Postoperative Radiation Therapy Refusal in Major Salivary Gland Cancers.
Major salivary gland cancers (MSGCs) are often treated with primary surgery followed by adjuvant therapy for high-risk pathology. Patients with these cancers may opt out of recommended postoperative radiation therapy (PORT) for many reasons and consequently may suffer worse outcomes. Retrospective cohort study. National Cancer Database. Patients diagnosed with MSGC from 2004 to 2016 were identified, and overall survival and risk factors for refusal of recommended PORT were analyzed based on demographic, socioeconomic, and clinical factors. Multivariable logistic regression and a Cox model were used to conduct the analysis. 211 out of 4704 qualifying patients (4.5%) refused recommended PORT. Multivariable analysis demonstrated increased PORT refusal for age >74 years (odds ratio OR 4.34, confidence interval [CI] [2.43-7.85]), Asian race (OR 2.25, CI [1.10-4.23]), and certain facility types (comprehensive cancer center, OR 2.39, CI [1.08-6.34]; academic research program, OR 3.29, CI [1.49-8.74]; and integrated network cancer program, OR 2.75, CI [1.14-7.7]). N2 stage was associated with decreased PORT refusal (OR 0.67, CI [0.45-0.98]). The 5-year overall survival for patients who received and refused PORT were significantly different at 65.8% and 53.8%, respectively (p < .001). When controlling for several factors, PORT refusal was independently associated with significantly lower overall survival (HR 1.54, CI [1.21-1.98]). Patient refusal of recommended PORT in MSGC is rare, associated with various disease and socioeconomic factors, and may decrease overall survival. Our findings can assist clinicians in counseling patients and identifying those who may be more likely to opt out of recommended PORT.


An attenuated coxsackievirus b3 vector: a potential tool for viral tracking study and gene delivery.
Cardiomyocytes are quite resistant to gene transfer using standard techniques. We developed an expression vector carrying an attenuated but infectious and replicative coxsackievirus B3 (CVB3) genome, and unique ClaI-StuI cloning sites for an exogenous gene, whose product can be released from the nascent viral polyprotein by 2A(pro) cleavage. This vector was tested as an expression vehicle for green fluorescent protein (GFP). The vector transiently expressed GFP in cell cultures for at least ten passages and delivered functional GFP to the infected cardiomyocytes for at least 6 days. Moreover, the recombinant viruses showed virulence attenuation in vitro and in vivo. The findings suggest that the recombinant CVB3 vector could be a useful tool for viral tracking study and delivering exogenous proteins to cardiomyocytes.


Synovial sarcoma: a review of 33 cases.
Thirty-three patients with synovial sarcoma were studied with respect to age, sex, site, clinical presentation, pathologic findings, and primary surgical treatment. Seventy percent of the patients were in the first three decades of life, and there was a 2:1 male predominance; the overall survival rate was 36%. There was a high local recurrence rate (64%) after simple local excision, and poor survival (27%). While wide local resection gave the best results (50% survival), it also carried a risk of high recurrence. Patients treated by amputation had a 42% survival rate. Thus, it can be concluded that adequate surgical treatment improved survival and reduced the recurrence rates. The lungs were the most common metastatic site, but lymph node metastasis occurred in 27% of the patients, often after tumor recurrence. Favorable prognostic factors included youth (patients younger than 20) and biphasic or epitheloid histologic types.


FDG PET/CT of carcinoma showing thymus-like differentiation.
Carcinoma showing thymus-like differentiation is a malignant, extremely rare neoplasm that arises in the thyroid gland or neighboring neck soft tissue and closely resembles thymic carcinoma. Long-term survival is possible if the disease is diagnosed early and is completely resected, followed by radical dose radiotherapy. We present the case report of a 65-year-old man who presented with neck mass and neck pain that increase with intensity with cough. He was evaluated by thyroid ultrasound, which showed an echogenic nodule. Baseline PET/CT imaging revealed a very hypermetabolic lesion in the right lobe of the thyroid gland.


The role of melatonin, sirtuin2 and FoXO1 transcription factor in the aging process of colon in male rats.
The protein family of sirtuins and FoXO1 transcription factor have been shown to play significant roles in the aging process. In this study we aimed to investigate the changes in the levels of SIRT2, NFκB and FoXO1 and oxidative parameters of colonic mucosa during aging, and the effects of exogenous melatonin (MLT). A total of twenty-four young (3-months-old) and aged (24 months old) male Wistar rats, divided into control [1% ethanol--phosphate-buffered saline (PBS), s.c. for 21 days] and melatonin (10 mg kg(-1) MLT 1% ethanol in PBS, s.c. for 21 days) were used in the study. The levels of malondialdehyde (MDA) as a parameter of lipid peroxidation, glutathione, NFkB pathway activation, SIRT2 expression, and FoXO1 transcription factor of colonic mucosa were assayed. The MDA levels and SIRT2 expression in the colonic mucosa were significantly increased in the aged group when compared to the younger group. However, the levels of FoXO1 transcription factor were significantly decreased in the aged group. Melatonin significantly decreased the MDA and SIRT2 expression levels of the colonic mucosa in the aged rats. In conclusion, our findings suggest a suppressive role of melatonin in the aging process of colonic tissue via decreasing SIRT2 expression.


Sensitive Top-Down Proteomics Analysis of a Low Number of Mammalian Cells Using a Nanodroplet Sample Processing Platform.
Top-down proteomics is a powerful tool for characterizing genetic variations and post-translational modifications at intact protein level. However, one significant technical gap of top-down proteomics is the inability to analyze a low amount of biological samples, which limits its access to isolated rare cells, fine needle aspiration biopsies, and tissue substructures. Herein, we developed an ultrasensitive top-down platform by incorporating a microfluidic sample preparation system, termed nanoPOTS (nanodroplet processing in one pot for trace samples), into a top-down proteomic workflow. A unique combination of a nonionic detergent dodecyl-β-d-maltopyranoside (DDM) with urea as protein extraction buffer significantly improved both protein extraction efficiency and sample recovery. We hypothesize that the DDM detergent improves protein recovery by efficiently reducing nonspecific adsorption of intact proteins on container surfaces, while urea serves as a strong denaturant to disrupt noncovalent complexes and release intact proteins for downstream analysis. The nanoPOTS-based top-down platform reproducibly and quantitatively identified ∼170 to ∼620 proteoforms from ∼70 to ∼770 HeLa cells containing ∼10 to ∼115 ng of total protein. A variety of post-translational modifications including acetylation, myristoylation, and iron binding were identified using only less than 800 cells. We anticipate the nanoPOTS top-down proteomics platform will be broadly applicable in biomedical research, particularly where clinical specimens are not available in amounts amenable to standard workflows.


Parenting styles and parents' perspectives on how their own emotions affect the functioning of children with autism spectrum disorders.
The grounded theory method was used to analyze the parenting styles used by caregivers to rear children with autism spectrum disorders (ASD) and to investigate parents' experiences regarding how to help their child overcome the symptoms. Thirty-two parents from 28 families of children with ASD in mainland China were interviewed. Analysis of interview transcripts revealed four patterns of parenting styles which varied in affiliation to the roles of caretaker and coach. Based on their experience, a sizable group of parents perceived that their own emotions influence the child's emotions and his/her symptoms. The results suggest the value of developing intervention programs on emotion regulation and positive parenting for the parents of children with ASD.


[Effects of different diet composition after weaning on the obesity in rats induced by high-energy diet].
To explore the effects of different diet composition on the obesity in rats induced by high-fat diet after weaning. Male Wistar rats weaned on 24 days were randomly divided into groups A, B and C and were assigned to high carbohydrate, i.e. basic diet, high protein, high non-saturated fat diets respectively for 3 weeks. Then all groups were fed with basic diet. After 2 weeks, rats from group A were randomly divided into groups A1 and A2, A1 was assigned to basic diet continuously and groups A2, B, C were fed with high-fat diet for 6 weeks. 8 rats from each group were sacrified at the end of different treatments to detect serum glucose, TG and hormones dynamicly. High nonsaturated fat diet after weaning significantly reduced the body weight, body fat content, increased the sensitiveness to insulin, the levels of glucagons, FT4, FT3, improved leptin resistance in rats fed with high-fat diet. High-protein diet also reduced body weight, body fat content and increase lipolysis in rats fed with high-fat diet, but blood glucose in which group was higher than in group A2. High non-saturated fat diet after weaning can significantly reduce the obesity of rats fed with high-fat diet.


