposed vs. self-controlled), (iii) to promote adaptive and creative behavioral variability during practice; (4) Conclusions: The challenge for the extreme sport practitioner is how to set up conditions of practice for efficient exploration in a manner that manages the dangers of performing in uncertain environments. Representing uncertainty within the relative safety of indoor settings may be one approach for preparing climbers for performance in extreme environments.


The benzil-cyanide reaction and its application to the development of a selective cyanide anion indicator.
The benzil-cyanide reaction is a cyanide-specific reaction that has been exploited to produce a colorimetric indicator for this toxic anion. This was done by producing a pi-extended analogue of benzil, 7, which is soluble in a 70:30 (v/v) mixture of methanol-water. In this medium, dilute solutions of 7 are yellow but produce colorless products when exposed to low concentrations of cyanide anion (> or = 1.7 microM; added as an aqueous NaCN solution), but no other common anions (e.g., OH(-), F(-), N3(-), benzoate(-), and H2PO4(-)). On the basis of these observations and supporting mechanistic analyses, it is concluded that the modified benzil system 7 is a promising cyanide anion indicator that is attractive in terms of its selectivity, ease-of-use, water compatibility, and the low, naked-eye discernible cyanide detection limit it provides.


[Evaluation of anti-inflammatory activity of extracts from Siberian plants].
Experimental investigations have shown that water-alcohol extracts from plants containing alkaloids (Aconitum baikalense, Aconitum septentrionale, Delphinium elatum L., Conium maculatum) and salicylic acid (Filipendula ulmaria, Salix viminalis, Fragaria vesca, Rubus idaeus) inhibited the development of main symptoms of inflammation, viz. exudation, pain, fever, to the same extent as non-steroidal anti-inflammatory agents. The substances studied in this work may be used to develop new efficient pharmacological preparations for the treatment of different inflammatory conditions associated with severe pain syndrome.


Detection of antibodies to the 97 kDa component of Toxoplasma gondii in samples of human serum.
This study was carried out to investigate the immune response against 97 kDa (p97) molecular marker of Toxoplasma gondii that has been characterized as a cytosolic protein and a component of the excreted-secreted antigens from this parasite. A total of 60 serum samples from patients were analyzed by enzime-linked immunosorbent assay and Western blot for toxoplasmosis. These samples were organized in three groups, based on clinical symptoms and results of serological tests. Group I: 20 samples reactive to IgG and IgM (acute phase); group II: 20 non-reactive samples (control group); and group III: 20 samples reactive only to IgG (chronic phase). Western blot was performed with total antigenic extracts or with excreted and secreted antigen from T. gondii to identify the fraction correspondent to p97. It was observed that this cytosolic component from T. gondii stimulates the immunologic system to produce both IgM and IgG antibodies in the beginning of the acute infection and IgG throughout the chronic stage of the asymptomatic toxoplasmosis.


Sub-millinewton thrust stand and wireless power coupler for microwave-powered small satellite thrusters.
The design and performance of a thrust stand for characterizing low-power electric propulsion thrusters are presented. The thrust stand is capable of sub-millinewton resolution for devices on the order of 1 kg. The architecture is based on a counter-weighted hanging pendulum design, a variant of the standard hanging pendulum that employs a counterweight to increase force resolution. Thrust is measured in a displacement mode using the change in position of the pendulum arm as measured by an optical displacement sensor. Passive eddy-current damping is used to offset oscillations and decrease setting time. An in situ calibration rig using known masses is used to calculate thrust. The thrust stand features an adjustable counterweight for in-vacuum sensitivity adjustment. In addition, the design of a broadband (600-2490 MHz) wireless microwave power coupler is presented. The device eliminates stiffness and thermal drift introduced by coaxial cables-typically the leading source of error in testing low-power microwave and radio frequency-powered thrusters. The thrust stand and coupler were tested using an electron cyclotron resonance magnetic nozzle thruster operating with xenon at flow rates from 1 to 10 sccm and powers ranging from zero (cold gas thrust) to 40 W. The resulting measurements showed a force resolution of ∼10μN over a range of thrusts from ∼14 to 600 µN.


