Surgery of upper GI gastrointestinal stromal tumors: our experience, prognostic analysis.
To review our treatment experience of gastrointestinal stromal tumors (GISTs) of the upper gastrointestinal tract and identify the prognostic factors that influence tumor recurrence. Data of 46 consecutive patients with upper GI GISTs who underwent surgery from 1988 to 2011 were reviewed. The overall and disease-free survival rates and influence of clinicopathologic variables on disease-free survival rate were evaluated. The median age was 64 years (range, 20-86 years). R0 resections were performed in 43 (93.5%) patients. With a median follow-up time of 33 months (1-275 months), there were 5 (10.9%) recurrences and 2 mortalities in the high-risk group. The overall survival and recurrence-free survival rates at 5 years were 92.1% and 84.6%, respectively. Male gender, tumor size of >10 cm, high numbers of mitotic figures, R1 resection, high risk according to the Joensuu criteria, and a Ki-67 index of >10% were associated with a poor prognosis. Surgical resection of low- and intermediate-risk GISTs has excellent results. High counts of mitotic figures, male gender, incomplete resection, large tumor size, and a high Ki-67 index are associated with a poor prognosis.


[Endoscopic posterior nasal neurectomy].
Surgical techniques for resistant chronic rhinitis (rhinorrhoea) vary, ranging from vidian neurectomy to post-nasal neurectomy. The techniques vary mainly on the basis of instrumentation, and the avoidance of post-operative epistaxis, transient hypoesthesia of the soft palate and dryness of the eye. Endoscopic visualisation, and cauterisation or resection of posterior nasal nerve branches, can prevent such complications. The technique and surgical steps of endoscopic posterior nasal neurectomy are presented. The critical steps include: bilateral sphenopalatine nerve blocks, transnasally or transorally via the greater palatine foramen; vertical incisions made behind the posterior fontanelle; and elevation of the mucoperiosteal flap. The sphenopalatine foramen and artery is identified. The posterior nasal nerve is located 4-5 mm inferior to the sphenopalatine artery, and is resected or cauterised. The flaps are repositioned back into place. No post-operative nasal packing is required. The same procedure is performed on the opposite side for effective results. This technique provides consistent, robust results, with long-term relief of allergic and vasomotor rhinitis related nasal symptoms, without risk of complication.


The association of mucinous histology with clinicopathological characteristics and long-term oncological outcome in patients with colorectal cancer.
This study aimed to evaluate clinicopathological characteristics and long-term oncological outcome with respect to mucinous histology of tumor in colorectal cancer (CRC) patients. A total of 372 patients who underwent resection surgery due to CRC between March 2006 and March 2019 were included in this retrospective study. Patients were divided into two groups according to degree of mucinous component including mucinous carcinoma group (n=48, ≥50% mucinous component) and non-mucinous carcinoma (n=324, <50% mucinous component) group. Data on patient demographics, tumor characteristics, treatment characteristics, metastasis and recurrence rates, disease free survival (DFS), and overall survival (OS) times were recorded. Mucinous vs. non-mucinous carcinoma was associated with higher rate of T4 stage (p=0.036) and high grade tumors (p=0.001) with extranodal invasion (p=0.019) Both the OS time (75.9±13.1 vs. 110.8±5.6 months, p=0.019) and DFS time (98.5±15.6 vs. 140.5±5.1 months, p=0.003) were significantly shorter in colon cancer patients with vs. without mucinous carcinoma despite their higher likelihood of receiving chemotherapy (89.6 vs. 71.9%, p=0.009). Multivariate analysis revealed presence of perineural invasion (HR 1.865, p=0.002), extranodal invasion (HR 1.869, p=0.009), T4 stage (HR 1.617, p=0.019), and M1 stage tumors (HR 3.643, p<0.001) but not mucinous carcinoma to significantly predict poor survival in CRC patients. In conclusion, our findings indicate colorectal tumors with mucinous carcinoma histology to have a more aggressive tumor characteristics and advanced disease stage on admission in CRC patients as well as shorter OS time and DFS time specifically in colon cancer patients despite receiving chemotherapy. Chemotherapy, Colorectal cancer, Long-term follow up, Mucinous histology, Survival.


Application of biotechnology methods to the study of cestodes.
The advent of biotechnology has invigorated research on the control of cestode diseases, especially cysticercosis infections in man and animals. The utilization of hybridoma technology to produce antigen-specific monoclonal antibodies has resulted in great strides towards obtaining pure antigens relevant for immunodiagnostic purposes and for research on vaccines. However, the isolation and identification of antigens is only the initial step in the development of such reagents. Production of antigens in quantities sufficient for research/development and commercialization is hampered by the scarcity of viable parasite material for extraction. Expectations are that this problem can be surmounted by application of recombinant DNA methods to produce cloned genes for antigen expression in cultured microorganisms or cells. Remarkable progress has been made recently in isolating and cloning genes from several important cestode species and antigens have been expressed in vitro with genes cloned from Taenia taeniaformis and T. hydatigena. Although these early efforts have not as yet resulted in practical antigen production, the prospects for doing so appear good. The complex epidemiology of cestode diseases is another research subject that has benefited from the successful application of the tools of biotechnology. For example, the greater precision in typing biological variants afforded by DNA analysis has led to important revisions of the understanding of hydatid disease. DNA probes are now available for Echinococcus spp, which are effective for typing isolates. These probes may also find use as reagents for distinguishing eggs of Echinococcus from other taeniid eggs, a serious difficulty for field investigations.(ABSTRACT TRUNCATED AT 250 WORDS)


[Knowledge and use of the Information System on Public Health Budgets (SIOPS) by municipal health administrators, Pernambuco State, Brazil].
Considering the importance of Brazil's Information System on Public Health Budgets (SIOPS) as a tool for planning, management, and social control of public expenditures in health, this article aimed to evaluate the relationship between the regularity of data entry into the SIOPS and knowledge and use of the system by municipal health administrators in Pernambuco State, Brazil. Ten municipalities were selected from the State's five meso-regions, five of which entered information into the system and five only on an irregular basis. Semi-structured interviews were performed with the municipal health secretaries. Analysis of the data showed that command of information technology and knowledge of the System do not affect the regularity of data entry, as a function of the distance between the Municipal Health Secretariat administrators and the SIOPS, such that the data are normally entered by outsourced services. Thus, the resulting information has not been fully explored by systems administrators as a management tool.


[Non-invasive positive pressure ventilation during the management of severe spinal muscular atrophy type I].
Patients with spinal muscular atrophy type Ⅰ (SMA Ⅰ) with the onset before the age of 3 months are considered as severe form of SMA Ⅰ (severe SMA Ⅰ) and have poor prognosis. Here, we report the efficacy of non-invasive positive pressure ventilation (NPPV) in a patient with severe SMA Ⅰ. She was born with generalized hypotonia and feeding difficulties, and had SMN1 gene mutations (the deletion of exons 7 and 8). At 1 month of age, she was intubated because of respiratory failure due to a respiratory tract infection, and extubation proved difficult. Her parents decided that NPPV and a mechanical in-exsufflator (MI-E) should be used for respiratory management rather than a tracheotomy. The NPPV improved her peripheral coldness, cold sweats, chest wall movement, and heart rate and enabled her to sleep well. At 1 year and 2 months, chest computed tomography revealed mild pneumonia and did not show any atelectasis. The NPPV facilitated discharge, and the patient had a good quality of life (QOL) from the point of view of voice production, the ability to move easily, the simplicity of bathing, and the low level of discomfort she experienced. However, she suffered repeated episodes of aspiration pneumonia and airway obstruction (by sputum) after 11 months of age. Thereafter, she required continuous NPPV and high-span inspiratory positive airway pressure (21 cmH2O). At 1 year and 4 months, she died of respiratory failure at home. As her bulbar weakness worsened, respiratory management with NPPV became difficult. However, the long-term use of NPPV together with high-span positive inspiratory pressure plus positive end-expiratory pressure, and a high-pressure MI-E at an early age might improve respiratory management outcomes and patient prognosis. In our case, NPPV was effective at improving ventilation and preventing atelectasis and helped to provide the patient with a good QOL.


Fine-resolution analysis of products of intrachromosomal homeologous recombination in mammalian cells.
Mouse Ltk- cell lines that contained a herpes simplex virus type 1 (HSV-1) thymidine kinase (tk) gene with a 16-bp insertion mutation linked to either a defective HSV-2 tk gene or a hybrid tk sequence comprised of HSV-1 and HSV-2 tk sequences were constructed. HSV-1 and HSV-2 tk genes have 81% nucleotide identity and hence are homeologous. Correction of the insertion mutant HSV-1 tk gene via recombination with the hybrid tk sequence required an exchange between homeologous tk sequences, although recombination could initiate within a region of significant sequence identity. Seven cell lines containing linked HSV-1 and HSV-1-HSV-2 hybrid tk sequences gave rise to tk+ segregants at an average rate of 10(-8) events per cell division. DNA sequencing revealed that each recombinant from these lines displayed an apparent gene conversion which involved an accurate transfer of an uninterrupted block of information between homeologous tk sequences. Conversion tract lengths ranged from 35 to >330 bp. In contrast, cell lines containing linked HSV-1 and HSV-2 tk sequences with no significant stretches of sequence identity had an overall rate of homeologous recombination of <10(-9). One such cell line produced homeologous recombinants at a rate of 10(-8). Strikingly, all homeologous recombinants from this latter cell line were due to crossovers between the HSV-1 and HSV-2 tk genes. Our results, which provide the first detailed analysis of homeologous recombination within a mammalian genome, suggest that rearrangements in mammalian genomes are regulated by the degree of sequence divergence located at the site of recombination initiation.


