[Study on activated carbon regeneration by heterogeneous catalytic wet oxidation].
The CuO-Al2O3 catalyzer was used to heterogeneous catalytic wet oxidation regeneration of activated carbon, which adsorbed the phenol saturated. The study found the effect of reaction factors on activated carbon regeneration by heterogeneous catalytic wet oxidation. And the optimum reaction condition was reaction temperature 210 degrees C, reaction time 60 min, catalyzer dosage 25 mg (calculated by Cu), reaction oxygen pressure 0.6 MPa at 25 degrees C, carbon 15 g (dry carbon), distilled water 300 mL. It was found that the catalyzer had good stability in this experiment by using X-rey radiation analysing catalyzer and experiment on catalyzer stability.


Temporal Dementia and Cognitive Impairment Trends in the Very Old in the 21st Century.
Long-increasing dementia incidence and prevalence trends may be shifting. Whether such shifts have reached the very old is unknown. To investigate temporal trends in the incidence of dementia and cognitive impairment and prevalence of dementia, cognitive impairment, Alzheimer's disease, vascular dementia, and unclassified dementia among 85-, 90-, and ≥ 95-year-olds in Sweden during 2000-2017. This study was conducted with Umeå 85 + /Gerontological Regional Database data from 2182 85-, 90-, and ≥ 95-year-olds in Sweden collected in 2000-2017. Using logistic regression, trends in the cumulative 5-year incidences of dementia and cognitive impairment; prevalences of dementia, cognitive impairment, Alzheimer's disease, and vascular dementia; and Mini-Mental State Examination thresholds for dementia diagnosis were estimated. Dementia and cognitive impairment incidences decreased in younger groups, which generally showed more-positive temporal trends. The prevalences of overall dementia, cognitive impairment, and Alzheimer's disease were stable or increasing; longer disease durations and increasing dementia subtype classification success may mask positive changes in incidences. Vascular dementia increased while unclassified dementia generally decreased. The cognitive health of the very old may be changing in the 21st century, possibly indicating a trend break.


Model of the proximal urethra: measurement of the urethral stress profile.
Research on the activity of the urinary tract has led to the creation of a theoretical mechanical model where elastic forces, affecting rigid segments represent the living tissue of the urethral walls whereby it is assumed that the tissue acts as an elastic material. Such a model provides a clearer picture of changes in the physical parameters of the elastic walls of the urethra and facilitates better analysis of measurement errors. Artefacts make it exceptionally difficult to accurately measure the urethral pressure profile. The known methods have a measurement error of at least 30%. We have been trying to eliminate the basic error caused by the size of the measuring sensor. The methods involves measuring the urethral pressure profile in one patients using several sensors of varying diameters. The problem was defined mathematically. By extrapolation of measuring points, the value of elastic force under normal conditions can be obtained. Preliminary results of pressure profile measurements in our patients are much more accurate than those of other currently known measuring techniques. It is too early, however, to predict the extent of increased objectivity in the results of the new method for measuring urethral pressure profile, with and without functional electrical stimulation. The parameters of stimuli produced by our electrical stimulators will be based upon these findings.


Workplace violence in healthcare: strategies for advocacy.
The Occupational Safety and Health Administration (OSHA) reports that over 2 million American workers are victims of workplace violence each year. Violence can strike any workplace; no area is immune. But who may be more at risk? Commonly, violence occurs at work and refers to a broad spectrum of behaviors (e.g., violent acts by patients, visitors, and/or coworkers) that result in a concern for personal safety. This article provides a brief overview of workplace violence, and discusses the settings where it often occurs. The authors consider the direct and indirect financial impact of violent acts, such as jury awards for injuries; higher than average turnover; increased requests for medical leaves; unusually high time and attendance issues; and stress related illnesses. Advocacy strategies for nurses are offered to address workplace violence on several levels, such as legislative advocacy, workplace policy, and education.


Ribosomal protein L3: influence on ribosome structure and function.
Early studies demonstrated roles for ribosomal protein L3 in peptidyltransferase center formation and the ability of cells to propagate viruses. More recent studies have linked these two processes via the effects of mutants and drugs on programmed -1 ribosomal frameshifting. Here, we show that mutant forms of L3 result in ribosomes having increased affinities for both aminoacyl- and peptidyl-tRNAs. These defects potentiate the effects of sparsomycin, which promotes increased aminoalcyl-tRNA binding at the P-site, while antagonizing the effects anisomycin, a drug that promotes decreased peptidyl-tRNA binding at the A-site. The changes in ribosome affinities for tRNAs also correlate with decreased peptidyltransferase activities of mutant ribosomes, and with decreased rates of cell growth and protein synthesis. In vivo dimethylsulfate (DMS) protection studies reveal that small changes in L3 primary sequence also have significant effects on rRNA structure as far away as 100 A, supporting an allosteric model of ribosome function.


Efficacy of PEGylated Interferon in Treatment-Experienced Chinese Patients With HBeAg Positive Chronic Hepatitis B.
After treatment cessation, a high prevalence of relapse was reported in chronic hepatitis B (CHB) patients in China, especially in nucleot(s)ide analogues (NUCs)-experienced patients. Re-treatment for these patients remains unsolved. This study aims to evaluate the efficacy of PEGylated interferon in HBeAg positive patients with exposure to antiviral therapy. A total of 55 treatment-experienced, HBeAg positive Chinese patients were enrolled in this study. Of these patients, 33 were NUCs-experienced and 22 were interferon-experienced. PEGylated interferon was administered to 34 patients; and 21 patients were retreated with conventional interferon. Of the 34 treatment-experienced patients who received PEGylated interferon, 52.9% achieved virologic response, and 41.2% achieved HBeAg loss and seroconversion. Patients who were treated with PEGylated interferon for 48 weeks achieved higher virologic response (80%); HBeAg loss (60%); HBeAg seroconversion (60%); and HBsAg loss (5%) than patients treated for 24 weeks with PEGylated interferon. Their responses were also higher than those who were treated with conventional interferon. HBeAg seroconversion in treatment-experienced patients was independently associated with 48-week PEGylated interferon therapy duration. PEGylated interferon was effective in treatment-experienced patients with HBeAg positive CHB, and showed higher rates of virological response, HBeAg loss, and seroconversion. The results provide important information regarding the role of re-treatment with PEGylated interferon in treatment-experienced HBeAg positive patients.


Brain Organoids-A Bottom-Up Approach for Studying Human Neurodevelopment.
Brain organoids have recently emerged as a three-dimensional tissue culture platform to study the principles of neurodevelopment and morphogenesis. Importantly, brain organoids can be derived from human stem cells, and thus offer a model system for early human brain development and human specific disorders. However, there are still major differences between the in vitro systems and in vivo development. This is in part due to the challenge of engineering a suitable culture platform that will support proper development. In this review, we discuss the similarities and differences of human brain organoid systems in comparison to embryonic development. We then describe how organoids are used to model neurodevelopmental diseases. Finally, we describe challenges in organoid systems and how to approach these challenges using complementary bioengineering techniques.


Experience of VA psychiatrists with pharmaceutical detailing of antipsychotic medications.
The interaction between physicians and the pharmaceutical industry has become a subject of increased interest and concern. This study surveyed a national sample of psychiatrists practicing within Department of Veterans Affairs (VA) medical centers in 2005. It specifically focused on the experiences of these physicians with representatives of the manufacturers of second-generation antipsychotics. VA psychiatrists were invited by e-mail to complete a Web-based questionnaire about their contact with representatives of each of the relevant pharmaceutical companies. Respondents were then questioned about several potential assertions about treatment effectiveness, side effects, and costs of these drugs. Of the 1,833 potential participants, 639 (35%) visited the Web site and completed the questionnaire. Among the responders, 558 (87%) reported at least one contact with company representatives. In the year before the survey the percentage of respondents reporting contact with representatives of each individual company varied from 58% to 70%. The three most commonly reported assertions made at any time in the past through direct speech during those meetings were that the representative's second-generation antipsychotic resulted in "a decreased risk of extrapyramidal symptoms" (79%), "greater symptom reduction than placebo" (78%), or "better negative symptom control than conventional antipsychotics" (77%). Statements least likely to be reported included that drugs resulted in "better positive symptom control than conventional antipsychotics" (36%), "better positive or negative symptom control than another atypical antipsychotic" (38%), and "increased risk of the development of diabetes mellitus" (39%). Comparing assertions reportedly made to VA psychiatrists with package insert information suggests that many assertions made by drug company representatives are inconsistent with prescribing information approved by the U.S. Food and Drug Administration, although assertions consistent with package insert information were more common than inconsistent ones.


[Diagnosis of urethral diverticulum in women].
Urethral diverticula have proved to be a common cause of recurrent urinary tract infections in female subjects. Positive-pressure urethrography, mostly performed by means of double-balloon catheters, has hitherto been regarded as the method of choice for their detection. Unfortunately, the few existing commercial catheter devices have certain disadvantages, which have led to a lack of acceptance of this important technique and restricted its use. We therefore present an improved tool for positive-pressure urethrography and a synopsis of diagnostic visualization procedures for urethral diverticula in women.


Classification of progressive massive fibrosis of coalminers by type of radiographic appearance.
In a pilot study the chest radiographic appearances of 112 coalminers who developed progressive massive fibrosis (PMF) over an 11 year period have been classified into six types based on the appearances of the large radiographic opacities. The most common type of PMF was one or more large shadows of homogeneous radiodensity. Less common types included markedly rounded shadows usually less than 3 cm in diameter, non-homogeneous shadows appearing to consist of conglomerations of small rounded opacities, and condensations of linear or streaky shadows. Good reproducibility by one reader between two readings were obtained. The lifetime exposures to mixed respirable coal mine dust, and to its quartz component, of these 112 men were compared with those of control subjects matched for age and starting category of simple pneumoconiosis but without PMF. Overall, the men with PMF had been exposed to more mixed dust than controls, confirming that one of the reasons some men with simple pneumoconiosis develop PMF is that they have inhaled more dust than others. Eleven of the 112 cases had large opacities that were not homogeneous and appeared to consist of conglomerations of "r" type small rounded opacities. The average quartz exposures of these men were much higher than in control subjects, suggesting that in this type of PMF quartz was an important causative factor.


