Interrater agreement of contouring of the neurovascular bundles and internal pudendal arteries in neurovascular-sparing magnetic resonance-guided radiotherapy for localized prostate cancer.
Radiation damage to neural and vascular tissue, such as the neurovascular bundles (NVBs) and internal pudendal arteries (IPAs), during radiotherapy for prostate cancer (PCa) may cause erectile dysfunction. Neurovascular-sparing magnetic resonance-guided adaptive radiotherapy (MRgRT) aims to preserve erectile function after treatment. However, the NVBs and IPAs are not routinely contoured in current radiotherapy practice. Before neurovascular-sparing MRgRT for PCa can be implemented, the interrater agreement of the contouring of the NVBs and IPAs on pre-treatment MRI needs to be assessed. Four radiation oncologists independently contoured the prostate, NVB, and IPA in an unselected consecutive series of 15 PCa patients, on pre-treatment MRI. Dice similarity coefficients (DSCs) for pairwise interrater agreement of contours were calculated. Additionally, the DCS of a subset of the inferior half of the NVB contours (i.e. approximately prostate midgland to apex level) was calculated. Median overall interrater DSC for the left and right NVB was 0.60 (IQR: 0.54 - 0.68) and 0.61 (IQR: 0.53 - 0.69) respectively and for the left and right IPA 0.59 (IQR: 0.53 - 0.64) and 0.59 (IQR: 0.52 - 0.64) respectively. Median overall interrater DSC for the inferior half of the left NVB was 0.67 (IQR: 0.58 - 0.74) and 0.67 (IQR: 0.61 - 0.71) for the right NVB. We found that the interrater agreement for the contouring of the NVB and IPA improved with enhancement of the MRI sequence as well as further training of the raters. The agreement was best in the subset of the inferior half of the NVB, where a good agreement is clinically most relevant for neurovascular-sparing MRgRT for PCa.


Health problems in children and adolescents before and after a man-made disaster.
The aims of this study were to examine health problems of children (4-12 years old at the time of the disaster) and adolescents (13-18 years old at the time of the disaster) before and after exposure to a fireworks disaster in the Netherlands (May 2000), to compare these health problems with a control group, and to identify risk factors for postdisaster psychological problems. Because the electronic medical records of family practitioners were used, longitudinal monitoring of health problems from 1 year predisaster until 2 years postdisaster for both victims (N=1,628) and controls (N=2,856) was possible. Health problems were classified according to the International Classification of Primary Care. Postdisaster increases were significantly larger in victims than in controls for psychological problems, musculoskeletal problems, stress reactions, and symptoms of the extremities. Children 4-12 years old presented larger increases in sleep problems compared with controls, whereas children 13-18 years old showed larger increases in anxiety problems than their controls. Significant predictors for postdisaster psychological problems included being relocated, presenting predisaster psychological problems, and a low to medium socioeconomic status. Children and adolescents exposed to a disaster are at risk of long-lasting increases in both psychological and physical health problems. Postdisaster interventions should focus on those who were relocated and presented predisaster psychological problems.


Social-ecological considerations for the sleep health of rural mothers.
Using a social-ecological framework, we identify social determinants that interact to influence sleep health, identify gaps in the literature, and make recommendations for targeting sleep health in rural mothers. Rural mothers experience unique challenges and protective factors in maintaining adequate sleep health during the postpartum and early maternal years. Geographic isolation, barriers to comprehensive behavioral medicine services, and intra-rural ethno-racial disparities are discussed at the societal (e.g., public policy), social (e.g., community) and individual levels (e.g., stress) of the social-ecological model. Research on sleep health would benefit from attention to methodological considerations of factors affecting rural mothers such as including parity in population-level analyses or applying community-based participatory research principles. Future sleep health programs would benefit from using existing social support networks to disseminate sleep health information, integrating behavioral health services into clinical care frameworks, and tailoring culturally-appropriate Telehealth/mHealth programs to enhance the sleep health of rural mothers.


Effect of VPAC1 Blockade on Adipose Tissue Formation and Composition in Mouse Models of Nutritionally Induced Obesity.
Background. The pituitary adenylate cyclase activating polypeptide (PACAP) may affect adipogenesis and adipose tissue formation through interaction with its G-protein-coupled receptor VPAC1. Methods. We have used a monoclonal antibody (MAb 23A11) blocking VPAC1 in mouse models of nutritionally induced obesity. Results. Administration of MAb 23A11 (25 mg/kg body weight i.p. twice weekly) to 5-week old male C57Bl/6 mice kept on a high-fat diet for 15 weeks had no significant effect on weight gain, nor on subcutaneous (SC) or gonadal (GON) adipose tissue mass, as compared to the control MAb 1C8. However, adipocyte hypertrophy was observed in SC adipose tissue of MAb 23A11 treated mice. In a second study, 24 weeks old obese mice were treated for 5 weeks with MAb 23A11, without effect on body weight or fat mass, as compared to treatment with MAb 1C8. In addition, MAb 23A11 had no significant effect on glucose tolerance or insulin resistance in lean or obese C57Bl/6 mice. Conclusion. Blocking VPAC1 does not significantly affect adipose tissue formation in mouse models of diet-induced obesity, although it may be associated with mild adipocyte hypertrophy.


Upgraded role of autophagy in colorectal carcinomas.
Autophagy is a basic catabolic process closely associated with degradation of cellular components. The role of autophagy in colorectal cancer (CRC) remains controversial. The mechanism of autophagy has been identified as protecting mechanism against tumorigenesis by isolation of damaged organelles or as cytoprotective provides energy in hypoxic regions of CRC tumors. Mutations in proto-oncogenes, such as RAS and BRAF, have been associated with autophagy initiation through signaling pathways of BRAF/MEK/ERK and PI3K/AKT/mTOR. A combination therapy of chemotherapeutic agents and autophagy inhibitors such as hydroxychloroquine or immunotherapy might represent a major step that could be evaluated as a putative novel therapeutic strategy in CRC patients.


Applications of confocal microscopy to the study of myelin development and neuron structure.
Confocal laser scanning microscopy has been used to study the localization of myelin basic proteins expressed in nonglial cells, and to probe the three-dimensional structure of central auditory neurons in the lateral superior olive. The paper focuses on the techniques used to obtain the results. The key roles of confocal microscopy and computer image processing of the images obtained are emphasized as they relate to the discovery of essential structural information about these specimens.


Evaluation of the efficacy of polymeric antigen BLSOmp31 formulated in a new cage-like particle adjuvant (ISPA) administered by parenteral or mucosal routes against Brucella ovis in BALB/c mice.
Brucella ovis is an economically important cause of epididymitis in rams worldwide. Polymeric BLSOmp31 was previously identified as a protective immunogen against this pathogen. In this study, BLSOmp31 was formulated with a modified version of ISCOMATRIX adjuvant called ISPA (BLSOmp31/ISPA) and was administered in BALB/C by the subcutaneous and ocular route. The systemic and mucosal immune responses, the opsonic activity of antibodies and the protection conferred against B. ovis were evaluated. BLSOmp31+ISPA injected subcutaneously or by ocular route induced significantly higher IgG antibody levels with a mixed Th1/Th2 profile compared to non-immunized mice. IgA and IgG were detected in sera and nasal, tracheobronchial, vaginal secretions, tears and faeces, from SC immunized mice while in the group immunized by the ocular route a slight increase in both isotypes was mainly observed in all secretions, except in vaginal fluid. Opsonic antibodies stimulated binding and increased uptake of PHrodo™ Green-labelled B. ovis by neutrophils and monocytes. BLSOmp31 administered subcutaneously induced the highest levels of IFN-ɣ. The ocular immunization not only produced significant levels of this cytokine but also IL-4 compared to non-immunized mice. Both, subcutaneous and ocular routes of immunization, significantly protected against B. ovis infection. These results indicate that BLSOmp31/ISPA administered parenterally or by ocular route is a safe and effective vaccine against B. ovis in the murine model.


Raynaud's disease: an update.
This often painful disease may be primary or secondary. Simple preventive measures sometimes provide symptomatic control. When such efforts fail, the most effective agents available are calcium channel blockers.


Managing Cystic Fibrosis in Polish Healthcare.
The quality and length of life of patients with cystic fibrosis (CF) are determined by a number of factors including the quality of healthcare received by patients, as well as access to drug programs dedicated to this particular disease. The purpose of this paper is to present an overview of changes in the average life expectancy and mortality rate of the CF population in Poland between 2000 and 2018. Furthermore, we would like to evaluate access to healthcare services, including the drug program, guaranteed by public healthcare system, and funded by National Health Fund (NHF). The average life expectancy of patients with CF increased in the period in question from ca. 14.5 ± 7.6-24.5 ± 8.9 years (mean ± SD, p = 0.0001). We have observed a drop in the number of deaths in paediatric age during that period. Despite the increase in life expectancy, the use of health resources in patients with CF, especially the drug program, is dramatically low. Considering the fact that in Poland there was no active countrywide CF registry, now it is possible to estimate the frequency of use of CF healthcare services in various provinces exclusively on the basis of database maintained by the Polish NHF.


Intermittent walking: a potential treatment for older people with postprandial hypotension.
Exercise has been proposed as a possible treatment for postprandial hypotension (PPH), yet, its use has not been extensively investigated. This study aimed to determine the effects of intermittent walking on blood pressure (BP) and heart rate (HR) following ingestion of a glucose drink in older people with PPH. Thirteen persons with PPH were recruited and studied on 2 randomized days (control, intervention). On both study days, participants ingested 200 mL of water containing 50 g glucose, followed by ambulatory BP and HR monitoring 6 minutely for 60 minutes, then 15 minutely until 120 minutes. On the intervention day, participants walked at their usual pace for 30 m every 30 minutes for 120 minutes. On the control day, significant falls in systolic blood pressure (SBP) (P < .005) and diastolic blood pressure (DBP) (P = .016) were demonstrated between t = 0-120 minutes. On the intervention day, over the same period, there was no significant fall in SBP (P = .520), however, DBP still fell significantly (P = .045). There was a statistically significant difference (P = .005) for the area under the curve for the change in SBP from baseline for the study days but not DBP (P = .716). There was no significant change in HR (control: P = .854; intervention, P = .168) nor between the area under the curve (P = .798) for the change in HR from baseline for the study days. This study suggests that in older people with PPH, intermittent walking at a usual pace attenuates the fall in SBP after ingestion of a glucose drink.


