Underutilization of Drug-Eluting Stents in Infrapopliteal Intervention for Chronic Limb-Threatening Ischemia.
Multiple randomized clinical trials have shown superiority of drug-eluting stents (DES) over bare-metal stents (BMS) for infrapopliteal disease. However, real-world data on DES utilization and outcomes in infrapopliteal chronic limb-threatening ischemia (CLTI) patients are unknown. We utilized the Nationwide Readmission Database (NRD) from 2016 to 2017 to extract patients undergoing infrapopliteal intervention with stents (BMS and DES) for CLTI using appropriate ICD-10 codes. Multilevel logistic regression with hospital ID as random effect was used to assess DES utilization. Primary outcome was the composite of target limb major amputation (TLmajA) and target limb revascularization (TLR). Multivariate Cox-proportional hazard regression was used to adjust for confounders. Our study included a total of 1817 patients. Of these patients, 1056 patients (58.1%) received DES; DES utilization was stable (relative change: +2.5%, p-trend: 0.867) between 2016 and 2017 and was higher in teaching hospitals (adjusted odds ratio [aOR] = 1.28, 95% CI = 1.03-1.61, p=0.029] and medium (aOR = 3.13, 95% CI = 2.17-4.55, p≤0.001) and large (aOR = 1.56, 95% CI = 1.14-2.17, p=0.005) bed-sized hospitals. Inter-class correlation was 0.44 suggesting ~44% variation in DES utilization between any 2 random hospitals; DES was associated with lower rate of the primary composite outcome (aHR = 0.75, 95% CI = 0.62-0.92, p=0.004) compared with BMS. In patients undergoing infrapopliteal intervention for CLTI, DES demonstrated significant underutilization despite supportive evidence of their superiority compared with BMS; DES was associated with improvement in the primary composite outcome compared with BMS.


Physiological responses of elite junior Australian rules footballers during match-play.
Australian Football (AF) is Australia's major football code. Despite research in other football codes, to date, no data has been published on the physiological responses of AF players during match play. Fifteen athletes (17.28 ± 0.76 yrs) participated in four pre-season matches, sanctioned by Australian Football League (AFL) Victoria, investigating Heart Rate (HR), Blood Lactate (BLa), Core Temperature (Tcore), and Hydration status. Match HR was measured continuously using HR monitors. BLa was measured via finger prick lancet at the end of each quarter of play. Tcore was measured by use of ingestible temperature sensor and measured wirelessly at the end of each quarter of play. Hydration status was measured using refractometry, measuring urine specific gravity, and body weight pre and post-match. Environmental conditions were measured continuously during matches. Results of HR responses showed a high exertion of players in the 85-95% maximum HR range. Elevated mean BLa levels, compared to rest, were observed in all players over the duration of the matches (p = 0.007). Mean Tcore rose 0.68 °C between start and end of matches. Mean USG increased between 0.008 g/ml (p = 0.001) with mean body weight decreasing 1.88 kg (p = 0.001). This study illustrates physiological responses in junior AF players playing in the heat as well as providing physiological data for consideration by AF coaching staff when developing specific training programs. Continued research should consider physiological measurements under varying environments, and at all playing levels of AF, to ascertain full physiological responses during AF matches. Key pointsSpecific conditioning sessions for junior athletes should include high intensity bouts; greater than 85% of heart rate maximum zone.Football anaerobic conditioning activities (e.g. sprint training) should be randomised throughout training sessions to replicate demands of the game (e.g. training in a fatigued state).Coaches and fitness staff should provide education and player management strategies for fluid replacement at key opportunities (pre-match, formal breaks and substation on and off the field) during matches.


Modeling of cw-EPR spectra of propagating radicals in methacrylic polymerization at different temperatures.
The temperature dependence of the cw-EPR spectra corresponding to the propagating radical responsible for the polymerization of methacrylic monomers has been simulated by an integrated computational approach that determines the structural and magnetic parameters (via quantum mechanical calculations) and diffusive properties (via hydrodynamic based methods), which represent the overall input of the stochastic Liouville equation that yields the spectrum. The system has been modeled as a rotator with only one relaxation process, the rotation around the C alpha-C beta bond. The simulations clearly indicate that the change of the spectral shape with the temperature is essentially related to the internal flexibility of the radical end.


Effect of Egg Albumen, Vegetable Oil, Corn Bran, and Cooking Methods on Quality Characteristics of Chicken Nuggets Using Response Surface Methodology.
Response surface methodology was used to study the effect of egg albumen (5-15 g), vegetable oil (5-15 g), and corn bran (5-15 g) on sensory and textural (firmness and toughness) quality of chicken nuggets cooked by the oven, steam, and microwave methods. The egg albumen and vegetable oil had a positive linear effect but corn bran had a negative linear effect at p<0.01 on sensory overall acceptability scores of nuggets. Firmness and toughness scores were increased significantly (p<0.01) with the increase in corn bran level in the formulation. The optimum level of egg albumen, vegetable oil, and corn bran were obtained and validated. Cooking methods also affected the sensory and textural quality of nuggets. Steam cooked nuggets had higher values of sensory scores than oven and microwave cooked nuggets. Oven cooked nuggets showed higher values of firmness and toughness than steam and microwave cooked nuggets. Results of this study suggest that emulsion based meat products can be enriched with dietary fiber source like corn bran without compromising the sensory and textural quality of the products.


Self-management by older people living with cancer and multi-morbidity: a qualitative study.
Over half of individuals diagnosed with cancer are aged over 70 years, and more than 75% of those with cancer report at least one other medical condition. Having multiple conditions alongside cancer in old age may lower functional status, greater likelihood of treatment complications and less favourable prognoses. This qualitative study explored how older people with long-term chronic conditions manage their health and meet their health-related goals after they have completed treatment for cancer. One-to-one face-to-face qualitative interviews were conducted with 8 older people and 2 informal caregivers based in the UK. Older adults were eligible to participate if they were over 70 and had completed primary cancer treatment with curative intent and had at least one other chronic health condition. A semi-structured interview schedule developed a priori based on Shippee's cumulative complexity model was used. We aimed to explore experiences that could influence self-management, utilisation of healthcare services and health outcomes. A framework analysis was used to describe and interpret the data. Four overarching themes were identified in the analysis. These themes related to factors that influenced the everyday health-related workload and capacity of the participants. These factors included their health, resources, and opportunities, as well their motivation and sense of perceived control over their lives. Fragmented healthcare systems and relationships with healthcare professionals also influenced the participants' self-management of their health. Our findings highlight the interaction between an individuals' needs, capacity, treatment burden, and the services and resources available to them. These findings support calls to promote person-centred care to better support older adults to manage their health.


Prevalence of overweight in Bolivia: data on women and adolescents.
Secondary analysis of Bolivian Demographic and Health Surveys 1994, 1998 and 2003 revealed a steady raising trend in levels of overweight and obesity among women in childbearing age (20-45 years), reaching 30% and 15% respectively in 2003. Adolescents' cross-sectional data suggest that overweight and obesity are mainly found in urban areas. Applying the Bolivian body mass index-for-age reference, obesity reached 5% in adolescents, while overweight affects 14% of adolescents. This overview highlights the importance of including the prevention of weight gain among the public health nutrition policies in Bolivia.


Limitations in the spectral method for graph partitioning: Detectability threshold and localization of eigenvectors.
Investigating the performance of different methods is a fundamental problem in graph partitioning. In this paper, we estimate the so-called detectability threshold for the spectral method with both un-normalized and normalized Laplacians in sparse graphs. The detectability threshold is the critical point at which the result of the spectral method is completely uncorrelated to the planted partition. We also analyze whether the localization of eigenvectors affects the partitioning performance in the detectable region. We use the replica method, which is often used in the field of spin-glass theory, and focus on the case of bisection. We show that the gap between the estimated threshold for the spectral method and the threshold obtained from Bayesian inference is considerable in sparse graphs, even without eigenvector localization. This gap closes in a dense limit.


[Correlation between anti-tumor effects and serum hepatocyte growth factor level in patients with liver metastases from gastric cancer treated by induced hypertensive chemotherapy with angiotensin II].
To clarify the clinical significance of serum hepatocyte growth factor (HGF), the possible correlation between anti-tumor effect and serum HGF level was examined in six patients with liver metastases from gastric cancer. These patients were treated by induced hypertensive chemotherapy with angiotensin II (IHC). We measured the serum concentration of HGF and compared them with the anti-tumor effect and conventional tumor makers (CEA, CA 19-9). The cut-off level of serum HGF was prescribed at 0.4 ng/ml from healthy volunteer's samples. As the result, anti-tumor effects were one case of CR, two of PR, one of NC and two of PD. Serum HGF levels before IHC were positive in all cases (0.44 to 1.35 ng/ml), whereas the levels were not related to the extent of liver metastases. With regard to the anti-tumor effect, the serum HGF level after IHC was more sensitively reflected compared with conventional tumor markers. In conclusion, it is considered that the serum HGF level might be a useful indicator for the treatment effect in gastric cancer.


Treatment and Survival of Patients with Colon Cancer Aged 80 Years and Older: A EURECCA International Comparison.
Colon cancer in older patients represents a major public health issue. As older patients are hardly included in clinical trials, the optimal treatment of these patients remains unclear. The present international EURECCA comparison explores possible associations between treatment and survival outcomes in elderly colon cancer patients. National data from Belgium, Denmark, The Netherlands, Norway, and Sweden were obtained, as well as a multicenter surgery cohort from Germany. Patients aged 80 years and older, diagnosed with colon cancer between 2001 and 2010, were included. The study interval was divided into two periods: 2001-2006 and 2007-2010. The proportion of surgical treatment and chemotherapy within a country and its relation to relative survival were calculated for each time frame. Overall, 50,761 patients were included. At least 94% of patients with stage II and III colon cancer underwent surgical removal of the tumor. For stage II-IV, the proportion of chemotherapy after surgery was highest in Belgium and lowest in The Netherlands and Norway. For stage III, it varied from 24.8% in Belgium and 3.9% in Norway. For stage III, a better adjusted relative survival between 2007 and 2010 was observed in Sweden (adjusted relative excess risk [RER] 0.64, 95% confidence interval [CI]: 0.54-0.76) and Norway (adjusted RER 0.81, 95% CI: 0.69-0.96) compared with Belgium. There is substantial variation in the rate of treatment and survival between countries for patients with colon cancer aged 80 years or older. Despite higher prescription of adjuvant chemotherapy, poorer survival outcomes were observed in Belgium. No clear linear pattern between the proportion of chemotherapy and better adjusted relative survival was observed. With the increasing growth of the older population, clinicians will be treating an increasing number of older patients diagnosed with colon cancer. No clear linear pattern between adjuvant chemotherapy and better adjusted relative survival was observed. Future studies should also include data on surgical quality.