Factors affecting reproductive traits in male snow leopards (Unciauncia).
The population of snow leopards (Unciauncia) maintained in US zoos is no longer sustainable due to poor reproductive success. Our objective was to assess reproductive traits in male snow leopards and identify factors (markers of oxidative stress in seminal fluid, surveys of husbandry practices, gonadal and adrenocortical activity, dietary intake of various nutrients, and genetics) that may affect ejaculate traits and subsequent fertility. Ejaculates (2.9 ± 0.2 mL) from 32 male snow leopards (9.8 ± 0.7 years; 38.6 ± 0.8 kg) housed at 27 institutions contained 119.2 + 26.0 x 106 spermatozoa, of which 75.1 ± 2.3% were motile and 28.6 ± 2.6% exhibited normal morphology. Overall, 34% of males produced <5 million spermatozoa and 27% of males produced spermatozoa with <20% normal morphology. Activity of superoxide dismutase (SOD) in the seminal fluid was negatively correlated (P < 0.05, r2 = 0.90) with normal sperm morphology. Husbandry practices, mean concentrations of fecal androgen metabolites (fAM), and baseline concentrations of fecal glucocorticoid metabolites (fGM), inbreeding coefficients, and generations each male was removed from the founders in their lineages were not correlated (P > 0.05) with the total number of spermatozoa or the proportion of spermatozoa with normal morphology. Total sperm count was positively correlated (P < 0.05, R2 = 0.86) with the weekly intake of polyunsaturated fatty acids (PUFA) and the proportion of spermatozoa with normal morphology tended (P < 0.10, R2 = 0.31) to be positively correlated with copper intake. Altering the nutrient composition of snow leopard diets could provide managers with a possible method of improving reproductive traits in this endangered species. The population of snow leopards (Uncia uncia) maintained in US zoos has been declining since 1993 due to poor breeding success. Our objective was to assess the reproductive traits of male snow leopards and identify factors (e.g. hormones, diet, genetics) that may be affecting the quality of semen produced and therefore subsequent fertility. Within a cohort of 32 male snow leopards maintained at 27 US zoos, we found that 34% produced less than 5 million sperm and 27% of males produced sperm where less than 20% looked normal. The quantity and quality of the recovered sperm was not correlated with husbandry practices, concentrations of hormones (androgens and glucocorticoids) in feces, or genetics. However, the number of sperm was positively correlated with polyunsaturated fatty acids in the diet. Altering the nutrient composition of snow leopard diets could provide managers with a possible method of improving reproductive traits in this endangered species.


Gamma Ventral Capsulotomy in Intractable Obsessive-Compulsive Disorder.
Despite the development of effective pharmacologic and cognitive behavioral treatments for obsessive-compulsive disorder (OCD), some patients continue to be treatment-refractory and severely impaired. Fiber tracts connecting orbitofrontal and dorsal anterior cingulate cortex with subcortical nuclei have been the target of neurosurgical lesions as well as deep brain stimulation in these patients. We report on the safety and efficacy of ventral gamma capsulotomy for patients with intractable OCD. Fifty-five patients with severely disabling, treatment-refractory OCD received bilateral lesions in the ventral portion of the anterior limb of the internal capsule over a 20-year period using the Leksell Gamma Knife. The patients were prospectively followed over 3 years with psychiatric, neurologic, and neuropsychological assessments of safety and efficacy, as well as structural neuroimaging. Thirty-one of 55 patients (56%) had an improvement in the primary efficacy measure, the Yale-Brown Obsessive Compulsive Scale, of ≥35% over the 3-year follow-up period. Patients had significant improvements in depression, anxiety, quality of life, and global functioning. Patients tolerated the procedure well without significant acute adverse events. Five patients (9%) developed transient edema that required short courses of dexamethasone. Three patients (5%) developed cysts at long-term follow-up, 1 of whom developed radionecrosis resulting in an ongoing minimally conscious state. Gamma Knife ventral capsulotomy is an effective radiosurgical procedure for many treatment-refractory OCD patients. A minority of patients developed cysts at long-term follow-up, 1 of whom had permanent neurological sequelae.


MUC5AC hypomethylation is a predictor of microsatellite instability independently of clinical factors associated with colorectal cancer.
Colorectal cancers (CRC) with microsatellite instability (MSI) display unique clinicopathologic features including a mucinous pattern with frequent expression of the secreted mucins MUC2 and MUC5AC. The mechanisms responsible for this altered pattern of expression remain largely unknown. We quantified DNA methylation of mucin genes (MUC2, MUC5AC, MUC4) in colonic cancers and examined the association with clinicopathological characteristics and molecular (MSI, KRAS, BRAF, and TP53 mutations) features. A control cohort was used for validation. We detected frequent hypomethylation of MUC2 and MUC5AC in CRC. MUC2 and MUC5AC hypomethylation was associated with MUC2 and MUC5AC protein expression (p = 0.004 and p < 0.001, respectively), poor differentiation (p = 0.001 and p = 0.007, respectively) and MSI status (p < 0.01 and p < 0.001, respectively). Interestingly, MUC5AC hypomethylation was specific to MSI cancers. Moreover, it was significantly associated with BRAF mutation and CpG island methylator phenotype (p < 0.001 and p < 0.001, respectively). All these results were confirmed in the control cohort. In the multivariate analysis, MUC5AC hypomethylation was a highly predictive biomarker for MSI cancers. MUC5AC demethylation appears to be a hallmark of MSI in CRC. Determination of MUC5AC methylation status may be useful for understanding and predicting the natural history of CRC.


Maximal Fluctuations of Confined Actomyosin Gels: Dynamics of the Cell Nucleus.
We investigate the effect of stress fluctuations on the stochastic dynamics of an inclusion embedded in a viscous gel. We show that, in nonequilibrium systems, stress fluctuations give rise to an effective attraction towards the boundaries of the confining domain, which is reminiscent of an active Casimir effect. We apply this generic result to the dynamics of deformations of the cell nucleus, and we demonstrate the appearance of a fluctuation maximum at a critical level of activity, in agreement with recent experiments [E. Makhija, D. S. Jokhun, and G. V. Shivashankar, Proc. Natl. Acad. Sci. U.S.A. 113, E32 (2016)PNASA60027-842410.1073/pnas.1513189113].


Assessing the effects of antipsychotic medications on schizophrenia functional analysis: a postmortem proteome study.
Antipsychotic drugs (APDs) are effective in treating positive symptoms of schizophrenia (SCZ). However, they have a substantial impact on postmortem studies. As most cohorts lack samples from drug-naive patients, many studies, rather than understanding SCZ pathophysiology, are analyzing the drug effects. We hypothesized that comparing SCZ-altered and APD-influenced signatures derived from the same cohort can provide better insight into SCZ pathophysiology. For this, we performed LCMS-based proteomics on dorsolateral prefrontal cortex (DLPFC) samples from control and SCZ subjects and used statistical approaches to identify SCZ-altered and APD-influenced proteomes, validated experimentally using independent cohorts and published datasets. Functional analysis of both proteomes was contrasted at the biological-pathway, cell-type, subcellular-synaptic, and drug-target levels. In silico validation revealed that the SCZ-altered proteome was conserved across several studies from the DLPFC and other brain areas. At the pathway level, SCZ influenced changes in homeostasis, signal-transduction, cytoskeleton, and dendrites, whereas APD influenced changes in synaptic-signaling, neurotransmitter-regulation, and immune-system processes. At the cell-type level, the SCZ-altered and APD-influenced proteomes were associated with two distinct striatum-projecting layer-5 pyramidal neurons regulating dopaminergic-secretion. At the subcellular synaptic level, compensatory pre- and postsynaptic events were observed. At the drug-target level, dopaminergic processes influenced the SCZ-altered upregulated-proteome, whereas nondopaminergic and a diverse array of non-neuromodulatory mechanisms influenced the downregulated-proteome. Previous findings were not independent of the APD effect and thus require re-evaluation. We identified a hyperdopaminergic cortex and drugs targeting the cognitive SCZ-symptoms and discussed their influence on SCZ pathology in the context of the cortico-striatal pathway.


Multiplex RT-PCR-based detections of CEA, CK20 and EGFR in colorectal cancer patients.
To develop a multiplex reverse transcription polymerase chain reaction (RT-PCR) method detecting circulating tumor cells in the peripheral blood of colorectal cancer (CRC) patients. Peripheral blood samples were collected from 88 CRC patients and 40 healthy individuals from the blood donors' clinic and subsequently analyzed by multiplex RT-RCR for the expression of carcinoembryonic antigen (CEA), cytokeratin 20 (CK20) and epidermal growth factor receptor (EGFR) mRNA. The analysis involved determining the detection rates of CEA, CK20 and EGFR transcripts vs disease stage and overall survival. Median follow-up period was 19 mo (range 8-28 mo). Rates of CEA, CK20 and EGFR detection in CRC patients were 95.5%, 78.4% and 19.3%, respectively. CEA transcripts were detected in 3 healthy volunteer samples (7.5%), whereas all control samples were tested negative for CK20 and EGFR transcripts. The increasing number of positive detections for CEA, CK20 and EGFR transcripts in each blood sample was positively correlated with Astler-Coller disease stage (P < 0.001) and preoperative serum levels of CEA (P = 0.029) in CRC patients. Data analysis using Kaplan-Meier estimator documented significant differences in the overall survival of the different CRC patient groups as formed according to the increasing number of positivity for CEA, CK20 and EGFR transcripts. These data suggest that multiplex RT-PCR assay can provide useful information concerning disease stage and overall survival of CRC patients.


Oncogenic Osteomalacia: An Approach to Diagnosis with a Case Report.
Oncogenic osteomalacia, also known as tumour induced osteomalacia, is a rare paraneoplastic syndrome caused by mesenchymal tumours secreting Fibroblast Growth Factor-23 (FGF-23). The characteristic biochemical findings include hypophosphatemia and low 1,25-dihydroxy vitamin D. The differential diagnosis for hypophosphatemia are varied. We present a case of oncogenic osteomalacia in a 29-year-old female, who presented with complaints of generalized diffuse bone pain and walking difficulty for six months duration. Thus, we have discussed the approach to diagnosis in such a case.