Building midwifery educator capacity in teaching in low and lower-middle income countries. A review of the literature.
midwifery educators play a critical role in strengthening the midwifery workforce in low and lower-middle income countries (LMIC) to ensure that women receive quality midwifery care. However, the most effective approach to building midwifery educator capacity is not always clear. This paper will explore approaches used to build midwifery educator capacity in LMIC and identify evidence to inform improved outcomes for midwifery education. a structured search of bibliographic electronic databases (CINAHL, OVID, MEDLINE, PubMed) and the search engine Google Scholar was performed. It was decided to also review peer reviewed research, grey literature and descriptive papers. Papers were included in the review if they were written in English, published between 2000 and 2014 and addressed building knowledge and/or skills in teaching and/or clinical practice in midwifery educators who work in training institutions in LMIC. The Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) was used to guide the reporting process. The quality of papers was appraised in discussion with all authors. The findings sections of the research papers were analysed to identify successful elements of capacity building approaches. eighteen (six research and 12 discursive) papers were identified as related to the topic, meeting the inclusion criteria and of sufficient quality. The findings were themed according to the key approaches used to build capacity for midwifery education. These approaches are: skill and knowledge updates associated with curriculum review, involvement in leadership, management and research training and, participation in a community of practice within regions to share resources. the study provides evidence to support the benefits of building capacity for midwifery educators. Multilevel approaches that engaged individuals and institutions in building capacity alongside an enabling environment for midwifery educators are needed but more research specific to midwifery is required. these findings provide insight into strategies that can be used by individuals, faculties and institutions providing development assistance to build midwifery educator capacity in LMIC.


[Critical evaluation of prophylactic splenectomy in total gastrectomy for stomach cancer].
In gastric cancer surgery, an extended radical operation is commonly performed, and in cases of total gastrectomy, there is a tendency to perform splenectomy at the same time. In order to examine the value of prophylactic splenectomy in gastric cancer surgery, a comparable patient group was followed up, and it was formed that the non-splenectomized group showed a better late survival rate than the splenectomized group. Although these results do not necessarily contraindicate combined splenectomy, it seems desirable to reappraise the value of prophylactic splenectomy in cases having no metastasis in the splenic hilar and adjuvant lymph nodes.


A method to quantitate the relative nuclear area of colorectal polyps by image analysis.
Image analysis of the nuclear area was performed on Feulgen-stained sections from 94 colorectal polyps: 57 colorectal adenomas with or without invasive growth, 28 hyperplastic polyps and 9 Peutz-Jeghers hamartomas (without dysplasia or carcinoma). The lowest mean values of nuclear area were recorded in control cases: in hyperplastic polyps (27.3%), followed by hamartomatous polyps (34.7%). The nuclear area was significantly increased in tubular adenomas with low-grade dysplasia (37.9%), in villous adenomas with low-grade dysplasia (41.16%) and in tubular and villous adenomas with high-grade dysplasia (47.0% and 46.0%, respectively). The nuclear area in villous adenomas with invasive growth was significantly higher than in all other adenomas without invasive growth (56.0%). The present data suggest that the nuclear area in colorectal polyps (as deduced by image analysis studies) correlates well with the degree of nuclear atypia. Thus, measurements of nuclear area appear to be an important parameter in studies aiming to elucidate the malignant potential of these lesions.


Fear of Falling Contributing to Cautious Gait Pattern in Women Exposed to a Fictional Disturbing Factor: A Non-randomized Clinical Trial.
Objective: This study aimed to investigate the gait pattern of elderly women with and without fall-history, with high and low fear of falling, when exposed to a disturbing factor. Materials and Methods: Forty-nine elderly women without cognitive impairment agreed to participate. Participants were divided into four groups, considering the history of falls and fear of falling. Three-dimensional gait analysis was performed to assess gait kinematics before and after exposure to the fictional disturbing factor (psychological and non-motor agent). Results: After being exposed to the perturbation, all showed shorter step length, stride length and slower walking speed. Those without fall-history and with high fear of falling showed greater changes and lower Gait Profile Score. Conclusion: The gait changes shown in the presence of a fear-of-falling causing agent led to a cautious gait pattern in an attempt to increase protection. However, those changes increased fall-risk, boosted by fear of falling. Clinical Trial Registration: www.residentialclinics.gov.br, identifier: RBR-35xhj5.


New phenolic components and chromatographic profiles of green and fermented teas.
A standardized profiling method based on liquid chromatography with diode array and electrospray ionization mass spectrometric detection (LC-DAD-ESI/MS) was applied to establish the phenolic profiles of 41 green teas and 25 fermented teas. More than 96 phenolic compounds were identified that allowed the teas to be organized into five groups. Epigallocatechin gallate (EGCG) was the major phenolic component of green tea made from mature leaves (group 2), while green tea made from the younger buds and leaves (group 1) contained lower flavonoid concentrations. Partially fermented teas (group 3) contained one-half the EGCG content of the green tea. Fully fermented black teas (group 4) had a trace of EGCG, but contained theaflavins. Highly overfermented black tea (group 5) contained only trace amounts of flavonol glycosides and theaflavins. Over 30 phenolics are new for tea, and this is the first phenolic profile to simultaneously detect C- and O-glycosylated flavonoids, catechins, proanthocyanidins, phenolic acid derivatives, and purine alkaloids.


Rhodotorula spp. in the gut - foe or friend?
Rhodotorula spp. belong to the basidiomyceteous fungi. They are widespread in the environment. Transmission to humans occur mainly through air and food. Intestinal colonization is rather common, but an overgrowth is normally suppressed, since their optimal growth temperature is exceeded in the body. A massive presence in the gut indicates a disturbance of the balance of the microbial flora due to different causes. One particular reason will be the treatment with azoles because this will create an advantage for these azole resistant fungi. First of all, the finding of increased numbers of Rhodotorula in stool specimen is not alarming. In contrast, the colonized human will profit from such a situation since these fungi produce a lot of useful nutrients such as proteins, lipids, folate, and carotinoids. Furthermore, a probiotic effect due to regulation of multiplication of pathogenic bacteria and by neutralizing or destroying their toxins can be anticipated. On the other hand, their massive presence may increase the risk of fungemia and ensuing organ infections especially when the host defense system is hampered. Indeed, Rhodotorula spp. range among the emerging fungal pathogens in the compromised host. However, it can be doubted whether all these opportunistic infections reported originate primarily from the gut.


Severe thoracic pyomyositis in a patient with systemic lupus erythematosus.
Pyomyositis may mimic deep vein thrombosis and be misdiagnosed in patients with systemic lupus erythematosus (SLE). We report here on patient with SLE with severe thoracic pyomyositis presented with right upper arm swelling and fever. The patient fully recovered after a serial surgical debridement and antibiotic therapy. Pyomyositis, as well as deep vein thrombosis, should be considered during the differential diagnosis of patients with SLE experiencing fever and unilateral limb oedema. CT and identification of causal pathogens are crucial in the diagnosis of pyomyositis. Early effective antibiotic treatment as well as surgical intervention can together bring about a better outcome.


Comparative Analysis of Host-Associated Variation in Phytophthora cactorum.
Phytophthora cactorum is often described as a generalist pathogen, with isolates causing disease in a range of plant species. It is the causative agent of two diseases in the cultivated strawberry, crown rot (CR; causing whole plant collapse) and leather rot (LR; affecting the fruit). In the cultivated apple, P. cactorum causes girdling bark rots on the scion (collar rot) and rootstock (crown rot), as well as necrosis of the fine root system (root rot) and fruit rots. We investigated evidence for host specialisation within P. cactorum through comparative genomic analysis of 18 isolates. Whole genome phylogenetic analysis provided genomic support for discrete lineages within P. cactorum, with well-supported non-recombining clades for strawberry CR and apple infecting isolates specialised to strawberry crowns and apple tissue. Isolates of strawberry CR are genetically similar globally, while there is more diversity in apple-infecting isolates. We sought to identify the genetic basis of host specialisation, demonstrating gain and loss of effector complements within the P. cactorum phylogeny, representing putative determinants of host boundaries. Transcriptomic analysis highlighted that those effectors found to be specific to a single host or expanded in the strawberry lineage are amongst those most highly expressed during infection of strawberry and give a wider insight into the key effectors active during strawberry infection. Many effectors that had homologues in other Phytophthoras that have been characterised as avirulence genes were present but not expressed in our tested isolate. Our results highlight several RxLR-containing effectors that warrant further investigation to determine whether they are indeed virulence factors and host-specificity determinants for strawberry and apple. Furthermore, additional work is required to determine whether these effectors are suitable targets to focus attention on for future resistance breeding efforts.


Robot-Assisted Laparoscopic Living Donor Nephrectomy: The University of Florence Technique.
Objective: To provide a step-by-step overview of the University of Florence technique for robotic living donor nephrectomy (LDN), focusing on its technical nuances and perioperative outcomes. Methods: A dedicated robotic LDN program at our Institution was codified in 2012. Data from patients undergoing robotic LDN from 2012 to 2019 were prospectively collected. All robotic LDNs were performed by a highly experienced surgeon, using the da Vinci Si robotic platform in a three-arm configuration. In this report we provide a detailed overview of our surgical technique for robotic LDN. The main objective of the study was to evaluate the technical feasibility and safety of the technique, including perioperative surgical complications rate and mid-term functional outcomes. Results: Overall, 36 patients undergoing robotic LDNs were included in the study. Of these, 28 (78%) were left LDNs. Median (IQR) donor pre-operative eGFR was 88 (75.6-90) ml/min/1.73 m2. In all cases, robotic LDN was completed without need of conversion. The median (IQR) overall operative time was 230 (195-258) min, while the median console time was 133 (IQR 117-166) min. The median (IQR) warm ischemia time was 175 (140-255) s. No intraoperative adverse events or 90-d major surgical complications were recorded. At a median (IQR) follow-up of 24 months (IQR 11-46), median (IQR) eGFR patients undergoing in living donor nephrectomy was 57.4 (47.9; 63.9) ml/min/1.73 m2. Conclusions: In our experience, robotic LDN is technically feasible and safe. The use of robotic surgery for LDN may provide distinct advantages for surgeons while ensuring optimal donors' perioperative and functional outcomes.


Proton and nitrogen sequential assignments and secondary structure determination of the human FK506 and rapamycin binding protein.
Sequential 1H and 15N assignments of human FKBP, a cytosolic binding protein for the immunosuppressive agents FK506 and rapamycin, are reported. A combination of homonuclear and relayed heteronuclear experiments has enabled assignment of 98 of 99 backbone amide NHs, 119 of 120 C alpha Hs, 97 of 99 non-proline amide 15Ns, and 375 of 412 side-chain resonances of this 107-residue protein. Long-range NOEs are used to demonstrate that FKBP has a novel folding topology consisting of a five-stranded antiparallel beta sheet with +3, +1, -3, +1 loop connectivity.