Mapping local microstructure and mechanical performance around carbon nanotube grafted silica fibres: methodologies for hierarchical composites.
The introduction of carbon nanotubes (CNTs) modifies bulk polymer properties, depending on intrinsic quality, dispersion, alignment, interfacial chemistry and mechanical properties of the nanofiller. These effects can be exploited to enhance the matrices of conventional microscale fibre-reinforced polymer composites, by using primary reinforcing fibres grafted with CNTs. This paper presents a methodology that combines atomic force microscopy, polarised Raman spectroscopy, and nanoindentation techniques, to study the distribution, alignment and orientation of CNTs in the vicinity of epoxy-embedded micrometre-scale silica fibres, as well as, the resulting local mechanical properties of the matrix. Raman maps of key features in the CNT spectra clearly show the CNT distribution and orientation, including a 'parted' morphology associated with long grafted CNTs. The hardness and indentation modulus of the epoxy matrix were improved locally by 28% and 24%, respectively, due to the reinforcing effects of CNTs. Moreover, a slower stress relaxation was observed in the epoxy region containing CNTs, which may be due to restricted molecular mobility of the matrix. The proposed methodology is likely to be relevant to further studies of nanocomposites and hierarchical composites.


Study protocol of a pilot study evaluating feasibility and acceptability of a psychosexual intervention for couples postallogeneic haematopoietic stem cell transplantation.
Sexual dysfunction is one of the most common side effects of allogeneic haematopoietic stem cell transplantation (HSCT) for haematological cancers. Problems can persist between 5 and 10 years post-transplant and impact mood, couple intimacy and relationship satisfaction. Few intervention studies, however, target sexual dysfunction in patients post-HSCT. This pilot study aims to examine the feasibility and acceptability of implementing a psychosexual intervention for HSCT survivors and their partners post-transplantation. Fifteen allogeneic HSCT survivors and their partners will be recruited. Patients who are more than 3 months post-transplantation will be sent invitation letters describing the couples' psychosexual intervention that will be offered through this study. The intervention will comprise two components: (1) psychosexual education about medical and behavioural treatment options for sexual dysfunction delivered by a haematology nurse consultant; (2) emotionally focused therapy-based relationship education programme for couples delivered by a clinical psychologist (four sessions of 1.5 hours each). Couples who consent to participate will be administered a series of measures assessing mood, relationship satisfaction and sexual dysfunction preintervention and post-intervention, as well as satisfaction with the intervention postintervention. Feasibility of the intervention will be examined via recording enrolment rate, adherence, compliance with completing outcome measures and fidelity of intervention delivery. Ethics approval has been obtained at the Peter MacCallum Cancer Centre in Melbourne, Australia. Results will be presented at national and international conferences and published in a peer-reviewed journal so that in can be accessed by clinicians involved in the care of allogeneic HSCT patients. If this intervention is found to be feasible and acceptable, its impact will be examined in a future randomised controlled trial and subsequently implemented as part of routine care in the allogeneic HSCT population.


[Treatment of lingual angiocavernoma by selective arteriocatheterization with urea injection].
Selective arteriocatheterization with urea injection was administered to 36 cases of lingual angiocavernoma. There were 20 males and 16 females, ranging in age from 6 to 18 years with an average of 12 years. Two to five mililiters of 40% urea were injected once a day for 10-15 days as a course of treatment, 29 cases (80.6%) were cured in one course of treatment. The other 7 cases (19.4%) were cured in the 2nd course of treatment. The results suggest that selective arteriocatheterization with urea injection is a safe, convenient and effective technique in the treatment of ingual angiocavernoma.


The influence of personality on nicotine craving: a hierarchical multivariate statistical prediction model.
The present study proposes a hierarchical multivariate statistical prediction model which enables to determine the most prominent variables (physiological, biochemical and personality factors) related to nicotine craving and dopaminergic activation. Based on animal studies reporting a reduction of the rewarding effects of psychotropic drugs after blockade or destruction of the mesolimbic dopamine (DA) system, changes in nicotine craving after pharmacological manipulation by means of a DA agonist (lisuride 0.2 mg) and a DA antagonist (fluphenazine 2 mg) were assessed in 36 healthy male heavy smokers. The major aim was the development of a multivariate prediction model which is applicable in samples lacking variance homogeneity or the prerequisite of a multivariate normal distribution. The model proposed is a combination of multivariate parametric and nonparametric methods taking advantage of their individual merits. Especially personality variables, such as sensation seeking, impulsivity, and neuroticism showed to be important predictors of craving in this responder approach.