Alterations of the ocular surface epithelial mucins 1, 2, 4 and the tear functions in patients with atopic keratoconjunctivitis.
An increased understanding of the ocular surface alterations at the cellular level in the conjunctiva and the cornea, may help explain the pathogenesis and the subsequent clinical appearance of atopic ocular allergies, which may be potentially blinding. To investigate MUC 1, 2 and 4 alterations, tear function and the ocular surface disorder in patients with atopic keratoconjunctivitis. Twenty-eight eyes of 14 atopic keratoconjunctivitis patients as well as 22 eyes of 11 age-and sex-matched normal subjects were studied. The subjects underwent corneal sensitivity measurements, Schirmer's test, tear film break-up time (BUT), fluorescein and Rose Bengal staining of the ocular surface, conjunctival impression cytology and brush cytology. Impression cytology samples underwent periodic acid-Schiff and immunohistochemical staining with MUC 1, 2 and 4 antibodies. Brush cytology specimens underwent evaluation for inflammatory cell numbers and quantitative real-time-PCR for MUC 1, 2 and 4 mRNA expression. Patient eyes with fluorescein and Rose Bengal scores greater than four points were regarded to have significant epithelial disease in this study. The mean corneal sensitivity and BUT values were significantly lower in atopic patients with significant epithelial disease, compared with patients with insignificant epithelial disease and controls (P < 0.01). Brush cytology specimens from patients with significant epithelial disease revealed significantly higher numbers of inflammatory cells (P < 0.01). Specimens from patient eyes showed positive staining for MUC 1, 2 and 4. MUC 1, 2 and 4 mRNA expressions were significantly higher in eyes with significant epithelial disease compared with eyes with insignificant epithelial disease and eyes of control subjects. Ocular surface inflammation, decline in corneal sensitivity, tear film instability, changes in conjunctival epithelial MUC 1, 2 and 4 mRNA expressions were thought to be important in the pathogenesis of atopic ocular surface disease.


Analysis of predicted full recovery time for venous leg ulcers treated with intermittent pneumatic compression.
Venous leg ulcers are difficult-to-heal wounds. Reduction of venous hypertension and eradication of oedema is of key importance in the treatment of clinical symptoms of venous hypertension and venous leg ulcers. This can be done by using compression therapy in which external pressure is applied to the skin surface, giving a positive effect on the venous, lymphatic and arterial systems of macro- and microcirculation. Analysis of full recovery predicted time for venous ulcers. The purpose of our study was to rate the intermittent pneumatic compression (IPC) therapy in venous leg ulcers treatment. In the study group, the IPC therapy (pressure of 60 mm Hg at the ankle) was used - one treatment daily for 4 weeks. The changes of the total area, circumference, maximum length and maximum width of ulcers were measured. Then, based on the collected values, we calculated healing progress (Gilman index), healing rate, predicted healing time and non-linear approximation of the treatment time needed to decrease the ulcer surface area by 50% and then we compared them the treatment times. Analysis of the results shows that a percentage change in the surface area in the treatment group was 52%. There was a statistically significant difference between the ulcer surface area before and after treatment (p < 0.05). There was no statistically significant difference between the healing rate in individual weeks of treatment (p > 0.05). The percentage reduction in circumferences of the lower limb showed a statistically significant advantage in the study group comparison baseline (p < 0.05). Treatment of venous leg ulcers with the IPC therapy is effective.


Effect of molting on the concentration of plasma 25-hydroxyvitamin D in captive African penguins (Spheniscus demersus).
Feed intake and body weight are drastically altered in penguins during peri-molting period, and molting is known to affect the nutritional status of vitamin A and E. Although vitamin D status is not known in penguins during peri-molting period, vitamin D intake is supposed to be remarkably altered. The objective of the present study was to clarify the alterations in plasma 25-hydroxyvitamin D (25(OH)D) concentration, the most reliable biomarker for assessing vitamin D status, and vitamin D intake during peri-molting period. Blood samples were collected from seven adult male African penguins (Spheniscus demersus) in the control period, pre-molting period, early-molting period, and late-molting period. The dietary content of vitamin D and calcium (Ca) were higher than that of the estimated requirements. Feed intake increased in the pre-molting period and drastically decreased during the molting periods. Body weight increased in the pre-molting period, followed by the loss of weight towards the end of the experiment. Although vitamin D and Ca intakes decreased during the molting periods, plasma 25(OH)D concentration increased during the molting periods and the increase in plasma Ca concentration was also observed in the late-molting period. These results suggest that the reduction in body fat induced by reducing feed intake stimulated the release of vitamin D from body fat, which increased plasma 25(OH)D and Ca concentrations in molting penguins. Penguins are unlikely to suffer from typical hypervitaminosis D even during molting and vitamin D toxicity is not a realistic problem in penguins because of the short duration of molting.


Older, sociable capuchins (Cebus capucinus) invent more social behaviors, but younger monkeys innovate more in other contexts.
An important extension to our understanding of evolutionary processes has been the discovery of the roles that individual and social learning play in creating recurring phenotypes on which selection can act. Cultural change occurs chiefly through invention of new behavioral variants combined with social transmission of the novel behaviors to new practitioners. Therefore, understanding what makes some individuals more likely to innovate and/or transmit new behaviors is critical for creating realistic models of culture change. The difficulty in identifying what behaviors qualify as new in wild animal populations has inhibited researchers from understanding the characteristics of behavioral innovations and innovators. Here, we present the findings of a long-term, systematic study of innovation (10 y, 10 groups, and 234 individuals) in wild capuchin monkeys (Cebus capucinus) in Lomas Barbudal, Costa Rica. Our methodology explicitly seeks novel behaviors, requiring their absence during the first 5 y of the study to qualify as novel in the second 5 y of the study. Only about 20% of 187 innovations identified were retained in innovators' individual behavioral repertoires, and 22% were subsequently seen in other group members. Older, more social monkeys were more likely to invent new forms of social interaction, whereas younger monkeys were more likely to innovate in other behavioral domains (foraging, investigative, and self-directed behaviors). Sex and rank had little effect on innovative tendencies. Relative to apes, capuchins devote more of their innovations repertoire to investigative behaviors and social bonding behaviors and less to foraging and comfort behaviors.


Soil ingestion in adults--results of a second pilot study.
Soil ingestion was evaluated in 10 adults as part of a larger study to evaluate soil ingestion in children. Each adult was followed for 4 weeks in a mass-balance study that was designed to evaluate the detection limit for soil ingestion in a similarly designed, concurrent children's study. After a baseline week, during Weeks 2 through 4, adults received daily soil capsules containing 20, 100, and 500 mg of soil, respectively. A 1-week period separated each study week. Based on the first 3 weeks of observation after subtracting the capsule ingestion amounts, the median, 75th percentile, and 95th percentile soil ingestion estimates were 1, 49, and 331 mg/day, with estimates calculated as the median of the three trace elements Al, Si, and Y. The average estimate of soil ingestion was 10 mg/day (SD = 94 mg/day). These findings augment sparse empirical data on adult soil ingestion, and suggest lower levels of soil ingestion in adults than previous studies.


The control of Chagas' disease in Mambaí, Brazil: the initial phases.
The control of Chagas' disease depends on breaking contact between Man and vector organisms living in the house fabric; the primary method utilized is residual insecticide spraying of houses. Ministries of health in afflicted countries have elaborated standard procedures for such combat programs. The first two phases of such a program in Mambaí, Goiaś, Brazil are described. In the third phase of vigilance, community participation is necessary to detect residual organism populations in houses. A house improvement scheme applied to houses with persistent infection, is recommended as being most practical at this time.


ELISA study of oocyst-sporozoite transition in malaria vectors.
Intrinsic vector characteristics and environmental factors affect the sporogonic development of P. falciparum in Anopheles mosquitoes. We tested for the presence of the circumsporozoite protein, as a marker of the oocyst to sporozoite transition in naturally infected Anopheles gambiae s.l. and Anopheles funestus. Malaria vectors were collected in a village in the Sahel of Niger during the rainy and dry seasons. ELISA-CSP was carried out on abdomen and head/thorax portions from more than 2000 samples. No significant difference was found in the overall rates of infection of An. gambiae s.l. (4.13%) and An. funestus (3.58%). Given the differences in duration of the two parasite stages, P. falciparum CSP antigen prevalence was nearly as high in the abdomen as in the head/thorax, and did not differ significantly between An. gambiae s.l. and An. funestus. These preliminary results suggest that development from oocysts to salivary gland sporozoites is similar in the two vectors. However, these developmental indices varied as a function of the season in which samples were collected, particularly for An. gambiae s.l. This simple method may be useful for field studies assessing the effect of environmental and genetic factors on parasite survival.


A new species of the genus Amyrsidea (Phthiraptera: Amblycera: Menoponidae) parasitizing domestic chickens in Saudi Arabia.
Amyrsidea Ewing, 1927 is a genus of chewing lice comprising 52 species, divided into five subgenera: Amyrsidea sensu stricto, Argimenopon Eichler, 1947, Cracimenopon Carriker, 1954, Desumenopon Carriker, 1954 and Numidimenopon Scharf & Price, 1977 (see Price et al. 2003: 86), which parasitise a wide range of hosts belonging to the avian order Galliformes (see Price et al. 2003: 321). Species of Amyrsidea can be distinguished from species of Menacanthus Neumann, 1912-the other menoponid genus with species parasitic on the same hosts-by lacking ventral spinous processes in the head (Scharf & Price 1977: 815). Revisions of all subgenera and species of Amyrsidea, including keys for their identification, were published by Scharf & Price (1977, 1983) and Scharf & Emerson (1983, 1984).