Increased leukotriene B4 and 8-isoprostane in exhaled breath condensate of patients with exacerbations of COPD.
Exacerbations are an important feature of chronic obstructive pulmonary disease (COPD), accounting for a large proportion of health care costs. They are associated with increased airway inflammation and oxidative stress. Concentrations of leukotriene B4 (LTB4), a marker of inflammation, and 8-isoprostane, a marker of oxidative stress, were measured in the exhaled breath condensate of 21 patients (11 M) with COPD during an exacerbation and 2 weeks after treatment with antibiotics. In 12 patients who had no further exacerbations these markers were also measured after 2 months. LTB4 concentrations were raised during the COPD exacerbation (mean (SE) 15.8 (1.1) pg/ml and fell after treatment with antibiotics to 9.9 (0.9) pg/ml (p<0.0001). In 12 patients the level of LTB4 fell further from 10.6 (1.1) pg/ml to 8.5 (0.8) pg/ml (p<0.005) after 2 months. In 12 normal age matched subjects the LTB4 levels were 7.7 (0.5) pg/ml. Concentrations of 8-isoprostane were also increased during the exacerbation (13.0 (0.9) pg/ml) and fell after antibiotic treatment to 9.0 (0.6) pg/ml (p<0.0001). In 12 patients there was a further fall from 9.3 (0.7) pg/ml to 6.0 (0.7) pg/ml (p<0.001) after 2 months compared with normal subjects (6.2 (0.4) pg/ml). Non-invasive markers of inflammation and oxidative stress are increased during an infective exacerbation of COPD and only slowly recover after treatment with antibiotics.


Coreceptor blockade targeting CD4 and CD8 allows acceptance of allogeneic human pluripotent stem cell grafts in humanized mice.
We have previously demonstrated that short-term coreceptor blockade with non-lytic monoclonal antibodies enables the long-term survival of fully allogeneic embryonic stem cell (ESC) transplants in mice. Here, we describe the use of Hu-PBL humanized mice to determine whether short-term coreceptor blockade with humanized anti-human CD4 and CD8 antibodies can achieve the same outcome towards human ESC derivatives. While control Hu-PBL mice rejected allogeneic hESC-derived transplants within weeks, mice treated with coreceptor blocking antibodies held their grafts for 7 weeks, the duration of the study. Rejection in the control mice was associated with demonstrable infiltrates of human CD45 white blood cells, predominantly of CD8 T-cells, whereas anti-CD4, but not anti-CD8 antibody treated mice showed remarkably reduced lymphocyte infiltration and prolonged allograft survival, indicating that the CD4+ T-cells were crucial to the rejection process. Our results give support to the principle that short-term blockade of T-cell co-receptors can achieve long-term acceptance of regenerative cell transplants in humans.


A theoretical study of the mechanism of the atmospherically relevant reaction of chlorine atoms with methyl nitrate, and calculation of the reaction rate coefficients at temperatures relevant to the troposphere.
The reaction between atomic chlorine (Cl) and methyl nitrate (CH3ONO2) is significant in the atmosphere, as Cl is a key oxidant, especially in the marine boundary layer, and alkyl nitrates are important nitrogen-containing organic compounds, which are temporary reservoirs of the reactive nitrogen oxides NO, NO2 and NO3 (NOx). Four reaction channels HCl + CH2ONO2, CH3OCl + NO2, CH3Cl + NO3 and CH3O + ClNO2 were considered. The major channel is found to be the H abstraction channel, to give the products HCl + CH2ONO2. For all channels, geometry optimization and frequency calculations were carried out at the M06-2X/6-31+G** level, while relative electronic energies were improved to the UCCSD(T*)-F12/CBS level. The reaction barrier (ΔE(‡)0K) and reaction enthalpy (ΔH(RX)298K) of the H abstraction channel were computed to be 0.61 and -2.30 kcal mol(-1), respectively, at the UCCSD(T*)-F12/CBS//M06-2X/6-31+G** level. Reaction barriers (ΔE(‡)0K) for the other channels are more positive and these pathways do not contribute to the overall reaction rate coefficient in the temperature range considered (200-400 K). Rate coefficients were calculated for the H-abstraction channel at various levels of variational transition state theory (VTST) including tunnelling. Recommended ICVT/SCT rate coefficients in the temperature range 200-400 K are presented for the first time for this reaction. The values obtained in the 200-300 K region are particularly important as they will be valuable for atmospheric modelling calculations involving reactions with methyl nitrate. The implications of the results to atmospheric chemistry are discussed. Also, the enthalpies of formation, ΔHf,298K, of CH3ONO2 and CH2ONO2 were computed to be -29.7 and 19.3 kcal mol(-1), respectively, at the UCCSD(T*)-F12/CBS level.


Treatment of canine osteoarthritis with insulin-like growth factor-1 (IGF-1) and sodium pentosan polysulfate.
The potential therapeutic effects of insulin-like growth factor-1 (IGF-1) and sodium pentosan polysulfate (PPS) were evaluated in an anterior cruciate ligament-deficient canine model of osteoarthritis (OA). A control group of animals received no treatment or surgery (N). The remaining four groups of animals received anterior cruciate transection and either no treatment (OA), intra-articular IGF-1 (IGF-1), intra-muscular PPS (PPS), or a combination of intra-articular IGF-1 and intra-muscular PPS (IGF-1/PPS). All therapy was begun 3 weeks after surgery and continued for 3 weeks. At 6 weeks, articular cartilage from the femoral condyle was evaluated for anatomy, histology (Mankin grade) and biochemistry. Anatomically, only cartilage from dogs in the IGF-1/PPS group approximated that found in N. Mankin scores indicated less severe disease in both PPS and IGF-1/PPS groups compared with the OA group. Consistent with histology, the level of active neutral metalloproteinase was lower in cartilage from the PPS group compared with the OA group. Active and total neutral metalloproteinase, tissue inhibitor of metalloproteinases (TIMP), total collagenase, uronate and hydroxyproline contents were all near normal in the IGF-1/PPS group. In a model of mild OA, therapeutic intervention with IGF-1 and PPS appeared to successfully maintain cartilage structure and biochemistry. From these data, it is hypothesized that proteinase activity was successfully blocked by PPS, and that this allowed the observed growth factor induced effects. As we unravel the various factors that regulate cartilage metabolism, it is becoming apparent that combinations of agents will be needed to effectively control cartilage repair in OA. The addition of PPS to IGF-1 shows promise as a therapeutic intervention and introduces a new rational approach to therapy of OA.


Seroprevalence of bovine tuberculosis infection in yaks (Bos grunniens) on the Qinghai-Tibetan Plateau of China.
Bovine tuberculosis (BTB), a chronic disease caused by Mycobacterium bovis, has been widely reported in bovines in developing countries, but there is little information on this infection in domestic yaks. Seroprevalence of antibodies to M. bovis in yaks from six and three regions of Tibet and Qinghai plateau, China, respectively, was investigated in 2011 by enzyme-linked immunosorbent assay kits. A total of 1,244 (Tibet 938, Qinghai 306) blood samples was collected and the results showed that 24 (2.6%) of Tibetan samples and 3 (1%) of Qinghai's samples were positive for BTB. The findings of the present study indicated that M. bovis infection is prevalent in Chinese yaks in Qinghai and Tibet. These observations should raise a serious public health concern considering the extent to which the herdsmen of the study areas are in contact with their animals and the levels at which they use untreated livestock products. This is the first study showing the infection of M. bovis in domestic yaks.


Palladium-catalyzed cyclization/carboalkoxylation of alkenyl indoles.
Reaction of 1-methyl-2-(4-pentenyl)indole with a catalytic amount of PdCl2(CH3CN)2 (5 mol %) and a stoichiometric amount of CuCl2 (3 equiv) in methanol under CO (1 atm) at room temperature for 30 min led to cyclization/carboalkoxylation to form the corresponding tetrahydrocarbazole in 83% isolated yield as a single regioisomer. Palladium-catalyzed cyclization/carboalkoxylation of 2-(4-pentenyl)indoles tolerated substitution along the alkenyl chain and at the internal and cis-terminal olefinic positions. Palladium-catalyzed cyclization/carboalkoxylation tolerated a range of alcohols and was effective for the cyclization of 2-(3-butenyl)indoles, 3-(3-butenyl)indoles, 3-(4-pentenyl)indoles, and 2-(5-hexenyl)indoles.


Effect of CO2 Laser Microperforation Pretreatment on the Dehydration of Apple Slices during Refractive Window Drying.
This research studied the use of CO2 LASER microperforation as a pretreatment for the refractive window (RW) drying of apple slices with respect to total polyphenol content (TPC), antioxidant capacity, color ΔE, and product stability under accelerated storage. For this purpose, the processing variables assessed were pore size (200-600 µm), pore density (9-25 pores/cm2), and drying temperature (70-90 °C). As baseline criteria, a comparison with respect to the control without microperforations and samples subjected to conventional tunnel and lyophilization were also considered. The increase in the pore size from 200 to 600 µm resulted in shorter drying times (≤40 min), minimal change in color (ΔE) and loss of TPC, while DPPH was negatively affected by the combined effect of the pore density and the drying temperature. In general, the use of RW with CO2 resulted in apples of higher quality than those obtained in conventional drying and comparable to those obtained through the use of freeze-drying. Finally, during accelerated storage, quality attributes decreased significantly for samples dried at 90 °C regardless of whether microperforations were used, suggesting that a compromise between drying temperature and pore size must be weighed to reduce processing time and to avoid further quality losses during storage.


Drug use in patients with short bowel syndrome and intestinal failure.
In patients with short bowel syndrome (SBS), severe malabsorption may cause a need for parenteral support and, by definition, these patients suffer from SBS intestinal failure. Absorption of oral medications is likely diminished in patients with SBS intestinal failure and higher than normal doses may be required to achieve sufficient pharmacologic effect. We investigated the prescription patterns and oral dosages in a well-defined population of patients with non-malignant SBS intestinal failure. This was a cross-sectional analysis based on a cohort of adult patients with SBS intestinal failure treated with home parenteral support and registered in 2016 at the Department of Gastroenterology at the Copenhagen University Hospital - Rigshospitalet. The patients' clinical data and prescription patterns were extracted from electronic medical and medications records. The patients in our cohort (n = 74) were primarily females (58%), the median age was 63 years (interquartile range (IQR): 52-72 years) and the median BMI was 22 kg/m2 (IQR: 19-26 kg/m2). Each patient was treated with a median of eight drugs (range: 1-20). Most (75%) of the medications were administered orally. Only codeine, levothyroxine and loperamide were prescribed in higher dosages than recommended in their product labelling. All medication-treated patients were prescribed between one and four different analgesics. In our single-centre cohort of patients with SBS intestinal failure, orally administered medications were generally prescribed in recommended dosages. none Trial registration. Approved by the Danish Data Protection Agency (BFH-2016-058, I-Suite no.: 04906) and the Danish Patient Safety Authority (3-3013-1884/1/).