"Plasmo2D": an ancillary proteomic tool to aid identification of proteins from Plasmodium falciparum.
Bioinformatics tools to aid gene and protein sequence analysis have become an integral part of biology in the post-genomic era. Release of the Plasmodium falciparum genome sequence has allowed biologists to define the gene and the predicted protein content as well as their sequences in the parasite. Using pI and molecular weight as characteristics unique to each protein, we have developed a bioinformatics tool to aid identification of proteins from Plasmodium falciparum. The tool makes use of a Virtual 2-DE generated by plotting all of the proteins from the Plasmodium database on a pI versus molecular weight scale. Proteins are identified by comparing the position of migration of desired protein spots from an experimental 2-DE and that on a virtual 2-DE. The procedure has been automated in the form of user-friendly software called "Plasmo2D". The tool can be downloaded from http://184.108.40.206/Plasmo2D.zip.


Reductant-independent ATP hydrolysis catalyzed by homologous nitrogenase proteins from Azotobacter vinelandii and heterologous crosses with Clostridium pasteuranium.
Reductant-independent ATPase activity was initiated and studied for Azotobacter vinelandii and Clostridium pasteuranium nitrogenase proteins (Av1, Cp1 and Av2, Cp2, 1 designating the iron molybdenum protein and 2 the iron protein) and their heterologous crosses by two methods: (1) allowing dithionite to be depleted from a normal assay in the presence of substrate levels of MgATP and (2) using reduced but reductant-free nitrogenase proteins in the presence of substrate levels of MgATP. In both cases, at a 1:1 protein ratio, MgATP is converted initially to MgADP with a specific activity of 400-500 nmol MgATP hydrolyzed/min.mg Av1, but in slower steps the MgADP is converted to AMP and, after 12 h, AMP is ultimately converted to adenosine. This reactivity requires the presence of both proteins, increases with increasing Av2/Av1 ratio, and is not a result of unique redox states of either protein. For Av1-Av2, ATP hydrolysis in the absence of Mg2+ occurred at nearly the same rate as reductant-dependent MgATP hydrolysis. Reductant-independent ATPase activity also occurred for the Av1-Cp2 and Cp1-Av2 heterologous crosses and was 2-fold and 18-fold slower than the Av1-Av2 or Cp1-Cp2 combinations. In both cases further hydrolysis of MgADP to AMP and AMP to adenosine occurred. A unique nucleotide hydrolysis system is apparently operating in the complex formed between the two nitrogenase proteins in the absence of reductant. The relationship between the reductant-independent and reductant-dependent activities of nitrogenase catalysis is explored.


Gas-flow humidity control system for neutron reflectivity measurements.
We developed a novel humidity control system for neutron reflectivity measurements based on the two-way gas-flow method that can generate up to 85% relative humidity (RH) within a temperature range of 5 °C-85 °C. The system consists of a gas-flow-type humidity generator and a thermostatic sample chamber, each of which can independently control the temperature. The key features include rapid humidity response and long stable operation time. The humidity reaches equilibrium within 2 to 5 min during the humidity change, and the system exhibited acceptable stability over a three-day, nonstop experimental measurement duration, with a precision of ±1% RH at 85 °C and 85% RH. The sample chamber is capable of measuring substrate samples with dimensions of up to 2-in. in diameter and 5-mm in thickness. We demonstrate the reflectivity data measured at a pulsed neutron facility, MLF BL17, in the Japan Proton Accelerator Research Complex. The combined use of this system with neutrons permits in situ, time-resolved studies of the swelling process of polyvinyl alcohol and adhesive materials.


Sleep-dependent memory processing.
While the functions of sleep remain largely unknown, one exciting hypothesis is that sleep contributes importantly to processes of memory and brain plasticity. Over the last decade, a large body of work has provided substantive evidence supporting this role of sleep in what is becoming known as sleep-dependent memory processing. This review offers a summary of these data, focusing specifically on the role of sleep in (1) memory encoding, (2) memory consolidation (along with the brain basis of this process), and (3) neural plasticity. The clinical ramifications of such findings are also explored.