[Stomal recurrence after total laryngectomy].
Stomal recurrence after total laryngectomy is a very serious complication, in general with dismal prognosis. There are only a few possibilities of treatment, so stress should be put on prevention. In the ENT Department Poznań University of Medical Sciences between 1997-2004 829 total laryngectomy were performed, because of advanced laryngeal cancer (T3, T4). In this group until may 2005 37 cases of stomal recurrence were found. The aim of this study was to analyse the group of patients stomal recurrence. Stomal reccurence developed in 35 men and 2 women. The age of patients was 43-79 years (mean 59 years). The time of lasting the symptoms before laryngectomy was 6-12 months (mean 8 months). The emergency tracheotomy was performed in 16 patients (43%). The time between tracheotomy and laryngectomy was 2 days to 3 weeks (mean 6 days). The subglottic extension was observed in 24 patients (65%). 19 patients (51%) was classified as T3, 18 (49%) as T4. 12 patients (32%) was classified as N0, 5 (14%) as N1, 16 (43%) as N2 and 4 (11%) as N3. 4 patients were earlier treated because of larynx cancer (2 of them has laser chordectomy and 2 fronto-lateral laryngectomy). The time between laryngectomy and radiotehrapy was 4-15 weeks (mean 7 weeks). 22 patients (59%) were classified (due Sisson at al) as type I, 12 (32%) type II, 2 (6%) type III and 1 (3%) type IV. The treatment of stomal recurrences consisted of surgical resection of tumor, chemiotherapy, radiotherapy, brachytherapy or palliative treatment. 34 patients died, 2 are presently treated and 1 is near 5 years free of disease after surgical treatment. Patients with stomal recurrences begun primary treatment in locally and regionally advanced disease. In more that 60% of patients subglottic extension was observed. Emergency tracheotomy may predispose to stomal recurrence. Limited possibilities of treatment of stomal recurrences are the reason of very poor prognosis in this group of patients. During total laryngectomy paratracheal lymphatic nodes should be looked for and dissect.


[Research and Application of Quality Inspection Information System in Medical Device Manufacturers].
To improve the production and inspection efficiency of medical device manufacturers, improve the quality system management level of manufacturers, and ensure the safety and effectiveness of medical devices. Sort out the business process of the medical device manufacturer, connect the database of production and ERP system to inspection system, and build the operation software for the quality control department. The system has covered all the products of the manufacturer, and has realized the informatization and visualization of the inspection process. The research and application of the system can improve the quality management traceability system of medical device manufacturers, and improve the efficiency and accuracy of medical device quality inspection.


Myeloid cells are tunable by a polyanionic polysaccharide derivative and co-determine host rescue from lethal virus infection.
Insight into molecular and cellular mechanisms of innate immunity is critical to understand viral pathogenesis and immunopathology and might be exploited for therapy. Whereas the molecular mechanisms of the IFN defense are well established, cellular mechanisms of antiviral immunity are only emerging, and their pharmacological triggering remains unknown. COAM is a polysaccharide derivative with antiviral activity but without comprehension about its mechanism of action. The COAM mixture was fractionated, and prophylactic treatment of mice with COAM polymers of high MW resulted in a conversion from 100% lethal mengovirus infection to an overall survival rate of 93% without obvious clinical sequelae. Differential and quantitative analysis of peritoneal leukocytes demonstrated that COAM induced a profound influx of neutrophils. Selective cell depletion experiments pointed toward neutrophils and macrophages as key effector cells in the rescue of mice from lethal mengovirus. COAM was able to induce mRNA and protein expression of the mouse neutrophil chemokine GCP-2. Binding of GCP-2 to COAM was demonstrated in solution and confirmed by SPR technology. Although COAM was not chemotactic for neutrophils, COAM-anchored muGCP-2 retained chemotactic activity for human and mouse neutrophils. In conclusion, this study established that COAM rescued mice from acute and lethal mengovirus infection by recruiting antiviral leukocytes to the site of infection, as proposed through the induction, binding, and concentration of endogenous chemokines. These findings reinforce the role of neutrophils and macrophages as critical cells that can be manipulated toward antiviral defense.


Variation of tumor markers in 277 breast cancer cases.
Breast cancer is the most frequently diagnosed cancer in women in the world, Advances in paraclinical methods have resulted in dramatic changes in determining the survival of patients. Serial evaluation of serum levels of tumor markers is one of these methods. During 1993-2002, 277 cases with breast cancer after mastectomy were included in this cross sectional study. Data were extracted from the patients records. Characteristics of the patients associated with serum levels of tumor markers like CEA,CA15-3 and receptor markers like ER,PR with P53,Cathepsin-D and HER-2 were evaluated. The most common involved age was in the 4th decade, accounting for 43.3%of the total. Most of the cases (54.3%) had stage II disease; Ductal carcinoma with frequency of 83.3% was the most common pathology involved and bone metastasis with 59% was prominent. There were elevated serum levels of CEA and CA15-3 in 50.6% and 41.7%, respectively. There was no statistical relation between serum levels of these markers with disease stage (CEA: pearson chi-square = 0.133 CAl5-3: Pearson chi-square = 0.064). There was a great increase in serum level of tumor markers during relapse (CEA P = 0.000 CA15-3 P = 0.000). Because diagnosis of breast cancer is generally at advanced stage in our country, serum levels of tumor markers demonstrate great differences from those published for the Western world. It seems, however, that serum levels of tumor markers might be reliable for predicting relapses.


Lesion topography in capsulotomy for refractory anxiety--is the right side the right side?
A previous report on bilateral capsulotomy in obsessive-compulsive disorder showed common topographic features of lesions in the right-sided internal capsule in all patients responding to the treatment. The aims of the present study were to test if the same region was involved in anxiety patients responding to surgery and to examine whether lesion area and site correlated with adverse events and effect on target symptoms. Eleven anxiety patients who had undergone bilateral thermocapsulotomy were examined after 8-23 years. A quantitative MRI evaluation of the lesions within the internal capsule was conducted in three axial planes. None of the eight responders had lesions that corresponded to the earlier reported right-sided anatomical denominator. Four patients out of 11 were rated as having significant clinical symptoms indicating frontal lobe dysfunction. The total sum of the lesion area determined in each of the three anatomical levels did not correlate with the degree of anxiety reduction. However, the lesion area appeared to be related to a rating of executive dysfunctioning, apathy and disinhibition.


Withaferin-A Inhibits Growth of Drug-Resistant Breast Carcinoma by Inducing Apoptosis and Autophagy, Endogenous Reactive Oxygen Species (ROS) Production, and Inhibition of Cell Migration and Nuclear Factor kappa B (Nf-κB)/Mammalian Target of Rapamycin (m-TOR) Signalling Pathway.
BACKGROUND The main purpose of this study was to assess in vitro and in vivo the anticancer effect of withaferin-A in human breast carcinoma cells (MDA-MB-231), and to assess its effects on autophagy, cell apoptosis, ROS production, cell migration and invasion, and Nf-kappaB/m-TOR signalling pathway. MATERIAL AND METHODS Proliferation of MDA-MB-231 cells at various doses of the drug was studied by CCK8 cell viability assay. Effects on cell apoptosis were studied by fluorescence microscopy in combination with flow cytometry and Western blot analysis. Effects on autophagy were evaluated by transmission electron microscopy and Western blot. Effects on cellular migration were examined in vitro by wound healing assay. RESULTS The results indicated that withaferin-A led to significant reduction of MDA-MB-231 cell viability. The anticancer action of withaferin-A was shown to be due to the stimulation of autophagy, which was accompanied by enhancement of LC3 expression. Withaferin-A prompted mitochondrial apoptosis, which was also associated with increased level of Bax and decreased Bcl-2 in MDA-MB-231 cells. It was also observed that withaferin-A has decreases cellular migration and invasion of the tested human breast cancer cells. The effects of withaferin-A were also investigated in vivo, and it was found that this molecule could inhibit the growth of tumor xenografts in tested mice. Withaferin-A led to suppression of the Nf-kappaB/m-TOR signalling pathway. CONCLUSIONS In brief, the withaferin-A molecule has great potential as an anticancer agent against drug-resistant breast cancer, and as such needs to be further studied in detail.


Impact of the COVID-19 pandemic on disease stage and treatment for patients with pancreatic adenocarcinoma: A French comprehensive multicentre ambispective observational cohort study (CAPANCOVID).
The COVID-19 pandemic caused major oncology care pathway disruption. The CAPANCOVID study aimed to evaluate the impact on pancreatic adenocarcinoma (PA) - from diagnosis to treatment - of the reorganisation of the health care system during the first lockdown. This multicentre ambispective observational study included 833 patients diagnosed with PA between September 1, 2019 and October 31, 2020 from 13 French centres. Data were compared over three periods defined as before the outbreak of COVID-19, during the first lockdown (March 1 to May 11, 2020) and after lockdown. During the lockdown, mean weekly number of new cases decreased compared with that of pre-pandemic levels (13.2 vs. 10.8, -18.2%; p = 0.63) without rebound in the post-lockdown period (13.2 vs. 12.9, -1.7%; p = 0.97). The number of borderline tumours increased (13.6%-21.7%), whereas the rate of metastatic diseases rate dropped (47.1%-40.3%) (p = 0.046). Time-to-diagnosis and -treatment were not different over periods. Waiting neoadjuvant chemotherapy in resectable tumours was significantly favoured (24.7%-32.6%) compared with upfront surgery (13%-7.8%) (p = 0.013). The use of mFOLFIRINOX preoperative chemotherapy regimen decreased (84.9%-69%; p = 0.044). After lockdown, the number of borderline tumours decreased (21.7%-9.6%) and advanced diseases increased (59.7%-69.8%) (p = 0.046). SARS-CoV-2 infected 39 patients (4.7%) causing 5 deaths (12.8%). This cohort study suggests the existence of missing diagnoses and of a shift in disease stage at diagnosis from resectable to advanced diseases with related therapeutic modifications whose prognostic consequences will be known after the planned follow-up. Clinicaltrials.gov NCT04406571.