Statin, testosterone and phosphodiesterase 5-inhibitor treatments and age related mortality in diabetes.
To determine how statins, testosterone (T) replacement therapy (TRT) and phosphodiesterase 5-inhibitors (PDE5I) influence age related mortality in diabetic men. We studied 857 diabetic men screened for the BLAST study, stratifying them (mean follow-up = 3.8 years) into: (1) Normal T levels/untreated (total T > 12 nmol/L and free T > 0.25 nmol/L), Low T/untreated and Low T/treated; (2) PDE5I/untreated and PDE5I/treated; and (3) statin/untreated and statin/treated groups. The relationship between age and mortality, alone and with T/TRT, statin and PDE5I treatment was studied using logistic regression. Mortality probability and 95%CI were calculated from the above models for each individual. Age was associated with mortality (logistic regression, OR = 1.10, 95%CI: 1.08-1.13, P < 0.001). With all factors included, age (OR = 1.08, 95%CI: 1.06-1.11, P < 0.001), Low T/treated (OR = 0.38, 95%CI: 0.15-0.92, P = 0.033), PDE5I/treated (OR = 0.17, 95%CI: 0.053-0.56, P = 0.004) and statin/treated (OR = 0.59, 95%CI: 0.36-0.97, P = 0.038) were associated with lower mortality. Age related mortality was as described by Gompertz, r2 = 0.881 when Ln (mortality) was plotted against age. The probability of mortality and 95%CI (from logistic regression) of individuals, treated/untreated with the drugs, alone and in combination was plotted against age. Overlap of 95%CI lines was evident with statins and TRT. No overlap was evident with PDE5I alone and with statins and TRT, this suggesting a change in the relationship between age and mortality. We show that statins, PDE5I and TRT reduce mortality in diabetes. PDE5I, alone and with the other treatments significantly alter age related mortality in diabetic men.


The contexts for managing depression and its stigma among black West Indian Canadian women.
There is a paucity of literature available to assist nurses and other care providers in knowing how to meet the needs of depressed women from non-dominant cultural backgrounds. To begin to address this need, we conducted a grounded theory study on black West Indian Canadian Women's strategies for managing depression. We discovered a basic social process, Being Strong, that the women used to manage or ameliorate depression. Being strong occurs within the overlapping areas of three social contexts: the cultural stigma of depression, male-female roles and relationships, and belief in Christian doctrine. These contexts are located against a backdrop of visible minority status within a eurocentric society. This socio-cultural contextual material provides the setting within which black West Indian Canadian women live and make decisions. In this article, we present findings related to the social and cultural aspects of the women's situation.


The long-range temporal correlations of broadband EEG oscillations in poststroke depression subjects with basal ganglia infarction.
Recent studies have found long-range temporal correlations (LRTC) of neuronal oscillation under different physiological and pathological state. In this paper we aimed to explore the temporal correlations of broadband neuronal oscillation in poststroke depression. Resting state EEGs of 16 electrodes in 16 poststroke depression (PSD), 18 poststroke non-depression (PSND) and 18 healthy control (HC) subjects were analyzed by means of detrended fluctuation analysis (DFA), a quantitative measurement of LRTC. The results indicated that LRTC of broadband oscillation in PSD subjects was still preserved and had similar spatial distribution to non-depression subjects, but attenuated especially in left hemisphere and frontal and posterior temporal regions of right hemisphere. Moreover, a linear correlation between the severity of psychiatric symptoms and attenuation of LRTC was observed in stroke subjects. ROC curves indicated a high discriminating ability of scaling exponents in prefrontal regions distinguishing PSD from PSND, suggesting the feasibility for LRTC as assessment indicators to PSD.


Genetic and molecular targets in lymphoma: implications for prognosis and treatment.
Lymphomas are the most common hematologic malignancies with approximately 79,000 new cases estimated for 2013 in the USA. Despite improved outcomes, relapse or recurrence remains a common problem with conventional cytotoxic therapy. Recently, many genetic and molecular mechanisms that drive various cellular events like apoptosis, angiogenesis and cell motility have been more clearly delineated. These new findings, coupled with the advent of high-throughput screening technology have led to the discovery of many compounds that can target specific mutations and/or influence deregulated transcription. In this review, we intend to provide a concise overview of genetic and molecular events that drive cellular processes in lymphomas and represent potential therapeutic targets. Additionally, we briefly discuss the prognostic significance of select biological markers.


Does having a gastrectomy delay time to feeding and prolong hospital stay in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy?
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is routinely used to treat selected patients with peritoneal carcinomatosis, but can be associated with prolonged hospital stay, significant morbidity and mortality. Our objective was to assess whether patients undergoing gastrectomy as part of CRS/HIPEC were at increased risk of delayed feeding time and prolonged hospital stay. Two hundred and fourteen consecutive patients with peritoneal carcinomatosis treated with CRS/HIPEC between 2001 and 2016 were stratified by whether CRS included gastrectomy (n = 19, 9%) and compared. Primary outcomes were time to full feeds and rate of serious morbidity (Clavien-Dindo grades III-V). Secondary outcomes were durations of ICU and hospital stays. Of 214 patients undergoing CRS/HIPEC, those undergoing gastrectomy (19, 8.9%) had increased time to full feeds (8 vs. 5 days, p < 0.01), and duration of ICU (2 vs. 1 days, p < 0.01) and total hospital stays (16 vs. 14 days, p = 0.013). There was no significant increase in serious complications, although increased risk of pneumonia was noted (21% vs. 4.1%, p = 0.011). Undergoing gastrectomy was not independently prognostic in multivariable analysis including high peritoneal tumour load (PCI >12), multiple CRS procedures (number >2) and operation duration (>480 min) in which operative duration remained independently prognostic (p < 0.01). After surgery, early oral refeeding may be beneficial in the majority of patients undergoing CRS/HIPEC. However, patients found to have high peritoneal tumour load with extended surgery and those who underwent gastrectomy should be considered for early post-operative TPN due to the significant risk of delayed time to full feeds.


Drug safety evaluation of lenvatinib for thyroid cancer.
Lenvatinib is an oral multitargeted tyrosine kinase inhibitor of VEGFR1,2,3,4, FGFR1,2,3,4, PDGFR-α as well as RET and KIT signaling network. Its activity against radioiodine-resistant differentiated thyroid cancer (DTC) has been recently demonstrated. Patients, who were given lenvatinib, showed significantly longer median progression free survival than placebo group, 18.3 vs 3.6 months, respectively. This review is focused on lenvatinib safety profile in patients treated due to DTC and medullary thyroid carcinoma. Among the most frequent lenvatinib-related adverse events (AEs) were hypertension, proteinuria, diarrhea, appetite decrease, weight loss, nausea and stomatitis. Although a lot of them were manageable, in 35-68% of patients dose reduction was required. Nevertheless, only 15% of subjects withdrew the drug due to its toxicity. published results of clinical trials phase II and III investigating both safety and efficacy of lenvatinib in thyroid cancer. Lenvatinib shows acceptable safety profile in patients with thyroid carcinoma. Treatment-related side effects are usually manageable by dose modifications or by concomitant non-pharmacological and pharmacological treatment. However, the early recognition of any potential drug toxicity is crucial to avoid serious complications as well as to keep a patient on drug as long as the treatment is beneficial.


Role of the Q10 class I regulatory element region 1 in controlling tissue-specific expression in vivo.
The MHC class I regulatory element (CRE) region 1 has been previously described as a positive cis-acting regulatory element essential for class I gene expression. We have generated transgenic mice (CBA x C57BL/6) with the MHC class I gene H-2Dd driven by two different 400-bp promoter regions of Q10, a nonpolymorphic MHC class I gene expressed in the liver, kidney, and fetal yolk sac. One transgene contained the wild-type Q10 promoter (Q10WT/Dd). The second construct (Q10M3/Dd) had 2 bp substitutions introduced in region 1 of the CRE that reconstituted the CRE inverted repeat present in classical class I genes. Mice containing the wild-type Q10/Dd gene expressed membrane-bound H-2Dd molecules in a tissue-restricted expression pattern similar to that observed for endogenous Q10. In mice containing the mutant construct (Q10M3/Dd), H-2Dd was also expressed in the thymus, a tissue not normally associated with Q10 expression but, surprisingly, the Dd was not expressed in other lymphoid tissues. Furthermore, thymic expression was greatest on double positive (CD4+ CD8+) thymocytes. Thymic Dd expression was correlated with the presence of what appears to be a previously unidentified transcription factor in thymocytes that is capable of interacting with the CRE-inverted repeat. These results show that the mutations in region 1 altered the tissue-specific regulation of the Q10 promoter in vivo, although an intact inverted repeat did not restore the ubiquitous pattern of expression characteristic of classical class I genes. Thus, these results indicate that elements in addition to CRE region 1 in the Q10 promoter region serve to limit ubiquitous tissue expression.


Necrotic platelets provide a procoagulant surface during thrombosis.
A subpopulation of platelets fulfills a procoagulant role in hemostasis and thrombosis by enabling the thrombin burst required for fibrin formation and clot stability at the site of vascular injury. Excess procoagulant activity is linked with pathological thrombosis. The identity of the procoagulant platelet has been elusive. The cell death marker 4-[N-(S-glutathionylacetyl)amino]phenylarsonous acid (GSAO) rapidly enters a subpopulation of agonist-stimulated platelets via an organic anion-transporting polypeptide and is retained in the cytosol through covalent reaction with protein dithiols. Labeling with GSAO, together with exposure of P-selectin, distinguishes necrotic from apoptotic platelets and correlates with procoagulant potential. GSAO(+) platelets form in occluding murine thrombi after ferric chloride injury and are attenuated with megakaryocyte-directed deletion of the cyclophilin D gene. These platelets form a procoagulant surface, supporting fibrin formation, and reduction in GSAO(+) platelets is associated with reduction in platelet thrombus size and fibrin formation. Analysis of platelets from human subjects receiving aspirin therapy indicates that these procoagulant platelets form despite aspirin therapy, but are attenuated by inhibition of the necrosis pathway. These findings indicate that the major subpopulation of platelets involved in fibrin formation are formed via regulated necrosis involving cyclophilin D, and that they may be targeted independent of platelet activation.