Excretion characteristics of tetrabromobisphenol-A in Wistar rats following mouth and nose inhalation exposure.
Tetrabromobisphenol-A (TBBPA), a brominated flame retardant with the largest production volume worldwide, is employed as a reactive and additive flame retardant, and also as an intermediate in the production of other retardants. The constant release of TBBPA into the environment has attracted increasing attention to its potent health effects. To date, the vast majority of health-related research on TBBPA has focused on oral exposure. This study aims to explore the excretion characteristics of TBBPA in living organisms following inhalation exposure. An inhalation exposure system was established in which the experimental animal model was exposed to inhalable particles (diameter < 10 μm) of TBBPA. The TBBPA aerosol doses used were 12.9, 54.6, 121.6, and 455.0 mg/m3 according to tuning system parameters. Following 14 d (2 h/d) of repeated inhalational exposure, the primary route of elimination was in feces for all exposed groups, and the values showed a significant positive linear relationship with exposure dose. In contrast, the elimination amount in urine was less than 0.4% of the inhaled dose. Trace levels of TBBPA (less than 0.1% of the inhaled dose) were also detected in serum, with amounts varying from 0 to 844 ng (per rat) among all groups.


Bouveret's syndrome: description of a case.
Bouveret's syndrome is a rare condition usually caused by a single large stone impacted in the duodenum. This is a cause of gastric outlet. Even if endoscopy is the mainstay of diagnosis, the radiographic examinations are also important too. Generally, the stones are too large to be removed endoscopically. Conservative endoscopic treatment should be attempted initially, and if it fails, surgical approach should be performed.


Transradial intervention of iliac and superficial femoral artery disease is feasible.
Percutaneous intervention of iliac artery (IA) and superficial femoral artery (SFA) disease is often performed via ipsilateral or contralateral femoral access. However, this approach may be difficult in patients with severe iliac or common femoral artery atherosclerosis, morbid obesity, or conditions prohibiting prolonged bed rest. Percutaneous transradial coronary intervention has gained popularity due to the low frequency of access site complications, early ambulation, and perhaps cost savings with early discharge. Transradial intervention (TRI) of IA and SFA disease has been previously described only in anecdotal case reports. Out of 159 patients who underwent IA and SFA intervention, 15 had their intervention attempted via the radial artery. TRI was attempted at the operator's discretion for one of the following reasons: absent femoral pulses, severe bilateral IA disease, obesity, or conditions prohibiting prolonged supine rest. Clinical and procedural characteristics were collected retrospectively. Fourteen patients (93%) had successful intervention completed through the transradial approach. One patient needing an intervention of the distal SFA was converted to contralateral femoral approach because of the inadequate stent shaft length. Eighteen IA lesions and six SFA lesions were treated successfully with a good final angiographic result via a 6 FR radial access system. The ankle brachial index improved from a mean of 0.66 to 0.93. None of the patients had any procedural or access site-related complications. TRI is a feasible and safe alternative for percutaneous treatment of IA and SFA disease in carefully selected patients.


The efficacy and safety of combined tiotropium and olodaterol via the Respimat(®) inhaler in patients with COPD: results from the Japanese sub-population of the Tonado(®) studies.
The efficacy and safety of once-daily tiotropium + olodaterol (T+O) maintenance treatment was demonstrated in the large, multinational, replicate, randomized, Phase III, Tonado(®) 1 (NCT01431274) and 2 (NCT01431287) studies in patients with moderate to very severe COPD. However, there may be racial differences in the effects of T+O on lung function in patients with COPD. In this Tonado(®) subgroup analysis, we assessed efficacy and safety of T+O in Japanese participants. Versus the overall population, the 413 Japanese patients randomized and treated were slightly older, with more men, lower body mass index, lower baseline St George's Respiratory Questionnaire (SGRQ) scores, fewer current smokers, but with higher pack-year smoking history. A lower proportion of Japanese patients used inhaled corticosteroids, short-acting muscarinic antagonists, or short- or long-acting β-adrenergic agonists at baseline, but use of long-acting muscarinic antagonists was higher. At Week 24, mean improvements with T+O 5/5 μg in forced expiratory volume in 1 second area under the curve from 0-3 hours response were 151 mL versus olodaterol and 134 mL versus tiotropium 5 μg; mean improvements with T+O 2.5/5 μg were 87 mL versus olodaterol and 70 mL versus tiotropium 2.5 μg. Mean improvements with T+O 5/5 μg in trough forced expiratory volume in 1 second were 131 mL versus olodaterol and 108 mL versus tiotropium 5 μg; mean improvements with T+O 2.5/5 μg were 60 mL versus olodaterol and 47 mL versus tiotropium 2.5 μg. SGRQ scores improved from baseline to a greater extent with both doses of T+O versus monotherapies. Responses were similar in the overall population. Adverse-event incidence was generally balanced across treatment groups. Consistent with results from the overall population, T+O 5/5 μg was superior to each monotherapy for lung function and SGRQ in the Japanese sub-population of patients with COPD in Tonado(®).