Current treatment and outcome of esophageal perforations in adults: systematic review and meta-analysis of 75 studies.
The current prognosis of esophageal perforation and the efficacy of available treatment methods are not well defined. We performed a systematic review of esophageal perforations published from January 2000 to April 2012 and subjected a proportion of the retrieved data to a meta-analysis. Meta-regression was performed to determine predictors of mortality immediately after esophageal perforation. Analysis of 75 studies resulted in a pooled mortality of 11.9 % [95 % confidence interval (CI) 9.7-14.3: 75 studies with 2,971 patients] with a mean hospital stay of 32.9 days (95 % CI 16.9-48.9: 28 studies with 1,233 patients). Cervical perforations had a pooled mortality of 5.9 %, thoracic perforations 10.9 %, and intraabdominal perforations 13.2 %. Mortality after esophageal perforation secondary to foreign bodies was 2.1 %, iatrogenic perforation 13.2 %, and spontaneous perforation 14.8 %. Treatment started within 24 h after the event resulted in a mortality rate of 7.4 % compared with 20.3 % in patients treated later (risk ratio 2.279, 95 % CI 1.632-3.182). Primary repair was associated with a pooled mortality of 9.5 %, esophagectomy 13.8 %, T-tube or any other tube repair 20.0 %, and stent-grafting 7.3 %. Results of recent studies indicate that mortality after esophageal perforation is high despite any definitive surgical or conservative strategy. Stent-grafting is associated with somewhat lower mortality rates, but studies may be biased by patient selection and limited experience.


Human Serum Albumin Nanoparticles: Synthesis, Optimization and Immobilization with Antituberculosis Drugs.
The aim of this study was to create nanoparticles of human serum albumin immobilized with anti-TB drugs (rifampicin, isoniazid) using the desolvation method. Central Composite Design (CCD) was applied to study the effect of albumin, urea, L-cysteine, rifampicin and isoniazid concentration on particle size, polydispersity and loading degree of the drugs. The optimized nanoparticles were spherical in shape with an average particle size of 216.7 ± 3.7 nm and polydispersity of 0.286 ± 4.9. The loading degree of rifampicin and isoniazid in the optimized nanoparticles were 44% and 27%, respectively. The obtained nanoparticles were examined by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC); the results showed the absence of drug-polymer interactions. The drug release from the polymer matrix was studied using dialysis membranes.


Visualized Lateral Flow Assay for Dual Viral RNA Fragment Detection.
In this technical note, we report an easy-to-produce, reverse-transcription-free, and protein-enzyme-free lateral flow assay for detection of viral RNA fragments by taking SARS-CoV-2 ORF1ab and N as target models. Catalytic hairpin assembly is utilized for dual RNA fragment orthogonal reaction to generate copious amounts of opened hairpin duplexes, which bridge DNA-modified gold nanoparticles and capture strands on the strip to induce coloration. The dual RNA fragments are simultaneously visualized during one time of sample flow, and single-base-mismatched nontarget sequences can be differentiated. The test strip can be flexibly adapted to detect evolutional SARS-CoV-2 variants such as Delta and Omicron. It also shows potential in visually detecting long-sequence virus simulants and achieves a sensitivity comparable to that of RT-qPCR by incorporation with upstream sample amplification. The lateral flow assay should offer a convenient and reliable technique for viral nucleic acid detection.


Norcantharidin inhibits viability and induces cell cycle arrest and apoptosis in osteosarcoma.
Osteosarcoma is the most frequent malignant bone tumor in children and adolescents. Norcantharidin (NCTD) is a purified component from blister beetles and has been identified to exert antitumor effects in a variety of cancer types. However, the antitumor effect of NCTD in osteosarcoma remains to be elucidated. In the current study, it was first demonstrated that NCTD inhibited proliferation and induced G2/M-phase arrest and cell apoptosis in human osteosarcoma cells. Furthermore, NCTD significantly decreased the phosphorylation of Akt and the mammalian target of rapamycin in human osteosarcoma cells. These results suggest that NCTD is a promising candidate for the treatment of osteosarcoma patients in the future.


PiTMaP: A New Analytical Platform for High-Throughput Direct Metabolome Analysis by Probe Electrospray Ionization/Tandem Mass Spectrometry Using an R Software-Based Data Pipeline.
A new analytical platform called PiTMaP was developed for high-throughput direct metabolome analysis by probe electrospray ionization/tandem mass spectrometry (PESI/MS/MS) using an R software-based data pipeline. PESI/MS/MS was used as the data acquisition technique, applying a scheduled-selected reaction monitoring method to expand the targeted metabolites. Seventy-two metabolites mainly related to the central energy metabolism were selected; data acquisition time was optimized using mouse liver and brain samples, indicating that the 2.4 min data acquisition method had a higher repeatability than the 1.2 and 4.8 min methods. A data pipeline was constructed using the R software, and it was proven that it can (i) automatically generate box-and-whisker plots for all metabolites, (ii) perform multivariate analyses such as principal component analysis (PCA) and projection to latent structures-discriminant analysis (PLS-DA), (iii) generate score and loading plots of PCA and PLS-DA, (iv) calculate variable importance of projection (VIP) values, (v) determine a statistical family by VIP value criterion, (vi) perform tests of significance with the false discovery rate (FDR) correction method, and (vii) draw box-and-whisker plots only for significantly changed metabolites. These tasks could be completed within ca. 1 min. Finally, PiTMaP was applied to two cases: (1) an acetaminophen-induced acute liver injury model and control mice and (2) human meningioma samples with different grades (G1-G3), demonstrating the feasibility of PiTMaP. PiTMaP was found to perform data acquisition without tedious sample preparation and a posthoc data analysis within ca. 1 min. Thus, it would be a universal platform to perform rapid metabolic profiling of biological samples.


Ab initio spin-orbit calculations on the lowest states of the nickel dimer.
Potential energy curves of the lowest electronic states of the Ni(2) dimer are calculated near the equilibrium using the multireference ab initio methods including the spin-orbit interaction. Scalar-relativistic results fully confirm previous qualitative interpretations based on the correlation with atomic limits and the symmetry of vacancies in the atomic 3d(9) shells. Spin-orbit calculations firmly establish the symmetry of the ground state as 0(+)(g) and give the excitation energies 70 ± 30 cm(-1) and 200 ± 80 cm(-1) for the lowest 0(-)(u) and 5(u) states, respectively. The model electronic spectrum of the Ni(2) shows some trends that might be observed in matrix isolation far-infrared and electron spin resonance spectra.


Are ataques de nervios in Puerto Rican children associated with psychiatric disorder?
To provide the first empirical analysis of a cultural syndrome in children by examining the prevalence and psychiatric correlates of ataques de nervios in an epidemiological study of the mental health of children in Puerto Rico. Probability samples of caretakers of children 4-17 years old in the community (N = 1,892; response rate: 90%) and in clinical services (N = 761; response rate 72%) were administered structured interviews to assess the presence and correlates of ataques de nervios. Nine percent of children in the community sample and 26% of children in the clinical sample had a reported history of an ataque de nervios. In contrast to the overall community and clinical samples, which had more boys in them, the ataque de nervios groups in both samples had more girls in them. Family history of ataques de nervios was associated with ataques de nervios in children in both samples. Across a wide range of depression, anxiety, and disruptive disorders, children who reported an ataque de nervios were more likely to meet research criteria for psychiatric disorder in both samples. Ataques de nervios are a frequently reported cultural syndrome among children in Puerto Rico. Adolescent girls are more likely to report this experience. Ataques de nervios have a significant relationship with psychiatric disorder and impairment in Puerto Rican children.


Preliminary Evaluation of the Research-Use-Only (RUO) iCubate iC-GPC Assay for Identification of Select Gram-Positive Bacteria and Their Resistance Determinants in Blood Culture Broths.
The iC-GPC assay (iCubate, Huntsville, AL) provides a molecular option for the rapid, on-demand analysis of positive blood cultures. A preliminary evaluation of the iC-GPC assay using 203 clinical or seeded specimens demonstrated a sensitivity of 93.8% to 100% and a specificity of 98.0% to 100% for the identification of five Gram-positive bacterial species (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Enterococcus faecalis, and Enterococcus faecium) and three associated genetic resistance determinants (mecA, vanA, and vanB) in positive blood culture broths.


Prospective analysis of the association between skeletal-related events and quality of life in patients with advanced lung cancer (CSP-HOR13).
A prospective study has previously reported on the incidence of bone metastasis (BM) and skeletal-related events (SREs) in patients with advanced lung cancer. The aim of the present study was to prospectively investigate how the quality of life (QOL) of patients with advanced lung cancer was affected by SREs. Patients with stage IIIB or IV non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) at any stage were followed up every four weeks to determine if they had developed SREs. QOL questionnaires were conducted at enrollment, at 3- and 12-months later and at 1 month after the onset of SREs, using QOL scores including the EuroQOL-5 Dimension (EQ-5D), Functional Assessment of Cancer Therapy-General (FACT-G) and activities of daily living (ADL) scores obtained by the Barthel Index. A total of 274 patients were enrolled in the study. At enrollment the EQ-5D and Barthel Index scores were lower in patients with SREs compared with patients without SREs. A chronological analysis revealed no statistically significant changes in either QOL or ADL in any of the patients. For 14 patients in whom QOL data was collected following the onset of SREs, the evaluation undertaken on the four subscales of the FACT-G revealed a significant decline in emotional functioning following the onset of SREs.