The protective effect of silk fibroin on high glucose induced insulin resistance in HepG2 cells.
The therapeutic use of silk-derived materials such as fibroin in biomedicine is well-established in Southeast Asian countries. Studies indicated that silk fibroin (SF) peptide enhances insulin sensitivity and glucose metabolism phenomena associated with type 2 diabetes mellitus (T2DM) suggesting this peptide may be beneficial to treat this disease. However, the mechanisms underlying protective effect of SF in insulin-mediated hepatic metabolic dysfunction remains unclear. The aim of this study was to investigate the influence of SF on insulin resistant HepG2 cells which were used a model of T2DM. Treatment of cells with 30 mmol/L of glucose and 10-6 mol/L insulin for 48 h significantly reduced glucose consumptions and intracellular glycogen levels but increased triglyceride (TG) levels. SF or metformin alone elevated glucose consumptions and glycogen accumulation accompanied by lower TG content. Greater effects in these metabolic parameters were found when SF and metformin were combined. Treatment of insulin resistant cells with SF or metformin alone decreased levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF-α) and interleukin-6 (IL-6); whereas antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) activity, as well as total antioxidant capacity (T-AOC) ability increased. The combination of SF and metformin produced greater changes in these parameters compared to metformin alone. Data indicated that the protective effect of SF or metformin in insulin resistant HepG2 cells involves inhibition of oxidant processes and that the combination of agents may prove more effective therapeutically.


Environmental safety review of methoprene and bacterially-derived pesticides commonly used for sustained mosquito control.
Some pesticides are applied directly to aquatic systems to reduce numbers of mosquito larvae (larvicides) and thereby reduce transmission of pathogens that mosquitoes vector to humans and wildlife. Sustained, environmentally-safe control of larval mosquitoes is particularly needed for highly productive waters (e.g., catchment basins, water treatment facilities, septic systems), but also for other habitats to maintain control and reduce inspection costs. Common biorational pesticides include the insect juvenile hormone mimic methoprene and pesticides derived from the bacteria Bacillus thuringiensis israelensis, Lysinibacillus sphaericus and Saccharopolyspora spinosa (spinosad). Health agencies, the public and environmental groups have especially debated the use of methoprene because some studies have shown toxic effects on non-target organisms. However, many studies have demonstrated its apparent environmental safety. This review critically evaluates studies pertinent to the environmental safety of using methoprene to control mosquito larvae, and provides concise assessments of the bacterial larvicides that provide sustained control of mosquitoes. The review first outlines the ecological and health effects of mosquitoes, and distinguishes between laboratory toxicity and environmental effects. The article then interprets non-target toxicity findings in light of measured environmental concentrations of methoprene (as used in mosquito control) and field studies of its non-target effects. The final section evaluates information on newer formulations of bacterially-derived pesticides for sustained mosquito control. Results show that realized environmental concentrations of methoprene were usually 2-5µg/kg (range 2-45µg/kg) and that its motility is limited. These levels were not toxic to the vast majority of vertebrates and invertebrates tested in laboratories, except for a few species of zooplankton, larval stages of some other crustaceans, and small Diptera. Studies in natural habitats have not documented population reductions except in small Diptera. Bacterial larvicides showed good results for sustained control with similarly limited environmental effects, except for spinosad, which had broader effects on insects in mesocosms and temporary pools. These findings should be useful to a variety of stakeholders in informing decisions on larvicide use to protect public and environmental health in a 'One Health' framework.


Comparison of serological tests based on outer membrane or internal antigens for detecting antibodies to Brucella ovis in infected flocks.
The aim of this work was to compare the performance of 6 serological tests using outer or internal antigens from Brucella for the diagnosis of Brucella ovis infection in sheep in an endemic area. Outer membrane antigens included a hot saline extract (HS) and the rough lipopolysaccharide (R-LPS) from B. ovis. Internal antigens were LPS-free total cytosolic proteins (CP) and an 18-kDa cytosolic protein (p18) from Brucella spp. Sera from 200 sheep from naturally infected flocks were assayed by agar gel immunodiffusion test (AGID) and by complement fixation test (CFT), both using HS, and by 4 ELISA using HS, R-LPS, CP, and p18, respectively. The percentage of positive results was 45.5% for ELISA with HS, 42.0% for ELISA with p18, 39.5% for CFT, 33.5% for ELISA with R-LPS, 29.0% for ELISA with CP, and 18.0% for AGID. Taking CFT as the reference test for calculating relative test parameters, the ELISA with HS had the best sensitivity (96.2%), while AGID and the ELISA with R-LPS had the best specificity (96.6%). The ELISA with CP was not more sensitive than the ELISA with p18 (67.1% vs. 79.7%) in spite of the higher number of antigens in CP. The lower relative sensitivity of tests using internal antigens might reflect a lack of antibodies to cytosolic proteins in some infected animals or a shorter persistence of these antibodies relative to antibodies to outer membrane components after recovery from infection.


A nonsense porcn mutation in severe focal dermal hypoplasia with natal teeth.
Focal dermal hypoplasia (FDH, Goltz syndrome), is an X-linked dominant mesoectodermal developmental disorder, involving skin, skeleton, eyes, teeth, and other organs. Mutations in PORCN, which stimulates the secretion of wingless family signal proteins, are found in FDH patients. A female fetus presented at 34 weeks gestation with interuterine growth restriction (IUGR), asymmetry, limb anomalies, microphthalmia, and lung anomaly. Focal dermal hypoplasia was confirmed at birth, with hypoplastic areas of skin, malformation of the limbs, diaphragmatic hernia, and ocular anomalies. Mutation analysis of PORCN revealed a nonsense mutation-Y359X. She presented natal teeth, an unexpected feature considering the role of the Wnt pathway in tooth development.


[Impact assessment on enamel remineralization after orthodontic treatment with casein phosphopeptide calcium phosphate complex].
To compare the effect on enamel demineralization following fluoride rinse or casein phosphopeptide calcium phosphate complex (CPP-ACP) after fixed appliance orthodontic treatment. The study population consisted of 21 post-orthodontic patients (13 females, 8 males, 84 affected teeth) with white spot lesions (WSL). They were divided into 3 groups with 28 affected teeth in each group. Participants in the control group were brushed with fluoride toothpaste twice a day. Participants in the fluoride group were instructed to rinse the mouth with 20mL 0.01% sodium fluoride rinse in addition to brushing twice a day. Participants in CPP-ACP group were instructed to use tooth moss after brushing their teeth twice a day for 6 months. SPSS 17.0 software package was used to analyze the data. Within 6 months after orthodontic treatment, white spot lesions areas of the three groups caused by enamel demineralization were all reduced in different degrees, and the differences of success rate were significant among three groups (P<0.05). CPP-ACP group achieved the highest success rate (51%) than the other group, the fluoride group (44%) and the control group (42%). Brushing teeth, fluoride rinse and CPP-ACP have certain effect on remineralization of demineralized teeth in 6 months after orthodontic treatment. Compared with brushing and fluoride rinse, CPP-ACP can reduce the area of enamel demineralization more effectively.


Evaluation of chemical parameters in breast cyst.
During our studies on breast diseases, the following biochemical values were measured: chlorine, sodium, potassium and albumin. We examined 153 syringe biopsies from women aged between 34 and 55 years, and an analysis of the above mentioned parameters enabled us to classify the breast cyst fluid into 2 groups: group I was definitely benign, while group II was calculated as having a risk factor two to four times greater than the control group in developing breast cancer.


Acute and Life-threatening Complications in Cushing Syndrome: Prevalence, Predictors, and Mortality.
Cushing syndrome (CS) results in significant morbidity and mortality. To study acute and life-threatening complications in patients with active CS. We performed a retrospective cohort study using inpatient and outpatient records of patients with CS in a tertiary center. A total of 242 patients with CS were included, including 213 with benign CS (pituitary n = 101, adrenal n = 99, ectopic n = 13), and 29 with malignant disease. We collected acute complications necessitating hospitalization, from appearance of first symptoms of hypercortisolism until 1 year after biochemical remission. Mortality data were obtained from the national registry. Baseline factors relating to and predicting acute complications were tested using uni- and multivariate analysis. The prevalence of acute complications was 62% in patients with benign pituitary CS, 40% in patients with benign adrenal CS, and 100% in patients with ectopic CS. Complications observed in patients with benign CS included infections (25%), thromboembolic events (17%), hypokalemia (13%), hypertensive crises (9%), cardiac arrhythmias (5%), and acute coronary events (3%). Among these patients, 23% had already been hospitalized for acute complications before CS was suspected, and half of complications occurred after the first surgery. Glycated hemoglobin (HbA1c) and 24-hour urinary free cortisol positively correlated with the number of acute complications per patient. Patients with malignant disease had significantly higher rates of acute complications. Mortality during the observation period was 2.8% and 59% in benign and malignant CS, respectively. This analysis highlights the whole spectrum of acute and life-threatening complications in CS, and their high prevalence even before disease diagnosis and after successful surgery.


Transpulmonary artery needle aspiration of hilar masses with endobronchial ultrasound: a necessary evil.
The safety with regard to bleeding complications of endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) of hilar and mediastinal lymphadenopathy has been well established. The real-time visualization of targeted and surrounding structures allows the operator to avoid puncturing even small vessels. However, on occasions, the only way to reach the target is by traversing vessels. We report 2 cases of right hilar masses that were successfully diagnosed with EBUS-TBNA performed by traversing the pulmonary artery without any complications. We suggest that transpulmonary artery needle aspiration can be safely conducted but should be performed only by experienced operators and should be reserved as a last resort for making a diagnosis.


[Development and prospect of digital technology in the field of prosthodontics].
The development of digital technology is gradually changing clinical practice and laboratory procedure of prosthodontics. After decades of exploration and development, the modern digital technology has been perfectly merged with prosthodontics and created a brand new treatment mode. The application of digital impression, digital design and digital processing has changed the way we treat patients and the way we communicate with patients. The data storage also provides a basis for long-term follow-up. The establishment of digital remote system, transferring data through internet, has improved communication in dental technique, tracing analysis of patient's condition, sharing and management of medical data, and popularization and promotion of knowledge. Digital technology promoted the development of prosthodontics in the direction of more precision, more convenience, more efficiency and more simulation in functional recovery, which will be one of the development directions of dentistry and even the medical science in the future.