Efficient and Stable Red Emissive Carbon Nanoparticles with a Hollow Sphere Structure for White Light-Emitting Diodes.
Red-emissive solid-state carbon nanoparticles (CNPs) with a hollow sphere structure for white light-emitting diodes (WLEDs) were designed and synthesized by molecular self-assembly and microwave pyrolysis. Highly ordered graphite-like structures for CNPs were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, and ultraviolet-visible (UV-vis) spectroscopy. The emission mechanism of the red-emissive solid-state CNPs was investigated in detail by steady-state and time-resolved photoluminescence (PL) spectroscopy. The as-prepared CNPs showed a red emission band centered at 620 nm with excitation wavelength independence, indicating uniform size of sp2 carbon domains in the CNPs. The CNPs also had a PL quantum yield (QY) of 17% under 380 nm excitation. Significantly, the PL QY of the organosilane-functionalized CNPs was 47%, which is the highest value recorded for red-emissive solid-state carbon-based materials under UV-light excitation. More importantly, the red-emissive CNPs exhibited a PL QY of 25% after storage in air for 12 months, indicating their excellent stability. The red-emissive CNP powders were used as environmentally friendly and low-cost phosphors on a commercial 460 nm blue GaN-based chip, and a pure white light with CIE coordinates of (0.35, 0.36) was achieved. The experimental results indicated that the red-emissive CNP phosphors have potential applications in WLEDs.


Characterization of an insoluble polyimide oligomer by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
In the past two years, papers have appeared in the literature which demonstrate that matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectra can be obtained from matrix-analyte preparations which have been produced by grinding the two materials together until a powder of small particle size is obtained. In the present study that methodology was modified and applied to an insoluble polyimide oligomer, poly(4,4'-oxydiphenylenepyromellitimide) (POPM). Two matrix materials were employed in this analysis, 1,8 dihydroxyanthrone (dithranol) and 3-aminoquinoline, with and without an additional cationizing agent. The spectra obtained by this method are shown to be sensitive to the matrix employed in the analysis as well as the quantity of cationizing agent combined with the matrix.


Improved Gene Fusion Detection in Childhood Cancer Diagnostics Using RNA Sequencing.
Gene fusions play a significant role in cancer etiology, making their detection crucial for accurate diagnosis, prognosis, and determining therapeutic targets. Current diagnostic methods largely focus on either targeted or low-resolution genome-wide techniques, which may be unable to capture rare events or both fusion partners. We investigate if RNA sequencing can overcome current limitations with traditional diagnostic techniques to identify gene fusion events. We first performed RNA sequencing on a validation cohort of 24 samples with a known gene fusion event, after which a prospective pan-pediatric cancer cohort (n = 244) was tested by RNA sequencing in parallel to existing diagnostic procedures. This cohort included hematologic malignancies, tumors of the CNS, solid tumors, and suspected neoplastic samples. All samples were processed in the routine diagnostic workflow and analyzed for gene fusions using standard-of-care methods and RNA sequencing. We identified a clinically relevant gene fusion in 83 of 244 cases in the prospective cohort. Sixty fusions were detected by both routine diagnostic techniques and RNA sequencing, and one fusion was detected only in routine diagnostics, but an additional 24 fusions were detected solely by RNA sequencing. RNA sequencing, therefore, increased the diagnostic yield by 38%-39%. In addition, RNA sequencing identified both gene partners involved in the gene fusion, in contrast to most routine techniques. For two patients, the newly identified fusion by RNA sequencing resulted in treatment with targeted agents. We show that RNA sequencing is sufficiently robust for gene fusion detection in routine diagnostics of childhood cancers and can make a difference in treatment decisions.