Improved El Nino forecasting by cooperativity detection.
Although anomalous episodic warming of the eastern equatorial Pacific, dubbed El Niño by Peruvian fishermen, has major (and occasionally devastating) impacts around the globe, robust forecasting is still limited to about 6 mo ahead. A significant extension of the prewarning time would be instrumental for avoiding some of the worst damages such as harvest failures in developing countries. Here we introduce a unique avenue toward El Niño prediction based on network methods, inspecting emerging teleconnections. Our approach starts from the evidence that a large-scale cooperative mode--linking the El Niño basin (equatorial Pacific corridor) and the rest of the ocean--builds up in the calendar year before the warming event. On this basis, we can develop an efficient 12-mo forecasting scheme, i.e., achieve some doubling of the early-warning period. Our method is based on high-quality observational data available since 1950 and yields hit rates above 0.5, whereas false-alarm rates are below 0.1.


Novel insights into molecular and cellular aspects of delayed drug hypersensitivity reactions.
Delayed drug hypersensitivity reactions (DDHRs) represent a major health problem. They are unpredictable and can cause life-long disability or even death. The pathophysiology of DDHRs is complicated, multifactorial, and not well understood mainly due to the lack of validated animal models or in vitro systems. The role of the immune system is well demonstrated but its exact pathophysiology still a matter of debate. This review summarizes the current understanding of DDHRs pathophysiology and abridges the available new evidence supporting each hypothesis. A comprehensive literature search for relevant publications was performed using PubMed, Google Scholar, and Medline databases with no date restrictions and focusing on the most recent 10 years. Although multiple milestones have been achieved in our understanding of DDHRs pathophysiology as a result of the development of useful experimental models, many questions are yet to be fully answered. A deeper understanding of the mechanistic basis of DDHRs would not only facilitate the development of robust and reliable diagnostic assays for diagnosis, but would also inform therapy by providing specific target(s) for immunomodulation and potentially permit pre-therapeutic risk assessment to pursue the common goal of safe and effective drug therapy.


Airborne enteric bacteria and viruses from spray irrigation with wastewater.
The relationship between bacterial concentrations in wastewater used for spray irrigation and in the air was examined. Aerosolized coliforms were detected when their concentration was 10(3)/ml or more in the wastewater. Relative humidity and solar irradiation appeared to affect viable bacteria in the air; a positive correlation was found between relative humidity and the number of aerosolized bacteria. The correlation between solar irradiation and bacterial level, on the other hand, was negative. During night irrigation, up to 10 times more aerosolized bacteria were detected than with day irrigation. Wind velocity did not play an important role in the survival of aerosolized bacteria. Echovirus 7 was isolated in 4 out of 12 air samples collected 40 m downwind from the sprinkler.


[Venous circulatory resistance in the diagnosis and follow-up of venous thromboses].
Using a mercury plethysmograph, the venous resistance (a novel venous parameter) is determined separately for the veins of the thigh and lower leg, using the Brakkee and Kuiper (1982) method. In a retrospective study of acute and subacute thrombosis, the authors detected sensitivity of 91 and 36% respectively in proximal and distal thromboses. Specificity was 100 percent. Although differences from the control grop were detected, it would seem that the presence of a varicose trunk or lymphedema does not affect either sensitivity or specificity.


Oxygen tension modulates Ca2+ response to flow stimulus in endothelial cells exposed to hydrostatic pressure.
The effects of oxygen gas tensions and hydrostatic pressure on intracellular calcium, [Ca2+]i, response to a flow stimulus in endothelial cells were investigated. Cultured bovine aortic endothelial cells (BAECs) were exposed to a hydrostatic pressure of 100 mmHg under low oxygen gas tensions and were subsequently subjected to a 1 minute mechanical stimulation of fluid shear stress of 20 dynes/cm2. The [Ca2+]i response in BAECs was measured using a fluorescent indicator, Calcium Green-1. The maximum intensity for low oxygen tension was significantly lower than that for normal oxygen tension, which provides evidence that low oxygen tension regulates cellular functions downward. Moreover, preloading of hydrostatic pressure also reduced the increases in [Ca2+]i. These results suggest that BAECs in venous system, where oxygen tension and hydrostatic pressure are lower than those in arterial system, may be less sensitive to fluid flow. A separate observation showed that low oxygen tension did not significantly affect the cell morphology. In contrast, BAECs exposed to hydrostatic pressure showed marked elongation with no predominant orientation and the F-actin filament distributions were rearranged, indicating centrally located thick stress fibers. For better understanding of endothelial cell physiology, it is very important to elucidate the effect of oxygen gas tensions together with mechanical environment on endothelial cell responses.


Noninvasive Ventilation in Acute Hypoxemic Nonhypercapnic Respiratory Failure: A Systematic Review and Meta-Analysis.
To evaluate the effectiveness of noninvasive ventilation in patients with acute hypoxemic nonhypercapnic respiratory failure unrelated to exacerbation of chronic obstructive pulmonary disease and cardiogenic pulmonary edema. PubMed, EMBASE, Cochrane library, Web of Science, and bibliographies of articles were retrieved inception until June 2016. Randomized controlled trials comparing application of noninvasive ventilation with standard oxygen therapy in adults with acute hypoxemic nonhypercapnic respiratory failure were included. Chronic obstructive pulmonary disease exacerbation and cardiogenic pulmonary edema patients were excluded. The primary outcome was intubation rate; ICU mortality and hospital mortality were secondary outcomes. Demographic variables, noninvasive ventilation application, and outcomes were retrieved. Internal validity was assessed using the risk of bias tool. The strength of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation methodology. Eleven studies (1,480 patients) met the inclusion criteria and were analyzed by using a random effects model. Compared with standard oxygen therapy, the pooled effect showed that noninvasive ventilation significantly reduced intubation rate with a summary risk ratio of 0.59 (95% CI, 0.44-0.79; p = 0.0004). Furthermore, hospital mortality was also significantly reduced (risk ratio, 0.46; 95% CI, 0.24-0.87; p = 0.02). Subgroup meta-analysis showed that the application of bilevel positive support ventilation (bilevel positive airway pressure) was associated with a reduction in ICU mortality (p = 0.007). Helmet noninvasive ventilation could reduce hospital mortality (p = 0.0004), whereas face/nasal mask noninvasive ventilation could not. Noninvasive ventilation decreased endotracheal intubation rates and hospital mortality in acute hypoxemia nonhypercapnic respiratory failure excluding chronic obstructive pulmonary disease exacerbation and cardiogenic pulmonary edema patients. There is no sufficient scientific evidence to recommend bilevel positive airway pressure or helmet due to the limited number of trials available. Large rigorous randomized trials are needed to answer these questions definitely.


Detection of Epstein-Barr virus genomes in AIDS related lymphomas: sensitivity and specificity of in situ hybridisation compared with Southern blotting.
Eighteen cases of AIDS related, non-Hodgkin's lymphomas were examined for the presence of Epstein-Barr virus (EBV) genomes using in situ hybridisation with a 35S-labelled probe. The results were compared with those obtained independently by Southern blot analysis with a 32P-labelled probe of frozen tissue from the same tumours. Technically satisfactory results were obtained with both methods in 15 lymphomas. EBV DNA was detected in seven of 15 (47%) cases by in situ hybridisation and in eight of 15 (53%) cases by Southern blotting (including all the cases positive by in situ hybridisation). The results of EBV DNA detection by the two techniques were identical in 14 of 15 (93%) cases. In situ hybridisation gave no false positive results. This study shows that the sensitivity and specificity of in situ hybridisation for the detection of EBV genomes in AIDS related lymphomas approaches that of Southern blotting, even when using routinely processed archival, paraffin wax embedded material.


Heterogeneity in externalizing problems at age 3: Association with age 15 biological and environmental outcomes.
Investigating heterogeneity in antisocial behavior early in life is essential for understanding the etiology, development, prognosis, and treatment of these problems. Data from the longitudinal National Institute of Child Health and Development (NICHD) study of Early Child Care were used to identify homogeneous groups of young antisocial children differentiated on externalizing problems, internalizing problems, and callous-unemotional (CU) traits using latent profile analysis (LPA). We examined how identified subgroups were differentiated on adolescent social, biological, cognitive, and environmental outcomes, controlling for dispositional and contextual antecedents during the first 2 years of life. The sample consisted of 1,167 children (52% male) followed from toddlerhood to adolescence. LPA identified a large "low problems" group (n = 795; 49.9% male) as well as 3 antisocial groups at age 3: the first scored high on internalizing and externalizing problems but low on CU traits (Ext/Int, n = 125), the second scored high on CU traits and externalizing problems but low on internalizing problems (primary CU variant, n = 135), and the third scored high on CU traits, internalizing, and externalizing problems (secondary CU variant, n = 112), and these differences persisted into adolescence. Primary and secondary CU variants were further differentiated from one another on adolescent measures of aggression (reactive and relational), biological indices (cortisol, heart rate), cognitive abilities, and parental psychopathology, after controlling for early life risk factors (i.e., maternal sensitivity, difficult temperament, and maternal depression). We discuss implications of our findings for research, theory, and practice on early childhood externalizing problems. (PsycINFO Database Record


Do arrhythmias still deserve our intellectual efforts?: The 2002 Wenckebach Lecture of the Netherlands Society of Cardiology.
At the 74th meeting of the American Medical Association in San Francisco (1923) Professor Karel Frederik Wenckebach (figure 1) reported how favourably quinine converted atrial fibrillation. He honestly told the audience that his observations relied on the experience of a Dutch merchant who used to terminate his palpitations with quinine, a drug that he took daily for malaria while staying in the Dutch colonies. During his presentation he also emphasised that quinine worked better for atrial fibrillation of recent onset, an observation that is well known today. This story teaches us that simply listening to the patient and thinking about the significance of the patient's words can lead to diagnostic or therapeutic progress. Such a professional attitude is perfectly illustrated by Sir James Mackenzie's statement in 1918: 'The progress of medicine will be hampered, till the general practitioner becomes an investigator.'


Angiojet thrombectomy for Blalock-Taussig shunt and pulmonary artery thrombus in an infant with tetralogy of fallot.
We describe a new technique for treatment of shunt thrombosis in infants with complex anatomical defects. A 2-month-old girl with Tetralogy of Fallot underwent placement of a modified Blalock-Taussig shunt (MBTS) at day of life (DOL) 6 with revision at DOL 20. Following this surgery, the patient became hypotensive and hypoxic with new evidence of lack of flow through the MBTS on echocardiography. Angiography showed an occluded MBTS and right pulmonary artery with patent distal branches with normal pulmonary venous return. Balloon angioplasty was attempted but failed to fully recanalize the right pulmonary artery (RPA) and MBTS. An AngioJet catheter was then passed through the shunt and RPA to perform rheolyticthrombectomy. Subsequent angiogram showed a widely patent RPA and MBTS. An echocardiogram at 1-month post-thrombectomy showed a widely patent MBTS with continuous flow seen entering both branch pulmonary arteries. The AngioJet system for thrombectomy provides a viable option for complex thrombus removal in patients refractory to other methods.