Multiple Primary Cancers in the United States.
The distribution of multiple primary cancers has been described previously using data from the Surveillance, Epidemiology, and End Results (SEER) Program. However, a complete picture regarding the distribution of multiple primary cancers in the United States is still lacking. The objective of the current study is to present a comprehensive description of multiple primary cancers in the United States. Invasive cancer cases (including in situ bladder cancers) diagnosed between 2001 and 2016 from 49 population-based state cancer registries in the United States were evaluated for this study. The sequence number central assigned to each tumor was used to determine whether a tumor was a first primary cancer or a subsequent multiple primary cancer. Tumors with a sequence number 00 or 01 were classified as the first primary cancer, while tumors with a sequence number 02 or above were classified as a multiple primary cancer. The percentage of multiple primary cancers was calculated by sex, age, race/ethnicity, cancer site, registry, and diagnosis year. In addition, the percentage of cancers diagnosed at a local stage among multiple primaries was compared with that among first primaries. Overall, about 19.0% of cases were reported as multiple primary cancers; the percentage was higher among non-Hispanic Whites and among older patients. Bladder, melanoma of the skin, and lung cancers had the highest percentage of cases reported as multiple primaries. The percentage of multiple primary cancers also varied by registry and has been increasing over time. Cancers reported as multiple primaries were more likely to be diagnosed at a local stage than those reported as first primaries. Cancers registered as multiple primaries are common in the United States, showing an increasing trend over time and wide variation by race/ethnicity, age, cancer type, and registry. The findings have some practical implications for cancer registries that collect data and for researchers conducting investigations using information on multiple primary cancers.


Diffusion-controlled first contact of the ends of a polymer: crossover between two scaling regimes.
We report on Monte Carlo simulations of loop formation of an ideal flexible polymer consisting of N bonds with two reactive ends. We determine the first-passage time associated with chain looping that yields a conformation in which the end monomers are separated by a distance a--the reaction radius. In particular, our numerical results demonstrate how this time scale crosses over from tau(first) approximately N(3/2)/a to the a-independent tau(first) approximately N2 as N is increased. The existence and characteristics, of the two scaling regimes and the crossover between the two, are further illuminated by a scaling argument.


n-3 Docosapentaenoic acid-derived protectin D1 promotes resolution of neuroinflammation and arrests epileptogenesis.
Epilepsy therapy is based on drugs that treat the symptoms rather than the underlying mechanisms of the disease (epileptogenesis). There are no treatments for preventing seizures or improving disease prognosis, including neurological comorbidities. The search of pathogenic mechanisms of epileptogenesis highlighted that neuroinflammatory cytokines [i.e. interleukin-1β (IL-1β), tumour necrosis factor-α (Tnf-α)] are induced in human and experimental epilepsies, and contribute to seizure generation in animal models. A major role in controlling the inflammatory response is played by specialized pro-resolving lipid mediators acting on specific G-protein coupled receptors. Of note, the role that these pathways have in epileptogenic tissue remains largely unexplored. Using a murine model of epilepsy, we show that specialized pro-resolving mechanisms are activated by status epilepticus before the onset of spontaneous seizures, but with a marked delay as compared to the neuroinflammatory response. This was assessed by measuring the time course of mRNA levels of 5-lipoxygenase (Alox5) and 15-lipoxygenase (Alox15), the key biosynthetic enzymes of pro-resolving lipid mediators, versus Il1b and Tnfa transcripts and proteins. In the same hippocampal tissue, we found a similar delayed expression of two main pro-resolving receptors, the lipoxin A4 receptor/formyl peptide receptor 2 and the chemerin receptor. These receptors were also induced in the human hippocampus after status epilepticus and in patients with temporal lobe epilepsy. This evidence supports the hypothesis that the neuroinflammatory response is sustained by a failure to engage pro-resolving mechanisms during epileptogenesis. Lipidomic LC-MS/MS analysis showed that lipid mediator levels apt to resolve the neuroinflammatory response were also significantly altered in the hippocampus during epileptogenesis with a shift in the biosynthesis of several pro-resolving mediator families including the n-3 docosapentaenoic acid (DPA)-derived protectin D1. Of note, intracerebroventricular injection of this mediator during epileptogenesis in mice dose-dependently reduced the hippocampal expression of both Il1b and Tnfa mRNAs. This effect was associated with marked improvement in mouse weight recovery and rescue of cognitive deficit in the novel object recognition test. Notably, the frequency of spontaneous seizures was drastically reduced by 2-fold on average and the average seizure duration was shortened by 40% after treatment discontinuation. As a result, the total time spent in seizures was reduced by 3-fold in mice treated with n-3 DPA-derived protectin D1. Taken together, the present findings demonstrate that epilepsy is characterized by an inadequate engagement of resolution pathways. Boosting endogenous resolution responses significantly improved disease outcomes, providing novel treatment avenues.


Induction of sarcomas in rats by subcutaneous injection of dinitropyrenes.
The carcinogenicities of potent mutagenic dinitropyrenes were examined by their subcutaneous injections into male F344/ DuCrj rats. Animals were injected with 0.2 mg each of 1,3- and 1,8-dinitropyrenes (1,3- and 1,8- DNPs ) dissolved in 0.2 ml of dimethyl sulfoxide (DMSO) twice a week for 10 weeks. In rats treated with 1,8-DNP, sarcomas were induced at the sites of injection in all 10 animals tested between the 113th and 127th experimental days. In rats treated with 1,3-DNP, 10 of 10 rats developed sarcomas between days 119 and 320. Some tumors induced by these chemicals were transplantable into the same strain of rats. No tumors developed in control rats, which received only DMSO.


Women's decision making about antidepressant use during pregnancy: A narrative review.
Depression is common, particularly among women of childbearing age, and can have far-reaching negative consequences if untreated. Efficacious treatments are available, but little is known about how women make depression treatment decisions during pregnancy. The purpose of this narrative review is to interpretively synthesize literature on women's decision making (DM) regarding antidepressant use during pregnancy. The databases PubMed, CINAHL, and PsycINFO were searched between May 2015 and August 2017 for peer-reviewed, English-language papers using terms such as "depression," "pregnancy," and "DM." The literature matrix abstraction method was used to systematically abstract data from full articles that met criteria for inclusion. Of the articles abstracted (N = 10), half did not cite a DM theory on which the work was based. Key aspects of DM for this population were need for information and decision support, desire for active participation in DM, reflection on beliefs and values, evaluation of treatment option sequelae, and societal expectations. Treatment DM for depression during pregnancy is particularly impacted by the stigma associated with depression and societal expectations of pregnant women related to medication use during pregnancy. These findings, however, were based on studies of predominantly Caucasian and well-educated women. Women require a nonjudgmental environment, in which shared DM feels safe, to foster positive DM experiences and outcomes. Future research is needed to define how to best support women to make depression treatment decisions in pregnancy, with particular attention to DM in the second and third trimesters of pregnancy.


Aberrant Rab11-dependent trafficking of the neuronal glutamate transporter EAAC1 causes oxidative stress and cell death in Huntington's disease.
Oxidative stress contributes to neurodegeneration in Huntington's disease (HD). However, the origins of oxidative stress in HD remain unclear. Studies in HD transgenic models suggest involvement of mitochondrial dysfunction, which would lead to overproduction of reactive oxygen species (ROS). Impaired mitochondria complexes occur in late stages of HD but not in presymptomatic or early-stage HD patients. Thus, other mechanisms may account for the earliest source of oxidative stress caused by endogenous mutant huntingtin. Here, we report that decreased levels of a major intracellular antioxidant glutathione coincide with accumulation of ROS in primary HD neurons prepared from embryos of HD knock-in mice (HD(140Q/140Q)), which have human huntingtin exon 1 with 140 CAG repeats inserted into the endogenous mouse huntingtin gene. Uptake of extracellular cysteine through the glutamate/cysteine transporter EAAC1 is required for de novo synthesis of glutathione in neurons. We found that, compared with wild-type neurons, HD neurons had lower cell surface levels of EAAC1 and were deficient in taking up cysteine. Constitutive trafficking of EAAC1 from recycling endosomes relies on Rab11 activity, which is defective in the brain of HD(140Q/140Q) mice. Enhancement of Rab11 activity by expression of a dominant-active Rab11 mutant in primary HD neurons ameliorated the deficit in cysteine uptake, increased levels of intracellular glutathione, normalized clearance of ROS, and improved neuronal survival. Our data support a novel mechanism for oxidative stress in HD: Rab11 dysfunction slows trafficking of EAAC1 to the cell surface and impairs cysteine uptake, thereby leading to deficient synthesis of glutathione.


Isolated crater-like tumour in a renal transplant recipient.
Compared with asymptomatic pulmonary cryptococcosis, secondary cutaneous cryptococcosis may be the first clinical manifestation of disseminated infection but it can be difficult to diagnose clinically. The clinical manifestation of cutaneous cryptococcosis is not pathognomonic, varying from nodules to ulcers and plaques, and frequently mimics other pathologies. This case highlights that an isolated tumour can be an initial manifestation of systemic cryptococcosis in a kidney transplant patient.


Simulations of a mortality plateau in the sexual Penna model for biological aging.
The Penna model is a strategy to simulate the genetic dynamics of age-structured populations, in which the individual genomes are represented by bit strings. It provides a simple metaphor for the evolutionary process in terms of the mutation accumulation theory. In its original version, an individual dies due to inherited diseases when its current number of accumulated mutations, n, reaches a threshold value T. Since the mean number of diseases increases with age, the probability to die is zero for very young ages (n < T) and equals 1 for the old ones (n > or = T). Here, instead of using a step function to determine the genetic death age, we test several other functions that may or may not slightly increase the death probability at young ages (n < T), but that decrease this probability at old ones. Our purpose is to study the oldest old effect, that is, a plateau in the mortality curves at advanced ages. By imposing certain conditions, it has been possible to obtain a clear plateau using the Penna model. However, a more realistic one appears when a modified version, that keeps the population size fixed without fluctuations, is used. We also find a relation between the birth rate, the age structure of the population, and the death probability.