Multifunctional AIEgens for Future Theranostics.
The combination of diagnosis and therapeutics into one theranostics system has attracted great interest in life science and biomedical fields. The current theranostic platform largely relies on the integration of multiple materials with different functionalities. The all-in-one approach has the risk of high complicity with reduced reproducibility. Smart design of simple molecules born with multifunctions should represent one of the future directions in theranostics. Fluorogens with aggregation-induced emission (AIEgens) are one type of such smart materials, which have attracted increasing attentions in recent years. In this concept, the key frontier developments of simple AIEgens with multifunctions for imaging and therapy are presented, which include fluorescence-photoacoustic imaging, fluorescence-magnetic resonance imaging, fluorescence image-guided photodynamic therapy, fluorescence image-guided chemotherapy and photoacoustic image-guided photothermal therapy. The smart molecular design to endow each AIEgen with strong capability to simultaneously offer two or more theranostic functions should attract more scientists into this exciting research direction.


The Development of Self-Control in Late Adolescence: An Analysis of Trajectories and Predictors of Change Within Trajectories.
Gottfredson and Hirschi argue that parenting is the primary source of self-control. Research on the etiology of self-control has provided partial support for this proposition. Studies have shown parenting is an important determinant of self-control; however, research has also shown that other social and biological/genetic factors also influence the development of self-control. The current study contributes to the literature by examining the possibility that sources of self-control may vary across subgroups, which exhibit different developmental patterns of self-control. Analyses are based on 6-year panel data from a sample of South Korean youths. The results indicate that youths are clustered into three subgroups showing stable, increasing, and decreasing levels of self-control over time. Similarities/differences in the relationships among family, school, peer, and community variables and self-control appeared across the subgroups. Theoretical and policy implications are discussed.


Evaluation of image guided motion management methods in lung cancer radiotherapy.
To evaluate the accuracy and reliability of three target localization methods for image guided motion management in lung cancer radiotherapy. Three online image localization methods, including (1) 2D method based on 2D cone beam (CB) projection images, (2) 3D method using 3D cone beam CT (CBCT) imaging, and (3) 4D method using 4D CBCT imaging, have been evaluated using a moving phantom controlled by (a) 1D theoretical breathing motion curves and (b) 3D target motion patterns obtained from daily treatment of 3 lung cancer patients. While all methods are able to provide target mean position (MP), the 2D and 4D methods can also provide target motion standard deviation (SD) and excursion (EX). For each method, the detected MP/SD/EX values are compared to the analytically calculated actual values to calculate the errors. The MP errors are compared among three methods and the SD/EX errors are compared between the 2D and 4D methods. In the theoretical motion study (a), the dependency of MP/SD/EX error on EX is investigated with EX varying from 2.0 cm to 3.0 cm with an increment step of 0.2 cm. In the patient motion study (b), the dependency of MP error on target sizes (2.0 cm and 3.0 cm), motion patterns (four motions per patient) and EX variations is investigated using multivariant linear regression analysis. In the theoretical motion study (a), the MP detection errors are -0.2 ± 0.2, -1.5 ± 1.1, and -0.2 ± 0.2 mm for 2D, 3D, and 4D methods, respectively. Both the 2D and 4D methods could accurately detect motion pattern EX (error < 1.2 mm) and SD (error < 1.0 mm). In the patient motion study (b), MP detection error vector (mm) with the 2D method (0.7 ± 0.4) is found to be significantly less than with the 3D method (1.7 ± 0.8,p < 0.001) and the 4D method (1.4 ± 1.0, p < 0.001) using paired t-test. However, no significant difference is found between the 4D method and the 3D method. Based on multivariant linear regression analysis, the variances of MP error in SI direction explained by target sizes, motion patterns, and EX variations are 9% with the 2D method, 74.4% with the 3D method, and 27% with the 4D method. The EX/SD detection errors are both < 1.0 mm for the 2D method and < 2.0 mm for the 4D method. The 2D method provides the most accurate MP detection regardless of the motion pattern variations, while its performance is limited by the accuracy of target identification in the projection images. The 3D method causes the largest error in MP determination, and its accuracy significantly depends on target sizes, motion patterns, and EX variations. The 4D method provides moderate MP detection results, while its accuracy relies on a regular motion pattern. In addition, the 2D and 4D methods both provide accurate measurement of the motion SD/EX, providing extra information for motion management.