Prognostic value of tumour budding in oesophageal cancer: a meta-analysis.
Recently, tumour budding (TB) has been suggested as a strong prognostic marker in oesophageal cancer. The aim of this systematic review is to test the prognostic value of TB in oesophageal cancer by a meta-analysis of previously published studies. We systematically reviewed the literature related to TB by using the bibliographic databases of Scopus, PubMed, and Web of Science. The search was limited to publications in the English language up to and including December 2014. There are 11 retrospective studies in which TB has been evaluated in oesophageal cancer. Two authors independently extracted the results from eligible studies. The meta-analysis of eligible studies revealed that TB is a significant prognosticator for overall survival in oesophageal cancer, with a risk ratio (RR) of 2.97 [95% confidence interval (CI) 1.81-4.85; P = 0.0023] in univariate analysis, and with an RR of 2.07 (95% CI 1.22-3.52; P = 0.017) in multivariate analysis. We conclude that a high TB score is a promising prognostic marker of poor survival in oesophageal cancer. Because of its simplicity, reproducibility and high predictive power, TB is strongly recommended to be included in the routine pathology report of oesophageal cancer.


Modified Spot CAMP Test: A rapid, inexpensive and accurate method for identification of group B streptococci.
A rapid modified spot CAMP test using 183 clinical isolates of beta haemolytic streptococci was compared with the standard CAMP test described by Christie et al. The scheme of biochemical identification and serological confirmation was taken as reference method. The sensitivity of both tests was 100%, and the specificity of the rapid and standard tests was 96.8% and 88.9% respectively. The modified spot CAMP test is a rapid, inexpensive and accurate method for the identification of group B streptococci, and is more specific than the standard CAMP test.


Effects of pentoxifylline on in-vitro development of preimplantation mouse embryos.
In-vitro culture of 1-cell mouse embryos was used to assess the influence of pentoxifylline or early embryonic development. If cultured in concentrations of 5, 10 or 50 microM, early embryonic development was unaffected and no differences in cell numbers were noted in embryos reaching the blastocyst stage. However, at 3.6 and 7.2 mM, pentoxifylline inhibited cleavage from the 2-cell stage onwards. If 1-cell mouse embryos were exposed for only 30 min to these concentrations, blastocyst formation was found to be morphologically normal. However, cell numbers of such blastocysts were significantly decreased after exposure to pentoxifylline. These results may indicate that exposure of gametes or zygotes to pentoxifylline should be avoided as much as possible when this drug is used in human assisted reproduction. If administered at regular therapeutic doses, it is probable that no adverse effect on early embryonic development in vivo will occur. Further research is needed to confirm and elucidate the above findings.


Lab-on-paper with dual electrochemical/colorimetric detection for simultaneous determination of gold and iron.
A novel lab-on-paper device combining electrochemical and colorimetric detection for the rapid screening of Au(III) in the presence of a common interference, Fe(III), in industrial waste solutions is presented here. With dilute aqua regia (0.1 M HCl + 0.05 M HNO(3)) as the supporting electrolyte, square wave voltammetry on paper provided a well-defined reduction peak for Au(III) at approximately 287 +/- 12 mV vs Ag/AgCl. Under the optimized working conditions, the calibration curve showed good linearity in the concentration range of 1-200 ppm of Au(III) with a correlation coefficient of 0.997. The limit of detection (LOD) of the proposed method is 1 ppm. Interferences from various cations were also studied. Fe(III) is the only metal that affects the electrochemical determination of Au(III) when present above a 2.5-fold excess concentration of that of the Au(III). To overcome this limitation, a colorimetric method was used to simultaneously detect Fe(III) as a screening tool. The procedure was then successfully applied to determine Au(III) in gold-refining waste solutions. The results are in agreement with those obtained from inductively coupled plasma-atomic emission spectrometry (ICP-AES).


Cost Implications of Varying the Surgical Setting and Anesthesia Type for Dorsal Wrist Ganglion Cyst Excision Surgery.
Minimizing expenses attributed to dorsal wrist ganglion cyst excisions, a common minor surgical procedure, presents potential for health care cost savings. Varying the surgical setting (operating room versus procedure room) and type of anesthesia (local-only, monitored anesthesia care, or monitored with regional or general anesthesia) may affect total operative costs. Patients who underwent an isolated unilateral dorsal wrist ganglion cyst excision between January of 2014 and October of 2019 at a single academic medical center were identified by CPT code. The total direct costs for each surgical encounter that met inclusion criteria were calculated. The relative total direct costs were compared between surgical setting and anesthesia type groups. Univariate and multivariable gamma regression models were used to identify factors associated with surgical costs. A total of 192 patients were included; 26 cases (14 percent) were performed in the procedure room and 166 cases (86 percent) were performed in the operating room. No significant differences in demographic factors were identified between groups. Univariate analysis demonstrated that use of operating room/monitored anesthesia care, operating room/monitored anesthesia care with regional anesthesia, and operating room/general anesthesia groups, as compared to procedure room/local-only, yielded significantly greater median costs (1.76-, 2.34-, and 2.44-fold greater, respectively). Multivariable analysis demonstrated 1.80-, 2.10-, and 2.31-fold greater costs with use of operating room/monitored anesthesia care, operating room/monitored anesthesia care with regional anesthesia, and operating room/general anesthesia relative to procedure room/local-only, respectively. Performing dorsal wrist ganglion cyst excisions in a procedure room with local-only anesthesia minimizes operative direct costs relative to use of the operating room and other anesthetic types.


A novel Natural killer cell-related gene signature for improving the prediction of prognosis and immunotherapy response in bladder cancer.
Bladder cancer (BLCA) is a commonly diagnosed cancer worldwide that exhibits high rates of recurrence and metastasis. Immunotherapy is increasingly being recognised in the clinical management of bladder cancer. In addition, the prospect of developing Natural Killer (NK) cell-related immunotherapy is promising in BLCA. We established and verified a prognostic signature based on NK cell-related gene expression. We then calculated the NKscore of BLCA samples and correlated it with the clinical outcomes, molecular subtypes of BLCA, tumour microenvironment (TME), and predicted efficacy of immune checkpoint inhibitors (ICI) and chemotherapy drugs to thoroughly explore the implications of the NKscore. Finally, the role of the NK signature gene HECTD1 in BLCA was verified by Quantitative Real-time PCR, Cell Counting Kit-8 Assay (CCK-8), Transwell Assay and Colony Formation Experiment. We analysed NK cell-associated genes and identified six genes with significant prognostic relevance. A high NK score significantly represents a worse prognosis. NKscore was significantly correlated with seven types of classical molecular subtype classifications of BLCA. In addition, NKscore positively correlates with NK-related immune checkpoints, suggesting that emerging NK cell immune checkpoint inhibitors, such as monalizumab, may have potential therapeutic promise for patients with high NKscore. The results of the T cell inflamed score (TIS) and tumour immune dysfunction exclusion (TIDE) score confirmed the suitability of immunotherapy for patients with a high NK score. Likewise, patients with a high NK score may be more suitable for several significant chemotherapeutic drugs. Functional experiments showed that the knockdown of HECTD1 significantly attenuated the proliferation, migration, and invasion ability of tumour cells. to sum up, the capability of our signature to predict prognosis and immunotherapy response was robust. Hopefully, these results will provide new insights for BLCA research and patient immunotherapy.


Takayasu's disease with cutaneous involvement.
Takayasu's arteritis (TA) is a chronic inflammatory and fibrosing arteriopathy that can also involve cutaneous vessels. The disease typically presents with a prepulseless phase that overlaps or is followed by the characteristic pulseless stage. In both phases of TA, cutaneous manifestations may be present. Lesions considered to be 'specifically' associated with TA have been described most frequently simulating erythema nodosum, erythema induratum and pyoderma gangrenosum. We report 2 Caucasian patients with TA and nodular cutaneous lesions. Nine skin biopsies from these patients were studied. A necrotizing vasculitis was present in 5 biopsies. We review those patients with TA and well-documented cutaneous manifestations in the English literature, with special interest in nodular lesions, the most frequent cutaneous manifestation of TA in Caucasian patients. Biopsies from lesions with similar morphology frequently show different histological findings.


Calcified parathyroid glands detected by computed tomography.
Computed tomographic demonstration of single calcified parathyroid glands in two patients corresponded to operative findings of a calcified carcinoma and a calcified adenoma. The CT demonstration of a calcified parathyroid gland should suggest carcinoma, and the operative approach should be planned to permit an en bloc resection.


Flexibility of BIV TAR-Tat: models of peptide binding.
A new approach in determining local residue flexibility from base-amino acid contact frequencies is applied to the twelve million lattice chains modeling BIV Tat peptide binding to TAR RNA fragment. Many of the resulting key features in flexibility correspond to RMSD calculations derived from a set of five NMR derived structures (X. Ye, R. A. Kumar, and D. J. Patel, Protein Data Bank: Database of three-dimensional structures determined from NMR (1996)) and binding studies of mutants (L. Chen and A. D. Frankel, Proc. Natl. Acad. Sci. USA 92, 5077-5081 (1995)). The lattice and RMSD calculations facilitate the identification of peptide hinge regions that can best utilize the introduction of Gly or other flexible residues. This approach for identifying potential sites amenable to substitution of more flexible residues to enhance peptide binding to RNA targets could be a useful design tool.


Model-Based Prediction of an Effective Adhesion Parameter Guiding Multi-Type Cell Segregation.
The process of cell-sorting is essential for development and maintenance of tissues. Mathematical modeling can provide the means to analyze the consequences of different hypotheses about the underlying mechanisms. With the Differential Adhesion Hypothesis, Steinberg proposed that cell-sorting is determined by quantitative differences in cell-type-specific intercellular adhesion strengths. An implementation of the Differential Adhesion Hypothesis is the Differential Migration Model by Voss-Böhme and Deutsch. There, an effective adhesion parameter was derived analytically for systems with two cell types, which predicts the asymptotic sorting pattern. However, the existence and form of such a parameter for more than two cell types is unclear. Here, we generalize analytically the concept of an effective adhesion parameter to three and more cell types and demonstrate its existence numerically for three cell types based on in silico time-series data that is produced by a cellular-automaton implementation of the Differential Migration Model. Additionally, we classify the segregation behavior using statistical learning methods and show that the estimated effective adhesion parameter for three cell types matches our analytical prediction. Finally, we demonstrate that the effective adhesion parameter can resolve a recent dispute about the impact of interfacial adhesion, cortical tension and heterotypic repulsion on cell segregation.