Kinetic and structural characterization of spinach carbonic anhydrase.
We have carried out kinetics studies of spinach carbonic anhydrase (CA) using stopped-flow spectrophotometry at steady state and 13C-NMR exchange at chemical equilibrium. We found that the rate of CO2<-->HCO3- exchange catalyzed by spinach CA at pH 7.0 to be 3-5 times faster than the maximal kcat for either CO2 hydration or HCO3- dehydration at steady state, suggesting a rate-determining H+ transfer step in the catalytic mechanism. Correspondingly, we measured a pH-independent solvent deuterium isotope effect on kcat of approximately 2.0, and found that the rate of catalysis was significantly decreased at external buffer concentrations below 5 mM. Our results are consistent with a zinc-hydroxide mechanism of action with for spinach CA, similar to that of animal carbonic anhydrases. We have also collected X-ray absorption spectra of spinach CA. Analysis of the extended fine structure (EXAFS) suggests that the coordination sphere of Zn in spinach CA must have one or more sulfur ligands, in contrast to animal CAs which have only nitrogen and oxygen ligands. The models which best fit the data have average Zn-N(O) distances of 1.99-2.06 A, average Zn-S distances of 2.31--2.32 A, and a total coordination number of 4-6. We conclude that animal and spinach CAs are convergently evolved enzymes which are structurally quite different, but functionally equivalent.


Simultaneous LC-MS/MS analysis of the plasma concentrations of a cocktail of 5 cytochrome P450 substrate drugs and their metabolites.
A "cocktail" approach, which involves simultaneous administration of multiple CYP-specific probes, concurrently detects the activity of multiple CYP enzymes. We developed and validated a rapid and selective LC-MS/MS method for determining the plasma concentrations of 5 CYP probe drugs and metabolites (caffeine/paraxanthine, CYP1A2 substrate; losartan/losartan carboxylic acid (E3174), CYP2C9 substrate; omeprazole/5-hydroxyomeprazole, CYP2C19 substrate; dextromethorphan/dextrorphan, CYP2D6 substrate; and midazolam/1'-hydroxymidazolam, CYP3A4 substrate) by single-step extraction, followed by a single LC-MS/MS run. An Ostro™ 96-well plate was used for extraction of CYP substrates and metabolites from human plasma and urine. Following optimization of the chromatographic conditions, all the peaks were well separated, and retention times ranged between 4.4 and 11.7 min. The total run time for a single injection was within 13 min. The accuracy and precision values suggested that the assay had high accuracy and reliability in plasma and urine samples. No significant matrix interference was observed. To demonstrate the efficacy of this method, plasma and urine concentrations of 5 CYP probe substrates and their metabolites were determined after simultaneous oral administration of 5 drugs to 4 healthy volunteers. All the substrates and metabolites were detected over an 8 h period, and the plasma concentrations of each substrate at 8 h after administration were above the lower limit of quantification. Urine concentrations of drugs and their metabolic ratio were evaluated after the administration. In conclusion, the advantage of our cocktail approach is that it enables in vivo assessment of the activity of various drug-metabolizing enzymes in a single assay.


Estimation of G-quartet-forming guanines in parallel-type G-quadruplexes by optical spectroscopy measurements of their single-nucleobase substitution sequences.
Since much attention has been paid to in vivo biological functions of G-quadruplexes, structural analyses of G-quadruplexes are essential for understanding their functional mechanisms. Here, we established a simple optical-spectroscopy-based method for the estimation of G-quartet-forming guanines in parallel-type G-quadruplexes using measurements of circular dichroism and the thermal melting temperature.


Hyporeactivity to interferon induction in newborn piglets.
The aim of this study was to produce sustained activation of natural killer (NK) cells in newborn piglets by interferon (IFN) induction with polyinosinic:polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose [poly(ICLC)]. When a second dose of poly(ICLC) was given 24 or 48 h after the first dose, the piglets were found to be hyporeactive, and the levels of induced IFN were insufficient to activate NK cells in vivo or in vitro. A hyporeactive factor was demonstrated in the serum of piglets 24 and 48 h after they were treated with poly(ICLC), which inhibited IFN induction in vitro with poly(ICLC) but not with Newcastle disease virus. The IFN response of hyporeactive piglets was partially restored by the administration of prostaglandin (PG) F2 alpha at the same time as the second dose of poly(ICLC); piglets treated in this way at 3 days of age showed significantly higher lymphocytic NK activity at 5 days and 7 days than the activity in untreated piglets and in those given one or two doses of poly(ICLC) in the absence of PG F2 alpha. It was concluded that piglets develop hyporeactivity to IFN induction, but the IFN and NK cell activation responses to poly(ICLC) can be restored by treatment with PG.


Caries Severity, Decayed First Permanent Molars and Associated Factors in 6-7 Years Old Schoolchildren Living in Palermo (Southern Italy).
To date, there are very few epidemiologic studies on caries disease in 6-7 year old children living in Sicily (Southern Italy). The first permanent molar (FPM) is the most commonly affected tooth in this target population, and a one-unit increase in the number of decayed FPMs is predictive of caries in other teeth and in adulthood. The primary aim of this research is to estimate the prevalence of caries in 6-7 year old schoolchildren living in Palermo and, as a secondary aim, to estimate the prevalence of affected FPMs. It was designed as a cluster cross-sectional survey on 995 children from 16 schools, selected based on their geographical location, in one of the eight city districts. Caries data were recorded using the International Caries Detection and Assessment System for each tooth surface. The relation between socio-economic status, behavioural determinants, and clinical information and the number of teeth with initial caries (IC), moderate caries (MC), or extensive caries (SC) was analysed through the ordinal logistic regression. Among the 995 schoolchildren, 662 (66.5%) had at least one lesion and 742 (74.6%) had FPMs. Of the latter, 238 (32.0%) were affected by IC, 86 (11.6%) were affected by MC, and only 3 (0.4%) were affected by SC. During multivariable analysis, there was evidence of an increased risk of MC and SC related to the deprivation of the district in which the children lived and went to school, as well as to the protective role of parental education and employment. The same significant determinants were found for IC and MC FPMs. The study showed the important role of socio-economic determinants, unhealthy behaviours, and social deprivation related to the increased risk of moderate and extensive caries in 6-7 year old schoolchildren. Investigating this target population is very important, as early development of caries in FPMs may have serious consequences in the prognostics of oral health in an adult.


Retrospective analysis of the effect of acid-suppressant therapy on clinicopathologic parameters of cats with chronic kidney disease.
Objectives The aim was to retrospectively evaluate the effects of acid-suppressant therapy in a population of cats with chronic kidney disease (CKD). The study objectives were to evaluate the effects of acid-suppressant therapy on clinicopathologic variables and progression of CKD over time. Methods The databases of two institutions were searched over an 11 year time span for cats fitting inclusion criteria for CKD. A total of 89 cats met the criteria for inclusion and were grouped according to either early (ie, stages 1-2) or advanced (ie, stages 3-4) CKD. Variables were statistically analyzed before and after treatment with either: (1) proton pump inhibitors (PPIs; n = 17), (2) histamine-2 receptor antagonists (H2RAs; n = 30), (3) combined acid-suppressant therapy (PPI + H2RA; n = 6) or (4) no acid-suppressant therapy (n = 36). Shapiro-Wilk testing and Q-Q plots were used to assess normality and variance, respectively. A complete randomized design with a mixed-effects repeated measures ANOVA was used to evaluate for differences in stage, treatment and time, as well as the interaction between these effects. Results A significant increase in blood creatinine concentration was found over time independent of severity of CKD and treatment group ( P = 0.0087). A significant increase in blood sodium concentration (change of 3.12 mmol/l) was found independent of stage in cats receiving PPI therapy ( P = 0.0109). A significant decrease in total blood magnesium (change of 0.15 mmol/l) was detected in two cats with early CKD receiving combined acid suppressants ( P = 0.0025). Conclusions and relevance Results of this retrospective study suggest that cats with CKD receiving PPI therapy may develop alterations in blood sodium concentrations but do not experience more rapid progression of CKD.


Three Nordic berries inhibit intestinal tumorigenesis in multiple intestinal neoplasia/+ mice by modulating beta-catenin signaling in the tumor and transcription in the mucosa.
Berries contain a number of compounds that are proposed to have anticarcinogenic properties. We studied the effects and molecular mechanisms of wild berries with different phenolic profiles on intestinal tumorigenesis in multiple intestinal neoplasia/+ mice. The mice were fed a high-fat AIN93-G diet (Con) or AIN93-G diets containing 10% (w:w) freeze-dried bilberry, lingonberry (LB), or cloudberry (CB) for 10 wk. All 3 berries significantly inhibited the formation of intestinal adenomas as indicated by a 15-30% reduction in tumor number (P < 0.05). CB and LB also reduced tumor burden by over 60% (P < 0.05). Compared to Con, CB and LB resulted in a larger (P < 0.05) proportion of small adenomas (43, 69, and 64%, respectively) and a smaller proportion of large adenomas (56, 29, and 33%, respectively). Beta-catenin and cyclin D1 in the small and large adenomas and in the normal-appearing mucosa were measured by Western blotting and immunohistochemistry. CB resulted in decreased levels of nuclear beta-catenin and cyclin D1 and LB in the level of cyclin D1 in the large adenomas (P < 0.05). Early changes in gene expression in the normal-appearing mucosa were analyzed by Affymetrix microarrays, which revealed changes in genes implicated in colon carcinogenesis, including the decreased expression of the adenosine deaminase, ecto-5'-nucleotidase, and prostaglandin E2 receptor subtype EP4. Our results indicate that berries are potentially a rich source of chemopreventive components.