Standardization and quality control studies of 'real-time' quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia - a Europe Against Cancer program.
Detection of minimal residual disease (MRD) has proven to provide independent prognostic information for treatment stratification in several types of leukemias such as childhood acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and acute promyelocytic leukemia. This report focuses on the accurate quantitative measurement of fusion gene (FG) transcripts as can be applied in 35-45% of ALL and acute myeloid leukemia, and in more than 90% of CML. A total of 26 European university laboratories from 10 countries have collaborated to establish a standardized protocol for TaqMan-based real-time quantitative PCR (RQ-PCR) analysis of the main leukemia-associated FGs within the Europe Against Cancer (EAC) program. Four phases were scheduled: (1) training, (2) optimization, (3) sensitivity testing and (4) patient sample testing. During our program, three quality control rounds on a large series of coded RNA samples were performed including a balanced randomized assay, which enabled final validation of the EAC primer and probe sets. The expression level of the nine major FG transcripts in a large series of stored diagnostic leukemia samples (n=278) was evaluated. After normalization, no statistically significant difference in expression level was observed between bone marrow and peripheral blood on paired samples at diagnosis. However, RQ-PCR revealed marked differences in FG expression between transcripts in leukemic samples at diagnosis that could account for differential assay sensitivity. The development of standardized protocols for RQ-PCR analysis of FG transcripts provides a milestone for molecular determination of MRD levels. This is likely to prove invaluable to the management of patients entered into multicenter therapeutic trials.


An evolved wavelet library based on genetic algorithm.
As the size of the images being captured increases, there is a need for a robust algorithm for image compression which satiates the bandwidth limitation of the transmitted channels and preserves the image resolution without considerable loss in the image quality. Many conventional image compression algorithms use wavelet transform which can significantly reduce the number of bits needed to represent a pixel and the process of quantization and thresholding further increases the compression. In this paper the authors evolve two sets of wavelet filter coefficients using genetic algorithm (GA), one for the whole image portion except the edge areas and the other for the portions near the edges in the image (i.e., global and local filters). Images are initially separated into several groups based on their frequency content, edges, and textures and the wavelet filter coefficients are evolved separately for each group. As there is a possibility of the GA settling in local maximum, we introduce a new shuffling operator to prevent the GA from this effect. The GA used to evolve filter coefficients primarily focuses on maximizing the peak signal to noise ratio (PSNR). The evolved filter coefficients by the proposed method outperform the existing methods by a 0.31 dB improvement in the average PSNR and a 0.39 dB improvement in the maximum PSNR.


[New inhibitors of adrenal androgen synthesis enzymes].
The androgen sensitivity of prostate cancer is enhanced during hormonal therapy and prostate cancer develops to CRPC in response to DHT of low concentration synthesized from adrenal androgen and signals (cytokines) that activate androgen receptor (AR). New medicines in consideration of these mechanisms were developed recently. They are already used for a clinic abroad, or clinical studies are conducted, and may be introduced in near future in Japan. Therefore, it is extremely important that we master fundamental knowledge of the new medicines for CRPC. Here, I want to describe adrenal androgen synthesis inhibitors among medicines targeting Androgen-AR axis.


Protective effect of metallothionein on oxidative stress-induced DNA damage.
Metallothioneins (MTs) are a family of low molecular weight proteins with a high cysteine and metal ion content. They are found in most cells and tissues and can be induced by a number of substances, including various forms of oxidative stress. MTs play a central role in essential trace element homeostasis and in metal detoxification. Because of their peculiar structure, characterized by a large content of thiol groups, MTs also act as a potent antioxidant by protecting against various injuries resulting from reactive oxygen (ROS) or nitrogen species (RNS). In this review, the involvement of MT in the protection of DNA against oxidative stress is discussed.


Oxytetracycline Degrading Potential of Lysinibacillus sp. Strain 3+I Isolated from Poultry Manure.
Oxytetracycline (OTC) which is a broad-spectrum veterinary tetracycline antibiotic is extensively used in poultry farms as a prophylactic, therapeutic, and growth stimulator. Upon administration, unmetabolized OTC is excreted from the animal body through droppings and accumulated in litter in the poultry industry. This study aimed at investigating the OTC degradation potential of an-OTC tolerant bacterial strain, isolated from poultry manure. The isolated strain's morphology, biochemical properties, and 16S ribosomal RNA (rRNA) gene sequence confirmed that it belonged to the Lysinibacillus genus. To measure the residual OTC concentration, a high-performance liquid chromatography method was used. OTC degradation rates were 2.579 mg L-1d-1 with Lysinibacillus strain 3+I and 1.149 mg L-1d-1 without Lysinibacillus strain 3+I. In the presence of strain 3+I, the half-life significantly reduced to 2.68 days, compared to 6.03 days without strain 3+I. The strain demonstrated 85% removal with the OTC concentration of 10 μg/ml. The influence of pH, temperature, carbon sources, and nitrogen source, which influence degradation, were also investigated. The optimum condition favouring degradation was pH 6 at a temperature of 30°C. In addition, Lysinibacillus sp. strain 3+I's ability to degrade OTC in poultry litter offers a promising approach to treat poultry manure and effluent containing OTC, preventing its contamination in the environment.


[Changes in the properties of the plasma membrane of Acholeplasma laidlawii under the action of tetracycline].
The role of physico-chemical rearrangements in the cell plasmalemma of Acholeplasma laidlawii in the development of resistance to tetracycline was investigated. The cells of A.laidlawii were shown to be tolerant to tetracycline and to preserve a rather high titre of the cells even at a concentration of the antibiotic in the inoculation medium much higher than the MIC. The results of the investigation of the structural rearrangements in the plasmatic membrane of the cells grown in the presence of tetracycline revealed changes in the lipid flow in the surface layer and an increase in the cholesterol and phospholipid contents. The size of the changes depended on the time of tetracycline addition and the phase of the culture growth.


[The role of cyclooxygenases in neurotoxicity of amyloid beta peptides in Alzheimer's disease].
In the course of Alzheimer's disease (AD), chronic inflammation is initiated by amyloid beta (Ab) peptide aggregates that extensively participate in neurodegeneration. Epidemiological studies have shown that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing AD. NSAIDs are inhibitors of cyclooxygenases (COXs), enzymes involved in synthesis of eicosanoids, a major component of the inflammatory process. Recent studies have brought two new findings: 1) the toxic form of Ab is its intra- and extracellular oligomers, rather than aggregates; 2) COX-2 activation is an early event in AD, preceding plaque formation and microglia activation. This finding suggests that COX might participate in Ab toxicity in neurons in the early stage of AD independently of its role in the inflammatory reaction in glial cells in the advanced stage of AD. However, further studies on the role of COXs in the pathogenesis/pathomechanism of AD are needed.


Tunable coupling-induced resonance splitting in a self-coupled silicon ring cavity with robust spectral characteristics.
We propose and demonstrate a self-coupled micro-ring resonator for resonance splitting by mutual mode coupling of a cavity mode and a counter-propagating mode in a silicon-on-insulator platform. The resonator is constructed with a self-coupling region that can excite a counter-propagating mode. We experimentally study the effect of self-coupling on the resonance splitting, resonance extinction, and quality-factor evolution and stability. Based on the coupling, we achieve 72% of the free spectral range (FSR) splitting for a cavity with an FSR of 2.1 nm with <5% variation in the cavity quality factor. The self-coupled resonance splitting shows a highly robust spectral characteristic that can be exploited for sensing and optical signal processing.


The Impact of the No Jab No Play and No Jab No Pay Legislation in Australia: A Scoping Review.
Australia has a long history of population-based immunisation programs including legislations. This paper reports on a review of evaluations of the impact of the federal No Jab No Pay (NJNPay) and state implemented No Jab No Play (NJNPlay) legislations on childhood immunisation coverage and related parental attitudes. Five databases were searched for peer-review papers (Medline (Ovid); Scopus; PsycInfo; ProQuest; and CINAHL). Additional searches were conducted in Google Scholar and Informit (Australian databases) for grey literature. Studies were included if they evaluated the impact of the Australian NJNPay and/or NJNPlay legislations. Ten evaluations were included: nine peer-review studies and one government report. Two studies specifically evaluated NJNPlay, five evaluated NJNPay, and three evaluated both legislations. Findings show small but gradual and significant increases in full coverage and increases in catch-up vaccination after the implementation of the legislations. Full coverage was lowest for lower and higher socio-economic groups. Mandates are influential in encouraging vaccination; however, inequities may exist for lower income families who are reliant on financial incentives and the need to enrol their children in early childhood centres. Vaccine refusal and hesitancy was more evident among higher income parents while practical barriers were more likely to impact lower income families. Interventions to address access and vaccine hesitancy will support these legislations.


Neglected squamous cell carcinoma of the frontal area: a clinical report.
Neglected skin carcinomas are not very often in our days. It is known that skin is the most common site of malignancy Squamous cell carcinoma (SCC) is the second most common malignancy of the skin. We report a combined surgical treatment in an unusual case of a squamous cell carcinoma (T4 n0 m0) localized on scalp, presented primarily as a frontal ulcerative bloody mass, with no palpable lymph nodes and a whole body negative computed tomography. Three months after the first surgical procedure, the tumour reappeared presenting left frontal lobe invasion. A combined surgical management (neurosurgery and plastic surgery) was realized, in order to remove the tumour and to cover the defect. Three months later the tumour recrudesced invading the left antrum, infiltration of remained parotid gland and an ipsilateral mandible osteolysis, besides a 2 cm size distal metastasis at the right upper lobe of the lung was revealed. This article, through case report and a brief review of the literature, offers criteria for the surgical treatment of SCC that arise on the scalp.


Development of spot size and lateral intensity distribution generated by exponential, logarithmic, and linear axicons.
Axicons are known to produce a nearly Bessel beam transverse intensity distribution. It has been previously recognized that linear axicons and logarithmic axicons with a predefined distant depth of field (DOF) and no blocking present a development region characterized by an enlarged central spot size. In this paper, we aim to obtain a better insight on the formation of lateral light distribution in this development region. We also examine the spot size and transverse intensity distribution of the recently developed exponential axicon. We present experiments and detailed nonparaxial numerical simulations for a plane wave passing through these optical elements and show that the lateral intensity distribution they generate differs from that of a Bessel beam for a significant part of their DOF. This anomaly/irregularity in the formation of nondiffracting Bessel beams has to be taken into account in applications of these axicons, such as imaging or optical trapping.