Impact of COVID-19 lockdown on professional soccer players' match physical activities.
The COVID-19 pandemic forced the 2019-20 Italian Serie A competition to stop and players went into lockdown. During lockdown, players only trained at home, likely having a detrimental effect on players' physical fitness and capacity. This study investigated the effect of the COVID-19 lockdown on professional soccer players' match physical activities. Match activities of 265 male professional soccer players were assessed in two periods prior to (PRE1 and PRE2) and one period following the lockdown (POST) using a video tracking system. Linear mixed models were used to examine differences between-periods in total (TD), very high-speed (VHS), sprint (SPR), high-acceleration (ACC) and high-deceleration (DEC) distances, considering full match data and data from six 15-min intervals. TD and VHS during POST were lower than the two other competitive periods (p < 0.001, d small-moderate). SPR did not show differences between periods (p > 0.636). ACC and DEC during POST were lower than PRE2 (p < 0.015, d small). Declines in most 15-min intervals after lockdown were observed in TD and VHS. There were small differences in the temporal distribution of SPR, ACC and DEC at POST. After the COVID-19 lockdown, soccer players' higher-intensity running activities were similar to those of games played before the lockdown, but TD and VHS decreased, both considering the entire match and 15-min intervals. The temporal distribution of running activities was mostly stable throughout the season.


Pattern of non-methanogenic and methanogenic degradation of cellulose in anoxic rice field soil.
Rice field soils turn anoxic upon flooding. The complete mineralization of organic matter, e.g. cellulose, to gaseous products is then accomplished by the sequential reduction of nitrate, ferric iron, sulfate and finally by methanogenesis. Therefore, the anaerobic turnover of [U-(14)C]cellulose was investigated in fresh, non-methanogenic and in preincubated, methanogenic slurries of Italian rice field soil. In anoxic soil slurries freshly prepared from air-dried soil [U-(14)C]cellulose was converted to (14)CO(2) and (14)CH(4) in a ratio of 3:1. In methanogenic soil slurries, on the other hand, which had been preincubated for 45 days under anaerobic conditions, [U-(14)C]cellulose was converted to (14)CO(2) and (14)CH(4) in the ratio of 1:1. The turnover times (7-14 days) of cellulose degradation were not significantly different (P0.05) in fresh and methanogenic soil. Chloroform addition abolished CH(4) production, but only slightly (30%) inhibited cellulose degradation in both fresh and methanogenic soil. Under both soil conditions, [(14)C]acetate was the only labeled intermediate detected. A maximum of 24% of the applied radioactivity was transiently accumulated as [(14)C]acetate in both fresh and methanogenic soil slurries. However, when methanogenesis was inhibited by chloroform, 46% and 66% of the applied radioactivity were recovered as [(14)C]acetate in fresh and methanogenic soil, respectively. Only non-radioactive propionate accumulated during the incubation with [U-(14)C]cellulose, especially in the presence of chloroform, indicating that propionate was produced from substrates other than cellulose.


Age-related reversal of postural adjustment characteristics during motor imagery.
Physical and imagined movements show similar behavioral constraints and neurophysiological activation patterns. An inhibition mechanism is thought to suppress overt movement during motor imagery, but it does not effectively suppress autonomic or postural adjustments. Inhibitory processes and postural stability both deteriorate with age. Thus, older people's balance is potentially vulnerable to interference from postural adjustments induced by thoughts about past or future actions. Here, young and older adults stood upright and executed or imagined manual reaching movements. Reported arm movement time (MT) of all participants increased with target distance. Older participants reported longer MT than young participants when executing arm movements, but not when imagining them. Older adults' anteroposterior (AP) and mediolateral (ML) postural sway was higher than young adults' at baseline, but their AP sway fell below their baseline level during manual imagery. In contrast, young adults' AP sway increased during imagery relative to their baseline. A similar tendency to reduce sway in the ML direction was also observed in older adults during imagery in a challenging stance. These results suggest that postural response during manual motor imagery reverses direction with age. Motor imagery and action planning are ubiquitous tasks, and older people are likely to spend more time engaged in them. The shift toward restricting body sway during these tasks is akin to a postural threat response, with the potential to interfere with balance during activities of daily living. (PsycINFO Database Record


A monoclonal antibody against cytochrome P-450 enhances mutagen activation of N-nitrosodimethylamine by mouse liver S9: studies on the mode of action.
The effect of the monoclonal antibody MAb 2-66-3, directed against the major rat liver phenobarbital (PB)-induced cytochrome P-450 (P-450), on the S9-mediated mutagenicity of N-nitrosodimethylamine (DMN) in Salmonella typhimurium strain TA1530 was studied using liver S9 from PB-treated mice. This MAb enhanced approximately 2-fold S9-mediated mutagenicity of DMN but inhibited both its N-demethylation and N-denitrosation by 50%. Thus MAb-mediated enhancement of DMN mutagenesis does not result from altered activation/inactivation pathways, both known to involve P-450 isozymes. DMSO, a hydroxyl radical (HO.) scavenger and desferrioxamine, an inhibitor of HO.-dependent reactions, quenched the MAb-mediated enhancement of DMN mutagenesis, implicating the HO.-dependent activation of DMN to mutagenic species. As a mechanism, we propose that the binding of this MAb to P-450 isozyme implicated in DMN metabolism decreases the functional coupling between the reductase and the P-450 complex, leading to an increased electron flow from the reductase towards molecular oxygen to form reduced oxygen species (HO.) at the expense of the monooxygenase functions.


Transient responses of nitrogenase to acetylene and oxygen in actinorhizal nodules and cultured frankia.
Nitrogenase activity in root nodules of four species of actinorhizal plants showed varying declines in response to exposure to acetylene (10% v/v). Gymnostoma papuanum (S. Moore) L. Johnson. and Casuarina equisetifolia L. nodules showed a small decline (5-15%) with little or no recovery over 15 minutes. Myrica gale L. nodules showed a sharp decline followed by a rapid return to peak activity. Alnus incana ssp. rugosa (Du Roi) Clausen. nodules usually showed varying degrees of decline followed by a slower return to peak or near-peak activity. We call these effects acetylene-induced transients. Rapid increases in oxygen tension also caused dramatic transient decreases in nitrogenase activity in all species. The magnitude of the transient decrease was related to the size of the O(2) partial pressure (pO(2)) rise, to the proximity of the starting and ending oxygen tensions to the pO(2) optimum, and to the time for which the plant was exposed to the lower pO(2). Oxygen-induced transients, induced both by step jumps in pO(2) and by O(2) pulses, were also observed in cultures of Frankia. The effects seen in nodules are purely a response by the bacterium and not a nodule effect per se. Oxygen-induced nitrogenase transients in actinorhizal nodules from the plant genera tested here do not appear to be a result of changes in nodule diffusion resistance.


Holmium: yttrium-aluminum-garnet laser with Moses: does it make a difference?
Moses effect is an inherent physical principle of Ho:YAG laser functioning. Moses Technology is a pulse modulation modality of Ho:YAG laser, which became commercially available for the treatment of two urological conditions: urinary stones and benign prostatic obstruction. The purpose of this narrative review is to distinguish between Moses effect and Moses Technology, as well as to summarize the latest evidence on Moses Technology and its main application in the urological field. During laboratory lithotripsy, Moses Technology seems to reduce stone retropulsion and determine higher ablation volume compared with regular lithotripsy. However, this technology presents similar characteristics to long pulse Ho:YAG laser, and several studies showed no significant difference between Moses Technology and standard lasers. When used in prostate enucleation, Moses Technology promises to reduce operating time by increasing the efficiency of prostate resection and improve the hemostasis. Moreover, some studies state that it is possible to reduce the HoLEP morbidity. Despite this, the clinical impact of the time reduction remains uncertain and different studies either present relevant limitations or are burdened by significant bias. Although Moses effect has been extensively described and characterized, and several studies have been published on the usage of Moses Technology for both laser lithotripsy and laser enucleation of the prostate with Holmium YAG, solid clinical evidence on the real improvement of surgical outcomes is still missing.


Passive symmetry breaking of the space-time propagation in cavity dissipative solitons.
Dissipative solitons are fundamental wave-pulses that preserve their form in the presence of periodic loss and gain. The canonical realization of dissipative solitons is Kerr-lens mode locking in lasers, which delicately balance nonlinear and linear propagation in both time and space to generate ultrashort optical pulses. This linear-nonlinear balance dictates a unique pulse energy, which cannot be increased (say by elevated pumping), indicating that excess energy is expected to be radiated in the form of dispersive or diffractive waves. Here we show that Kerr-lens mode-locked lasers can overcome this expectation. Specifically, by breaking the spatial symmetry between the forward and backward halves of the round-trip in a linear cavity, the laser can modify the soliton in space to incorporate the excess energy. Increasing the pump power leads therefore to a different soliton solution, rather than to dispersive/diffractive loss. We predict this symmetry breaking by a complete numerical simulation of the spatio-temporal dynamics in the cavity, and confirm it experimentally in a Kerr-lens mode-locked Ti:Sapphire laser with quantitative agreement to the simulation. The simulation opens a window to directly observe the nonlinear space-time dynamics that molds the soliton pulse, and possibly to optimize it.


Neutrophil Extracellular Traps in Coronavirus Disease-19-Associated Ischemic Stroke: A Novel Avenue in Neuroscience.
Ischemic stroke is one of the catastrophic neurological events that are being increasingly recognized among Coronavirus Disease (COVID)-19 patients. The recent studies have revealed about a possible connection among COVID-19, ischemic stroke, and excessive Neutrophil Extracellular Traps (NETs) formation. This paper establishes an overview of coronaviruses and NETs, NETs in pathogenesis of COVID-19 induced-ischemic stroke, and future directions using related recent literatures. NETs are normally functioned for a defense against pathogens, but in immoderate amount, they can trigger series of destructive events. Vasculopathy and neuroinflammation are the pathological mechanisms of NETs suggested to link COVID-19 and ischemic stroke. Based on newly discovered possible mechanisms, the potential clinical implications that could be applied consists of inhibition of NET formation, disrupting cholesterol synthesis, and interfering inflammatory pathway. A considerable number of scientific works are needed in order to complete the current understanding of the emerging relationship among COVID-19, NETs, and ischemic stroke. Although the exact mechanism is still unknown, these novel findings are a worthwhile contribution in defining future studies, suitable future frameworks, and therapeutic strategies.