Single-suture craniosynostosis: a review of neurobehavioral research and theory.
To review research and theory regarding the neurobehavioral correlates and outcomes of single-suture, or isolated, craniosynostosis in children. A critical review of 17 studies of the hypothesized association between isolated craniosynostosis and neurodevelopment. Isolated craniosynostosis is associated with a three- to fivefold increase in risk for cognitive deficits or learning/language disabilities. The causal basis for this association is unclear. No particular calvarial suture (sagittal, metopic, left or right unilateral coronal) has been associated with higher risk of problems. There is little evidence from quasi-experimental studies that cranioplastic surgery prevents or reduces risk of neurobehavioral impairment. Future studies would benefit from larger samples and larger control groups; measures of specific neuropsychological functions (in addition to global cognition); analyses of neuropsychological status in relation to the severity and cortical impact of synostosis; and an examination of interactions between synostosis and social/family risk factors on neurodevelopment. Routine neurodevelopmental screening of young children with isolated craniosynostosis is recommended.


Sources of Vaccine Hesitancy: Pregnancy, Infertility, Minority Concerns, and General Skepticism.
The coronavirus disease 2019 (COVID-19) epidemic continues to evolve, with variants of concern and new surges of COVID-19 noted over the past months. The limited data and evolving recommendations regarding COVID-19 vaccination in pregnancy have led to some understandable hesitancy among pregnant individuals. On social media, misinformation and unfounded claims linking COVID-19 vaccines to infertility are widespread, leading to vaccine skepticism among many men and women of reproductive age. The disproportionate impact of COVID-19 on communities of color, coupled with the unfortunate and troubled history of abuses of African Americans by the biomedical research community in the US, has also led to hesitancy and skepticism about the COVID-19 vaccines among some of our most vulnerable. The complex nature of vaccine hesitancy is evidenced by further divides between different demographic, political, age, geographical, and socioeconomic groups. Better understanding of these concerns is important in the individualized approaches to each patient.


Long-term outcome of percutaneous transluminal coronary angioplasty and coronary artery bypass grafting in patients with end-stage renal disease.
This study was conducted to investigate therapeutic methods for end-stage renal disease (ESRD) by retrospectively analyzing in-hospital outcome and long-term outcome in patients who underwent either percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). Ninety-two patients underwent PTCA and 47 underwent CABG, and the initial success rates were 87% and 85%, respectively. As major in-hospital complications, in the PTCA group 1 died (1%), 2 required emergency CABG (2%), and 2 had Q-wave myocardial infarction (2%); in the CABG group, 7 died (15%) and 3 had Q-wave myocardial infarction (6%). As for the long-term outcome, although there were no differences in the incidence of death or the incidence of cardiac death between the 2 groups, the cumulative proportion of patients free of death, myocardial infarction, CABG and repeat PTCA was lower in the PTCA group, which was mainly due to a higher incidence of repeat PTCA in that group. The incidence of cardiac death was low for both groups among the patients attaining complete revascularization. Twenty-three percent of the patients required cross-over implementation of PTCA and CABG. In conclusion, it is necessary to aim for complete revascularization using both treatments for a better prognosis in patients with ESRD.


Body Pain Intensity and Interference in Adults (45-53 Years Old): A Cross-Sectional Survey in Chongqing, China.
Culture and national care models matter both in reporting and treatment of pain status. However, most findings on body pain intensity and interference in adults are from Western studies, with little reliable evidence from China. This study aimed to assess body pain intensity and interference and its associations with demographic, socioeconomic characteristics, and health behaviors in adults. A cross-sectional survey was performed to collect data from 1224 adults, who were recruited via multistage stratified random sampling. The SF-36 quality-of-life instrument was used to investigate body pain intensity and interference. Ordinal logistic regression analysis was used in this study. Our results showed that 64.1% of the participants (males: 687; females: 537) reported body pain, and 45.7% of the participants reported body pain interference. Middle-aged respondents who were female, were unmarried/divorced or separated/widowed, had a negative relationship with their family, had poor sleep quality, and were not satisfied with their current living conditions had a higher body pain intensity rating (ordered logistic regression/six-level pain intensity criterion; odds ratios, p < 0.05). Respondents who were unmarried/divorced or separated/widowed, with a low education level, were unemployed, had lower incomes, had a negative relationship with their family, and were not satisfied with their current living conditions had a higher body pain interference rating (ordered logistic regression/five-level pain interference criterion; odds ratios, p < 0.05). In conclusion, an estimated 64.1% of middle-aged adults reported body pain, and 45.7% of middle-aged adults reported body pain interference. These results provide a clue for possible interventions for improving body pain intensity and interference in adults, especially among middle-aged people. These factors should be taken into consideration in the prevention of pain, pain management and treatment planning in order to help relieve the stress of pain among adults.


Parental stress and satisfaction during children's hospitalization: differences between immigrant and autochthonous population.
This study explored the relation between parents' stress and satisfaction during children's hospitalization, seeking possible differences between immigrant and autochthonous population and also as a function of gender in a sample of parents of hospitalized children in Andalusia, Spain. A total of 1347 parents participated in this study. Of the sample, 50% were immigrants and the other 50% were autochthonous. The assessment instruments were the Hospitalization Stress Scale and the Satisfaction with Hospitalization Scale. The results show that stress was associated with the manifestations of the child's illness, the alteration of family life or of parental roles during the process and some aspects of the clinical staff's work. General satisfaction in immigrant parents was higher than in the autochthonous population and the levels of satisfaction were higher in men than in women. Small changes and initiatives in relation to care could substantially improve the satisfaction of patients and their relatives during the process of hospitalization.


Studies on water transport through the sweet cherry fruit surface. 7. Fe3+ and Al3+ reduce conductance for water uptake.
The effects of the chloride salts LiCl, CaCl(2), MgCl(2), AlCl(3), EuCl(3), and FeCl(3) and the iron salts FeCl(2), FeCl(3), Fe(NO(3))(3), FeSO(4), and Fe(2)(SO(4))(3) on water conductance of exocarp segments (ES) and rates of water uptake into detached sweet cherry fruit (Prunus avium L. cv. Adriana, Early Rivers, Namare, Namosa, and Sam) were studied. ES were excised from the cheek of mature fruit and mounted in stainless steel diffusion cell; water penetration was monitored gravimetrically from donor solutions containing the above mineral salts into a PEG 6000 (osmolality = 1.14 osM, pH 4.8, 25 degrees C) receiver solution. Conductance of ES was calculated from the amount of water taken up per unit of surface area and time by dividing by the gradient in water activity across ES. LiCl, CaCl(2), MgCl(2), FeCl(2), and FeSO(4) had no significant effect on conductance, but AlCl(3), FeCl(3), Fe(NO(3))(3), and Fe(2)(SO(4))(3) significantly reduced conductance compared to water only as a donor. Also, EuCl(3) lowered conductance; however, this effect was not always significant. Effects of salts on water conductance of ES and rates of water uptake into detached fruit were closely related (R 2 = 0.97***). Upon application of an FeCl(3)-containing donor conductance decreased instantaneously. FeCl(3) concentrations of <6.6 x 10(-)(4) M had no effect on conductance, but concentrations at or above this threshold decreased conductance. FeCl(3) lowered water conductance at a receiver pH of 4.8, but not at pH < or =2.6. The effect of FeCl(3) on conductance was largest in cv. Namare and smallest in cv. Adriana. There was no significant effect of FeCl(3) on conductance for transpiration. Formation of aluminum and iron oxides and hydroxides in the exocarp as a result of a pH gradient between donor and receiver solution is discussed as the potential mechanism for Fe(3+) and Al(3+) reducing conductance for water uptake.


Trend of strengthening clearance regulation in Japan and concerns about its worldwide effects on regulations for natural and artificial radionuclides.
The Nuclear Regulation Authority (NRA) of Japan invited comments from the public on a revised guide on measurement and evaluation for clearance in 2019, which included a strict decision on how to treat uncertainties in the measurement and the nuclide vector. To resolve the issue on the uncertainty in clearance, a probabilistic approach had been established previously in the Atomic Energy Society of Japan Standard and incorporated into International Atomic Energy Agency (IAEA) Safety Report No. 67. NRA's new decision on the uncertainty in clearance was up to 10 times stricter than the probabilistic approach. This issue has been discussed at an international level in the framework of the ongoing revision of IAEA Safety Guide RS-G-1.7. This discussion on the uncertainty in clearance has raised serious concerns about its effects on other radiological protection regulations worldwide. This is because if we need strict treatment for the uncertainty in clearance, the same or even stricter treatment for conformity assessment may have to be applied to other radiological protection criteria for doses exceeding 10 µSv year-1. Radiological protection experts including regulators, professionals, and operators should be aware of the essential meaning of the radiological protection criteria by considering the background scientific basis on which they were established.


Epigenetic markers for bladder cancer in urine.
Many tumor markers for bladder cancer have been evaluated for use in detecting and monitoring bladder cancers tissue specimens, bladder washes, and urine specimens. However, none of the biomarkers reported to date has shown sufficient sensitivity and specificity to detect the entire spectrum of bladder cancers in routine clinical practice. The limited value of the established prognostic markers demands analysis of new molecular parameters having the potential to predict the prognosis of bladder cancer patients, particularly, the high-risk patients at risk of cancer progression and recurrence. Abnormal methylation of CpG islands can efficiently repress transcription of the associated gene in a manner akin to mutations and deletions. Several tumor suppressor genes correlated with bladder cancer contain CpG islands in their promoters. Markers for aberrant methylation may be a potential gateway for monitoring bladder cancer. Hypermethylation of several gene promoters was detected in urine sediment DNA from bladder cancer patients. Detection of DNA methylation in voided urine is feasible and noninvasive. Methylation is an important molecular mechanism in the development of bladder cancer and could be used as a prognostic and diagnostic marker. Aberrant patterns of epigenetic modification could, in the near future, be crucial indicators in cancer diagnosis, prognosis, and may additionally be good targets for developing novel therapies while maintaining quality of life.