Secondary drowning in the Cape Peninsula.
Secondary drowning is a respiratory distress syndrome which develops after a latent period following apparently successful resuscitation from near-drowning. Eighteen cases of near-drowning have been reviewed and one case history is presented in detail to illustrate the importance of anticipating the development of this syndrome. Successful management of these patients involves ventilatory support and careful monitoring of the neurological and cardiovascular status. Because many doctors are unaware of the syndrome and because it has a good prognosis if recognized and treated early, a review of the clinical features and treatment is warranted.


Host plant resistance, foliar insecticide application and natural enemies play a role in the management of Melanaphis sorghi (Hemiptera: Aphididae) in grain sorghum.
The invasive Melanaphis sorghi (Theobald; =Melanaphis sacchari Zehntner) is a serious pest of sorghum production in the southern USA. Demonstration of technologies that provide effective control is key to management of this pest. Here, we investigated the effect of host plant resistance (resistant cultivar: DKS37-07 and susceptible cultivar: DKS53-53) and a single foliar insecticide (flupyradifurone: Sivanto Prime) application on M. sorghi infestations and the role of natural enemy populations in grain sorghum production across five locations in four states in southeastern USA. Foliar insecticide application significantly suppressed M. sorghi infestations on both the resistant and susceptible sorghum cultivars across all locations. Planting the host plant resistant cultivar (DKS37-07) significantly reduced aphid infestation across all locations. Plant damage ratings did not vary widely, but there was generally a positive association between aphid counts and observed plant damage, suggesting that increasing aphid numbers resulted in corresponding increase in plant damage. Planting a host plant resistant cultivar and foliar insecticide application generally preserved grain yield. Both sorghum hybrids supported an array of different life stages of natural enemies (predators [lady beetle larvae and adults; hoverfly larvae and lacewing larvae] and parasitoids [a braconid and aphelinid]) for both the sprayed and non-sprayed treatments. We found a strong and significant positive relationship between the natural enemies and the M. sorghi infestation. Results suggest that planting a host plant resistant cultivar and the integration of natural enemies with insecticide control methods in the management of M. sorghi is central to the development of an effective pest management strategy against this invasive pest.


Development and evaluation of loop-mediated isothermal amplification (LAMP) for the rapid diagnosis of Penicillium marneffei in archived tissue samples.
Penicillium marneffei is the etiologic agent of a severe systemic disease in immunocompromised hosts in Southeast Asia. In the present study, a novel method, known as loop-mediated isothermal amplification (LAMP), is described for the rapid and specific detection of the species, using a primer set derived from the internal transcribed spacer (ITS) region of the rRNA gene. Amplification products can be detected macroscopically by visual inspection in vials using SYBR Green I as well as by electrophoresis on agarose gel. The LAMP assay resulted in specific amplification of P. marneffei ITS using pure cultures after a 1-h reaction at 65 degrees C in a water bath; no cross-reactivity with other fungi including other biverticillate penicillia was observed. The detectable DNA limit was two copies. In addition, specific amplification was achieved using paraffin wax-embedded tissue samples from patients with penicilliosis marneffei and tissue samples from bamboo rats. The method provides a powerful tool for rapid diagnostics in the clinical lab, and has potential for use in ecological studies.


Fatigue in cancer: a review of literature.
Fatigue is a common symptom of advanced cancer limiting one's activity and affecting the quality of life. It is a multidimensional symptom complex with subjective and objective components. Hence, its definition and assessment seems arbitrary, incomplete, and elusive. Components of fatigue often merge with other 'disease states' as anemia, depression and so on, compounding difficulty to assess it separately. Fatigue has a high prevalence rate, and lasts longer in chronic diseases like cancer. Its association with treatment modalities like chemotherapy, radiotherapy alongside the primary disease process makes it seemingly ubiquitous in many cases. Systemic manifestation of cancer causes excess demand on body resources on cell repair, uncontrolled growth with metabolite accumulation causing fatigue. Co-morbid conditions of organic and psychological nature causes fatigue. There are many assessment tools for fatigue with different uses and objectives, simple and reproducible tools like Brief Fatigue Inventory, Edmonton Symptom assessment scale seem feasible in everyday practice. Management of fatigue is not straightforward and rewarding. Although treatment of cause appears to be an attractive option, it is not possible in all cases. Therapeutic agents targeting cytokine load is in early stages of study and available results are not favorable. Specific measures aimed at pain relief, prevention/treatment of sepsis, management of depression, avoidance of drugs causing fatigue, restoring the metabolic profile are important. Methyl phenidate, megestrol, and modafinil are some drugs with promising effect to treat fatigue, though confirmatory studies are yet to be established. Non-pharmacological methods are also helpful. Forewarning patients on upcoming fatigue, active regular exercise, and stress management are some of them. Fatigue being a multidimensional entity, single mode of therapy is insufficient. Combined modality tailored to individual patient need and understanding may be the right way to battle this ill-understood symptom. This review article examines the etiopathogenesis and management strategies of fatigue in cancer.


Widespread, depth-dependent cortical microstructure alterations in paediatric focal epilepsy.
Tissue abnormalities in focal epilepsy may extend beyond the presumed focus. The underlying pathophysiology of these broader changes is unclear, and it is not known whether they result from ongoing disease processes, treatment-related side-effects, or whether they emerge earlier. Few studies have focused on the period of onset for most focal epilepsies, childhood. Fewer still have utilised quantitative MRI, which may provide a more sensitive and interpretable measure of tissue microstructural change. Here, we aimed to determine common spatial modes of changes in cortical architecture in children with heterogeneous drug-resistant focal epilepsy and, secondarily, whether changes were related to disease severity. To assess cortical microstructure, quantitative T1 and T2 relaxometry (qT1 and qT2) was measured in 43 children with drug-resistant focal epilepsy [age-range=4-18 years] and 46 typically-developing children [age-range=2-18 years]. We assessed depth-dependent qT1 and qT2 values across the neocortex, as well as their gradient of change across cortical depths. We also determined whether global changes seen in group analyses were driven by focal pathologies in individual patients. Finally, as a proof-of-concept, we trained a classifier using qT1 and qT2 gradient maps from patients with radiologically-defined abnormalities (MRI-positive) and healthy controls, and tested if this could classify patients without reported radiological abnormalities (MRI-negative). We uncovered depth-dependent qT1 and qT2 increases in widespread cortical areas in patients, likely representing microstructural alterations in myelin or gliosis. Changes did not correlate with disease severity measures, suggesting they may represent antecedent neurobiological alterations. Using a classifier trained with MRI-positive patients and controls, sensitivity was 71.4% at 89.4% specificity on held-out MRI-negative patients. These findings suggest the presence of a potential imaging endophenotype of focal epilepsy, detectable irrespective of radiologically identified abnormalities.


Condyloma acuminatum in Rochester, Minn, 1950-1978. II. Anaplasias and unfavorable outcomes.
A total of 746 patients residing in Rochester, Minn, received the diagnosis of condyloma acuminatum between 1950 and 1978. Anaplasia was present in six and subsequently developed in 36 patients during follow-up examination in 42 patients (one male and 41 female). One had invasive squamous cell carcinoma (vulva), six had severe dysplasias, 21 had moderate to mild dysplasias, and 14 had carcinomas in situ (CIS), of which 11 were cervical. In the female patients, 37 of the anaplasias were cervical and the other four were vulval or vaginal. The 11 cervical CIS amounted to 3.8 times the expected number of 2.9, based on an earlier study of cervical cancer incidence in the community. The risk of cervical CIS developing among patients with condyloma is significantly higher than expected. Neither laryngeal papilloma nor other unfavorable outcomes substantially affected the conceptus of 51 pregnancies in women with concurrent condyloma. There appears to be an association between condyloma and genital malignant neoplasms and a relationship of condyloma with sexually transmitted disease and warts.


Quality of life and self-esteem in patients submitted to surgical treatment of skin carcinomas: long-term results.
Cancer is a multifactorial disease and skin carcinomas are the most common type of cancer. Assessing quality of life and self-esteem outcomes in skin cancer patients is important because these are indicators of the results of the treatment, translating how patients face their lives and their personal relationships. To assess the late impact of the surgical treatment of head and/or neck skin carcinomas on quality of life and self-esteem of the patients. Fifty patients with head or neck skin carcinomas were enrolled. Their age ranged between 30 and 75 years, 27 were men and 23 were women. Patients were assessed with regard to quality of life and self-esteem, preoperatively and five years postoperatively. Validated instruments were used: the MOS 36-item Short-form Health Survey (SF-36) and the Rosenberg Self-esteem/EPM-UNIFESP Scale. The Wilcoxon signed-rank test was used for the statistical analysis. Twenty-two patients completed the five-year follow-up, 54.5% women and 45.5% men. Compared to the preoperative assessment, patients had an improvement in mental health (p=0.011) and in self-esteem (p=0.002). There was no statistical difference with regard to the other domains of the SF-36. Patients submitted to surgical treatment of skin carcinoma improved mental health and self-esteem in the late postsurgical testing.


[Structure and mechanism of functioning of centers of fibrin polymerization].
Fibrinogen takes part in a lot of physiological and pathological processes in the organism. Its most important function consists in preventing blood leakage through the injured wall of the blood vessel. Proteolytic enzyme thrombin generated in the site of the injury splits low-molecular fibrinopeptides A and B from fibrinogen and transforms the latter into the monomeric fibrin which is spontaneously polymerized with formation of a clot of blood closing a lumen of the injured vessel. Fibrin polymerization that completes the stages of blood coagulation is the example of self-assembling of supermolecular biological structures in blood coagulation system. Clearing-up of this process mechanisms is of great theoretical and practical importance, in particular, for clinical medicine connected with treatment of hemorrhages and thromboses.