Walking on Exoplanets: Is Star Wars Right?
As the number of detected extrasolar planets increases, exoplanet databases become a valuable resource, confirming some details about planetary formation but also challenging our theories with new, unexpected properties. Exoplanets-Gravity-Planetary habitability and biosignatures. Astrobiology 16, 325-327.


L-Cysteine as a chiral linker in lanthanide-cucurbit[6]uril one-dimensional assemblies.
The reaction of neodymium, europium, or terbium nitrate with cucurbit[6]uril (CB6) in the presence of the α-amino acid L-cysteine (L-cys) gives the complexes [Nd(L-cys)(CB6)(NO(3))(H(2)O)(4)]·2NO(3)·10H(2)O (1) and {[Ln(L-cys)(CB6)(H(2)O)(5)][Ln(L-cys)(CB6)(NO(3))(H(2)O)(4)]}·5NO(3)·22H(2)O with Ln = Eu (2) or Tb (3). 2 and 3 only differ from 1 by the presence of two independent metal ions in slightly different environments. In all cases, each metal atom is bound to the bidentate CB6 and the monodentate L-cys molecules, with the latter being in its zwitterionic form. The ammonium group of L-cys is directed away from CB6 and is involved in ion-dipole and hydrogen bonding interactions with the uncomplexed portal of the neighboring molecule, which gives rise to the formation of chiral one-dimensional assemblies of columnar shape.


Crystallization and preliminary X-ray analysis of the formiminotransferase domain from the bifunctional enzyme formiminotransferase-cyclodeaminase.
Formiminotransferase-cyclodeaminase (E.C. 188.8.131.52-E.C. 126.96.36.199) is a bifunctional enzyme involved in the histidine-degradation pathway which exhibits specificity for polyglutamylated folate substrates. The first function of the enzyme transfers the formimino group of formiminoglutamate to the N5 position of tetrahydrofolate, while the second function catalyses the cyclodeamination of the formimino group, yielding N5,10-methenyl-tetrahydrofolate, with efficient channeling of the intermediate between these activities. Initial studies have shown that the enzyme consists of eight identical subunits of 62 kDa each, arranged as a circular tetramer of dimers. It is this formation which results in two different dimeric interfaces, which are necessary for the two different activities. The identical subunits have been shown to consist of two domains, each of which can be obtained as dimers. The formiminotransferase domain has been crystallized in the presence of the substrate analogue folinic acid. The crystals belong to space group P212121, with unit-cell dimensions a = 64.4, b = 103.7, c = 122.3 A. Both a native data set and a mercurial derivative data set have been collected to 2.8 A resolution.


Molecular identification of a further branched-chain aminotransferase 7 (BCAT7) in tomato plants.
Although the branched-chain amino acids (BCAAs) are essential components of the mammalian diet, our current understanding of their metabolism in plants is still limited. It is however well known that the branched-chain amino acid transaminases (BCATs) play a crucial role in both the synthesis and degradation of the BCAAs leucine, isoleucine and valine. We previously characterized the BCAT gene family in tomato, revealing it to be highly diverse in subcellular localization, substrate preference, and expression. Here we performed further characterization of this family and provide evidence for the presence of another member, BCAT7. On mapping the chromosomal location of this enzyme, it was possible to define the exact chromosome map position of the gene. Although in Arabidopsis thaliana the AtBCAT7 has been considered a pseudo-gene, quantitative evaluation of the expression levels of this gene revealed that the expression profile of the BCAT7 in different tissues of tomato (Solanum lycopersicum cv. M82) plants is highly variable with the highest expression found in developed flowers. By using a C-terminal E-GFP gene fusion we demonstrate that the BCAT7 is extraplastidial and in combination with the kinetic characterization of BCAT7 our results suggest that it most likely operates in BCAA degradation in vivo and support our hypothesis of another functional member of BCAT family. The combined data presented are discussed within the context of BCAA metabolism and its functions in higher plants.


Expression of intermediate filament in endometrial glands changes with the onset of pregnancy and in endometriosis.
Appropriate endometrial differentiation is believed to be a prerequisite for pregnancy success. This study investigates the expression of two intermediate filament proteins, cytokeratin and vimentin, in human endometrium and first trimester decidua and in ectopic endometrium from women with endometriosis. Stromal elements, including vascular endothelial cells, were consistently vimentin-positive and cytokeratin-negative. Surface and glandular epithelial cells of human endometrium co-expressed vimentin and cytokeratin during all stages of the menstrual cycle, but failed to express vimentin after the onset of pregnancy. This suggests that intermediate filaments, and especially vimentin, may have a role to play in the proliferation and/or differentiation of the endometrial glands during decidualization. Ectopic endometrium showed a staining pattern similar to normal endometrium.


Evaluation of the effect of endodontic irrigation solutions on the microhardness and the roughness of root canal dentin.
The purpose of this study was to evaluate the effect of 0.2% chlorhexidine gluconate on the microhardness and roughness of root canal dentin compared with widely used irrigation solutions. Ninety, mandibular, anterior teeth extracted for periodontal reasons were used. The crowns of the teeth were removed at the CEJ. The roots were separated longitudinally into two segments, embedded in acrylic resin, and polished. A total of 180 specimens were divided into 6 groups of 30 teeth at random according to the irrigation solution used: group 1: 5.25% NaOCl for 15 min; group 2: 2.5% NaOCl for 15 min; group 3: 3% H2O2 for 15 min; group 4: 17% EDTA for 15 min; group 5: 0.2% chlorhexidine gluconate for 15 min; and group 6: distilled water (control). Each group was then divided into 2 subgroups of 15 specimens: groups 1a, 2a, 3a, 4a, 5a, and 6a were submitted to Vickers microhardness indentation tests; groups 1b, 2b, 3b, 4b, 5b, and 6b were used for determination of the roughness of root dentin. The data were recorded as Vickers numbers and Ra, microm for roughness test. The results were analyzed statistically by using one-way ANOVA and Tukey tests. The results indicated that all the irrigation solutions except chlorhexidine significantly decreased microhardness of root canal dentin (p < 0.05); 3% H2O2 and 0.2% chlorhexidine gluconate had no effect on roughness of the root canal dentin (p > 0.05). Although there are many other factors for irrigation solution preference, according to the results of this study, 0.2% chlorhexidine gluconate seems to be an appropriate endodontic irrigation solutions because of its harmless effect on the microhardness and roughness of root canal dentin.


Inhibitory effects of 3,3',4,5'-tetrahydroxystilbene and 3,3',4,5'-tetrahydroxybibenzyl, the constituents of Cassia garrettiana on antigen-induced histamine release in vitro.
3,3',4,5'-Tetrahydroxystilbene (I) and 3,3',4,5'-tetrahydroxybibenzyl (II), isolated from the heartwood of Cassia garrettiana Craib (Leguminosae), showed inhibitory effects on antigen-induced histamine release from rat peritoneal mast cells in vitro. The inhibitory effect of I (IC50 = 30.2 microM) was much stronger than that of II (greater than 100 microM). Compound II, as well as I (IC50 = 7.3 microM) reported previously, also inhibited the histamine release from human peripheral basophils induced by anti-immunoglobulin E (IgE) in vitro, and its IC50-value was 68.0 microM. These results suggest that the trans-olefin structure in the molecule may be necessary for I to have an inhibitory effect on histamine release. Considering that disodium cromoglycate did not show any significant inhibitory effect on anti-IgE-induced histamine release from human basophils, the strong inhibitory effects of I in both tests are of considerable interest.


Mechanisms of anemia in protein-energy malnutrition in Johannesburg.
Studies of red cell metabolism, erythropoeitin concentration, iron and folate status were made in 48 children with protein-energy malnutrition in Johannesburg (altitude 1800 m). Biochemical evidence of iron deficiency was presented in 26% cases on admission and developed in 90% during recovery. Biochemical evidence of folate deficiency was present in 14% of cases on admission and resolved on dietary therapy alone. Serum erythropoeitin was increased on admission and remained elevated during recovery. There was no relationship between serum erythropoeitin and Hb concentrations. Key enzymes in the red cell glycolytic and hexose monophosphate pathways and red cell membrane showed increased activity. Red cell adenosine triphosphate concentration was increased and unstable. Red cell potassium was decreased and, in the fatal cases, red cell sodium was increased. The possible significance and practical implications of these findings are discussed.


In vivo characterization of a dual adenosine A2A/A1 receptor antagonist in animal models of Parkinson's disease.
The in vivo characterization of a dual adenosine A(2A)/A(1) receptor antagonist in several animal models of Parkinson's disease is described. Discovery and scale-up syntheses of compound 1 are described in detail, highlighting optimization steps that increased the overall yield of 1 from 10.0% to 30.5%. Compound 1 is a potent A(2A)/A(1) receptor antagonist in vitro (A(2A) K(i) = 4.1 nM; A(1) K(i) = 17.0 nM) that has excellent activity, after oral administration, across a number of animal models of Parkinson's disease including mouse and rat models of haloperidol-induced catalepsy, mouse model of reserpine-induced akinesia, rat 6-hydroxydopamine (6-OHDA) lesion model of drug-induced rotation, and MPTP-treated non-human primate model.


Site-specific discrimination by cyanovirin-N for alpha-linked trisaccharides comprising the three arms of Man(8) and Man(9).
Cyanovirin-N (CVN) is a novel cyanobacterial protein that selectively binds with nanomolar affinities the mammalian oligosaccharides Man(8) and Man(9). Consequently, CVN potently blocks HIV entry through highly avid carbohydrate-mediated interactions with the HIV-envelope glycoprotein gp120, and is under preclinical investigation as an anti-HIV microbicide. CVN contains two non-overlapping carbohydrate-binding sites that bind the disaccharide Manalpha(1-2)Manalpha (which represents the terminal disaccharide of all three arms of Man(9)) with low to sub-micromolar affinities. The solution structure of a 1:2 CVN:Manalpha(1-2)Manalpha complex revealed that CVN recognizes the stacked conformation of Manalpha(1-2)Manalpha through a deep hydrophilic-binding pocket on one side of the protein (site 2) and a semi-circular cleft on the other (site 1). With the prominent exception of the C1 hydroxyl group of the reducing mannopyranose ring, the bound disaccharide is positioned so that each hydroxyl group is involved in a direct or water-mediated hydrogen bond to the polar or charged side-chains comprising the binding pocket. Thus, to determine whether the next-most reducing mannopyranose ring will augment CVN affinity and selectivity, we have characterized by NMR and ITC the binding of CVN to three synthetic trisaccharides representing the full-length D1, D2 and D3 arms of mammalian oligomannosides. Our findings demonstrate that site 1 is able to discriminate between the three related trisaccharides methyl Manalpha(1-2)Manalpha(1-2)Man, methyl Manalpha(1-2)Manalpha(1-3)Man and methyl Manalpha(1-2)Manalpha(1-6)Man with remarkable selectivity, and binds these trisaccharides with K(A) values ranging from 8.1x10(3)M(-1) to 6.6x10(6)M(-1). Site 2 is less selective in that it binds all three trisaccharides with similar K(A) values ranging from 1.7 to 3.7(+/-0.3)x10(5)M(-1), but overall binds these trimannosides with higher affinities than site 1. The diversity of pathogenic organisms that display alpha(1-2)-linked mannosides on their cell surfaces suggests a broad defensive role for CVN in its cyanobacterial source.