Comparison of silk-elastinlike protein polymer hydrogel and poloxamer in matrix-mediated gene delivery.
The silk-elastinlike protein polymer, SELP 815K, and poloxomer 407, a commercially available synthetic copolymer, were evaluated to compare their relative performance in matrix-mediated viral gene delivery. Using a xenogenic mouse tumor model of human head and neck squamous cell carcinoma, the efficacy of viral gene-directed enzyme prodrug therapy with these polymers was characterized by viral gene expression in the tumor tissue, tumor size reduction, and survivability with treatment. Viral injection in SELP 815K produced a greater level and more prolonged extent of gene expression in the tumor, a statistically greater tumor size reduction, a longer time until tumor rebound, and a significantly increased survivability, as compared to injection of virus alone or in Poloxamer 407. Safety of treatment with these polymers was evaluated in a non-tumor bearing immunocompetent mouse model. Compared to virus injected alone or in Poloxamer 407, virus injected in SELP 815K had fewer and less severe indications of toxicity related to treatment as assessed by blood analysis, body weight, and histopathology of distant organs and the injection sites. Similar to virus alone or in Poloxamer 407, virus injected in SELP 815K elicited a mild injection site inflammatory response characterized primarily by a mononuclear leukocyte infiltrate and the formation of granulation tissue. Virus injected in SELP 815K resulted in fewer animals with elevated white blood cell counts and a less pronounced local toxicity reaction than was observed with virus in Poloxamer 407. In contrast to virus injected alone or in Poloxamer 407, which were not retained in the injection site tissues beyond week 1, SELP 815K was retained at the injection sites and by the end of the study (week 12), displayed limited absorption, and mild encapsulation. These results demonstrate the benefits of SELP 815K for matrix-mediated gene delivery over the injection of free virus and the injection of virus in Poloxamer 407. Virus in SELP 815K had greater efficacy of tumor suppression, promoted greater levels and greater duration of viral gene expression, and displayed reduced levels of injection site toxicity. Combining these performance and safety benefits with the degree of control with which they can be designed, synthesized and formulated, SELPs continue to show promise for their application in viral gene delivery.


An ab initio quantum mechanical charge field molecular dynamics simulation of a dilute aqueous HCl solution.
An ab initio quantum mechanical charge field (QMCF) molecular dynamics simulation has been performed to study the structural and dynamical properties of a dilute aqueous HCl solution. The solute molecule HCl and its surrounding water molecules were treated at Hartree-Fock level in conjunction with Dunning double-zeta plus polarization function basis sets. The simulation predicts an average H-Cl bond distance of 1.28 A, which is in good agreement with the experimental value. The H(HCl)...O(w) and Cl(HCl)...H(w) distances of 1.84 and 3.51 A were found for the first hydration shell. At the hydrogen site of HCl, a single water molecule is the most preferred coordination, whereas an average coordination number of 12 water molecules of the full first shell was observed for the chloride site. The hydrogen bonding at the hydrogen site of HCl is weakened by proton transfer reactions and an associated lability of ligand binding. Two proton transfer processes were observed in the QMCF MD simulation, demonstrating acid dissociation of HCl. A weak structure-making/breaking effect of HCl in water is recognized from the mean residence times of 2.1 and 0.8 ps for ligands in the neighborhood of Cl and H sites of HCl, respectively.


Ischemic Stroke in a Child after a Probable Scorpion Sting.
Scorpion stings are common emergencies in the tropics. Species-specific antivenom therapies are available. However, fatalities resulting from scorpion stings remain a public health concern in many settings. Children residing in rural towns and peri-urban areas represent the most vulnerable populations. Delays in the diagnosis of scorpion stings often occur as a result of the non-specific clinical presentations, which then lead to life-threatening complications. We report a 2-year-old Venezuelan boy presenting with acute pancreatitis and pulmonary edema without an identifiable cause 48 hours after his initial symptoms. We administered antivenom therapy when an undetected scorpion sting was suspected. Despite some initial clinical improvement with respect to his acute pancreatitis, pulmonary edema, and coagulation abnormalities, our patient experienced an ischemic stroke. Fortunately, our patient did demonstrate some neurological improvement. Although acute pancreatitis and pulmonary edema are known end-organ damage manifestations of the sting of Tityus in the Americas, our particular case illustrates the risk of ischemic stroke.


Brainstem Dysfunction in SARS-COV-2 Infection can be a Potential Cause of Respiratory Distress.
A terrible pandemic, Covid-19, has captivated scientists to investigate if SARS-CoV-2 virus infects the central nervous system (CNS). A crucial question is if acute respiratory distress syndrome (ARDS), the main cause of death in this pandemic, and often refractory to treatments, can be explained by respiratory center dysfunction. To discuss that ARDS can be caused by SARS-CoV-2 infection of the respiratory center in the brainstem. I reviewed literature about SARS-CoV-2 mechanisms to infect the respiratory center in the brainstem. An increasing amount of reports demonstrates that neurotropism is a common feature of coronavirus, which have been found in the brains of patients and experimental models, where the brainstem was severely infested. Recent studies have provided tremendous indication of the incidence of acute respiratory failure due to SARS-CoV-2 infection of the brainstem. SARS-CoV-2 might infect the CNS through the olfactory bulb, spreading from the olfactory nerves to the rhinencephalon, and finally reaching the brainstem. Hence, the virus infection causes respiratory center dysfunctions, leading to ARDS in COVID-19 patients. I conclude that acute ARDS in Covid-19 can be caused by SARS-CoV-2 invasion of brainstem respiratory center, suggesting the needs of more specific and aggressive treatments, with the direct participation of neurologists and neurointensivists.


A novel der(16)t(3;16)(p25;q24) in a patient with ovarian cancer.
Non-random simple chromosomal aberrations in various malignancies provide important insights into the molecular pathogenesis of human cancer. Although extensive data exist on recurring chromosomal abnormalities in hematological cancer, data on individual solid tumor types remain limited. Here we present the case of a patient with ovarian cancer with a specific chromosomal abnormality. Cytogenetic analysis utilized a G-banding technique, which was performed with direct culture of the surgically removed cancer cells from a 23-year-old woman with grade II ovarian serous cystadenocarcinoma. The patient had no family history of ovarian cancer. We report a novel der(16)t(3;16)(p25;q24) accompanied by terminal deletion of 3p25 as the simple chromosomal aberration in this case. To the best of our knowledge, no such translocation has been previously reported. The present study supports the possible role of both del(3)(p25) and the translocation t(3;16)(p25;q24) in ovarian cancer; nevertheless, the significance of these chromosomal changes in the development of ovarian cancer remains unknown. The significance of this finding and its role in the pathogenesis of ovarian cancer requires further clarification.


A case of giant cell glioblastoma: a mimicker of a cerebral metastasis.
We report a rare case of giant cell glioblastoma that was difficult to distinguish from cerebral metastasis. The MRI finding was a ring-enhancing well-circumscribed solitary brain tumor that was very similar to cerebral metastasis. Even when MRI results were considered together with the findings by magnet resonance spectroscopy and perfusion-weighted MRI, it was hard to distinguish between giant cell glioblastoma and cerebral metastasis before surgery. When we find a solitary ring-enhancing intracranial mass with little tendency of invasion, we need to consider the possibility of giant cell GBM as a differential diagnosis.


Early introduction of everolimus immunosuppressive regimen in liver transplantation with extra-anatomic aortoiliac-hepatic arterial graft anastomosis.
Liver transplantation is the treatment of choice for patients with acute and chronic end-stage liver disease, when no other medical treatment is possible. Despite high rates of 1- to 5-year survival, long-term adverse effects of immunosuppressant agents remain of major concern. Current research and clinical efforts are made to develop immunosuppressant agents that minimize adverse effects along with a low rate of graft rejection. Tailoring immunosuppressive therapy to individual patients by the use of proliferation signal inhibitors seems to be the best way to minimize toxicity and increase efficacy. Recently everolimus has been introduced in clinical practice; among its adverse effects an increased incidence of arterial graft thrombosis in renal transplants, vascular anastomosis leakage, impaired wound healing, and thrombotic microangiopathy have been reported. We present the case of a 54-year-old patient submitted to liver transplantation for end-stage liver disease treated by an extra-anatomic aortoiliac-hepatic arterial graft anastomosis and early postoperative introduction of everolimus for acute renal failure. Postoperative period was characterized by two abdominal collections and reactivation of cytomegalovirus infection that were treated by percutaneous drainage and antiviral therapy, respectively; the patient is well after 8-month followup with patency of the arterial conduit and no leakage.


Exploring the clinical approach to the bimodal fitting of hearing aids and cochlear implants: results of an international survey.
The results show that the fitting of a contralateral hearing aid (HA) in the non-implanted ear of cochlear implant (CI) recipients is now well established as standard clinical practice. However, there is a lack of experience in HA fitting within the CI centres and the use of published bimodal fitting procedures is poor. The HA is often not refitted after CI switch-on and this may contribute to rejection. Including a bimodal fitting prescription and process in the CI fitting software would make applying a balancing procedure easier and may increase its implementation in routine clinical practice. This survey was designed to investigate and understand the current approach to bimodal fitting of HAs and CIs across different countries and the recommendations made to recipients. Clinicians working with HAs and/or CIs were invited to participate in an international multicentre clinical survey, designed to obtain information on the various approaches towards bimodal hearing and CI and HA device fitting. Forty-one questions were presented to clinicians in experienced CI centres across a range of countries and answers were collected via an online survey. In all, 65 responses were obtained from 12 different countries. All clinicians said they would advise a CI user to wear a contralateral HA if indicated. However, a significant number (45%) had either never fitted HAs before or had less than 1 year of experience. In general, there were no specific criteria for selecting candidates to fit with an HA. A strategy to balance the HA with the CI was not used as a standard practice for any of the adults and was used in only 12% of the children. Only half the respondents were aware of the bimodal literature. The majority of professionals (18/30) did not refit the HA after CI switch-on. However, if users complained of sound quality or loudness issues or had poor test results, a follow-up session was provided. The main benefit reported by recipients was improvement in overall sound quality.