Cocaine alters vesicular dopamine sequestration and potassium-stimulated dopamine release: the role of D2 receptor activation.
Cocaine is a psychostimulant that inhibits the inward transport of dopamine (DA) via the neuronal DA transporter, thereby increasing DA concentrations in the synaptic cleft. Cocaine administration also causes a redistribution of striatal vesicular monoamine transporter (VMAT)-2-containing vesicles that co-fractionate with synaptosomal membranes after osmotic lysis (referred to herein as membrane-associated vesicles) to a nonmembrane-associated, cytoplasmic subcellular fraction. Although previous studies from our laboratory have focused on the impact of cocaine on cytoplasmic vesicles, the present report describes the pharmacological effects of cocaine on the membrane-associated vesicle population. Results revealed that the redistribution of VMAT-2 and associated vesicles away from synaptosomal membranes is associated with a decrease in total DA transport and DA content in the membrane-associated VMAT-2-containing subcellular fraction. Cocaine also decreases the velocity and magnitude of K+-stimulated exocytotic DA release from whole striatal suspensions. The cocaine-induced VMAT-2 redistribution, decrease in DA release, and decrease in total DA transport are mediated by D2 receptors as these events were prevented by pretreatment with the D2 receptor antagonist, eticlopride [S-(-)-3-chloro-5-ethyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-hydroxy-2-methoxybenzamide hydrochloride]. These data suggest that after cocaine administration, D2 receptors are activated because of increased synaptic DA, resulting in a redistribution of DA-containing vesicles away from synaptosomal membranes, thus leading to less DA released after a depolarizing stimulus. These findings provide insight into not only the mechanism of action of cocaine but also mechanisms underlying the regulation of dopaminergic neurons.


Myocardial texture and cardiac calcification in uremia.
Seventy patients with advanced chronic renal failure were examined by 2D echocardiography in an effort to determine the prevalence of changes in myocardial texture and of valvular calcification. Changes in myocardial texture may be due to calcium deposition in the myocardium, the relationship between changes in myocardial texture and factors that may enhance myocardial calcification (blood levels of parathyroid hormone, PTH, and calcium-phosphorus product) were also evaluated. Myocardial texture was abnormal in 36 patients. In 68 patients, structural calcification could be assessed; a high degree of calcification was found. No correlation was found between either the echocardiographic parameter and blood levels of PTH or calcium-phosphorus product. We conclude that myocardial textural changes and intracardiac calcification are common in chronic renal failure and that these abnormalities do not correlate with blood PTH levels or calcium-phosphorus product.


Platelet Contributions to Myocardial Ischemia/Reperfusion Injury.
Obstruction of a coronary artery causes ischemia of heart tissue leading to myocardial infarction. Prolonged oxygen deficiency provokes tissue necrosis, which can result in heart failure and death of the patient. Therefore, restoration of coronary blood flow (reperfusion of the ischemic area) by re-canalizing the affected vessel is essential for a better patient outcome. Paradoxically, sudden reperfusion also causes tissue injury, thereby increasing the initial ischemic damage despite restoration of blood flow (=ischemia/reperfusion injury, IRI). Myocardial IRI is a complex event that involves various harmful mechanisms (e.g., production of reactive oxygen species and local increase in calcium ions) as well as inflammatory cells and signals like chemokines and cytokines. An involvement of platelets in the inflammatory reaction associated with IRI was discovered several years ago, but the underlying mechanisms are not yet fully understood. This mini review focusses on platelet contributions to the intricate picture of myocardial IRI. We summarize how upregulation of platelet surface receptors and release of immunomodulatory mediators lead to aggravation of myocardial IRI and subsequent cardiac damage by different mechanisms such as recruitment and activation of immune cells or modification of the cardiac vascular endothelium. In addition, evidence for cardioprotective roles of distinct platelet factors during IRI will be discussed.


Mapping Loci for fox domestication: deconstruction/reconstruction of a behavioral phenotype.
During the second part of the twentieth century, Belyaev selected tame and aggressive foxes (Vulpes vulpes), in an effort known as the "farm-fox experiment", to recapitulate the process of animal domestication. Using these tame and aggressive foxes as founders of segregant backcross and intercross populations we have employed interval mapping to identify a locus for tame behavior on fox chromosome VVU12. This locus is orthologous to, and therefore validates, a genomic region recently implicated in canine domestication. The tame versus aggressive behavioral phenotype was characterized as the first principal component (PC) of a PC matrix made up of many distinct behavioral traits (e.g. wags tail; comes to the front of the cage; allows head to be touched; holds observer's hand with its mouth; etc.). Mean values of this PC for F1, backcross and intercross populations defined a linear gradient of heritable behavior ranging from tame to aggressive. The second PC did not follow such a gradient, but also mapped to VVU12, and distinguished between active and passive behaviors. These data suggest that (1) there are at least two VVU12 loci associated with behavior; (2) expression of these loci is dependent on interactions with other parts of the genome (the genome context) and therefore varies from one crossbred population to another depending on the individual parents that participated in the cross.


Systemic Metronidazole May Not Reduce Posthemorrhoidectomy Pain: A Meta-Analysis of Randomized Controlled Trials.
Hemorrhoidectomy is associated with significant postoperative pain. Oral metronidazole has been recommended as an adjunct to improve posthemorrhoidectomy analgesia. This study aimed to evaluate the impact of oral metronidazole on patient-reported pain following hemorrhoidectomy. We conducted a systematic search in the MEDLINE, EMBASE, ISI Web of Science, and Cochrane Central Register of Controlled Trials databases. Randomized controlled trials examining adults who underwent surgical hemorrhoidectomy were included. Participants in an active intervention group received oral metronidazole postoperatively, and those in a control group received placebo or usual care. Postoperative pain was assessed for at least 3 days postoperatively. A random-effects model was used. The primary outcome was pain during the first 2 postoperative weeks, measured on a visual analogue scale. The secondary outcome was time to return to normal activities. Patients who received oral metronidazole had significantly lower reported pain scores on postoperative day 1 (standardized mean difference, -0.87 ± 0.44; 95% CI, -1.73 to -0.015; p = 0.046; n = 4) and day 4 (standardized mean difference, -1.43 ± 0.71; 95% CI, -2.83 to -0.037; p = 0.044; n = 3). Metronidazole use was associated with a significantly shorter time to return to normal activities (standardized mean difference, -0.76 ± 0.34; 95% CI, -1.43 to -0.088, p = 0.027). The improvements disappeared in a sensitivity analysis excluding the largest trial with a high risk of bias, and no significance was observed during the remaining postoperative days. The meta-analysis was limited by lack of double blinding, absence of a placebo, and unclear or high risk of bias in a proportion of the included trials. Although a favorable adverse effect profile supports consideration of oral metronidazole to reduce posthemorrhoidectomy pain, pooled analysis reveals inconsistent results with no pain reduction on most postoperative days. The current recommendation for routine prescription of oral metronidazole should be reevaluated in the absence of additional well-designed trials.


Maternal high-fat diets cause insulin resistance through inflammatory changes in fetal adipose tissue.
Epidemiological and animal studies have shown that maternal obesity predisposes the offspring to obesity and the metabolic syndrome, possibly via late-onset metabolic programming of the fetus. Little is known, however, about the metabolic effect of maternal obesity on the fetus. This study investigated the effect of a maternal high-fat diet (HFD) on fetal growth and glucose metabolism using a diet-induced obesity mouse model. Female mice (6 weeks old; C57BL/6N) were fed either a normal chow diet (NCD, 10 kcal% fat) or an HFD (60 kcal% fat) for 4 weeks before mating and throughout pregnancy. At 17 days of gestation, gene expression of inflammatory markers and adipokines in fetal subcutaneous adipose tissue was analyzed by quantitative real-time polymerase chain reaction. HFD mice were overweight, glucose intolerant and insulin resistant compared with NCD mice of the same gestational age. Although fetal body weight was not significantly different, fetal plasma glucose and insulin levels were higher in the HFD group than the NCD group. Furthermore, examination of fetal subcutaneous adipose tissue in the HFD group revealed hypertrophy with an increase in the levels of cluster of differentiation-68, chemokine receptor-2 and tumor necrosis factor-α mRNA, but a decrease in the level of glucose transporter-4 mRNA. Maternal HFD causes inflammatory changes in the adipose tissue of offspring.