[New ways towards the improvement of the seniors health literacy].
The elderly population is one of the vulnerable groups due to their low health literacy. Health literacy represents a way of effective ensuring, comprehension and utilization of health information to be able to make the best possible decisions in the care of one's health. The presented systematic overview study was compiled using the analysis of 38 database publications. The goal was to find relevant resources concerning the relation between health literacy and compliance in the treatment of adult and elderly individuals. Another goal was to describe the influence of tools and the possibility of using e-health to improve the seniors' health literacy. The source analysis proves that limited health literacy correlates with the decrease of cognitive functions. Some studies show that health literacy directly correlates with the level of education and age. The elderly individuals who show higher health literacy observe their doctors' advice more frequently and are, moreover, active recipients of health care. One of the tools of how to improve health literacy is e-health technology using internet, mobile phones, tablets or other information media.Key words: health literacy, health care, patient, senior, compliance, e-health.


Scanning electron microscope studies of lymphatic tissues with special reference to the structure of the reticulum.
Reticular cells of the lymph nodule in the rabbit appendix and the lymphatic pulp including the germinal center in the dog mesenteric lymph node were observed under the scanning electron microscope after removal of free cells. Three dimensional architecture and arrangement of the reticular cells varied by regions in the lymph nodule. The appendix lymph nodule encapsulated with the endothelium of lymphatic sinuses was subdivided into two regions: (1) a central region of sparsely arranged stellate cells with coarse processes and (2) a peripheral zone of densely arranged stellate cells with many delicate processes. In the lymph node, the germinal center contained a loosely formed network of delicate stellate cells. Peripheral reticular cells of the nodule were thread-like, extending concentrically around the germinal center or along the sinus wall. Many lateral bridges of the threads occurred segmentally. The reticular framework of the medullary cord formed spongy meshes by anastomoses of stellate cells. Cytoplasmic perforations were observed in the sinus wall of the medullary cord. Those may be for lymphocyte migration.


Transcriptome analysis of genes related to resistance against powdery mildew in wheat-Thinopyrum alien addition disomic line germplasm SN6306.
Wheat powdery mildew, which is mainly caused by Blumeria graminis f. sp. tritici (Bgt), seriously damages wheat production. The wheat-Thinopyrum intermedium alien addition disomic line germplasm SN6306, being one of the important sources of genes for wheat resistance, is highly resistant to Bgt E09 and to many other powdery mildew physiological races. However, knowledge on the resistance mechanism of SN6306 remains limited. Our study employed high-throughput RNA sequencing based on next-generation sequencing technology (Illumina) to obtain an overview of the transcriptome characteristics of SN6306 and its parent wheat Yannong 15 (YN15) during Bgt infection. The sequencing generated 104,773 unigenes, 9909 of which showed varied expression levels. Among the 9909 unigenes, 1678 unigenes showed 0 reads in YN15. The expression levels in Bgt-inoculated SN6306 and YN15 of exactly 39 unigenes that showed 0 or considerably low reads in YN15 were validated to identify the genes involved in Bgt resistance. Among the 39 unigenes, 12 unigenes were upregulated in SN6306 by 3-45 times. These unigenes mainly encoded kinase, synthase, proteases, and signal transduction proteins, which may play an important role in the resistance against Bgt. To confirm whether the unigenes that showed 0 reads in YN15 are really unique to SN6306, 8 unigenes were cloned and sequenced. Results showed that the selected unigenes are more similar to SN6306 and Th. intermedium than to the wheat cultivar YN15. The sequencing results further confirmed that the unigenes showing 0 reads in YN15 are unique to SN6306 and are most likely derived from Th. intermedium (Host) Nevski. Thus, the genes from Th. intermedium most probably conferred the resistance of SN6306 to Bgt.


Sulfonyl group-containing compounds in the design of potential drugs for the treatment of diabetes and its complications.
Sulfonyl group-containing compounds constitute an important class of therapeutical agents in medicinal chemistry presumably because of the tense chemical structure and functionality of the sulfonyl, which could not only form hydrogen bonding interactions with active site residues of biological targets but also, as incorporated into core ring structure, constrain the side chains and allowed their specific conformations that fit the active sites. This review focuses on sulfonamides and sulfones, which cover more than 40 series and are associated with at least 10 potential pharmaceutical targets in pathways of glucose metabolism and insulin signaling. A large number of such compounds have been reported as pharmaceuticals every year in the last decade. In particular, increasing studies suggest that sulfonamides and sulfones play a key role in the design of pharmaceutical agents with potential application for the treatment of diabetes and its complications. First, they are inhibitors of a variety of enzymes including 11β-hydroxysteroid dehydrogenase type 1, α- glucosidase, carnitine palmitoyltransferase and cytosolic phosphoenolpyruvate carboxykinase, and in turn involved in the regulation of the metabolism of glucose. In addition, they are active as activators of glucokinase and as antagonists of ghrelin receptors. These enzyme and receptors are tightly associated with the regulation of glucose metabolism and the improvement of insulin resistance. Secondly, sulfonamides and sulfones act in the insulin secretion. As agonists, they activate insulin receptor tyrosine kinase and thus increase insulin sensitivity. Moreover, they as inhibitors suppress protein tyrosine phosphatase 1B and dipeptidyl peptidase IV, and thus normalize the insulin signaling pathway. Finally, a number of sulfonamides and sulfones are inhibitors of aldose reductase, which have been linked to diabetic complications.


Prenatal presentation and diagnosis of Baraitser-Winter syndrome using exome sequencing.
Baraitser-Winter cerebrofrontofacial syndrome (BWCFF) is a rare autosomal dominant developmental disorder associated with missense mutations in the genes ACTB or ACTG1. The classic presentation of BWCFF is discerned by the combination of unique craniofacial characteristics including ocular coloboma, intellectual disability, and hypertelorism. Congenital contractures and organ malformations are often present, including structural defects in the brain, heart, renal, and musculoskeletal system. However, there is limited documentation regarding its prenatal presentation that may encourage healthcare providers to be aware of this disorder when presented throughout pregnancy. Herein we describe a case of a pregnancy with large cystic hygroma and omphalocele. Whole exome sequencing (WES) was performed and a de novo, heterozygous, likely pathogenic mutation in ACTB was detected, c.1004G>A (p.Arg335His), conferring a diagnosis of BWCFF.


Unexpected Return for Follow-up During the First Year of Multidisciplinary Care May Be Predictive of Rapid Deterioration of Renal Function.
Multidisciplinary predialysis education and team care (MDC) may slow the decline in renal function in patients with chronic kidney disease (CKD). However, associations between unexpected return during MDC and progression of renal dysfunction have not been characterized in patients with CKD. Our study aimed to determine the association between exacerbation of renal dysfunction and the frequency of unexpected return during follow-up.A total of 437 patients with CKD receiving multidisciplinary care between January 2009 and June 2013 at the Shin-Kong Wu Ho-Su Memorial Hospital were included in this retrospective observational cohort study, and multiple imputations were performed for missing data. The predictor was the frequency of unexpected return for follow-up during the first year after entering MDC. Main outcome was monthly declines in estimated glomerular filtration rates (eGFR). Moreover, the demographic data, comorbidities, history of medication, and routine laboratory data for patients with CKD were collected.Among all patients, 59.7% were male, the mean age at initiation of MDC was 69.4 ± 13.2 years, and the duration of follow-up was 21.4 ± 3.3 months. The subjects were divided into 2 groups according to frequencies of follow-up (≤4 and > 4 visits) during the 1st year of MDC. The patients with CKD were regularly followed up every 3 months as a part of MDC in our hospital, and patients who returned for more than 4 follow-up visits were included in the unexpected return group. In crude regression analyses, unexpected return was significantly associated with higher monthly declines of eGFR (β = 0.092, 95% confidence interval, 0.014-0.170). This association remained after adjustments for multiple variables, and subgroup analyses of unexpected return showed that male gender, older age, CKD stage 1 to 3, hypertension, history of coronary artery disease, and use of renin-angiotensin system blockade were significantly associated with declines in renal function.In conclusion, unexpected return for follow-up during the 1st year of MDC was significantly associated with the deterioration of renal function.


3-Deoxy-beta-D-ribo-hexopyranose (3-deoxy-beta-D-glucopyranose).
The beta-pyranose form, (III), of 3-deoxy-D-ribo-hexose (3-deoxy-D-glucose), C(6)H(12)O(5), crystallizes from water at 298 K in a slightly distorted (4)C(1) chair conformation. Structural analyses of (III), beta-D-glucopyranose, (IV), and 2-deoxy-beta-D-arabino-hexopyranose (2-deoxy-beta-D-glucopyranose), (V), show significantly different C-O bond torsions involving the anomeric carbon, with the H-C-O-H torsion angle approaching an eclipsed conformation in (III) (-10.9 degrees ) compared with 32.8 and 32.5 degrees in (IV) and (V), respectively. Ring carbon deoxygenation significantly affects the endo- and exocyclic C-C and C-O bond lengths throughout the pyranose ring, with longer bonds generally observed in the monodeoxygenated species (III) and (V) compared with (IV). These structural changes are attributed to differences in exocyclic C-O bond conformations and/or hydrogen-bonding patterns superimposed on the direct (intrinsic) effect of monodeoxygenation. The exocyclic hydroxymethyl conformation in (III) (gt) differs from that observed in (IV) and (V) (gg).


Systematic review of the efficacy and purpose of student surgical interest groups.
There is concern around projected unmet need in the surgical workforce internationally. Current barriers to medical students pursuing surgical careers include lack of early exposure, low confidence in surgical skills, and perceived lifestyle barriers. This review aimed to examine both the purpose of student surgical interest groups (SIGs) globally, and their effect on metrics representing student surgical career interest. barriers. MEDLINE, EMBASE, PubMed, and Google Scholar were searched for papers analysing surgical interest group purpose and efficacy. Risk of bias was assessed for survey-based papers using a 20-point checklist. Descriptive analysis was performed based on qualitative data. Twenty-eight papers were included in the analysis including 13 surveys. These were of moderate quality. The analysed SIGs had 100-1000 student members and a diverse range of funding sources. Purpose of SIGs was described by 26 of 28 papers with common themes including promotion of surgical career choice and developing theoretical/practical surgical skills. Common initiatives of SIGs included surgical lectures/teaching and practical skills workshops. Data from 15 papers analysing efficacy of SIGs suggested they positively influenced self-reported student interest in surgical careers (78.6%) and confidence in surgical knowledge (80%), as well as confidence in practical skills, knowledge about surgical careers/lifestyle, mentorship opportunity, and research involvement. Student SIGs make a unique contribution to early medical student experience through positive effect on promoting surgical careers. They target relevant metrics such as surgical knowledge and confidence that are known to influence surgical career choice in the modern surgical landscape.