The 13C-octanoic acid breath test: validation of a new noninvasive method of measuring gastric emptying in rats.
Currently available rat models for measuring gastric emptying are hampered by the necessity to kill the animals at the end of each experiment, which makes repetitive testing impossible. We have developed and validated a noninvasive test model, adapted from the 13C-octanoic breath test in humans, for repetitive measurements of gastric emptying in rats. Male Wistar rats were trained on a fixed protocol to eat a piece of pancake doped with 1 microg 13C-octanoic acid after 12 h fasting, and to stay thereafter in cylindrical glass cages. Breath tests were performed by a fully automated system of computer-guided switching valves, which collected consecutive breath samples. All breath samples were analysed by gas chromatography and isotope mass spectrometry. The area under the curve (AUC) from the cumulative 13CO2 excretion from 0 to 6 h was determined by the trapezium method to calculate the gastric half-emptying times (t(1/2)). Inter-day variability was determined. The effect of subcutaneous or intraperitoneal injection of saline was studied. The test was further validated for pharmacological interventions by oral administration of cisapride and parenteral administration of atropine, to induce, respectively. acceleration and delay of gastric emptying. Mean gastric emptying times +/- SD of 24 rats were 119.3 +/- 28.2 min, 138.7 +/- 26.0 min, and 124.5 +/- 30.9 min on three different test days. The mean coefficient of variation of three repeated measurements in the same 24 rats was 17.5%. No significant differences were observed after subcutaneous or intraperitoneal injection of saline. In a second test series of eight rats, cisapride significantly accelerated gastric emptying (mean t(1/2) 112.7 +/- 33.1 min, P < 0.05), while atropine caused a significant delay (mean t(1/2) 205.9 +/- 24.9 min, P < 0.05) when compared to control test results (mean t(1/2) 140.7 +/- 16.7 min) in the same rats. We validated the 13C-octanoic breath test to study gastric emptying in rats. This test method obviates the necessity to kill laboratory animals and allows repetitive measurements of gastric emptying to study its physiology or pathophysiology as well as the effect of pharmacological agents.


Neutrophil elastase inhibitor (ONO-5046) decreases cytokine-induced neutrophil chemoattractant after reperfusion of pancreaticoduodenal transplantation in rats.
The protective effects of a neutrophil elastase inhibitor (ONO-5046) on reperfusion injury following pancreaticoduodenal transplantation in rats were studied by measuring serum concentrations of cytokine-induced neutrophil chemoattractant (CINC). Male Wistar rats were transplanted with syngeneic pancreaticoduodenal grafts. ONO-5046 was injected intravenously 5 min before vascular clamping and immediately after reperfusion at a dose of 10 mg/kg. No significant differences were observed in the peak serum concentrations of amylase between the groups treated with and treated without ONO-5046. The serum lipase concentrations in the untreated animals increased and peaked 3 hr after reperfusion. ONO-5046 significantly decreased the peak serum lipase concentration. The serum CINC concentrations, which were determined by enzyme-linked immunosorbent assay, increased and peaked 3 hr after reperfusion, decreasing gradually thereafter. However, pretreatment with ONO-5046 significantly inhibited the rise in serum CINC concentrations after reperfusion. Expression of CICN transcripts in the pancrease grafts was evaluated by Northern blot analysis and peaked 3 hr after reperfusion in untreated animals. Pretreatment with ONO-5046 also significantly inhibited the expression of CINC mRNA transcripts in the graft. ONO-5046 significantly decreased the number of neutrophils accumulated in the pancreas graft 24 hr after transplantation. In vitro CINC production by peritoneal macrophages was increased by neutrophil elastase in dose-dependent fashion. However, ONO-5046 decreased CINC production by peritoneal macrophages in response to neutrophil elastase. These results suggest that ONO-5046 prevents early neutrophil accumulation in the pancreas following ischemia/reperfusion of pancreaticoduodenal transplantation.


Radiation Therapy for Advanced Mucinous Carcinoma of the Breast With a Malignant Wound: A Case Report.
Patients with breast cancer who refuse standard treatment often suffer from malignant wounds due to the growth of local tumors. However, treatment strategies for patients with unresectable locally advanced breast cancer who refuse standard treatment remain unclear. Usually, such cases are treated with palliative irradiation and do not achieve local control by irradiation alone. This is the first case report discussing the role of high-dose local irradiation and the treatment course for a patient with a massive breast tumor (mucinous adenocarcinoma) who refused standard treatment. A 44-year-old female was diagnosed with mucinous carcinoma of the breast in the right breast (cT1N0M0, cStage I). She refused standard treatment for six years. She visited the emergency department because of acute bleeding from the right breast with malignant wounds. Macroscopically, the tumor in the right breast measured over 20 cm in diameter. The tumor was exudative, exhibited ulceration and slight bleeding, and emitted an odor. Imaging findings showed multiple lymph nodes and bone metastases, and the final diagnosis was stage IV breast cancer (cT4bN1M1). Although the surgeon recommended chemotherapy for breast cancer, the patient refused chemotherapy or other therapy due to concerns regarding treatment-related complications. Considering the symptoms of advanced breast cancer with malignant wounds, she finally agreed to receive radiation therapy (RT). We performed RT at 70 Gy in 35 fractions over seven weeks. The tumor-associated symptoms disappeared after RT. Three months after RT, the tumor had almost disappeared. We administered luteinizing hormone-releasing hormone agonists after RT. Two years after RT, she died due to multiple liver metastases and ascites; however, there was no disease progression in the right breast. High-dose RT for locally advanced mucinous carcinoma of the breast with malignant wounds is considered an effective therapeutic option.


[EMBRYO AND HUMAN FETUS: LEGAL PROTECTION ISSUES].
The article deals with some problematic aspects of the legal protection of the human embryo and fetus. It is established that according to the legislation of Ukraine a live-born child will be considered a subject of legal relations irrespective of the week of pregnancy and state of health. Various scientific legal and medical approaches to the issue of completing the period of embryonic development have been investigated. The positions of scientists on the legal protection of embryos, which were conceived using reproductive technologies, namely, until their implementation in the body of the future mother, are analyzed. It is proved that all embryos need special protection, regardless of the method of their conception, and it has also been established that various manipulations with embryos are prohibited in order to conduct medical experiments. Foreign experience of legislative regulation of the beginning of life is investigated. It is established that in Ukraine the civil capacity of a natural person arises at the moment of its birth, but in the cases established by law, the interests of a conceived but not born child are protected. The case-law of the European Court of Human Rights on the protection of the «unborn life» is analyzed. It is proposed to characterize the legal status of «embryo» and «human fetus» as «subjective», which provides for separate elements of legal protection, and in the case of transition to a subjective state - protection of property rights, the grounds for which occurred during the «pre-subject» of the «state». The necessity to establish in the legislation of Ukraine a uniform approach to the determination of the period of embryonic development and its completion, as well as the corresponding changes to Part 2 of Art. 2 of the Law of Ukraine «On Prohibition of Human Reproductive Cloning».


Molecular markers of cartilage breakdown and synovitis at baseline as predictors of structural progression of hip osteoarthritis. The ECHODIAH Cohort.
To determine whether systemic markers of bone, cartilage, and synovium can predict structural progression of osteoarthritis (OA). Patients with painful hip OA were treated with diacerein or placebo in a multicentre, prospective, double blind, 3 year follow up trial. The following information was collected at entry: demographics, characteristics of hip OA, and 10 markers: N-propeptides of collagen types I and III, cartilage oligomeric matrix protein, YKL-40, hyaluronan (sHA), matrix metalloproteinases-1 and -3, C reactive protein, C-terminal crosslinking telopeptides of collagen types I and II (uCTX-II). Radiographs were obtained at entry and every year. Structural progression was defined as a joint space decrease > or =0.5 mm or requirement for total hip replacement. Grouped survival analysis was performed with time to structural progression as dependent variable, and clinical data, radiographic findings, treatment groups (diacerein versus placebo), and markers as explanatory measures. In the 333 patients in whom all markers were measured, high functional impairment, a joint space width <2 mm, and lateral migration of the femoral head at baseline increased the risk of progression, but diacerein had a protective effect (relative risk = 0.75; 95% confidence interval (CI) 0.54 to 0.96). In addition, patients in whom uCTX-II and sHA were in the upper tertile had a relative risk of progression of 3.73 (95% CI 2.48 to 5.61) compared with patients with markers in the two lower tertiles. In this large cohort, combined measurements of uCTX-II and sHA were a new predictor of the structural progression of hip OA.


Association of carotido-cavernous fistula and controlateral optic neuropathy secondary to cranial trauma.
to report a case of a woman who had a severe cranial trauma complicated by two ophalmologic potentially cecitating complications: right carotido-cavernous fistula and left traumatic optic neuropathy. A 56 years-old woman, without any medical history, referred, one month after fall from a height of 3 meters, for right exophthalmos. Ophthalmic examination of the right eye completed by retinal angiography suspected carotid-cavernous fistula which was confirmed by angio-MRI. In the left eye, the visual acuity was decreased to no light perception and fundus examination showed optic nerve head palor secondary to traumatic optic neuropathy. Arterial embolization was performed and allowed closing of the fistula. Optic neuropathy and carotido-cavernous fistula are two severe complications that can occur simultaneously in the same patient. The prognosis of the optic neuropathy may be compromised, and the treatment of carotido-cavernous fistula benefited from progress in interventional neuro-radiology.


Outgrowing olfactory axons contain the Reelin receptor VLDLR and navigate through the Reelin-rich cribriform mesenchyme.
Chemosensory neurons in the olfactory epithelium (OE) project axonal processes to the olfactory bulb (OB) of the brain. During embryonic stages, on their trajectory to the OB, the outgrowing axons traverse the so-called cribriform mesenchyme, which is located between the OE and the OB. The molecular cues guiding these axons through the cribriform mesenchyme are largely unknown. To identify molecules influencing the axonal trajectory in the murine cribriform mesenchyme, we performed microarray analyses focusing on extracellular matrix (ECM) proteins present in this tissue. Thereby, the ECM protein Reelin turned out to be an interesting candidate. Reelin was found to be expressed by numerous cells in the cribriform mesenchyme during the embryonic stages when the first axons navigate from the OE to the OB. These cells were closely associated with olfactory axons and apparently lack glial and neuronal markers. In the mesenchyme underlying the OE, localization of the Reelin protein was not confined to the Reelin-expressing cells, but it was also observed to be widely distributed in the ECM-most prominently in regions traversed by olfactory axons. Importantly, these axons were found to be endowed with the Reelin receptor very-low-density lipoprotein receptor (VLDLR). Finally, Reelin expression was also detectable in neuronal cells of the OB, which are contacted by VLDLR-positive olfactory axons. In summary, the results of the present study suggest that a Reelin/VLDLR signaling pathway might contribute to the formation of olfactory projections to the OB and the establishment of initial contacts between the incoming axons and neurons in the OB.