Use of regulated secretion in protein production from animal cells: an evaluation with the AtT-20 model cell line.
Regulated secretion, i.e., the ability of certain specialized animal cells to store secretory proteins intracellularly and release them upon stimulation, may be used to realize production schemes that facilitate downstream processing of protein products. Mouse AtT-20 cells expressing recombinant human insulin and human growth hormone (hGH) were found to secrete the proteins at relatively low and constant rates when exposed to media with no secretion agonists: basal rates were 1.0-1.6 microU insulin-related peptides and 0.38 ng hGH/10(5) cells-h. When induced with 8 brorno-cyclic AMP (BrcAMP), the cells secreted recombinant proteins at initial rates 3.5-9-fold higher. A cycling secretion experiment was conducted with the insulin-producing cells in which the cells were exposed alternately to complete growth medium and to secretion medium with BrcAMP. During the first three cycles, the cells secreted immunoreactive insulin at the foregoing high induced rates when they were exposed to BrcAMP. The cells then started to detach from the culture surface, leading to a reduction of BrcAMP-induced secretion. Operational modifications that may result in improved system performance are discussed.


An Alternate Synthesis of the Capsaicinoids.
Five capsaicinoids, the pungent ingredients of hot peppers, have been efficiently synthesized by a method involving the Wittig reaction between isobutyl triphenylphosphorane and the appropriate lactols (3), followed by the nitrous acid-induced isomerization of the resultant (Z)-olefins (4) to (E)-olefins (5).


An unusual cause of acute kidney injury due to oxalate nephropathy in systemic scleroderma.
Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration.


Power-time, force-time, and velocity-time curve analysis during the jump squat: impact of load.
The purpose of this investigation was to examine the impact of load on the power-, force- and velocity-time curves during the jump squat. The analysis of these curves for the entire movement at a sampling frequency of 200-500 Hz averaged across 18 untrained male subjects is the most novel aspect of this study. Jump squat performance was assessed in a randomized fashion across five different external loads: 0, 20, 40, 60, and 80 kg (equivalent to 0 +/- 0, 18 +/- 4, 37 +/- 8, 55 +/- 12, 74 +/- 15% of 1RM, respectively). The 0-kg loading condition (i.e., body mass only) was the load that maximized peak power output, displaying a significantly (p <or=.05) greater value than the 40, 60, and 80 kg loads. The shape of the force-, power-, and velocity-time curves changed significantly as the load applied to the jump squat increased. There was a significantly greater rate of power development in the 0 kg load in comparison with all other loads examined. As the first comprehensive illustration of how the entire power-, force-, and velocity-time curves change across various loading conditions, this study provides extensive evidence that a load equaling an individuals body mass (i.e., external load = 0 kg) maximizes power output in untrained individuals during the jump squat.


Intrauterine programming of the endocrine pancreas.
Epidemiological studies have revealed strong relationships between poor foetal growth and subsequent development of the metabolic syndrome. Persisting effects of early malnutrition become translated into pathology, thereby determine chronic risk for developing glucose intolerance and diabetes. These epidemiological observations identify the phenomena of foetal programming without explaining the underlying mechanisms that establish the causal link. Animal models have been established and studies have demonstrated that reduction in the availability of nutrients during foetal development programs the endocrine pancreas and insulin-sensitive tissues. Whatever the type of foetal malnutrition, whether there are not enough calories or protein in food or after placental deficiency, malnourished pups are born with a defect in their beta-cell population that will never completely recover, and insulin-sensitive tissues will be definitively altered. Despite the similar endpoint, different cellular and physiological mechanisms are proposed. Hormones operative during foetal life like insulin itself, insulin-like growth factors and glucocorticoids, as well as specific molecules like taurine, or islet vascularization were implicated as possible factors amplifying the defect. The molecular mechanisms responsible for intrauterine programming of the beta cells are still elusive, but two hypotheses recently emerged: the first one implies programming of mitochondria and the second, epigenetic regulation.


Similar structures in gamma-carboxymuconolactone decarboxylase and beta-ketoadipate succinyl coenzyme A transferase.
gamma-Carboxymuconolactone decarboxylase (EC 220.127.116.11) and beta-ketoadipate succinyl coenzyme A transferase (EC 184.108.40.206) mediate different steps in the beta-ketoadipate pathway. Antisera prepared against the Pseudomonas putida transferase cross-reacted immunologically with the decarboxylase from the same organism. The transferase is formed by association of two nonidentical protein subunits. The NH2-terminal amino acid sequences of the two nonidentical transferase subunits resembled each other and also were similar to the NH2-terminal amino acid sequence of the decarboxylase.


MONTE CARLO SIMULATION OF THE BREMSSTRAHLUNG RADIATION FOR THE MEASUREMENT OF AN INTERNAL CONTAMINATION WITH PURE-BETA EMITTERS IN VIVO.
Rapid measurement techniques are required for a large-scale emergency monitoring of people. In vivo measurement of the bremsstrahlung radiation produced by incorporated pure-beta emitters can offer a rapid technique for the determination of such radionuclides in the human body. This work presents a method for the calibration of spectrometers, based on the use of UPh-02T (so-called IGOR) phantom and specific (90)Sr/(90)Y sources, which can account for recent as well as previous contaminations. The process of the whole- and partial-body counter calibration in combination with application of a Monte Carlo code offers readily extension also to other pure-beta emitters and various exposure scenarios.


The gravitostat protects diet-induced obese rats against fat accumulation and weight gain.
The gravitostat is a novel homeostatic body weight-regulating mechanism, mostly studied in mice, and recently confirmed in obese humans. In the present study, we explored the effect of weight loading on metabolic outcomes, meal patterns and parameters linked to energy expenditure in both obese and lean rats. Diet-induced obese (DIO) and lean rats were implanted with capsules weighing either 15% of biological body weight (load) or empty capsules (1.3% of body weight; controls). Loading protected against fat accumulation more markedly in the DIO group. In line with this, the obesity-related impairment in insulin sensitivity was notably ameliorated in DIO rats upon loading, as revealed by the reduction in serum insulin levels and homeostatic model assessment for insulin resistance index scores. Although 24-hour caloric intake was reduced in both groups, this effect was greater in loaded DIO rats than in loaded lean peers. During days 10-16, after recovery from surgery, loading: (i) decreased meal size in both groups (only during the light phase in DIO rats) but this was compensated in lean rats by an increase in meal frequency; (ii) reduced dark phase locomotor activity only in lean rats; and (iii) reduced mean caloric efficiency in DIO rats. Muscle weight was unaffected by loading in either group. Dietary-obese rats are therefore more responsive than lean rats to loading.


The blood supply of the papillary muscles of the left ventricle in the Hereford cattle.
The blood supply of the Papillary Muscle (PM) of the left ventricle, cranial (PM) and caudal (PM), in Hereford cattle was studied. The results obtained from the dissection of 50 hearts injected with neoprene latex, indicated that the cranial PM is supplied by collateral of the Ramus descendens paraconalis in all cases, alone or together with vessels from the Ramus circumflexus of the Arteria coronaria sinistra. The caudal PM is supplied from arteries coming mainly from the Ramus circumflexus of the A. coronaria sinistra, and also from the Ramus descendens subsinuosus and Ramus descendens paraconalis. When present, the A. diagonalis supplies the cranial PM and in some cases the caudal PM too. Thus this vessel can be termed "artery of the papillary muscle".


Congenital myotonic dystrophy in Britain. I. Clinical aspects.
A clinical and genetic study of congenital myotonic dystrophy in Britain has been carried out in 70 patients from 54 sibships. The clinical aspects are analysed here, and the existence of a syndrome clinically distinct from myotonic dystrophy of later onset is confirmed. Characteristic features included neonatal hypotonia, motor and mental retardation, and facial diplegia. A high incidence of talipes occurs at birth together with hydramnios and reduced fetal movements during pregnancy, factors suggesting prenatal onset of the disorder in many cases. Prolonged survival is the rule after infancy, but the occurrence of numerous neonatal deaths in the sibships suggests the existence of unrecognized cases dying in the neonatal period.


Study on the plant and fish production in the aquaponic system as affected by different hydraulic loading rates.
Aquaponics is the combined culture of fish and plants in recirculating aquaculture systems, considered to be an innovative, eco-friendly and sustainable technology. The effect of the hydraulic loading rate (HLR) on the performance of fish and plants in the aquapoinc system was the main aim of this study. Four hydraulic loading rates were applied, 1.2, 1.8, 2.4 and 3.0 m day-1 under stocking density tilapia fish of 5 kg m-3 and lettuce population of 25 plant m-2 for a period of January to March, 2023. Water parameters, plant and fish parameters were determined. The most important results revealed that the highest plant nutrients removal was at HLR of 2.4 m day-1. The highest value of water parameters were found at the HLR of 2.4 m day-1. Root length increased with increasing HLR. Fresh and dry shoot and root weight values were higher at 2.4 m day-1 compared to other treatments under study. Meanwhile, fish growth parameter showed higher values at the HLR of 3.0 m day-1 compared to other treatments. The highest values of weight gain, feed growth rate, specific growth rate and feed conversion ratio were 81.72 g, 1.36 g day-1, 1.88% day-1 and 1.20 g feed g-1 fish, respectively, for all treatments under study.