"I have been refused to be treated by three dentists": Barriers to patient care.
Factor X deficiency (known as; Stuart-Prower factor deficiency or F10 deficiency) is a rare inherited bleeding disorder. It affects one per 1 million individuals worldwide. Patients with inherited bleeding disorder reported difficulty in accessing primary dental care either due to their medical diseases or their related barriers. This article aims to identify barriers to oral health as perceived by the patient with factor X deficiency who had been refused treatment by three dentists. A further aim is to provide dentists with the knowledge required to manage patients diagnosed with factor X deficiency. A 30-year-old male with the inherited, severe factor X deficiency (<1%) was asked to complete a survey which includes 22 semistructured, validated questions to assess his perceived barriers to dental services. Dental examination revealed that the patient required having nonsurgical periodontal therapy under local anesthesia. The treatment plan was discussed with the patient and his hematologist. The patient's hematologist advised performing dental treatment shortly (ie, 1-2 h) after hematological cover with a prothrombin complex concentrate (1000 U; Octoplex® ) via intravenous infusion. The hematologist also prescribed tranexamic acid mouthwash (250 mg in 5 mL) and the patient was instructed to rinse his mouth for 3-5 min with 500 μg (10 mL) in case of bleeding following treatment. The patient reported several barriers to dental services such as high anxiety levels regarding oral bleeding, difficulty in finding a suitable dental clinic, high cost of dental treatment, and the need for hematological cover prior to dental treatment. The proper communication between dentist and hematologist was a vital step to render safe and effective dental care and to reduce the patient's anxiety toward the dentist.


Uterus didelphys associated with unilateral imperforate vagina.
Two cases of uterus didelphys associated with unilateral imperforate vagina are reported with a review of the literature. In all cases investigated, ipsilateral renal agenesis was found on the affected side. A summary of the embryologic development of the female reproductive tract is included, as well as a possible explanation for this rare anomaly. The authors describe their proposed method of management to achieve freedom from symptoms and maintenance of a relatively intact reproductive tract.


Reporting Correct p Values in VEGAS Analyses.
VEGAS (versatile gene-based association study) is a popular methodological framework to perform gene-based tests based on summary statistics from single-variant analyses. The approach incorporates linkage disequilibrium information from reference panels to account for the correlation of test statistics. The gene-based test can utilize three different types of tests. In 2015, the improved framework VEGAS2, using more detailed reference panels, was published. Both versions provide user-friendly web- and offline-based tools for the analysis. However, the implementation of the popular top-percentage test is erroneous in both versions. The p values provided by VEGAS2 are deflated/anti-conservative. Based on real data examples, we demonstrate that this can increase substantially the rate of false-positive findings and can lead to inconsistencies between different test options. We also provide code that allows the user of VEGAS to compute correct p values.


[Superior sagittal sinus occlusion due to calvarial metastasis of renal cell carcinoma: 2 cases report].
We report two cases of superior sagittal sinus (SSS) occlusion due to calvarial metastasis of renal cell carcinoma. Both cases were presented with bulging of the skull. No stigmata of increased intracranial pressure was detected. Cerebral angiogram showed the occlusion of the SSS. Tumor cells did not penetrate into the dura mater nor the galea and the tumors were able to be removed easily in both cases. One case without collateral circulation showed recanalization of the SSS on the postoperative angiography. Another case with development of collateral circulation did not show recanalization of SSS on the postoperative magnetic resonance angiography. In the latter case, cortical veins flowed into the occluded portion. We consider that SSS should be preserved to prevent venous congestion in the cases where collateral circulation has not developed.


Two sites of oxygen control in induced synthesis of respiratory nitrate reductase in Escherichia coli.
The time course of appearance of respiratory nitrate reductase in Escherichia coli after induction by nitrate was analyzed under different conditions, and the inhibitory effects of oxygen, chloramphenicol, and rifampin were compared. Oxygen appeared to inhibit the synthesis of nitrate reductase at the level of transcription. In addition, the translation or some later steps of enzyme formation were blocked.


Structural studies of Neurospora crassa LPMO9D and redox partner CDHIIA using neutron crystallography and small-angle scattering.
Sensitivity to hydrogen/deuterium and lack of observable radiation damage makes cold neutrons an ideal probe the structural studies of proteins with highly photosensitive groups such as the copper center of lytic polysaccharide monooxygenases (LPMOs) and flavin adenine dinucleotide (FAD) and heme redox cofactors of cellobiose dehydrogenases (CDHs). Here, neutron crystallography and small-angle neutron scattering are used to investigate Neurospora crassa LPMO9D (NcLPMO9D) and CDHIIA (NcCDHIIA), respectively. The presence of LPMO greatly enhances the efficiency of commercial glycoside hydrolase cocktails in the depolymerization of cellulose. LPMOs can receive electrons from CDHs to activate molecular dioxygen for the oxidation of cellulose resulting in chain cleavage and disruption of local crystallinity. Using neutron protein crystallography, the hydrogen/deuterium atoms of NcLPMO9D could be located throughout the structure. At the copper active site, the protonation states of the side chains of His1, His84, His157 and Tyr168, and the orientation of water molecules could be determined. Small-angle neutron scattering measurements provided low resolution models of NcCDHIIA with both the dehydrogenase and cytochrome domains in oxidized states that exhibited elongated conformations. This work demonstrates the suitability of neutron diffraction and scattering for characterizing enzymes critical to oxidative cellulose deconstruction.


Risk of Secondary Traumatic Stress in Treating Traumatized Military Populations: Results from the PTSD Clinicians Exchange.
This study examined risk factors for secondary traumatic stress (STS) in behavioral health clinicians and whether access to the Post-Traumatic Stress Disorder (PTSD) Clinicians Exchange website mitigated STS risk. A diverse sample of clinicians (N = 605) treating traumatized military populations in Department of Veterans Affairs (VA), Department of Defense, and community practice settings were randomized to a newsletter-only control group or the exchange group. The exchange website included resources for treating PTSD and promoting clinician well-being. Online surveys were administered at 0-, 6-, and 12-months postrandomization. Regression analyses were used to examine the link among risk factors, exchange access, and STS. Baseline clinician demographics, experience, total caseload, appeal of evidence-based practices (EBPs), and likelihood of adopting EBPs if required were not linked with STS at the 12-month assessment period. Providing care at the VA, more burnout, less compassion satisfaction, greater trauma caseload, less openness to new EBPs, and greater divergence from EBP procedures were linked with greater STS. Only burnout and divergence were associated with STS after accounting for other significant STS risk factors. Exchange and control group clinicians reported similar STS levels after accounting for burnout and divergence. Given that burnout was linked with STS, future intervention may use techniques targeting burnout and STS (eg, emotion regulation strategies). Research exploring the link between divergence from EBPs and STS may inform EBP dissemination efforts and STS interventions. Finally, results highlight the need for research optimizing STS intervention efficacy among clinicians treating military populations.


Characterization on the Expanding Nature of Graphite in Microwave-Irradiated Exfoliation.
Much still remains uncertain and controversial about the mechanophysical parameters involved in graphite exfoliation. Here, we quantify the expansion characteristics of natural graphite in the microwave-irradiated exfoliation where KMnO4 and HNO3 are used as an oxidant and an intercalant, respectively. As a mark of the degree to which graphite becomes exfoliated, the expansion ratio of graphite is investigated as a function of mix ratio by weight of 3 ingredients (i.e., graphite, KMnO4, and HNO3), mixing time, and graphite physical properties. The findings of this study will lead to a better understanding of graphite exfoliation and make it possible to achieve the industrial-scale production of defect-free graphene.


Therapeutic Potential of Myricetin in the Treatment of Neurological, Neuropsychiatric, and Neurodegenerative Disorders.
Myricetin (MC), 3,5,7,3',4',5'-hexahydroxyflavone, chemically belongs to a flavonoid category known to confer antioxidant, antimicrobial, antidiabetic, and neuroprotective effects. MC is known to suppress the generation of Reactive Oxygen Species (ROS), lipid peroxidation (MDA), and inflammatory markers. It has been reported to improve insulin function in the human brain and periphery. Besides this, it modulates several neurochemicals including glutamate, GABA, serotonin, etc. MC has been shown to reduce the expression of the enzyme Mono Amine Oxidase (MAO), which is responsible for the metabolism of monoamines. MC treatment reduces levels of plasma corticosterone and restores hippocampal BDNF (full form) protein in stressed animals. Further, MC has shown its protective effect against amyloid-beta, MPTP, rotenone, 6-OHDA, etc. suggesting its potential role against neurodegenerative disorders. The aim of the present review is to highlight the therapeutic potential of MC in the treatment of several neurological, neuropsychiatric, and neurodegenerative disorders.


Case Report: Dengue Virus-Triggered Parkinsonism in an Adolescent.
Dengue fever continues to be an important cause of morbidity and mortality in tropical and subtropical countries. A wide range of neurological manifestations including dengue encephalopathy, Guillain-Barre syndrome, acute disseminated encephalomyelitis, transverse myelitis, cranial nerve palsies, and myositis have been reported following dengue infection. But parkinsonism secondary to dengue virus infection is uncommon, with only three published case reports in adults and one in children. We describe a 13-year-old pre-morbidly normal boy, who presented with bradykinesia, bradyphonia, mask-like facies, and cogwheel rigidity while recovering from uncomplicated DF. He responded favorably to levodopa/carbidopa supplementation and had resolution of symptoms over the next 2 weeks. We also did a comparative review of all published cases of dengue-induced parkinsonism. Post-dengue, parkinsonism is uncommon, and treating clinicians should be aware of this uncommon but treatable neurological complication of a common arboviral infection.