Advantages of Relative versus Absolute Data for the Development of Quantitative Structure-Activity Relationship Classification Models.
The appropriate selection of a chemical space represented by the data set, the selection of its chemical data representation, the development of a correct modeling process using a robust and reproducible algorithm, and the performance of an exhaustive training and external validation determine the usability and reproducibility of a quantitative structure-activity relationship (QSAR) classification model. In this paper, we show that the use of relative versus absolute data in the representation of the data sets produces better classification models when the other processes are not modified. Relative data considers a reference frame to measure the chemical characteristics involved in the classification model, refining the data set representation and smoothing the lack of chemical information. Three data sets with different characteristics have been used in this study, and classifications models have been built applying the support vector machine algorithm. For randomly selected training and test sets, values of accuracy and area under the receiver operating characteristic curve close to 100% have been obtained for the generation of the models and external validations in all cases.


Tempting today, troubling tomorrow: the roots of the precarious couple effect.
The precarious couple effect occurs when men pair with women who are both critical and more verbally disinhibited than them. Evidence that dissatisfaction runs high in such relationships makes one ask why people enter them in the first place. In Study 1, respondents recalled that past partners who were verbally disinhibited were relatively active in initiating the relationship. In Study 2, verbally inhibited men evidenced ambivalence in that they disliked disinhibited women more than inhibited ones but these feelings of disliking did not translate into expectations of feeling tense during the interaction. Study 3 revealed that initial interactions between inhibited men and disinhibited women go smoothly unless (a) the women are critical and (b) the pair discusses a stressful topic. The authors suggest that members of precarious couples are drawn to one another because, in initial encounters, their communication styles are relatively symbiotic. Alas, this initial chemistry does not always endure.


[A case of an XX man with presence of H-Y antigen in his mother].
An adolescent of 17 years of age presented with delayed puberty and cryptorchidism underwent hormonal and cytogenetic investigation. The FSH and LH levels were raised and there was a significant response to LHRH. The karyotype was 46 XX. Cytogenetic studies showed no mosaic or translocation of the Y-chromosome. The HY antigen was present on the surface of the normal lymphocytes stimulated by phytohaemagglutinin or the pokeweed mitogen or the transformed lymphocytes. The mother also had the HY antigen at concentrations intermediary between those of normal men and women. These results suggest an autosomic location of the HY gene and of the determination of the gonadal orientation by the levels of HY antigen.


Gene organization and complete sequence of the Hyphantria cunea nucleopolyhedrovirus genome.
The whole-genome sequence of the Hyphantria cunea nucleopolyhedrovirus (HycuNPV) was analysed. The entire nucleotide sequence of the HycuNPV genome was 132 959 bp long, with a G+C content of 45.1 mol%. A total of 148 open reading frames (ORFs) consisting of more than 50 aa were encoded by the genome. HycuNPV shares more than 122 ORFs with other lepidopteran group I NPVs, including Autographa californica MNPV, Bombyx mori NPV, Choristoneura fumiferana MNPV (CfMNPV), Choristoneura fumiferana defective NPV, Epiphyas postvittana MNPV and Orgyia pseudotsugata MNPV (OpMNPV). Six ORFs are identified as being unique to HycuNPV. Most of the HycuNPV ORFs showed higher similarity to CfMNPV and OpMNPV ORFs than to those of the other group I NPVs. HycuNPV encodes two conotoxin-like homologues (ctls), which are observed only in OpMNPV in group I NPVs. HycuNPV encodes three inhibitors of apoptosis (iaps), hycu-iap-1, hycu-iap-2 and hycu-iap-3, a feature that it shares only with CfMNPV. In addition, six homologous regions (hrs) are identified in the HycuNPV genome. These hrs are located in regions similar to those of the OpMNPV hrs, but different from most of the CfMNPV hrs. Based on the close phylogenetic relationship and conservation of group I NPV-specific genes, such as gp64, ie-2 and ptp-1, it is concluded that HycuNPV belongs to the group I NPVs and is most similar to CfMNPV or OpMNPV.


Aflatoxin Estimation in Corn by Measurement of Bright Greenish-Yellow Fluorescence in Aqueous Extracts.
A procedure was developed for efficient extraction of bright greenish-yellow (BGY) fluorescent material from ground corn ( Zea mays L.) samples and subsequent quantitative determination of fluorescence emission in a fluorometer. The technique was designed to be inexpensive, rapid and utilizable at remote locations for estimation of aflatoxin levels. A simple, in vitro method for production of the BGY-fluorescing material from kojic acid was developed to provide a reference standard. Water was identified as an effective solvent for extraction of the BGY-fluorescence from corn; fluorescence in aqueous extracts was stable at pH 6-7 for up to 22 h at room temperature. Samples with aflatoxin concentrations of 0 to 12,000 ppb yielded BGY-fluorescence emission units of 0 to 175. A correlation coefficient of r = 0.77 was determined for BGY-fluorescence vs total aflatoxin levels (B1, B2, G1, G2) and r = 0.88 for the fluorescence vs aflatoxin B1, B2. The results provided a basis for effective determination of BGY-fluorescence as an estimate of aflatoxin levels in corn.


Pharmacist prescribing practices in a clinical pharmacy cardiac risk service.
Prescribing practices within a clinical pharmacy cardiac risk service (CPCRS) and their impact on treatment outcomes in patients with atherosclerotic cardiovascular disease (ASCVD) are described. National healthcare reforms have increased the population of insured patients and placed increased demands on physicians and other providers. Pharmacists are well trained and positioned to aid in patient care by providing expertise in medication management and patient safety that can result in pharmacotherapy optimization and cost savings. Kaiser Permanente Colorado (KPCO), a group-model health maintenance organization with about 675,000 members served by 30 medical offices throughout Colorado, has adopted a collaborative drug therapy management (CDTM) model that enables pharmacist prescribing to improve patient access, patient care, and healthcare cost-effectiveness. Within the CPCRS established by KPCO, qualified pharmacists are permitted to prescribe initial therapy, modify drug regimens, order laboratory tests, and perform follow-up activities within their professional scope of practice. The CPCRS focuses on the long-term management of patients with ASCVD. The primary goals of the CPCRS are to optimize secondary-prevention pharmacotherapy, monitor and ensure medication adherence, assist in the management of risk factors for ASCVD, provide patient education and counseling, and serve as a resource for physicians and other healthcare providers. Working under a CDTM agreement, pharmacists are authorized to prescribe therapies to minimize the risk of future ASCVD events. The CPCRS at KPCO has demonstrated successful maintenance of a clinical pharmacy service including pharmacist prescribing under a CDTM model to manage patients with ASCVD.


The effects of high molecular weight dextran on the preservation of human corneas.
Paired human corneas (48) were preserved at 31 degrees C for different periods of time up to 122 days in a modified MEM tissue culture medium free of or supplemented with 8% dextran T500. Cell density and vitality of the endothelial cells were analysed using morphometry, light microscopy after trypan blue staining, followed by sucrose provoked swelling and fine structural observations. Culturing for periods up to 7 weeks resulted in an endothelial cell loss of 11% of dextran-blue and of 15% in dextran-supplemented medium. For preservation periods between 9-13 weeks, these values were 43% and 36% respectively. The differences between dextran-free and dextran-supplemented preservation media were not significant. As deduced from trypan blue staining, sucrose provoked swelling and fine structural observations; the remaining cells were vital. Dextran was taken up by the endothelial cells. The practical consequences of endothelial cell loss and the toxic effects of dextran are discussed in relation to penetrating keratoplasty.


Nuclear receptors take center stage in Th17 cell-mediated autoimmunity.
Liver X receptors (LXRs) are nuclear receptors involved in cholesterol homeostasis. Notably, they are also expressed by T cells and are involved in regulating T cell proliferation and differentiation. In this issue of the JCI, Cui et al. have elucidated the molecular mechanism underlying the effects of LXR activation on a subset of T cells known as Th17 cells in mice and humans. Specifically, they showed that LXR-induced Srebp-1 inhibits Il17 transcription by binding to the Il17 promoter through interaction with the aryl hydrocarbon receptor (Ahr), a transcription factor known to enhance Th17 cell responses.


Maize leaf adenylate kinase : purification and partial characterization.
Adenylate kinase (EC 22.214.171.124) from leaves of maize (Zea mays) was purified to homogeneity using (NH(4))(2)SO(4) fractionation, followed by chromatography on DEAE-cellulose, hydroxyapatite, Sephadex G-75SF, and Green A dye-ligand columns. The purified enzyme had specific activity of about 1,550 micromoles ADP produced per minute per milligram protein, and the ratio of velocities of the reverse (utilization of ATP) to forward (formation of ATP) reaction was about 1.5. The M(r) value of adenylate kinase, determined by electrophoresis in dissociating conditions and by gel filtration, was 29,000 and 31,000 respectively, suggesting monomeric nature of the enzyme. Purified preparations were stable for at least 1 month at 0 to 4 degrees C. Magnesium ions were essential for activity of adenylate kinase in both directions of the reaction. Optimal rates in the forward direction were observed at the magnesium to ADP ratio of about 0.6 to 0.8. For the reverse reaction, ATP served as a substrate only when complexed with magnesium, while AMP reacted as a free species. The enzyme preferentially utilized adenine ribonucleotides in both directions of the reaction. The nucleoside triphosphate-binding site of adenylate kinase was fairly nonspecific with regard to nucleotide species. On the other hand, the primary amino group of either adenine and cytosine moieties was essential for effective binding to the nucleoside monophosphate site of the enzyme.