[The skill hand and the face: optic and haptic surgery].
For the surgeon of the face, there is an obvious ambiguity in the relationship between the hand and the face, because the first is etymologically linked to the grounds of the surgeon trade and which face does it mean? The face of the man, who, hidden behind his surgical mask, tries to repair the disfigured face or the face of the patient he cares about in the way to give him a new face and a new identity through even more complex surgeries? There is actually an analogy with the painter and his model, the sculptor and his hand which shapes, the pianist player and the works he performs, the writer and the memories which inspire his novel. The authors would like here to point out this facing of feelings but also theirs tangles in something which could be named the tactilisation of the seeing and visualisation of the touch; sort of requested community between optic and haptic. Applied to the facial transplantation this disturbing strangeness, the schizophrenic questioning dived ourselves in an abyssal vertigo from which only the ethics as aesthetics of the inside could save us.


Speed modulation of the continuous-flow total artificial heart to simulate a physiologic arterial pressure waveform.
This study demonstrated the concept of using speed modulation in a continuous-flow total artificial heart (CFTAH) to shape arterial pressure waveforms and to adjust pressure pulsatility. A programmable function generator was used to determine the optimum pulsatile speed profile. Three speed profiles [sinusoidal, rectangular, and optimized (a profile optimized for generation of a physiologic arterial pressure waveform)] were evaluated using the CFTAH mock circulatory loop. Hemodynamic parameters were recorded at average pump speeds of 2,700 rpm and a modulation cycle of 60 beats per minute. The effects of varying physiologically relevant vascular resistance and lumped compliance on the hemodynamics were assessed. The feasibility of using speed modulation to manipulate systemic arterial pressure waveforms, including a physiologic pressure waveform, was demonstrated in vitro. The additional pump power consumption needed to generate a physiologic pulsatile pressure was 16.2% of the power consumption in nonpulsatile continuous-flow mode. The induced pressure waveforms and pulse pressure were shown to be very responsive to changes in both systemic vascular resistance and arterial compliance. This system also allowed pulsatile pulmonary arterial waveform. Speed modulation in the CFTAH could enable physicians to obtain desired pressure waveforms by simple manual adjustment of speed control input waveforms.


Nil per os encodes a conserved RNA recognition motif protein required for morphogenesis and cytodifferentiation of digestive organs in zebrafish.
Digestive organ development occurs through a sequence of morphologically distinct stages, from overtly featureless endoderm, through organ primordia to, ultimately, adult form. The developmental controls that govern progression from one stage to the next are not well understood. To identify genes required for the formation of vertebrate digestive organs we performed a genetic screen in zebrafish. We isolated the nil per os (npo) mutation, which arrests morphogenesis and cytodifferentiation of the gut and exocrine pancreas in a primordial state. We identified the npo gene by positional cloning. It encodes a conserved protein, with multiple RNA recognition motifs, that is related to the yeast protein Mrd1p. During development npo is expressed in a dynamic fashion, functioning cell autonomously to promote organ cytodifferentiation. Antisense-mediated knockdown of npo results in organ hypoplasia, and overexpression of npo causes an overgrowth of gastrointestinal organs. Thus, npo is a gene essential for a key step in the gut morphogenetic sequence.


Site-specific analysis of dipole polarizabilities of heterogeneous systems: iron-doped Si(n) (n = 1-14) clusters.
Following the recent work of decomposing the total dipole moment and polarizability of a homogeneous system into site-specific contributions, we extend the study to the heterogeneous systems of iron-doped Sin (n = 1-14) clusters by introducing a weighting function. The structure-∕shape- and size-specific aspects of the dipole moments and polarizabilities of SinFe (n = 1-14) clusters are analyzed and compared with pure silicon clusters. It is shown that the polarizabilities associated with the individual constituent atoms vary considerably with the structure∕shape of the cluster and the location of the atom or site within a given structure. For atoms at peripheral sites, the polarizabilities are substantially larger than atoms at the interior sites, and the more peripheral an atom is, the larger is its polarizability. The polarizability of the Fe atom in SinFe clusters decreases as the cluster size increases. This is related to the position of Fe atom in SinFe clusters and indicates significant screening of the interior of the cluster by its surface. The correlation between the anisotropy of the total polarizability and the anisotropy of the cluster shape is also analyzed. Comparing with pure Sin clusters, the polarizabilities of Si atoms are increased after Fe atom doping. The structures are more compact for SinFe than the same sizes of Sin +1 clusters and the polarizabilities of SinFe are smaller than Sin +1 for the sizes of n = 7-14.


Heterotrimeric G proteins regulate nitrogen-use efficiency in rice.
The drive toward more sustainable agriculture has raised the profile of crop plant nutrient-use efficiency. Here we show that a major rice nitrogen-use efficiency quantitative trait locus (qNGR9) is synonymous with the previously identified gene DEP1 (DENSE AND ERECT PANICLES 1). The different DEP1 alleles confer different nitrogen responses, and genetic diversity analysis suggests that DEP1 has been subjected to artificial selection during Oryza sativa spp. japonica rice domestication. The plants carrying the dominant dep1-1 allele exhibit nitrogen-insensitive vegetative growth coupled with increased nitrogen uptake and assimilation, resulting in improved harvest index and grain yield at moderate levels of nitrogen fertilization. The DEP1 protein interacts in vivo with both the Gα (RGA1) and Gβ (RGB1) subunits, and reduced RGA1 or enhanced RGB1 activity inhibits nitrogen responses. We conclude that the plant G protein complex regulates nitrogen signaling and modulation of heterotrimeric G protein activity provides a strategy for environmentally sustainable increases in rice grain yield.


The importance of rhamnolipid-biosurfactant-induced changes in bacterial membrane lipids of Bacillus subtilis for the antimicrobial activity of thiosulfonates.
The antimicrobial properties of methyl (MTS) and ethyl (ETS) esters of thiosulfonic acid alone and in combination with rhamnolipid-biosurfactant (RL) have been characterized for their ability to disrupt the normal physiological functions of living pathogens. Bactericidal and fungicidal activities of MTS and ETS and their combination with rhamnolipid were demonstrated on strains of Pseudomonas aeruginosa, Bacillus subtilis, Alcaligenes faecalis, and Rhizopus ngtricans. It was found that the combination of rhamnolipid and thiosulfonic esters has a synergistic effect leading to decreasing of bactericidal and fungicidal concentrations of MTS and ETS. More extensively was studied the effect of rhamnolipid on the lipid composition of B. subtilis bacterial membrane. To our knowledge, in this article is reported for the first time a remarkable increase of negatively charged phospholipid cardiolipin in the presence of rhamnolipid. The capacity of RL as a surface-active substance was confirmed by scanning electron microscopy (SEM). The occurrence of surface infolds and blebs on B. subtilis shown by SEM, was not accompanied by changes in membrane permeability tested by a live/dead viability staining for fluorescence microscopy. When RL was applied in combination with MTS, a dramatic permeability shift for propidium iodide was observed in vegetative cells.


Alcohol consumption among Brazilian Adolescents according to the National Adolescent School-based Health Survey (PeNSE 2012).
To describe the prevalence of alcohol consumption among Brazilian students and identify the sociodemographic factors associated alcohol consumption in the last 30 days. Cross-sectional study with a cluster sample of 109,104 9th grade students in Brazilian public and private schools in 2012. The prevalence and 95% confidence intervals of the indicators of alcohol consumption were analyzed. Of the students analyzed, 50.3% (95%CI 49.0 - 51.6) experimented one dose of alcoholic beverages or more. The consumption of alcohol in the last 30 days was 26.1% (95%CI 24.5 - 27.7), and there was no difference in prevalence between students from public and private schools. Drunkenness episodes were reported by 21.8% (95%CI 21.1 - 22.5) of the students. The perception of students about the negative reaction of their family if they came home drunk occurred in 89,7% (95%CI 89,6 - 89,9) of cases, and 10% (95%CI 8.9 - 11.1) of them reported having problems with their families or friends because they had been drinking. Among adolescents aged less than 14 years old, the first alcoholic drink intake was predominantly at 12 to 13 years old. The most common way to get a drink was at parties, with friends, buying in them in supermarkets, stores or bars and at home. The consumption of alcohol in the last 30 days was less frequent among boys, increasing with age. The study demonstrates the extension of alcohol as a problem, making it important to advance in measures such as the improvement of protective legislation for children and adolescents and stricter enforcement in alcohol sales.


In vitro inhibiton of trophoblast maturation and expansion of early rat blastocysts by an oestrogen antagonist.
Rat blastocyst development and expansion were studied in an in vitro culture system. Early blastocysts collected from rats on the morning of day 5 were shown to develop normally and underwent expansion when placed in bovine serum albumin supplemented culture medium for 12 h at 37 degrees C. Nafoxidine, an oestrogen antagonist, prevented embryo expansion when added to the culture medium, and it was found that if oestradiol-17 beta was added to this medium this inhibitory effect was removed and the embryos again expanded. Ethanol, used as a solvent for steroids, and cholesterol were added to the medium containing nafoxidine but the blastocysts remained unexpanded after 12 h in culture. These results suggest a need for oestrogen action during blastocyst expansion in vitro. Cultured rat blastocysts were subjected to histochemical study for acid phosphatase (ACPase) and leucylnaphthylamidase (LNAse). In unexpanded blastocysts ACPase was found to be low while LNAse activity was higher when compared with enzyme distribution patterns in expanded blastocysts.


The role of mesenchymal stem cells in hair regeneration and hair cycle.
The health of hair is directly related to people's health and appearance. Hair has key physiological functions, including skin protection and temperature regulation. Hair follicle is a vital mini-organ that directly impacts hair growth. Besides, various signaling pathways and molecules regulate the growth cycle transition of hair follicles. Hair and its regeneration studies have attracted much interest in recent years with the increasing rate of alopecia. Mesenchymal stem cells (MSCs), as pluripotent stem cells, can differentiate into fat, bone, and cartilage and stimulate regeneration and immunological regulation. MSCs have been widely employed to treat various clinical diseases, such as bone and cartilage injury, nerve injury, and lung injury. Besides, MSCs can be used for treatment of hair diseases due to their regenerative and immunomodulatory abilities. This review aimed to assess MSCs treatment for alopecia, pertinent signaling pathways, and new material for hair regeneration in the last five years.


[Molecular parameters of the sensitization of tannined erythrocytes with human IgG].
A study was made of the molecular binding parameters during the sensitization of human IgG with tannin-treated sheep erythrocytes, depending on the concentration of the reacting components. The total amount of IgG molecules stably bound by all erythrocytes increased with the elevation of erythrocyte and IgG concentration. About 1.7 million IgG molecules were stably fixed on one erythrocyte under conditions providing the maximum binding. However, the level of hemosensitization approaching the maximum was provided by binding 400,000--600,000 IgG molecules by one erythrocyte. Apparently the level of specific IgG sensitization was determined not only by the amount of protein molecules stably bound by one erythrocyte, but also by the character of space position of the IgG molecules on the erythrocyte surface.