Bile components and amino acids affect survival of the newly excysted juvenile Clonorchis sinensis in maintaining media.
Clonorchis sinensis thrives on bile juice. The effects of bile and bile acids on newly excysted juvenile C. sinensis (CsNEJ) were studied in terms of survival. Survival of CsNEJs maintained in 1x Locke's solution, Dulbecco's modified Eagle's medium, NCTC 109, Eagle's, RPMI 1640, and 0.1% glucose was high, but dropped rapidly in 2x Locke's, 0.85% NaCl, and phosphate-buffered saline. Most amino acids in the media favored CsNEJ survival; however, aspartic and glutamic acids and adenine reduced survival. Survival was also significantly lower in media containing more than 0.1% bile. CsNEJs preconditioned in low bile media survived longer in higher bile media. All bile acids and conjugated bile salts were found to favor CsNEJ survival, except for lithocholic acid (LCA) which was toxic. NCTC 109 medium was found to be optimal for the in vitro maintenance of CsNEJs and 1x Locke's solution to be suitable for analyzing the biological effects of bioactive compounds and molecules. Based on these results, we propose that bile acids enhance activity of CsNEJs, but LCA deteriorate CsNEJs.


Successful desensitization after hypersensitivity reaction to cisplatin in a patient with nasopharyngeal carcinoma.
Hypersensitivity reaction to cisplatin can result in discontinuation of chemoradiotherapy in patients with head and neck squamous cell carcinoma. We describe a patient with nasopharyngeal carcinoma who developed cisplatin hypersensitivity and was successfully treated with cisplatin desensitization. Furthermore, it had little impact on the therapeutic performance of cisplatin-combined chemoradiotherapy.


Using AlphaFold to predict the impact of single mutations on protein stability and function.
AlphaFold changed the field of structural biology by achieving three-dimensional (3D) structure prediction from protein sequence at experimental quality. The astounding success even led to claims that the protein folding problem is "solved". However, protein folding problem is more than just structure prediction from sequence. Presently, it is unknown if the AlphaFold-triggered revolution could help to solve other problems related to protein folding. Here we assay the ability of AlphaFold to predict the impact of single mutations on protein stability (ΔΔG) and function. To study the question we extracted the pLDDT and <pLDDT> metrics from AlphaFold predictions before and after single mutation in a protein and correlated the predicted change with the experimentally known ΔΔG values. Additionally, we correlated the same AlphaFold pLDDT metrics with the impact of a single mutation on structure using a large scale dataset of single mutations in GFP with the experimentally assayed levels of fluorescence. We found a very weak or no correlation between AlphaFold output metrics and change of protein stability or fluorescence. Our results imply that AlphaFold may not be immediately applied to other problems or applications in protein folding.


The contribution of district prioritization on maternal and newborn health interventions coverage in rural India.
In 2001, India prioritized eight most socioeconomically disadvantaged states known as Empowered Action Group (EAG) states and in 2013, it prioritized 190 of the 718 as high priority districts (HPDs) to accelerate the decline in maternal and newborn mortality. This paper assesses whether the HPDs achieved a greater coverage of maternal and newborn health interventions than the non-HPDs and HPDs in EAG states achieved greater coverage than those in non-EAG states. We used data from the Sample Registration System to assess rural neonatal mortality trends in EAG states and all India. We computed a co-coverage index based on seven maternal and newborn health interventions from the 2015/16 National Family Health Survey. Difference in differences (DID) analyses were used to examine the contribution of district prioritization, considering the HPDs and the illiterate as treatment groups and 2013 as the time cut-off for the pre- and post-treatment. Neonatal mortality declined in rural India from 36 to 27 per 1000 live births during 2010-2016 at 4.5% per year. Four EAG states experienced faster rates of decline than the national rate. From 2013, the co-coverage index increased significantly more in the HPDs compared to non-HPDs (DID = 0.11, P ≤ 0.005). The district prioritization effect on co-coverage was statistically significant in only EAG states (DID = 0.13, P ≤ 0.05). The coverage gains for illiterate mothers were greater than for literate mothers, especially in the HPDs. The district prioritization in India is associated with greater improvements in the coverage of maternal and newborn health services in EAG states and the HPDs, including reductions in inequalities within those states and districts. There are however still large gaps between states and districts and within districts by the mother's literacy status that need further prioritization to make progress towards the SDG targets by 2030.


Vortex-trap-induced fusion of femtoliter-volume aqueous droplets.
This paper describes the use of an optical vortex trap for the transport and fusion of single femtoliter-volume aqueous droplets. Individual droplets were generated by emulsifying water in acetophenone with SPAN 80 surfactant. We demonstrate the ability of optical vortex traps to position trapped droplets precisely while excluding surrounding aqueous droplets from entering the trap, thereby preventing unwanted cross contamination by other nearby droplets. Additionally, the limitation of optical vortex traps for inducing droplet fusion is illustrated, and a remedy is provided through modulation of the spatial intensity profile of the optical vortex beam. Spatial modulation was achieved by translating the computer-generated hologram (CGH) with respect to the input Gaussian beam, thereby shifting the location of the embedded phase singularity (dark core) within the optical vortex beam. We present both simulated and experimentally measured intensity profiles of the vortex beam caused by translation of the CGH. We further describe the use of this technique to achieve controlled and facile fusion of two aqueous droplets.


Radiopharmaceuticals for Persistent or Recurrent Uterine Cervix Cancer.
Uterine cervix cancers pose therapeutic challenges because of an overactive ribonucleotide reductase, which provides on-demand deoxyribonucleotides for DNA replication or for a DNA damage repair response. Ribonucleotide reductase overactivity bestows cancer cell resistance to the effects of radiotherapy and chemotherapy used to treat disease; but nevertheless, this same biologic overexpression provides opportune vulnerabilities relatively specific to uterine cervix cancers for new therapeutic strategies to take advantage. The discovery of human epidermal growth factor receptor 2 (ErbB2 or HER2) overexpression on metastatic uterine cervix cancer cells provides an opportunity for clinical trials of targeted radiopharmaceuticals in combination with DNA damage response modifying drugs. The National Cancer Institute's clinical trial infrastructure and its experimental therapeutics portfolio can now offer clinical trial evaluation of molecularly-targeted and tolerated radiopharmaceutical-drug combinations for women with persistent or recurrent metastatic uterine cervix cancer. This article discusses the current thinking of the National Cancer Institute in regard to attractive radiopharmaceutical strategies for this disease and others.


2020 Taiwan consensus statement on the management of hepatitis C: part (I) general population.
Hepatitis C virus (HCV) infection remains a major public health issue with high prevalence in Taiwan. Recently, the advent of direct-acting antiviral (DAA) agents, with higher efficacy, excellent safety profile, and truncated treatment duration, has revolutionized the paradigm of hepatitis C treatment and made HCV elimination possible. To provide timely guidance for optimal hepatitis C management, the Taiwan Association for the Study of the Liver (TASL) established an expert panel to publish a 2-part consensus statement on the management of hepatitis C in the DAA era. After comprehensive literature review and a consensus meeting, patient-oriented, genotype-guided recommendations on hepatitis C treatment for the general and special populations have been provided based on the latest indications and scientific evidence. In the first part of this consensus, we present the epidemiology and treatment situation of hepatitis C in Taiwan, the development of DAA, pre-treatment evaluation, post sustained virologic response (SVR) monitoring, and most importantly the treatment recommendations for the general population with compensated liver disease. The second part will focus on the treatment recommendations for the special populations.


Concurrent sexual partnerships among African American women in Philadelphia: results from a qualitative study.
African American women are disproportionately affected by HIV/AIDS. Concurrent sexual partnerships may contribute to racial disparities in HIV infection. Little is known about attitudes and practices related to concurrency among African American women, or the social, structural and behavioural factors influencing concurrency. We recruited 19 heterosexual African American women engaging in concurrent sexual partnerships from a public clinic in Philadelphia in 2009. We conducted interviews exploring social norms, attitudes and practices about concurrency, and the structural, social and behavioural factors influencing concurrent sexual partnerships, guided by grounded theory. Seventeen women reported one main and one or more non-main partners; two reported no main partners. Many women used condoms more frequently with non-main than main partners, noting they trust main partners more than non-main partners. Social factors included social normalisation of concurrency, inability to negotiate partners' concurrent partnerships, being unmarried, and not trusting partners. Lack of trust was the most commonly cited reason that women engaged in concurrent partnerships. Structural factors included economic dependence on partners, partners' dependence on women for economic support and incarceration that interrupted partnerships. Behavioural factors included alcohol and cocaine use. Social, structural and behavioural factors strongly influenced these African American women's concurrent sexual partnerships. Many HIV interventions disseminated by the CDC focus largely on behavioural factors and may fail to address the social and structural factors influencing African American women's sexual networks. Novel HIV prevention interventions that address the social determinants of African American women's HIV risks are urgently needed.


Preoperative Renal Functional Reserve Predicts Risk of Acute Kidney Injury After Cardiac Operation.
Although acute kidney injury (AKI) frequently complicates cardiac operations, methods to determine AKI risk in patients without underlying kidney disease are lacking. Renal functional reserve (RFR) can be used to measure the capacity of the kidney to increase glomerular filtration rate under conditions of physiologic stress and may serve as a functional marker that assesses susceptibility to injury. We sought to determine whether preoperative RFR predicts postoperative AKI. We enrolled 110 patients with normal resting glomerular filtration rates undergoing elective cardiac operation. Preoperative RFR was measured by using a high oral protein load test. The primary end point was the ability of preoperative RFR to predict AKI within 7 days of operation. Secondary end points included the ability of a risk prediction model, including demographic and comorbidity covariates, RFR, and intraoperative variables to predict AKI, and the ability of postoperative cell cycle arrest markers at various times to predict AKI. AKI occurred in 15 patients (13.6%). Preoperative RFR was lower in patients who experienced AKI (p < 0.001) and predicted AKI with an area under the receiver operating characteristic curve (AUC) of 0.83 (95% confidence interval [CI]: 0.70 to 0.96). Patients with preoperative RFRs not greater than 15 mL · min-1 · 1.73 m-2 were 11.8 times more likely to experience AKI (95% CI: 4.62 to 29.89 times, p < 0.001). In addition, immediate postoperative cell cycle arrest biomarkers predicted AKI with an AUC of 0.87. Among elective cardiac surgical patients with normal resting glomerular filtration rates, preoperative RFR was highly predictive of AKI. A reduced RFR appears to be a novel risk factor for AKI, and measurement of RFR preoperatively can identify patients who are likely to benefit from preventive measures or to select for use of biomarkers for early detection. Larger prospective studies to validate the use of RFR in strategies to prevent AKI are warranted. ClinicalTrials.gov identifier: NCT03092947, ISRCTN Registry: ISRCTN16109759.