A new potential energy surface for OH(A 2Sigma(+))-Ar: the van der Waals complex and scattering dynamics.
New ab initio studies of the OH(A (2)Sigma(+))-Ar system reveal significantly deeper potential energy wells than previously believed, particularly for the linear configuration in which Ar is bound to the oxygen atom side of OH(A (2)Sigma(+)). In spite of this difference with previous ab initio work, bound state calculations based on a new RCCSD(T) potential energy surface yield an energy level structure in reasonable accord with previous theoretical and experimental studies. Preliminary open and closed shell quantum mechanical and quasiclassical trajectory scattering calculations are also performed on the new potential energy surface surface. The findings are discussed in the light of previous theoretical and experimental results for rotational energy transfer in collisions of OH(A (2)Sigma(+)) with Ar.


SPRY1 regulates mammary epithelial morphogenesis by modulating EGFR-dependent stromal paracrine signaling and ECM remodeling.
The role of the local microenvironment in influencing cell behavior is central to both normal development and cancer formation. Here, we show that sprouty 1 (SPRY1) modulates the microenvironment to enable proper mammary branching morphogenesis. This process occurs through negative regulation of epidermal growth factor receptor (EGFR) signaling in mammary stroma. Loss of SPRY1 resulted in up-regulation of EGFR-extracellular signal-regulated kinase (ERK) signaling in response to amphiregulin and transforming growth factor alpha stimulation. Consequently, stromal paracrine signaling and ECM remodeling is augmented, leading to increased epithelial branching in the mutant gland. By contrast, down-regulation of EGFR-ERK signaling due to gain of Sprouty function in the stroma led to stunted epithelial branching. Taken together, our results show that modulation of stromal paracrine signaling and ECM remodeling by SPRY1 regulates mammary epithelial morphogenesis during postnatal development.


Adsorption of Toxic Metals and Control of Mosquitos-borne Disease by Lysinibacillus sphaericus: Dual Benefits for Health and Environment.
Assessment of the bacterium L. sphaericus as a dual-action candidate for biological control of mosquito-borne diseases and bioremediation of toxic metals. Larvae of the mosquito, C. quinquefasciatus, were first evaluated for metal tolerance and then exposed to 5 ppm cadmium, chromium, arsenic, and lead in assays together with seven strains of L. sphaericus. A probit regression analysis was used to estimate the LC(50) of Cd, Cr, As, and Pb to C. quinquefasciatus. An analysis of covariance and multifactorial ANOVA examined the metal biosorption and larvicidal properties of the seven strains of L. sphaericus. We found that L. sphaericus adsorbed the toxic metal ions and was toxic against mosquito larvae. The L. sphaericus strain III(3)7 resulted in a larvae mortality of over 80% for all the tested metals. This strain also exhibited the capacity to adsorb 76% of arsenic, 32% of lead, 25% of chromium, and 7% of cadmium. This study found combined metal adsorption and larval toxicity associated with three strains of L. sphaericus [III(3)7, OT4b.31, and CBAM5]. This suggests that a combination of these strains shows strong dual potential for biological control of mosquitos in heavy metal-contaminated areas and remediate the heavy metal contamination as well.


Extracorporeal membrane oxygenation use in patients with traumatic brain injury.
Venovenous extracorporeal membrane oxygenation (ECMO) is used for patients with severe, potentially reversible, respiratory failure unresponsive to conventional management. It is relatively contraindicated in patients with traumatic brain injury (TBI) due to bleeding complications and use of anticoagulation. We report two cases of TBI patients treated with ECMO.


CuBr/NHPI co-catalyzed aerobic oxidative [3 + 2] cycloaddition-aromatization to access 5,6-dihydro-pyrrolo[2,1-a]isoquinolines.
An efficient and enviromentally friendly CuBr/NHPI co-catalyzed aerobic oxidative [3 + 2] cycloaddition-aromatization cascade was realized with N-substituted tetrahydroisoquinolines and electron-deficient olefins. Under the mild conditions, the reaction proceeded smoothly and displayed excellent functional group tolerance, affording 5,6-dihydro-pyrrolo[2,1-a]isoquinolines in good to high yields. This protocol exhibits a broad substrate scope to both N-alkyl tetrahydroisoquinolines and dipolarophile substrates.


Synthesis and antiproliferative activity of hydroxyferrocifen hybrids against triple-negative breast cancer cells.
We have recently shown that the combination of chemical motifs of vorinostat () and ferrocifen () in the single hybrid produced beneficial effects in terms of antiproliferative activity of both agents against cancer cells. Since hydroxylation of to form hydroxyferrocifen () improves the biological response, we explore in this work the anticancer effects of a new family of hybrid phenolic compounds bearing some molecular features of , and . Results concerning their cytotoxicity on both triple-negative MDA-MB-231 and hormone-dependent MCF-7 breast cancer cells are reported here. Organometallic compounds showed better antiproliferative activities than organic analogs. For instance, (IC50 = 1.5 μM) was around seven times more active than (IC50 = 10.9 μM) against MCF-7 cells. In the case of triple-negative MDA-MB-231 cells, the IC50 values for ferrocene compounds are in the range of 1.3-4.5 μM and those for organic derivatives are 5.2-34.5 μM. Studies concerning the isomerization and redox behaviors of these compounds are also presented. Despite the potential of to exhibit ex cellulo redox activation, it seems that this feature is not completely expressed in cellulo. This surprising behavior is related to the driving effect of the side chain to direct the new constructs to different targets.


Stressful life events, Type A behavior, and the prediction of cardiovascular and total mortality over six years. MRFIT Group.
The relationship between stressful life events and subsequent mortality and morbidity were determined prospectively over 6 years for 12,866 men participating in the Multiple Risk Factor Intervention Trial (MRFIT). Aslo evaluated was the impact of life events on cardiovascular outcomes for persons exhibiting and not exhibiting coronary prone (Type A) behavior. Subjects completed life events checklists at baseline and each of five annual visits. Participants were also administered the Jenkins Activity Survey measure of Type A behavior at baseline and a subsample of 3110 participants was categorized as to behavior type based on the structured interview assessment method. Cox proportional hazard analyses indicated that number of life events experienced during each of 6 years of follow-up was unrelated to risk in the subsequent year of CHD death or fatal plus nonfatal MI and was inversely related to total mortality. The impact of life events on cardiovascular risk did not differ by behavior type category.


Development and validation of a chronic disease nursing education program for enhancing clinical reasoning ability in undergraduate nursing students.
This study developed a chronic disease nursing educational program to enhance clinical reasoning in nursing students and then tested it for effectiveness. Before and after completing the program's five 90-minute sessions, 54 second-year students in a four-year nursing degree program at a university completed a self-administered survey to evaluate their clinical reasoning ability. The measure used was the Scale to assess the Critical Thinking of Clinical Nurses. Results showed significant improvement in total scores and in the reasoning subscale scores, indicating the overall effectiveness of the program. However, no significant improvement was found in any of the measure's subscales other than reasoning. Those skills could, potentially, be enhanced through clinical practicum.


Large granular lymphocyte lymphoma in the skin and urinary bladder of a dog.
A 10-year-old female Cavalier King Charles Spaniel presented with hematuria, pollakiuria and skin rash. Based on the histopathological and cytological examination of the skin and bladder mucosa, the dog was diagnosed with large granular lymphocytic (LGL) lymphoma of the bladder and skin. The dog responded well to the initial chemotherapy with nimustine for 3 months. Since recurrence of skin erosion and bladder wall thickening were observed, the dog was subsequently administered chemotherapy with other anticancer drugs, including chlorambucil, vincristine, doxorubicin, L-asparaginase, cytosine arabinoside, and cyclophosphamide. The dog survived for 11 months and died due to tumor-related disseminated intravascular coagulation. This is the first report of a canine case of LGL lymphoma in the skin and bladder.


Aryl sulfotransferase in rat liver: multiplicity and substrate specificity.
Rat liver aryl sulfotransferase was purified by chromatography on diethylaminoethyl-cellulose or chromatofocusing and three fractions, referred to by Sekura and Jakoby as I, II and IV, were obtained in the order of their elution, each containing sulfation activity. p-Nitrophenol (PNP) at mM order and beta-naphthol were substrates common to all three fractions, but PNP at microM order and tyramine were substrates only for IV. IV corresponded to the enzyme designated M by Rein et al. and was active with monoamine, as predicted from our previous results with rat liver cytosol. However, the effectiveness of IV in bringing about the sulfation of PNP at mM order was not evident from our previous results. The characteristics of aryl sulfotransferase multiplicity on the basis of thermostability of sulfation activity could not be determined since essentially the characteristics were the same for all three purified fractions. The multiplicity of aryl sulfotransferase purified from rat liver was different from that of human platelets, indicating possible species and/or tissue differences in this enzyme.


Exploring RdRp-remdesivir interactions to screen RdRp inhibitors for the management of novel coronavirus 2019-nCoV.
A novel coronavirus recently identified in Wuhan, China (2019-nCoV) has resulted in an increasing number of patients globally, and has become a highly lethal pathogenic member of the coronavirus family affecting humans. 2019-nCoV has established itself as one of the most threatening pandemics that human beings have faced, and therefore analysis and evaluation of all possible responses against infection is required. One such strategy includes utilizing the knowledge gained from the SARS and MERS outbreaks regarding existing antivirals. Indicating a potential for success, one of the drugs, remdesivir, under repurposing studies, has shown positive results in initial clinical studies. Therefore, in the current work, the authors have attempted to utilize the remdesivir-RdRp complex - RdRp (RNA-dependent RNA polymerase) being the putative target for remdesivir - to screen a library of the already reported RdRp inhibitor database. Further clustering on the basis of structural features and scoring refinement was performed to filter out false positive hits. Finally, molecular dynamics simulation was carried out to validate the identification of hits as RdRp inhibitors against novel coronavirus 2019-nCoV. The results yielded two putative hits which can inhibit RdRp with better potency than remdesivir, subject to further biological evaluation.


Population health and the hardcore smoker: Geoffrey Rose revisited.
The "hardening hypothesis" suggests that as smoking prevalence decreases, lighter smokers will quit first, leaving more "hardcore" smokers in the population. At a population level, however, the weight of evidence suggests that no hardening is occurring. By understanding the lessons from Geoffrey Rose's model of population-level risk factor change, we argue that the hardening of the smoking population is not inevitable. The Rose model predicts that the effect of policy interventions, and changes in social norms, can shift the population-level risk distribution for continuing to be a smoker, making it more likely that all smokers will quit. This analysis also suggests that further reductions in smoking prevalence will not come without further changes in the underlying--and largely cultural--root causes of smoking in a population.