Clozapine augmentation with long-acting antipsychotic injections: A case series and systematic review.
Up to 30% of patients with a diagnosis of treatment-resistant psychosis remain symptomatic despite an optimal trial with the gold standard treatment, clozapine. Emerging evidence suggests the clinical utility of long-acting injections (LAI) in such clinical scenarios. In this study, we aimed to describe clozapine augmentation with LAIs in an inner London hospital and explore the literature on the clinical effectiveness of this treatment modality. Patients prescribed clozapine, who were commenced on a LAI between 2007 and 2023 by the United Kingdom's largest mental health trust, were identified from electronic patient records. First, routine clinical data were used to describe the use, effectiveness, and safety of this augmentation strategy. Second, we conducted a literature search up to 1st June 2023 to identify published studies describing clinical outcomes after clozapine augmentation with a LAI. Clinical outcomes were collated and presented in a table, including hospitalisation rates and quantitative clinical assessments using validated scales. Of the 1248 patients prescribed clozapine in SLaM, three patients (0.2%) received augmentation with the following LAIs: olanzapine embonate, paliperidone palmitate and pipotiazine palmitate. This treatment strategy was clinically effective and generally well tolerated in all three cases. Twelve published studies between 2010 and 2022 were included in the review. Eight distinct LAIs were reported (4 first and 4 second generation antipsychotics), with risperidone and paliperidone most widely studied. All the identified studies were observational including mirror-image studies, case series and case reports. Duration of follow up varied from 3 months to 3 years. There was evidence that the use of LAIs with clozapine can significantly reduce clinical symptoms, hospitalisation rates and bed days. No serious adverse effects were reported. This preliminary evidence suggests clinical utility of LAIs in alleviating residual symptoms and subsequently reducing hospitalisation rates in patients optimised on clozapine treatment. The current study warrants further investigations including a randomised controlled study to establish the clinical efficacy, tolerability, and place in therapy of this treatment modality.


2017 Clinical practice guidelines for dyslipidemia of Korean children and adolescents.
The Committee on Dyslipidemia of Korean Pediatric and Adolescents of the Korean Society of Pediatric Endocrinology has newly developed evidence-based clinical practice guidelines for dyslipidemia in Korean children and adolescents. These guidelines were formulated with the Grading of Recommendations, which include both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. These guidelines are based on the 2011 National Heart, Lung, and Blood Institute Guidelines, which focus on the prevention of cardiovascular disease in children and draw from a comprehensive review of evidence. These guidelines contain the definition of and screening process for dyslipidemia and introduce new dietary methods: the Cardiovascular Health Integrated Lifestyle Diet (CHILD)-1, the CHILD-2-low-density lipoprotein cholesterol, and the CHILD-2-triglyceride. Potential drug therapies for dyslipidemia along with their main effects and doses were also included.


Role of diet on non-alcoholic fatty liver disease: An updated narrative review.
The purpose of this article review is to update what is known about the role of diet on non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common cause of chronic liver disease in the developed world and is considered to be a spectrum, ranging from fatty infiltration of the liver alone (steatosis), which may lead to fatty infiltration with inflammation known as non alcoholic steatohepatitis While the majority of individuals with risk factors like obesity and insulin resistance have steatosis, only few people may develop steatohepatitis. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Weight loss alone by dietary changes has been shown to lead to histological improvement in fatty liver making nutrition therapy to become a cornerstone of treatment for NAFLD. Supplementation of vitamin E, C and omega 3 fatty acids are under consideration with some conflicting data. Moreover, research has been showed that saturated fat, trans-fatty acid, carbohydrate, and simple sugars (fructose and sucrose) may play significant role in the intrahepatic fat accumulation. However, true associations with specific nutrients yet to be clarified.


Advancing geriatric education: development of an interprofessional program for health care faculty.
To improve the health care of older adults, a faculty development program was created to enhance geriatric knowledge. The University of Alabama at Birmingham (UAB) Geriatric Education Center leadership instituted a one-year, 36-hour curriculum focusing on older adults with complex health care needs. Content areas were chosen from the Institute of Medicine Transforming Health Care Quality report and a local needs assessment. Potential preceptors were identified and participant recruitment efforts began by contacting UAB department chairs of health care disciplines. This article describes the development of the program and its implementation over three cohorts of faculty scholars (n = 41) representing 13 disciplines, from nine institutions of higher learning. Formative and summative evaluation showed program success in terms of positive faculty reports of the program, information gained, and expressed intent by each scholar to apply learned content to teaching and/or clinical practice. This article describes the initial framework and strategies guiding the development of a thriving interprofessional geriatric education program.


Preclinical progress and first translational steps for a liposomal chemotherapy protocol against adrenocortical carcinoma.
Systemic therapy of adrenocortical carcinoma (ACC) is limited by heterogeneous tumor response and adverse effects. Recently, we demonstrated anti-tumor activity of LEDP-M (etoposide, liposomal doxorubicin, liposomal cisplatin, mitotane), a liposomal variant of EDP-M (etoposide, doxorubicin, cisplatin, mitotane). To improve the therapeutic efficacy and off-target profiles of the clinical gold standard EDP-M, we investigated liposomal EDP-M regimens in different preclinical settings and in a small number of ACC patients with very advanced disease. Short- and long-term experiments were performed on two ACC models (SW-13 and SJ-ACC3) in vivo We evaluated the anti-tumoral effects and off-target profiles of EDP-M, LEDP-M and a novel regimen L(l)EDP-M including liposomal etoposide. Furthermore, the role of plasma microRNA-210 as a therapeutic biomarker and first clinical data were assessed. Classical and liposomal protocols revealed anti-proliferative efficacy against SW-13 (EDP-M P < 0.01; LEDP-M: P < 0.001; L(l)EDP-M: P < 0.001 vs controls), whereas in SJ-ACC3, only EDP-M (P < 0.05 vs controls) was slightly effective. Long-term experiments in SW-13 demonstrated anti-tumor efficacy for all treatment schemes (EDP-M: P < 0.01, LEDP-M: P < 0.05, L(l)EDP-M P < 0.001 vs controls). The analysis of pre-defined criteria leading to study termination revealed significant differences for control (P < 0.0001) and EDP-M (P = 0.003) compared to L(l)EDP-M treatment. Raising its potential for therapy monitoring, we detected elevated levels of circulating microRNA-210 in SW-13 after LEDP-M treatment (P < 0.05). In contrast, no comparable effects were detectable for SJ-ACC3. However, overall histological evaluation demonstrated improved off-target profiles following liposomal regimens. The first clinical data indicate improved tolerability of liposomal EDP-M, thus confirming our results. In summary, liposomal EDP-M regimens represent promising treatment options to improve clinical treatment of ACC.


Ascorbic Acid interaction with analgesic effect of morphine and tramadol in mice.
Combining different analgesic drugs for improvement of drug efficacy is a recommended strategy intended to achieve the optimal therapeutic effects. The purpose of the present study was to assess the nature of the interaction between ascorbic acid and two analgesic drugs, morphine and tramadol. The analgesic activity was assessed by the acetic acid writhing test in male Naval Medical Research Institute (NMRI) mice. The results were obtained using four to six animals in each group. All the drugs were injected intraperitoneally. The effective doses (ED) that produced 20%, 50%, and 65% antinociception (ED20, ED50 and ED65) were calculated from the dose-response curve of each drug alone as well as co-administration of ascorbic acid and tramadol or morphine. The interaction index was calculated as experimental ED/theoretical ED. For each drug combination, ED50, ED20 and ED65 were determined by linear regression analysis of the dose-response curve, and they were compared to theoretical ED50, ED20 and ED65 using t-test. The antinociceptive effects of all drugs were dose-dependent (ED50was 206.1 mg/kg for ascorbic acid, 8.33 mg/kg for tramadol, and 0.79 mg/kg for morphine). The interaction index demonstrated additive effects at ED50 and ED65 for co-administration of ascorbic acid and tramadol or morphine. However, at ED20, combination of ascorbic acid and tramadol or morphine showed synergic effects. The interaction index values of the combinations demonstrated the potency ratio of ascorbic acid/morphine to be lower than ascorbic acid/tramadol. This study demonstrated the results of interactions between ascorbic acid and tramadol or morphine. The results showed that the interaction effects on antinociception may be synergistic or additive, depending on the level of effect.


Design and update of a classification system: the UCSD map of science.
Global maps of science can be used as a reference system to chart career trajectories, the location of emerging research frontiers, or the expertise profiles of institutes or nations. This paper details data preparation, analysis, and layout performed when designing and subsequently updating the UCSD map of science and classification system. The original classification and map use 7.2 million papers and their references from Elsevier's Scopus (about 15,000 source titles, 2001-2005) and Thomson Reuters' Web of Science (WoS) Science, Social Science, Arts & Humanities Citation Indexes (about 9,000 source titles, 2001-2004)-about 16,000 unique source titles. The updated map and classification adds six years (2005-2010) of WoS data and three years (2006-2008) from Scopus to the existing category structure-increasing the number of source titles to about 25,000. To our knowledge, this is the first time that a widely used map of science was updated. A comparison of the original 5-year and the new 10-year maps and classification system show (i) an increase in the total number of journals that can be mapped by 9,409 journals (social sciences had a 80% increase, humanities a 119% increase, medical (32%) and natural science (74%)), (ii) a simplification of the map by assigning all but five highly interdisciplinary journals to exactly one discipline, (iii) a more even distribution of journals over the 554 subdisciplines and 13 disciplines when calculating the coefficient of variation, and (iv) a better reflection of journal clusters when compared with paper-level citation data. When evaluating the map with a listing of desirable features for maps of science, the updated map is shown to have higher mapping accuracy, easier understandability as fewer journals are multiply classified, and higher usability for the generation of data overlays, among others.