How the question is asked makes a difference in the assessment of depressive symptoms in older persons.
The authors examined whether older adults respond comparably to two standard depression instruments rating symptoms by frequency/duration or degree of severity/"bother." Data for this cross sectional analysis of a prospective cohort came from 699 community-dwelling individuals within the communities of Durham, North Carolina, and New Haven, Connecticut. Differences in response between the Center for Epidemiological Studies-Depression (CES-D) survey, emphasizing symptom frequency, were compared with the Hopkins Symptom Checklist (HSCL) subscale, emphasizing bother or discomfort related to those symptoms. Socioeconomic, demographic, and clinical characteristics for subjects with the greatest difference between standardized scale scores were analyzed with multivariable logistic regression. Older persons differed in their responses between the two instruments, despite similar content. Individuals in the highest quartile of difference between the two scales (indicating more bother than symptom frequency) had significantly more education, higher income, and were less often African American, with no differences in health conditions. Moreover, these specific socioeconomic and ethnic characteristics remained significant in multivariable analyses. Older persons not only differed significantly in their responses between depression instruments based on one dimension or the other, although with similar content, but response was significantly associated with specific subject characteristics. The heterogeneity of older patient populations suggests that recognition of depressive symptoms should include both constructs of symptom-associated discomfort and symptom frequency to achieve more accurate assessment.


Implications of an aging population for mental health nurses.
The rapidly increasing numbers of older adults with dementia and other mental health problems throughout the world have huge ramifications for nurses who will care for these individuals, as well as for health care systems. This article explores some current problems in the health care systems and makes suggestions for better, more efficient ways to meet the growing mental health needs of the aging population. It also addresses moral-ethical dilemmas that will likely affect mental health nurses caring for this population.


A weak DD-carboxypeptidase activity explains the inability of PBP 6 to substitute for PBP 5 in maintaining normal cell shape in Escherichia coli.
Penicillin-binding protein (PBP) 5 plays a critical role in maintaining normal cellular morphology in mutants of Escherichia coli lacking multiple PBPs. The most closely related homologue, PBP 6, is 65% identical to PBP 5, but is unable to substitute for PBP 5 in returning these mutants to their wild-type shape. The relevant differences between PBPs 5 and 6 are localized in a 20-amino acid stretch of domain I in these proteins, which includes the canonical KTG motif at the active site. We determined how these differences affected the enzymatic properties of PBPs 5 and 6 toward beta-lactam binding and the binding and hydrolysis of two peptide substrates. We also investigated the enzymatic properties of recombinant fusion proteins in which active site segments were swapped between PBPs 5 and 6. The results suggest that the in vivo physiological role of PBP 5 is distinguished from PBP 6 by the higher degree of DD-carboxypeptidase activity of the former.


Impact of Temperature, Ethanol and Cell Wall Material Composition on Cell Wall-Anthocyanin Interactions.
The effects of temperature and ethanol concentration on the kinetics of anthocyanin adsorption and desorption interactions with five cell wall materials (CWM) of different composition were investigated. Using temperatures of 15 °C and 30 °C and model wine with ethanol concentrations of 0% and 15% (v/v) over 120 min, the adsorption and desorption rates of five anthocyanin-glucosides were recorded in triplicate. Small-scale experiments were conducted using a benchtop incubator to mimic a single berry fermentation. Results indicate that more than 90% of the adsorption occurs within the first 60 min of the addition of anthocyanins to CWM. However, desorption appears to occur much faster, with maximum desorption being reached after 30 min. The extent of both adsorption and desorption was clearly dependent not only on temperature and ethanol concentration but also on the CWM composition.


Ethnicity and rectal cancer management in New Zealand.
Research shows survival disparities between Maori and non-Maori colon cancer patients, with comorbidity and cancer care being major contributing factors. We studied rectal cancer management and survival in a cohort of Maori and non-Maori patients with a newly diagnosed rectal cancer. 194 Maori and non-Maori patients diagnosed with rectal cancer between 2006 and 2008 were identified from the New Zealand Cancer Registry. Medical records were reviewed and patients compared on presentation, patient and tumour characteristics, and receipt and timing of treatment. Cox regression models were fitted to compare cancer-specific survival. Compared to non-Maori patients, Maori patients were younger (mean age at diagnosis 63.5 and 69.2 for Maori and Non-Maori respectively; p<0.001) and had higher prevalence of comorbidity. Stage, grade and tumour size distributions were similar. Almost all stage I-III patients (97%) underwent definitive surgery, with no difference between Maori and non-Maori. Maori patients waited longer for referral to medical oncologists (40 days vs. 33 days; p=0.03). Results suggested Maori patients with stage IV disease may be less likely than non-Maori to be referred to palliative care (13% vs. 40%; p=0.07). The hazard ratio for cancer-specific death for Maori compared with non-Maori patients was 1.24 (95% CI 0.65-2.35). The findings suggest both similarities and some differences in treatment and outcomes between Maori and non-Maori rectal cancer patients, but firm conclusions are limited by small sample size.


Use of health fairs to develop public health nursing competencies.
This paper describes a community-campus partnership for health education established through the effort of faculty, students, and the community. Health fairs designed to address issues of concern to a community agency were originally conducted with nursing students. This partnership between nursing and a community was expanded to include social work, physical therapy, and medical students. A shared learning experience was structured through the presentation of health fairs in collaboration with agencies in Burlington, Vermont. One goal of nursing education is to produce professionals who have the beginning competencies of public health nursing. Reflection on the process, relationships, and outcomes of the health fairs revealed that students attained these beginning competencies in all eight public health nursing competency domains. Combining community-campus partnerships and an interdisciplinary focus enabled nursing students to become more responsive to community needs and to learn to work collaboratively toward creating healthier communities, thus building skills required for public health nursing.


The Dramaturgical Act of Positioning Within Family Meetings: Negotiation of Patients' Participation in Intermediate Care Services.
Family meetings are a cornerstone in intermediate care (IC) and a powerful tool in achieving patient participation. Staff in IC are nevertheless uncertain about how to run these meetings. This study explores the negotiation of patient participation in 14 family meetings by observing the interactions between patients, relatives, and staff. Using Goffman's dramaturgical theory, supplemented by positioning theory, we illustrate, through four cases, how the participants negotiate their opinions by enacting positions like performer, director, audience, and nonperson. Patient participation takes place when the family meetings are characterized by respect and empathy, when the staff restore and elicit patients' and relatives' preferences, and there exist real alternative outcomes of the meetings. The emphasis should be on meeting structure, group composition, and preparation of the patient team. The findings are valuable for staff, patient organizations, and policy makers responsible for program development and tools to optimize patient participation within family meetings.


Epilepsy, Ammon's horn sclerosis, and Camille Bouchet.
Increasing interest into the relationship between Ammon's horn sclerosis (hippocampal sclerosis) and epilepsy seems to have developed after 1880 when Sommer's paper appeared. Bouchet and Cazauvieilh had published the original description of the hippocampal anatomical abnormality in 1825 while attempting to locate the cerebral sites of origin of epilepsy and insanity. However, they offered no interpretation of the significance of the structural change. What has sometimes not been noticed in the subsequent literature is that, after a further investigation, in 1853, Bouchet described the change in 18 of 43 additional brains from persons with epilepsy. Despite this frequency of occurrence of the hippocampal abnormality, he concluded that epileptic seizures had no single site of origin in the brain. Before most of his contemporaries and their successors, he began to propose the idea that all epileptic seizures were symptoms of various, though mostly cerebral, disorders. In doing this, he tended to be reluctant to accept the view that epilepsy was a disease in its own right.


Germination of Spores of Clostridium botulinum Type G.
Germination of spores of Clostridium botulinum type G under various conditions of heat activation, incubation temperature and minimum nutrition was studied. The spores were optimally germinated in a mixture of L-cysteine + L-lactacte + bicarbonate. The rate and extent of germination were greatly increased when unheated spores were heat-activated at 75°C for 10 min before exposure to the germination medium. Maximum germination was obtained at incubation temperatures of 37 to 45°C within 1 h. However, germination occurred substantially even at 4°C if the incubation time was extended to 48 h.


MoS2 /MXene Aerogel with Conformal Heterogeneous Interfaces Tailored by Atomic Layer Deposition for Tunable Microwave Absorption.
In the design of electromagnetic (EM) wave absorbing materials, it is still a great challenge to optimize the relationship between the attenuation capability and impedance matching synergistically. Herein, a 3D porous MoS2 /MXene hybrid aerogel architecture with conformal heterogeneous interface has been built by atomic layer deposition (ALD) based on specific porous templates to optimize the microwave absorption (MA) performance comprehensively. The original porous structure of pristine Ti3 C2 Tx aerogel used as templates can be preserved well during ALD fabrication, which prolongs the reflection and scattering path and ameliorates the dielectric loss. Meanwhile, plenty of heterointerfaces between MoS2 and Ti3 C2 Tx have been fabricated based on conformally ALD-deposited MoS2 with controlled thickness on the porous surfaces of the templates, which can effectively optimize the impedance matching and transform its response to EM waves from shielding into absorbing. Moreover, the interaction between the attenuation capability and impedance matching can also be modulated by the number of ALD cycle in MoS2 fabrication. After optimization, MoS2 /MXene hybrid aerogel obtained under 300 ALD cycles shows a minimum reflection loss of -61.65 dB at the thickness of 4.53 mm. In addition, its preferable lightweight, high surface area, mechanical, and hydrophobicity properties will also be conducive to further practical applications.


A new small-bodied hominin from the Late Pleistocene of Flores, Indonesia.
Currently, it is widely accepted that only one hominin genus, Homo, was present in Pleistocene Asia, represented by two species, Homo erectus and Homo sapiens. Both species are characterized by greater brain size, increased body height and smaller teeth relative to Pliocene Australopithecus in Africa. Here we report the discovery, from the Late Pleistocene of Flores, Indonesia, of an adult hominin with stature and endocranial volume approximating 1 m and 380 cm3, respectively--equal to the smallest-known australopithecines. The combination of primitive and derived features assigns this hominin to a new species, Homo floresiensis. The most likely explanation for its existence on Flores is long-term isolation, with subsequent endemic dwarfing, of an ancestral H. erectus population. Importantly, H. floresiensis shows that the genus Homo is morphologically more varied and flexible in its adaptive responses than previously thought.