[Afferent pathways arising from the lower urinary tract. Physiology, pathophysiology, and clinical implications].
Voluntary control of bladder function is mainly influenced by sensations arising from the lower urinary tract. Conscious perception of these sensations is imperative for appropriate urine storage and voiding at a socially accepted time and place and depends on the integrity of the afferent axis urothelium -- peripheral nerves -- spinal cord -- pons -- mesencephalon -- sensory cortex. This review considers the current knowledge about normal and impaired sensations arising from the bladder and the sphincter and addresses their clinical significance.


Lactylated Histone H3K18 as a Potential Biomarker for the Diagnosis and Predicting the Severity of Septic Shock.
To date, there are no studies regarding the lactylation profile and its role in critically ill patients. Thus, we aimed to examine expression of histone H3 lysine 18 (H3K18) lactylation and its role in patients with septic shock. Thirteen healthy volunteers and 35 critically ill patients from the Department of Surgical Intensive Care Medicine, Beijing Hospital were enrolled in our study. Baseline information and clinical outcomes were obtained prospectively. Lactylation levels of all proteins and H3K18 from peripheral blood mononuclear (PBMC) were determined by western blotting and serum levels of inflammatory cytokines by flow cytometry. Arginase-1 (Arg1) and Krüppel-like factor-4 (Klf4) mRNA expression was evaluated by quantitative real-time PCR (qRT-PCR). Lactylation was found to be an all-protein post-translational modification and was detected in PBMCs from both healthy volunteers and critically ill patients, with a significantly higher relative density in shock patients (t=2.172, P=0.045). H3K18la was expressed in all subjects, including healthy volunteers, with the highest level in septic shock patients (compared with non-septic shock patients, critically ill without shock patients and healthy volunteers P=0.033, 0.000 and 0.000, respectively). Furthermore, H3K18la protein expression correlated positively with APACHE II scores, SOFA scores on day 1, ICU stay, mechanical ventilation time and serum lactate (ρ=0.42, 0.63, 0.39, 0.51 and 0.48, respectively, ρ=0.012, 0.000, 0.019, 0.003 and 0.003, respectively). When we matched patients with septic shock and with non-septic shock according to severity, we found higher H3K18la levels in the former group (t=-2.208, P =0.040). Moreover, H3K18la exhibited a close correlation with procalcitonin levels (ρ=0.71, P=0.010). Patients with high H3K18la expression showed higher IL-2, IL-5, IL-6, IL-8, IL-10, IL-17, IFN-α levels (ρ=0.33, 0.37, 0.62, 0.55, 0.65, 0.49 and 0.374 respectively, P=0.024, 0.011, 0.000, 0.000, 0.000 and 0.000 respectively). H3K18la expression also displayed a positive correlation with the level of Arg1 mRNA (ρ=0.561, P=0.005). Lactylation is an all-protein post-translational modification occurring in both healthy subjects and critically ill patients. H3K18la may reflect the severity of critical illness and the presence of infection. H3K18la might mediate inflammatory cytokine expression and Arg1 overexpression and stimulate the anti-inflammatory function of macrophages in sepsis.


CelLock TM: an innovative standardized cell-block preparation procedure.
The CelLock™ procedure kit is used to collect and prepare cellular specimens such as fine needle aspirates (FNA), cytology specimens, cultured cells, small tissue biopsies, and samples with scant tissue fragments or cells into a paraffin cell-block. This cell-block can be used for subsequent microtomy and staining using hematoxylin and eosin (H&E), special stains, immunohistochemistry (IHC), and applicable molecular techniques such as in situ hybridization (ISH). CelLock is a standardized method that provides optimal receipt, preservation, preparation, and processing of cell-blocks which, contain virtually all of the submitted specimens and are able to be embedded and sectioned in a reproducible fashion. The specimen contained within the cell-block is preserved such that all the cellular protein and genetic information is available for histological and ancillary testing.


Advances and Applications of Hollow Fiber Nanofiltration Membranes: A Review.
Hollow fiber nanofiltration (NF) membranes have gained increased attention in recent years, partly driven by the availability of alternatives to polyamide-based dense separation layers. Moreover, the global market for NF has been growing steadily in recent years and is expected to grow even faster. Compared to the traditional spiral-wound configuration, the hollow fiber geometry provides advantages such as low fouling tendencies and effective hydraulic cleaning possibilities. The alternatives to polyamide layers are typically chemically more stable and thus allow operation and cleaning at more extreme conditions. Therefore, these new NF membranes are of interest for use in a variety of applications. In this review, we provide an overview of the applications and emerging opportunities for these membranes. Next to municipal wastewater and drinking water processes, we have put special focus on industrial applications where hollow fiber NF membranes are employed under more strenuous conditions or used to recover specific resources or solutes.


Challenges and opportunities in setting up a phase III vaccine clinical trial in resource limited settings: Experience from Nepal.
Clinical trials are complicated, time-consuming and costly. From the initial screening, informed consent and recruitment of the participants' to study completion, the sponsor must undertake a wide array of complex and closely monitored operations, complying with international standards for human subject research and local requirements. Conducting these studies in an underdeveloped country, with limited resources, infrastructure, and experience with regulated clinical trials adds to this complexity. The initial site selection, set up and preparatory activities for the clinical trial are crucial to minimizing the risks to both participants and to successful completion during the subsequent study execution.In this paper, we describe the experience and lessons learned of building clinical trial site capacity in terms of infrastructure and human resource development for a Phase III vaccine clinical trial. We believe that sharing the experience of setting up a clinical trial in a resource-limited country will enable other entities contemplating clinical research in these countries, to prepare and plan ahead, to minimize the impact of barriers, and to contribute to bringing more studies to the countries where people live with the burden of vaccine-preventable, poverty-associated diseases.


Clinical analysis and outcome of interstitial lung disease complicated with juvenile dermatomyositis and juvenile polymyositis.
The aim of this study was to determine the clinical phenotype and outcome of interstitial lung disease (ILD) complicated with juvenile dermatomyositis (JDM) or juvenile polymyositis (JPM). This was a single-center retrospective study. From 1984 to 2015, we retrospectively reviewed 29 patients who were diagnosed with JDM/JPM, among whom eight cases were ILD and 21 were non-ILD. The clinical features and laboratory findings included chest computed tomography (CT) images that were compared between the patients with ILD and non-ILD. Eight cases (27.6%) were complicated with ILD. The mean age was 6.3 years, and 75% of the patients were women. We found that high fever, arthralgia, muscle weakness, and high serum Krebs von den Lungen-6 (KL-6) level were significantly associated with the presence of ILD (p < 0.05). Two patients were positive for the anti-Jo-1 antibody, and two other patients were positive for the anti-MDA5 antibody. Three cases were identified as rapidly progressive (RP)-ILD. The chest CT images of the ILD patients appeared to show ground glass opacity (GGO) with a lower lobe predominance, reticulation, and traction bronchiectasis consolidation. Three patients with RP-ILD showed random subpleural GGO with/without consolidation patterns. Further, three patients with RP-ILD died of respiratory failure (p < 0.01). ILD is one of the most serious complications of JDM/JPM. In the early phase of ILD, high levels of serum KL-6 can be detected, regardless of the respiratory symptoms. Additionally, RP-ILD can be predicted based on the presence of anti-MDA5 antibodies and the chest CT findings, including random subpleural GGO with/without consolidation patterns.


A new monoclonal antibody (KB61) recognizing a novel antigen which is selectively expressed on a subpopulation of human B lymphocytes.
The present paper describes a new monoclonal antibody (KB61) raised against hairy cell leukaemia cells. Antibody KB61 recognizes a molecule of approximately 40,000 molecular weight on human B cells. It reacts with B lymphocytes in the peripheral blood, in primary lymphoid follicles, in the mantle zone of secondary follicles, in interfollicular areas and in splenic marginal zone areas. However, germinal centre lymphoid cells do not express the antigen recognized by antibody KB61. The antibody shows limited reactivity outside the lymphoid system, i.e. polymorphs, tissue macrophages endothelial cells in the hepatic sinusoids. Antibody KB61 discriminates between different types of B-cell malignancies, reacting with the neoplastic cells in hairy cell leukaemia, chronic lymphocytic leukaemia (of B-cell type), prolymphocytic leukaemia and centrocytic lymphoma, but not with acute lymphoblastic leukaemia, germinal centre-derived lymphomas (other than centrocytic), Burkitt's lymphoma and lymphoblastic lymphoma. Antibody KB61 may be of value in the study of B-cell subpopulations and in the differential diagnosis of B-cell neoplasms.


Presenting a united front in Lansing.
Over the past five fiscal years--a period of unprecedented economic prosperity that witnessed overall funding increases for education, corrections and other state programs of 19 percent--Medicaid funding for Michigan's nonprofit hospitals increased by a meager 3 percent. Why aren't nonprofit hospitals getting a fair shake from the legislature in Lansing?


[Quality control during mammography-II (author's transl)].
The results of a pilot study on mammographic quality control in 58 x-ray departments in West Berlin are reported. Using a systematically developed phantom, an insight was gained into the present state of mammography and various unexpected faults which were diagnostically important, were revealed. Standard values for the type of radiation, effective image contrast, resolution, geometry and radiation dose could be ascertained, which can serve as a basis for mammographic quality control.


Aging of the hypothalamo-pituitary-ovarian axis: hormonal influences and cellular mechanisms.
Longitudinal studies employing heterochronic ovarian grafts and long-term ovariectomy indicate that there is no single pacemaker of reproductive aging. Neuroendocrine dysfunction, the declining follicular reserve, and ovarian secretions all contribute to reproductive decline, and their relative importance to the different stages of reproductive aging varies markedly. Moreover, although ovarian secretions during adulthood potentiate certain aspects of the reproductive aging process, their behavior does not fit a simple model of cumulative steroidal damage incurred over the lifespan. Current data are more consistent with temporally distinct windows of steroidal vulnerability for the events affected: cycle lengthening is affected by ovarian secretions during the period of cyclicity, and post-cyclic neuroendocrine failure is potentiated by ovarian secretions during the peri- and post-cyclic period of the lifespan. Recent examination of estradiol receptor dynamics reveals multiple, albeit selective, changes during aging that may contribute to the age-related impairments of tissue sensitivity to estrogen. These changes vary qualitatively and quantitatively among target tissues. Thus, aging of the hypothalamo-pituitary-ovarian axis at the cellular level mirrors, in its multifactorial nature, aging at the organismic level.