Homostachydrine (pipecolic acid betaine) as authentication marker of roasted blends of Coffea arabica and Coffea canephora (Robusta) beans.
The occurrence of pipecolic acid betaine (homostachydrine) and its biosynthetic precursor N-methylpipecolic acid was detected for the first time in green coffee beans of Robusta and Arabica species. The analyses were conducted by HPLC-ESI tandem mass spectrometry and the metabolites identified by product ion spectra and comparison with authentic standards. N-methylpipecolic acid was found at similar levels in green coffee beans of Robusta and Arabica, whereas a noticeable difference of homostachydrine content was observed between the two green coffee bean species. Interestingly, homostachydrine content was found to be unaffected by coffee bean roasting treatment because of a noticeable heat stability, a feature that makes this compound a candidate marker to determine the content of Robusta and Arabica species in roasted coffee blends. To this end, a number of certified pure Arabica and Robusta green beans were analyzed for their homostachydrine content. Results showed that homostachydrine content was 1.5±0.5mg/kg in Arabica beans and 31.0±10.0mg/kg in Robusta beans. Finally, to further support the suitability of homostachydrine as quality marker of roasted blends of Arabica and Robusta coffee beans, commercial samples of roasted ground coffee blends were analyzed and the correspondence between the derived percentages of Arabica and Robusta beans with those declared on packages by manufacturers was verified.


Generating a Murine Orthotopic Metastatic Breast Cancer Model and Performing Murine Radical Mastectomy.
In vivo mouse models to assess breast cancer progression are essential for cancer research, including preclinical drug developments. However, the majority of the practical and technical details are commonly omitted in published manuscripts which, therefore, makes it challenging to reproduce the models, particularly when it involves surgical techniques. Bioluminescence technology allows for the evaluation of small amounts of cancer cells even when a tumor is not palpable. Utilizing luciferase-expressing cancer cells, we establish a breast cancer orthotopic inoculation technique with a high tumorigenesis rate. Lung metastasis is assessed utilizing an ex vivo technique. We, then, establish a mastectomy model with a low local recurrence rate to assess the metastatic tumor burden. Herein, we describe, in detail, the surgical techniques of orthotopic implantation and mastectomy for breast cancer with a high tumorigenesis rate and low local recurrence rates, respectively, to improve breast cancer model efficiency.


Pharmaceutical care role model in psychiatry--pharmacist prescribing.
Pharmacist's expanded roles in a mental health clinic are described. A needs assessment identified problems which could be solved by expanding the pharmacist's scope of practice. Pharmacy, psychiatry, and medical center administration approved the pharmacist's psychiatric prescribing privileges and the authority to order appropriate laboratory tests, which provides the mechanism of solving the problems identified. Psychiatry's acceptance of pharmacists in this new role is demonstrated by the continued expansion of this program. By the end of a 4-year period, pharmacists were seeing 46% of all psychiatric medication visits. A description of the privileges, roles, and process is provided.


Inhibition of STAT3 reduces proliferation and invasion in salivary gland adenoid cystic carcinoma.
In this study, we accessed the expression and correlation of p-STAT3 with Survivin, Cyclin D1, CD147, Slug and Ki67 by immunohistochemical staining of human tissue microarray which contains 72 adenoid cystic carcinoma (AdCC), 12 pleomorphic adenoma (PMA) and 18 normal salivary gland (NSG) using digital pathological scanner and scoring system. We found that the expression of p-STAT3, Survivin, Slug, Cyclin D1 and CD147 was significantly increased in AdCC as compared with PMA and (or) NSG (p<0.05). While, the level of p-STAT3 and expression of Cyclin D1 and CD147 was not associated with pathological type of human AdCC (p>0.05). Correlation analysis of these proteins revealed that p-STAT3 up-regulates the expression of Survivin, Slug, Cyclin D1 and CD147 (p<0.05). Moreover, the activation of STAT3 was associated with proliferation marker Ki-67 (p<0.05). Selective inhibition of STAT3 by a small molecule S3I-201 significantly reduced human SACC-83 and SACC-LM cells proliferation, migration and invasion with the corresponding decrease in expression of Survivin, Slug, Cyclin D1 and CD147. These findings indicate that high phosphorylation level of STAT3 in AdCC is related to Survivin, Slug, Cyclin D1 and CD147. We suggest that the inhibition of STAT3 may be a novel strategy for neoadjuvant chemotherapeutic treatment of AdCC.


Surveillance and Sequestration Strategies to Reduce the Likelihood of Transporting Highly Pathogenic Avian Influenza Virus Contaminated Layer Manure.
Movement and land application of manure is a known risk factor for secondary spread of avian influenza viruses. During an outbreak of highly pathogenic avian influenza (HPAI), movement of untreated (i.e., fresh) manure from premises known to be infected is prohibited. However, moving manure from apparently healthy (i.e., clinically normal) flocks may be critical, because some egg-layer facilities have limited on-site storage capacity. The objective of this analysis was to evaluate targeted dead-bird active surveillance real-time reverse transcriptase polymerase chain reaction (rRT-PCR) testing protocols that could be used for the managed movement of manure from apparently healthy egg-layer flocks located in an HPAI control area. We also evaluated sequestration, which is the removal of manure from any contact with chickens, or with manure from other flocks, for a period of time, while the flock of origin is actively monitored for the presence of HPAI virus. We used stochastic simulation models to predict the chances of moving a load of contaminated manure, and the quantity of HPAI virus in an 8 metric ton (8000 kg) load of manure moved, before HPAI infection could be detected in the flock. We show that the likelihood of moving contaminated manure decreases as the length of the sequestration period increases from 3 to 10 days (e.g., for a typical contact rate, with a sample pool size of 11 swabs, the likelihood decreased from 48% to <1%). The total quantity of feces from HPAI-infectious birds in a manure load moved also decreases. Results also indicate that active surveillance protocols using 11 swabs per pool result in a lower likelihood of moving contaminated manure relative to protocols using five swabs per pool. Simulation model results from this study are useful to inform further risk evaluation of HPAI spread through pathways associated with manure movement and further evaluation of biosecurity measures intended to reduce those risks.


SLMP53-1 interacts with wild-type and mutant p53 DNA-binding domain and reactivates multiple hotspot mutations.
Half of human cancers harbour TP53 mutations that render p53 inactive as a tumor suppressor. As such, reactivation of mutant (mut)p53 through restoration of wild-type (wt)-like function represents one of the most promising therapeutic strategies in cancer treatment. Recently, we have reported the (S)-tryptophanol-derived oxazoloisoindolinone SLMP53-1 as a new reactivator of wt and mutp53 R280K with in vitro and in vivo p53-dependent antitumor activity. The present work aimed a mechanistic elucidation of mutp53 reactivation by SLMP53-1. By cellular thermal shift assay (CETSA), it is shown that SLMP53-1 induces wt and mutp53 R280K thermal stabilization, which is indicative of intermolecular interactions with these proteins. Accordingly, in silico studies of wt and mutp53 R280K DNA-binding domain with SLMP53-1 unveiled that the compound binds at the interface of the p53 homodimer with the DNA minor groove. Additionally, using yeast and p53-null tumor cells ectopically expressing distinct highly prevalent mutp53, the ability of SLMP53-1 to reactivate multiple mutp53 is evidenced. SLMP53-1 is a p53-activating agent with the ability to directly target wt and a set of hotspot mutp53. This work reinforces the encouraging application of SLMP53-1 in the personalized treatment of cancer patients harboring distinct p53 status.


Design and mechanism of core-shell TiO2 nanoparticles as a high-performance photothermal agent.
Photothermal agents (PTAs) with high biocompatibility and therapeutic efficacy have become particularly fascinating, however, knowledge of their photothermal performance is rather limited. Herein, rationally designed core-shell TiO2 nanoparticles have been fabricated using a mild hydrogenation method, where NaBH4 was used as the H2 source. The resultant TiO2 possesses strong optical absorption in the NIR region and remarkable photothermal conversion capability and stability, leading to a high inhibition rate on cancer cells. In particular, its photothermal conversion efficiency is as high as 55.2%, which is 204% that of the fully hydrogenated amorphous TiO2. More importantly, the underlying mechanism is proposed. It is revealed that while the oxygen vacancies induced by the hydrogenation can introduce defect levels in the band gap and enhance the optical absorption, the superfluous oxygen vacancies and defects reduce the photothermal conversion capability and thermal conductivity to a large extent. Controlling the hydrogenation degree and maintaining a certain extent of crystallization are, therefore, crucial to the photothermal properties. This new understanding of the photothermal conversion mechanism may have provided a fresh route to design and optimize PTAs and inspire considerable interest to turn a large variety of semiconductor metal oxides into competent PTAs by appropriate hydrogenation.


Chemopreventive effects of oral gallic acid feeding on tumor growth and progression in TRAMP mice.
Our recent studies have identified gallic acid as one of the major constituents of grape seed extract showing strong in vitro anticancer efficacy against human prostate cancer cells. Herein, for the first time, we established the in vivo chemopreventive efficacy of gallic acid against prostate cancer by evaluating its activity against prostate tumor growth and progression in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. At 4 weeks of age, male TRAMP mice were fed with drinking water supplemented with 0.3% and 1% (w/v) gallic acid until 24 weeks of age. Positive control group was fed with regular drinking water for the same period. Our results showed that gallic acid-fed groups had a higher incidence of differentiated lower-grade prostatic tumors at the expense of strong decrease ( approximately 60%; P < 0.01) in poorly differentiated tumors. Immunohistochemical analysis of prostate tissue showed a decrease in proliferative index by 36% to 41% (P < 0.05) in 0.3% to 1% gallic acid-fed groups, with an increase in the apoptotic cells by 3-fold (P < 0.05). Further, both doses of gallic acid completely diminished the expression of Cdc2 in the prostatic tissue together with strong decrease in the expression of Cdk2, Cdk4, and Cdk6. The protein levels of cyclin B1 and E were also decreased by gallic acid feeding. Together, for the first time, we identified that oral gallic acid feeding inhibits prostate cancer growth and progression to advanced-stage adenocarcinoma in TRAMP mice via a strong suppression of cell cycle progression and cell proliferation and an increase in apoptosis.


Preparation and characterization of gelatin hydrogel support for immobilization of Candida rugosa lipase.
A series of gelatin hydrogels were prepared by crosslinking method using glutaraldehyde (GA). The hydrogels were characterized by gel formation, swelling/degradation tests, and FTIR analysis. The variations of swelling percentages (S%) with time, temperature, and pH were determined. It is found that the increasing amount of GA causes the decreasing in S% values from 366 to 213% and G-1 was found to be the most swollen hydrogel at pH 7.4 and 37 °C. Degradation tests of hydrogel samples were carried out and G-1 hydrogel, which contained the least amount of GA, degraded more rapidly than the others. G-2 hydrogel was chosen for immobilization studies and this procedure was carried out by activation of the hydrogel disc with N-(3-dimethylaminopropyl)-N-ethylcarbodiimid (CDI) coupling agent. The kinetic parameters, K(m) and V(max), were calculated. K(m) values of free and immobilized lipases were found to be 0.290, 0.422 mM while V(max) values were calculated as 0.089, 0.080 mM.min(-1), respectively. For the free and immobilized system, the enzymes retained 32% and 92% of their initial activities, respectively, at the end of 48 days of storage. After using the mentioned immobilized system repeatedly 10 times, it retained 68% of its original activities.