Long non-coding RNA (lncRNA) CYTOR promotes hepatocellular carcinoma proliferation by targeting the microRNA-125a-5p/LASP1 axis.
This study investigated the function of long non-coding RNA (lncRNA) cytoskeleton regulator RNA (CYTOR) in hepatocellular carcinoma (HCC). In HCC, the expression of CYTOR and microRNA (miR)-125a-5p were measured by quantitative real-time PCR (qRT-PCR). The expression of actin skeletal protein 1 (LASP1) was evaluated by Western blot analysis. Flow cytometry assays, transwell assays, colony formation assay, and cell counting kit-8 (CCK-8) assay were used to evaluate the roles of miR-125a-5p and CYTOR in HCC cells. The target genes of CYTOR and miR-125a-5p were identified by bioinformatics analysis and Luciferase assay. CYTOR was upregulated in HCC cell lines, and knockdown of CYTOR inhibited HCC cell growth. MiR-125a-5p was downregulated in HCC cells and a target of CYTOR in regulating HCC progression. Furthermore, LASP1 was a downstream target of miR-125a-5p. Finally, CYTOR was found to be involved in HCC progression in vivo. CYTOR promotes HCC development by regulating the miR-125a-5p/LASP1 axis.


Congenital Erythropoietic Porphyria: Mutation of the Uroporphyrinogen III Cosynthase Gene in a Vietnamese Patient.
Congenital erythropoietic porphyria (CEP) arises from an autosomal recessive inherited disorder of the porphyrin metabolism, which leads to the accumulation of uroporphyrinogen I in bone marrow, skin and several other tissues by a deficiency of uroporphyrinogen III cosynthase (UROS). We studied a Vietnamese patient and her family suffering from severe cutaneous photosensitivity with skin fragility, bullous lesions and hypertrichosis on light-exposed areas. A missense mutation in the UROS gene was identified as a transversion of G to T at nucleotide 11,776, resulting in a substitution of valine by phenylalanine at codon 3 of exon 2. The patient showed a homozygous mutant profile, and the heterozygous state was observed in the parents. The activity of mutated UROS expressed in Escherichia coli was less than 16.1% that of the control, indicating that the markedly reduced activity of UROS is responsible for CEP. We described for the first time a mutation in the UROS gene in a Southeast Asian patient and a molecular diagnosis for the identification of clinically asymptomatic heterozygous mutation carriers and families with CEP.


Mesoporous silica encapsulating upconversion luminescence rare-earth fluoride nanorods for secondary excitation.
Mesoporous silica encapsulating upconversion luminescence NaYF(4) nanorods with uniform core-shell structures have been successfully synthesized by the surfactant-assistant sol-gel process. The thickness of ordered mesoporous silica shells can be adjusted from 50 to 95 nm by varying the amount of hydrolyzed silicate oligomer precursors from tetraethyl orthosilicate (TEOS), which further influences the BET surface area, pore volume, and the luminescence intensity. After coated with mesoporous silica shells, the hydrophobic nanorods is rendered to hydropholic simultaneously. The obtained beta-NaYF(4)@SiO(2)@mSiO(2) core-shell nanorods possess high surface area (71.2-196 m(2) g(-1)), pore volume (0.07-0.17 cm(3) g(-1)), uniform pore size distribution (2.3 nm), and accessible channels. Furthermore, the uniform core-shell nanorods show strong upconversion luminescence property similar to the hexagonal upconversion cores. The open mesopores can not only provide convenient transmission channels but also offer the huge location for accommodation of large molecules, such as fluorescent dyes and quantum dots. The secondary-excitation fluorescence of Rhodamine B is generated from the upconversion rare-earth fluoride nanorods cores to the fluorescent dyes loaded in the mesoporous silica shells.


Dually diagnosed: a retrospective study of the process of diagnosing autism spectrum disorders in children who are deaf and hard of hearing.
Utilizing a retrospective chart review of 30 children who have been dually diagnosed with hearing loss and autism spectrum disorders (ASDs), this study explores the process of arriving at the diagnosis of ASD in this population. Factors of interest include the age of ASD diagnosis in children who are deaf and hard of hearing, the types of professionals involved in making the diagnosis, and the measures used for assessment. Complications in the diagnostic process are highlighted.


Maternal antiretroviral use during pregnancy and infant congenital anomalies: the NISDI perinatal study.
We evaluated the association between maternal antiretrovirals (ARVs) during pregnancy and infant congenital anomalies (CAs), utilizing data from the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study. The study population consisted of first singleton pregnancies on study, > or =20 weeks gestation, among women enrolled in NISDI from Argentina and Brazil who delivered between September 2002 and October 2007. CAs were defined as any major structural or chromosomal abnormality, or a cluster of 2 or more minor abnormalities, according to the conventions of the Antiretroviral Pregnancy Registry. CAs were identified from fetal ultrasound, study visit, and death reports. Prevalence rates [number of CAs per 100 live births (LBs)] were calculated for specific ARVs, classes of ARVs, and overall exposure to ARVs. Of 1229 women enrolled, 995 pregnancy outcomes (974 LBs) met the inclusion criteria. Of these, 60 infants (59 LBs and 1 stillbirth) had at least 1 CA. The overall prevalence of CAs (per 100 LBs) was 6.2 [95% confidence interval (CI) 4.6 to 7.7]. The prevalence of CAs after first trimester ARVs (6.2; 95% CI 3.1 to 9.3) was similar to that after second (6.8; 95% CI 4.5 to 9.0) or third trimester (4.3; 95% CI 1.5 to 7.2) exposure. The rate of CAs identified within 7 days of delivery was 2.36 (95% CI 1.4 to 3.3). The prevalence of CAs after first trimester exposure to ARVs was similar to that after second or third trimester exposure. Continued surveillance for CAs among children exposed to ARVs during gestation is needed.


What have health care reforms achieved in Turkey? An appraisal of the "Health Transformation Programme".
Poor health status indicators, low quality care, inequity in the access to health services and inefficiency due to fragmented health financing and provision have long been problems in Turkey's health system. To address these problems a radical reform process known as the Health Transformation Programme (HTP) was initiated in 2003. The health sector reforms in Turkey are considered to have been among the most successful of middle-income countries undergoing reform. Numerous articles have been published that review these reforms in terms of, variously, financial sustainability, efficiency, equity and quality. Evidence suggests that Turkey has indeed made significant progress, yet these achievements are uneven among its regions, and their long-term financial sustainability is unresolved due to structural problems in employment. As yet, there is no comprehensive evidence-based analysis of how far the stated reform objectives have been achieved. This article reviews the empirical evidence regarding the outcomes of the HTP during 10 years of its implementation. Strengthening the strategic purchasing function of the Social Security Institution (SSI) should be a priority. Overall performance can be improved by linking resource allocation to provider performance. More emphasis on prevention rather than treatment, with an effective referral chain, can also bring better outcomes, greater efficiency gains and contribute to sustainability.


Prediction of histologic type and lymph node metastasis for advanced ovarian cancer on uterine cervical and endometrial cytology.
To evaluate usefulness of uterine cervical and endometrial cytology for detecting ovarian cancer and predicting histologic type. Retrospective analysis was performed on uterine cervical and endometrial cytology data on 163 patients with ovarian cancer. Cervical and endometrial abnormalities were detected in 10 and 19 of the patients evaluated. Patients whose cervical and endometrial cytology revealed abnormal cells were classified as having ovarian cancer at International Federation of Gynecology and Obstetrics (FIGO) stages III and IV Peritoneal cytology proved positive in many of the patients with abnormal findings on uterine cytologic analysis. Of the 19 patients with positive uterine cytologic findings, 12 had recurrence of ovarian cancer after radical therapies. Lymph node metastases were detected in 9 of 19 patients. Our findings indicated that it is possible to predict histologic type in ovarian cancer in 90% of cases of positive cervical smears and 79% ofabnormal endometrial smears. Our study showed that most of the ovarian cancer cases that had abnormalities in uterine cervical and endometrial cytologic tests exhibited progression of disease. As a consequence, our findings indicate that it is possible to predict development of ovarian cancer and its histologic type using cytology screening.


Flexible cystoscopy as an adjunct to extracorporeal shockwave lithotripsy.
Ancillary procedures associated with extracorporeal shockwave lithotripsy (ESWL) include placement and subsequent removal of double pigtail ureteric stents. A simple new technique has been developed for the insertion of these stents. Using the flexible cystoscope, the procedure is performed on an out-patient basis under local anaesthesia. Placement of the stents was successful in 30/34 patients and removal was successful in 14/14 patients.


A study on the impact of patient-related parameters in the ability to spare parotid glands by intensity-modulated radiotherapy for head and neck squamous cell carcinomas.
This study aims to study the effect of geometric- and patient-related variables in achieving the desired dose-volume constraints to parotid for patients undergoing definitive/adjuvant intensity-modulated radiotherapy (IMRT) for head and neck squamous cell carcinomas (HNSCC). This retrospective study considered HNSCC patients who underwent IMRT at our center between 2009 and 2014. Patients' details and dose-volume parameters were collected, and correlated with dose to parotids using Pearson's correlation test. Sixty-seven patients were found to be eligible. Oral primary predominated (37.3%) and 53 (79%) had locally advanced disease. The parotid volume (PV) had no impact on mean dose. There was a negative linear correlation between the ratio (Parotid-planning target volume [PTV] overlap)/PV and mean dose to the whole parotid (y = 1.14-0.011×; R2 = 0.509; P = 0.001), suggesting that a ratio of 0.7 resulted in mean dose ≥ 40 Gy and potentially irreversible xerostomia. No association was found between site of primary and parotid dose, but node-positive (N+) patients received significantly higher dose compared to N0 patients (34.5 Gy vs. 29.5 Gy; P = 0.001). N + patients persisted to receive higher dose even when T stage was accounted for (32.5 Gy vs. 28.9 Gy for </= T2, 35.4 Gy vs. 30.1 Gy for > T2; P = 0.003). On the last follow-up, 35 patients (52%) had >/=Grade II xerostomia. Average mean dose to combined PV was higher in patients with > grade I xerostomia compared to patients with </=Grade I (35 Gy vs. 29 Gy; P = 0.01). The degree of PTV overlap with parotid (≥30%) and N + disease are the strongest predictors of poor parotid sparing by IMRT.


Keyhole surgery for isolated pituitary stalk metastatic tumors: a case report and review of the literature.
Solitary metastatic pituitary stalk tumors account for approximately less than 1% of all pituitary gland tumors and present difficulties in clinical diagnosis because most of them are clinically silent and usually too small to cause radiological changes. With the advance of microsurgical techniques, keyhole surgery is indicated to obtain a specimen for pathological diagnosis and possible removal of the tumor. Here, we reported a patient who has a history of advanced breast cancer and who complained of polyuria and polydypsia. Magnetic resonance images revealed a solitary tumor over the pituitary stalk. A right supraorbital craniotomy was performed and the pathological report confirmed the diagnosis of metastatic breast cancer. This is the first case report using keyhole surgery to confirm the pathology and improve the clinical symptoms. The relevant literature is also reviewed.