Clonazepam improves dopamine supersensitivity in a schizophrenia patient: a case report.
Dopamine supersensitivity is an important consideration for assessing treatment-resistant schizophrenia. The emergence of dopamine supersensitivity might be related to upregulation of dopamine D2 receptor, which engenders tolerance to antipsychotics, rebound psychosis, and tardive dyskinesia (TD). A 24-year-old man with a history of treatment-resistant schizophrenia was hospitalized for treatment of bone fracture sustained during a suicide attempt. After the operation, his clinical symptoms implied malignant catatonia. The patient discontinued antipsychotics without rebound psychosis under clonazepam treatment. His psychotic symptoms were controlled further with 24 mg/day aripiprazole without relapse or worsening. Clonazepam might be an effective option for the management of dopamine supersensitivity psychosis (DSP).


[Effects of different light-dark cycles on total and differential leukocyte counts as well as spontaneous locomotor activity in mice].
To investigate the effect of different light-dark cycles on total and differential counts of leukocyte as well as spontaneous locomotor activity in mice. 144 ICR mice were raised under different light-dark cycles including LD 7 h/7 h, LD 12 h/12 h and LD 16 h/16 h for 8 weeks. Blood samples were obtained by enucleation of eye for total and differential counts of leukocyte. Another 9 mice were also divided into 3 groups and fed under same conditions as above. Their activities were recorded continuously. The change of spontaneous locomotor activity and leukocyte count were synchronized with the light-dark cycle. Different light-dark cycles can influence not only the spontaneous locomotor activity, but also total and differential leukocyte counts in mice.


Crystallographic studies on the complex behavior of nicotine binding to P450cam (CYP101).
Crystallographic and spectroscopic studies have been undertaken to characterize the binding behavior of the non-native substrate nicotine in the active site of the monooxygenase hemoprotein cytochrome P450cam. Despite the existence of a theoretical model that is consistent with the observed distribution of monooxygenation products, the crystal structure of the complex indicates that the primary binding mode of nicotine is unproductive. The structure is confirmed by spectral data that indicate direct coordination of substrate pyridine nitrogen with the heme iron. This would be the proper structure for evaluating binding affinity and inhibition. Reduction of the heme from Fe(III) to Fe(II) and introduction of carbon monoxide into crystals of the nicotine-P450cam complex, to simulate molecular oxygen binding, produces reorientation of the nicotine. This orientation is the appropriate one for predicting regioselectivity and the kinetic features of substrate oxidation. While it is not clear that such complicated behavior will be exhibited for other enzyme-substrate interactions, it is clear that a single crystal structure for a given substrate-enzyme interaction may not provide a good description of the binding mode responsible for product formation.


Comparative study of assisted reproductive outcomes between young patients with occult premature ovarian insufficiency and advanced-age patients.
The purpose of this study was to compare the pregnancy outcomes among young patients with occult premature ovarian insufficiency (OPOI), advanced-age patients with diminished ovarian reserve (DOR), and advanced-age patients with normal ovarian reserve. We retrospectively reviewed 324 women who underwent their first cycles of in vitro fertilization/intracytoplasmic sperm injection. The women were divided into the following groups: young women with OPOI, advanced-age women with DOR, and advanced-age women with normal ovarian reserve. The outcomes were compared among the different groups. The rates of live birth and embryo implantation in the young OPOI group were significantly higher than in the advanced-age DOR group, but comparable to those in the advanced-age normal ovarian reserve group. Moreover, the abortion rate was significantly lower in young OPOI patients compared with advanced-age patients with or without DOR. Higher embryo implantation and live birth rates and a lower abortion rate can be achieved in young patients with OPOI compared with older patients. The better outcomes in advanced-age patients with normal ovarian reserve compared with DOR may be related to egg quantity rather than quality.


Long-term transanal irrigation's continuation at home. Preliminary study.
To determine the long-term outcome of Peristeen's home use. Retrospective study on the 16 first patients treated by Peristeen in the department of physical and readaptation medicine of Limoges universitary hospital, by the mean of phone interviews. Successful outcome was achieved in 62.5% patients after a mean follow-up of 2.6 years. All patients had neurogenic bowel disorders, including 75% of constipation. Most of cases of Peristeen discontinuation occurred at the treatment beginning, one month after introduction in two thirds of cases. In patients who were still using transanal irrigation (TAI), mean grade of satisfaction with the Peristeen system was 9.12/10, despite the high rate of technical problems (77.8% of cases). This study highlights the limits of Peristeen's long-term using and suggests the interest of a specific therapeutic education to Peristeen and of a systematic control consultation within the 3 first months of treatment.


Radiolabelled agents for PET imaging of tumor hypoxia.
Hypoxia has been observed in a variety of human tumor types and evaluating tumor hypoxia is important because it increases resistance to radiotherapy and chemotherapy by inducing proteomic change that allow the tumor cell to survive in their hypoxic environment. One of the major proteomic changes is HIF-1 expression, and HIF-1 has become a target for anti-cancer drugs development because of its central role in hypoxia-mediated aggressiveness of tumor cells and their resistance to therapy. Since tumor hypoxia is a key mechanism that leads to resistance of treatment, a large number of challenges for hypoxia imaging including magnetic resonance, optical, and nuclear imaging have been reported. These hypoxia imaging techniques may have potential in selecting cancer patients who would benefit from treatments that overcome the presence of hypoxia. Hypoxia imaging could also be used to document whether or not and the extent to which reoxygenation of tumors occurs during cancer treatment. One of key requirements of ideal method for imaging hypoxia is that the method should be non-invasive. From an imaging perspective, PET is also one of leading tools for imaging hypoxia because of its high spatial resolution, high sensitivity, and advantages for visualizing molecular events in living human tissue. In this review, PET-based radiopharmaceuticals including (18)F-FMISO, (18)F-FETNIM, (18)F-FAZA, and radioactive Cu-ATSM were summarized from published studies about radiosyntheses, pre-clinical data, and clinical data, which are the lead contenders for human application.


Kinetic model for multidimensional opinion formation.
In this paper, we deal with a kinetic model to describe the evolution of the opinion in a closed group with respect to a choice between multiple options (e.g., political parties), which takes into account two main mechanisms of opinion formation, namely, the interaction between individuals and the effect of the mass media. We numerically test the model in some relevant cases and eventually provide an existence and a uniqueness result for it.


Control of canalization and evolvability by Hsp90.
Partial reduction of Hsp90 increases expression of morphological novelty in qualitative traits of Drosophila and Arabidopsis, but the extent to which the Hsp90 chaperone also controls smaller and more likely adaptive changes in natural quantitative traits has been unclear. To determine the effect of Hsp90 on quantitative trait variability we deconstructed genetic, stochastic and environmental components of variation in Drosophila wing and bristle traits of genetically matched flies, differing only by Hsp90 loss-of-function or wild-type alleles. Unexpectedly, Hsp90 buffering was remarkably specific to certain normally invariant and highly discrete quantitative traits. Like the qualitative trait phenotypes controlled by Hsp90, highly discrete quantitative traits such as scutellor and thoracic bristle number are threshold traits. When tested across genotypes sampled from a wild population or in laboratory strains, the sensitivity of these traits to many types of variation was coordinately controlled, while continuously variable bristle types and wing size, and critically invariant left-right wing asymmetry, remained relatively unaffected. Although increased environmental variation and developmental noise would impede many types of selection response, in replicate populations in which Hsp90 was specifically impaired, heritability and 'extrinsic evolvability', the expected response to selection, were also markedly increased. However, despite the overall buffering effect of Hsp90 on variation in populations, for any particular individual or genotype in which Hsp90 was impaired, the size and direction of its effects were unpredictable. The trait and genetic-background dependence of Hsp90 effects and its remarkable bias toward invariant or canalized traits support the idea that traits evolve independent and trait-specific mechanisms of canalization and evolvability through their evolution of non-linearity and thresholds. Highly non-linear responses would buffer variation in Hsp90-dependent signaling over a wide range, while over a narrow range of signaling near trait thresholds become more variable with increasing probability of triggering all-or-none developmental responses.


Long-term results of paediatric kidney transplantation at the University of Heidelberg: a 35 year single-centre experience.
Kidney transplantation remains the most effective treatment for children with end-stage renal disease. We analysed data from the University of Heidelberg transplant programme to present our results on paediatric kidney transplantations over the past 35 years. From 1967 to 2003, 354 paediatric kidney transplantations were performed at the University of Heidelberg. Data were obtained from the paediatric kidney transplantation records consisting of 291 (82%) cadaveric and 63 (18%) living donated transplants. Demographic data, family relationship of the living donors, surgical technique, immunosuppressive drugs, graft and patient survival rates were assessed. The mean age of cadaveric and living donors was 32.0+/-17.1 and 37.6+/-7.5 years, respectively. The family relationship of the living donors included the mother in 65% of cases, the father in 31%, and other relatives in 4%. In the last 4 years, the respective mean cold ischaemia time was 1.6+/-0.5 h for living donated and 13.5+/-4.1 h for cadaveric donors. The mean age of children who received kidneys from cadaveric and living donors was 11.3+/-4.5 and 10.4+/-4.5 years, respectively, with a male to female ratio of 57 to 43%. Overall patient survival rates were 95% after 1 year and 89% after 5 years. The patient 5 and 10 year survival rates for living donor renal transplantations were 95 and 95%, respectively. Graft survival rates improved since 1990 compared with the period prior to 1990: 82.5 vs 56.7% graft survival at 1 year and 82.5 vs 50% after 5 years (P = 0.03). Comparing the operating technique in a subgroup of our patients that received the same immunosuppressive regimen, anastomoses with the aorta and vena cava (51%, n = 31) were associated with a graft survival of 86.6 and 83.3% after 1 and 5 years, whereas anastomoses with iliac vessels (49%, n = 30) were associated with a graft survival of 55.8 and 51.6% after 1 and 5 years, respectively (P = 0.01). There has been a gradual improvement in our paediatric kidney transplantation results over time. Living donor paediatric kidney transplants have higher patient and better graft survival rates than cadaveric donor kidney transplants. Using the aorta and inferior vena cava for graft anastomosis, utilizing newer immunosuppressive drugs and implementing living kidney donation have positively affected the results of our paediatric kidney transplantations.