Atrophy of gluteus maximus among women with a history of chronic low back pain.
Although the relationship between low back pain (LBP) and the size of certain trunk muscles has been extensively studied, the relationship between gluteus maximus (GM) size and LBP has been only minimally examined. Determining whether such a relationship exists would help improve our understanding of the etiology of LBP, and possibly provide a rationale for the use of therapeutic exercise interventions targeting GM with LBP patients. The objective of this study was to compare gluteus maximus cross-sectional area in individuals with chronic LBP, and in a group of individuals without LBP. Our hypothesis was that individuals with LBP would have greater atrophy in their gluteus maximus muscles than our control group. For this case-control study, we analyzed medical history and pelvic computed tomography (CT) scans for 36 female patients with a history of chronic LBP, and 32 female patients without a history of LBP. Muscle cross-sectional area of gluteus maximus was measured from axial CT scans using OsiriX MD software, then was normalized to patient height, and used to compare the two groups. The number of back pain-related medical visits was also correlated with gluteus maximus cross-sectional area. Mean normalized cross-sectional area was significantly smaller in the LBP group than in the control group, with t = 2.439 and P<0.05. The number of back pain-related visits was found to be significantly correlated with normalized cross-sectional area, with r = -0.270 and P<0.05. The atrophy seen in the present research may reflect incidental disuse atrophy seen with LBP, which is present in many muscle groups after prolonged immobilization or with a sedentary lifestyle. This research demonstrated a previously only minimally explored relationship between gluteus maximus cross-sectional area and LBP in women. Further research is indicated in individuals with varying age, sex, and LBP diagnoses.


Evidence-based critical care medicine: a potential tool for change.
This issue of New Horizons is about change. While our traditional apprenticeship model of physician training has served us well, adaptation is required for the new millennium. Among several sectoral trends in medicine, two are particularly relevant for intensivists: a) the information explosion and b) increased accountability to society regarding effective, efficient, compassionate, and culturally sensitive care. Evidence-based medicine (EBM) (or any other single initiative, for that matter) is not going to address all of tomorrow's challenges. However, EBM does help by enhancing clinical informatics and critical appraisal skills so that clinicians are better able to keep up with the growing literature, and decide whether, and if so, this literature applies to individual patients. In addition, EBM can help to highlight the determinants of clinical decisions, which may include contributions of caregiver knowledge, patient pathophysiology, research evidence, patient and societal values, and increasingly, costs. While EBM is best practiced at the individual level, its application to other aspects of health care is growing.


Invasively measured and estimated central blood pressure using the oscillometric algorithm Antares in patients with and without obesity.
Obesity is a global health concern and risk factor for cardiovascular disease. The assessment of central blood pressure (cBP) has been shown to improve prediction of cardiovascular events. However, few studies have investigated the impact of obesity on cBP in adults, and invasive data on this issue are lacking. This study aimed to evaluate cBP differences between patients with and without obesity, identify cBP determinants, and evaluate the accuracy of the algorithm Antares for non-invasive cBP estimation. A total of 190 patients (25% female; 39% with BMI ≥30kg/m2; age: 67±12 years) undergoing elective cardiac catheterization were included. cBP was measured invasively and simultaneously estimated non-invasively using the custo screen 400 device with integrated Antares algorithm. No significant cBP differences were found between obese and non-obese patients. However, females, especially those with obesity, had higher systolic cBP compared to males (P<0.05). Multiple regression analysis showed that brachial mean arterial pressure, pulse pressure, BMI, and heart rate predicted cBP significantly (adjusted R2 = 0.82, P<0.001). Estimated cBP correlated strongly with invasive cBP for systolic, mean arterial, and diastolic cBP (r = 0.74-0.93, P<0.001) and demonstrated excellent accuracy (mean difference <5 and SD <8 mmHg). This study discovered no significant difference in cBP between obese and non-obese patients. However, it revealed higher cBP values in women, especially those with obesity, which requires further investigation. Additionally, the study highlights Antares' effectiveness in non-invasively determining cBP in obese individuals. This could improve the diagnosis and treatment of hypertension in this special patient population.


Ultra-low shrinkage hybrid photosensitive material for two-photon polymerization microfabrication.
Investigations into the structuring by two-photon polymerization of a nonshrinking, photosensitive, zirconium sol-gel material are presented. This hybrid material can be photostructured even when it contains up to 30 mol % of zirconium propoxide (ZPO); by varying the material's inorganic content, it is possible to modify and tune its refractive index. The introduction of ZPO significantly increases the photosensitivity of the resulting photopolymer. The fabricated three-dimensional photonic crystal structures demonstrate high resolution and a clear band-stop in the near-IR region. In contrast to common practice, no additional effort is required to precompensate for shrinkage or to improve the structural stability of the fabricated photonic crystals; this, combined with the possibility of tuning this material's optical, mechanical, and chemical properties, makes it suitable for a variety of applications by two-photon polymerization manufacturing.


Structural changes in brain morphology induced by brief periods of repetitive sensory stimulation.
There is a growing interest in identifying the neural mechanisms by which the human brain allows for improving performance. Tactile perceptual measurements, e.g. two-point discrimination (2ptD), can be used to investigate neural mechanisms of perception as well as perceptual improvement. Improvement can be induced in a practice-independent manner, e.g. in the tactile domain through repetitive somatosensory stimulation (rSS). With respect to tactile perception, the role of cortical excitability and activation within the somatosensory cortex has been investigated extensively. However, the role of structural properties, such as regional gray matter (GM) volume, is unknown. Using high resolution imaging and voxel-based morphometry (VBM), we sought to investigate how regional GM volume relates to individual 2ptD performance. Furthermore, we wanted to determine if electrical rSS has an influence on regional GM volume. 2ptD thresholds of the index fingers were assessed bilaterally. High-resolution (1 mm3), T1-weighted images were obtained using a 3T scanner pre-and post-stimulation. RSS was applied for 45 min to the dominant right hand, specifically to the fingertips of all fingers. At baseline, performance in the 2ptD task was associated with regional GM volume in the thalamus, primary somatosensory cortex, and primary visual cortex (negative association). After 45 min of rSS, we observed an improvement in 2ptD of the stimulated hand, whereas no improvement in tactile performance was seen on the non-stimulated side. These perceptual changes were accompanied by an increase in GM volume in the left somatosensory cortex and the degree of improvement correlated with GM volume changes in the insular cortex. Our results show that structural changes in the brain, specifically in regions receiving afferent input from the stimulated body site can be induced via a short-term intervention lasting only 45 min. However, the neurobiological correlates of these changes and the dynamics need to be further elucidated.


Effects of Dual-Release Hydrocortisone on Bone Metabolism in Primary and Secondary Adrenal Insufficiency: A 6-Year Study.
Patients with primary (PAI) and secondary adrenal insufficiency (SAI) experience bone metabolism alterations, possibly due to excessive replacement. Dual-release hydrocortisone (DR-HC) has shown promising effects on several parameters, but bone metabolism has seldom been investigated. We evaluated the long-term effects of once-daily DR-HC on bone in PAI and SAI. Patients on immediate-release glucocorticoid therapy were evaluated before and up to 6 years (range, 4-6) after switching to equivalent doses of DR-HC, yielding data on bone turnover markers, femoral and lumbar spine bone mineral density (BMD), and trabecular bone score (TBS). Thirty-two patients (19 PAI, 18 female), median age 52 years (39.4-60.7), were included. At baseline, osteopenia was observed in 38% of patients and osteoporosis in 9%, while TBS was at least partially degraded in 41.4%. Higher body surface area-adjusted glucocorticoid doses predicted worse neck (P < .001) and total hip BMD (P < .001). Longitudinal analysis showed no significant change in BMD. TBS showed a trend toward decrease (P = .090). Bone markers were stable, albeit osteocalcin levels significantly varied. PAI and SAI subgroups behaved similarly, as did patients switching from hydrocortisone or cortisone acetate. Compared with men, women exhibited worse decline in TBS (P = .017) and a similar trend for neck BMD (P = .053). After 6 years of chronic DR-HC replacement, BMD and bone markers remained stable. TBS decline is more likely due to an age-related derangement of bone microarchitecture rather than a glucocorticoid effect. Our data confirm the safety of DR-HC replacement on bone health in both PAI and SAI patients.


How can we optimise the pharmaceutical analysis of radiopharmaceutical pediatric prescriptions?
In France, dispensation is defined by the validation of a prescription associated with a pharmaceutical analysis, preparation of medication and provision of information necessary for proper use. There are very few data available in the literature that describe prescription analysis modality in radiopharmacy. The aim was to secure a place for paediatric prescription analysis in radiopharmacy by designing a flow chart validated by experts. Experts from different disciplines and health setups (ie, public, private) were selected to represent the various paediatric patient care processes. A review of the literature on pharmaceutical analysis and paediatric prescription in radiopharmacy was conducted. A Delphi approach comprising two rounds (Google Form survey) was used to validate the flow chart. Answers were graded according to a nine-point Likert scale for agreement. Open-ended questions allowed experts to comment on the propositions. A consensus between experts was reached if more than 70% of the experts agreed on an item and fewer than 30% disagreed. Sixty-five experts were solicited: two oncopaediatricians, three nuclear medicine physicians, 46 radiopharmacists, three residents in radiopharmacy, one hospital pharmacist, five medical physicists, one pharmacy technician, two X-ray technicians and two patients who are pharmacists. The first round survey included a draft of the flow chart: 31 experts answered (48%). All professional disciplines were represented except pharmacy technician. The second round survey was sent with a new flow chart that had been improved by the experts' comments. After 3 weeks, 18 answers were obtained (28%). After the first round, consensus was obtained for each item. Experts gave a total of 97 comments. The second flow chart had three steps: regulatory aspects, patient data, and radiopharmaceutical data, and it was accompanied by descriptive text explaining the field of application. The resulting flow chart will secure the pharmaceutical analysis step for this special patient population.