The protective effect of curcumin on Aβ induced aberrant cell cycle reentry on primary cultured rat cortical neurons.
Alzheimer's disease (AD) is a neurodegenerative disorder marked by progressive loss of memory and impairment of cognitive ability. One current hypothesis for AD pathogenesis is that neuronal death is linked to aberrant cell-cycle re-entry. In AD, neurons have been shown to enter the cell cycle inappropriately without the ability to complete it fully and the aberrant re-entry leads to its death. Curcumin has been reported as having a neural protective effect on the AD model, and could modulate the proliferation of tumor cells through the regulation of cyclin D1 and c-myc cell signaling pathways. In this study, we first observed the protective action of curcumin on Abeta-induced neuron damage, and then investigated whether this protective effect was a result of the inhibition of cell cycle advance. We used MTT assay and TUNEL assay to observe the effect of curcumin on Abeta-induced neuron death, and then examined the activated caspase-3 protein level to further confirm the protective effect of curcumin against Abeta-induced neuron toxicity. Next, we further investigate whether the inhibition of cell cycle reentry was mediated by the therapeutic effect of curcumin on Abeta induced primary cultured neuron damage by Brdu label assay and western blot assay. The results showed that administration of curcumin (1-10 microM) could inhibit Abeta25-35 (40 microg/ml) induced primary cultured rat cortical neuron death, down-regulating activated caspase-3 protein expression. Furthermore, treatment with curcumin could inhibit abnormal activated cyclin D1 protein level, and decrease the Brdu positive cells in proportion to the Abeta25-35 treatment neurons. All the results suggest that curcumin has a protective effect against Abeta-induced toxicity in cultured rat cortical neurons, the inhibition of cell cycle re-entry at least partly mediating the therapeutic effect of curcumin in the AD model in vitro.


Level of physical activity and CHD risk factors in black South African men.
Coronary heart disease (CHD) is uncommonly low among black South Africans. Although dietary and genetic influences probably contribute to their favorable serum lipid profile, other cardioprotective factors may also play a significant role in explaining the low incidence of CHD. From a socioeconomic perspective, it appears that the black community engages in regular physical activity (PA) more so than other populations. Since data are lacking, our aim was to provide preliminary data on the association between PA and the traditional CHD risk factors. The sample consisted of 212 working, middle-aged men drawn from an epidemiological database on the African population of metropolitan Cape Town. Analysis of responses to basic questions on PA behavior indicated i) 43% of the sample were employed in jobs requiring moderate to strenuous PA, and ii) the most favorable blood pressure and serum lipid profiles were associated with low to moderate levels of habitual exercise. As this community becomes more urbanized, job-related PA as well as PA of daily living will decline. The need for sports and leisure-time PA programs will become more important and should be considered as part of a public health strategic plan.


A Ca2+-dependent mechanism for the positive inotropic response to an increase in afterload in cat papillary muscle.
In cat papillary muscles, under control conditions (1.25 mmol/L Ca2+ bathing solution, 25 degrees C), increasing the afterload by switching from isotonic to isometric contraction elicited a positive inotropic response. Halving the bath [Ca2+] resulted in a percentagewise similar or greater positive inotropic response to increased afterload, while doubling the bath [Ca2+] reduced and caffeine abolished or reversed this response, indicating [Ca2+]i predictably influences it. Since it was markedly reduced by verapamil and unaffected by propranolol, the positive inotropic response to increased afterload was concluded to be largely due to increased Ca2+ influx, unrelated to catecholamine release, caused by increased mean muscle length over time owing to the changing from isotonic to isometric contraction. While at 25 degrees C, increasing the afterload caused a positive inotropic response at 12 to 48 stimulations/min, at 37 degrees C and at similar frequencies, a negative inotropic response occurred. This reversed to a positive inotropic response at 86 stimulations/min, well below the normal cat heart rate, suggesting an increased afterload would cause a positive inotropic response via this mechanism in vivo, as observed for years in intact mammalian hearts. Similarities between positive inotropic responses to increased afterload in isolated cardiac muscle, isolated hearts, and intact animals indicate all may be examples of the same phenomenon (Anrep effect).


Humoral and Cellular Immunity Changed after Traumatic Brain Injury in Human Patients.
Previous studies have suggested that there is a disproportionally higher risk of infection following traumatic brain injury (TBI). This predisposition to infection may be driven by a poorly understood, brain-specific response in the immune system after TBI. However, there is a lack of studies that have fully characterized TBI patients to understand the relationship between TBI and peripheral immune function. In the present study, markers for humoral immunity and cellular immunity were measured for up to 2 weeks in the peripheral blood of 37 patients with TBI in order to elucidate the time course and the type of the peripheral immune response following TBI. 12 relatively healthy individuals without TBI and other neurological diseases were enrolled into the control group. Our data indicated that TBI could induce significant changes in humoral immunity characterized by a decrease in IgG and IgM levels and an increase in the complements C3 and C4 levels in comparison with the control group. Moreover, compared with the control group, a significant reduction in peripheral blood CD3+ and CD3+CD4+ lymphocyte counts occurred early (days 1-3) following the onset of trauma. These results provide evidence that TBI is associated with substantial changes in humoral immunity and cellular immunity, which may explain the high incidence of infection encountered in these patients.


Physically Close yet Chemically Separate Reduction and Oxidation Sites in Double-Walled Nanotubes for Photocatalytic Hydrogen Generation.
The localization of photoexcitation leads to the proximity of photocatalytic reduction and oxidation sites, causing unfavorable side reactions. To address this issue, we designed a double-walled nanotube model system consisting of carbon nanotube (CNT) outside and carbon-nitride nanotube (CNNT) inside, with physically close yet chemically separate reduction and oxidation sites for safe photocatalytic hydrogen generation. First-principle calculations show that photoexcited charges in the system rapidly separate, leaving electrons at the reductive sites in CNNT and holes at the oxidative sites in CNT, respectively. Then protons generated by hole-assisted water dissociation at the CNT migrate to the CNNT and are reduced, producing H2. The selective permeability of protons through CNT ensures complete separation of hydrogen molecules and oxygen species, and thereby the reduction and oxidation half-reactions. Further, H2 products can be delivered via the double-walled nanotube for safe collection. The seamless integration of photocatalytic hydrogen generation and delivery in one system provides an alternative solution toward practical solar-driven hydrogen utilization.


[Biomechanical study of corneal stability after photorefractive keratectomy].
Photorefraktive keratectomy (PRK) is the most frequent refractive surgical procedure worldwide. The central corneal thickness is reduced due to removal of the anterior stroma, including Bowman's layer, with a laser beam. This procedure results in considerable alterations of the corneal structure. What does this mean for the mechanical properties of the cornea? Intraocular pressure was increased via a 180 degrees tilt. Before and during this procedure, corneal topography was measured by photokeratoscopy. We examined 26 patients after PRK and 25 controls who had not undergone any surgical procedure. The corneal center flattened by 0.038 +/- 0.05 dpt (P > 0.05) in the PRK patients and by 0.187 +/- 0.045 dpt (P < 0.05) in the control group. PRK patients within 1 year after operation showed a minimal central corneal steepening, whereas PRK patients after more than 1 year showed a reaction similar to that in normal corneas (P < 0.05). Corneal stability is altered after PRK. After 1 year corneal stability seems to normalize due to stromal remodelling.


Lactose-free frozen yogurt: production and characteristics.
Nowadays, consumer demand is driving better and more nutritious dairy products. Changing from traditional to new lactose-free products poses technological challenges for the food industry in order to maintain or improve their food characteristics and consumer preferences. This study investigates the production of lactose-free frozen yogurt by enzymati- cally hydrolysis of lactose, and its influence on the final product characteristics. In the case of lactose-free products, commercial Ha-lactase® was used for hydrolysis, and the reaction occurred simultaneously with fermentation. The effect of lactose hydrolysis on the physicochemical properties, texture, viscosity, overrun and sensory attributes in the final product was investigated. After yogurt maturation, the acidity of the lactose-free product was significantly higher than in the control, suggesting that breaking down lactose enhances the fermentation process. Lactose-free frozen yogurt had significantly lower hardness and stickiness and higher viscosity than control frozen yogurt. Moreover, lactose hydrolysis promoted a smooth and creamy consistency, whereas in the case of conventional prod- ucts a coarse structure, due to the presence of large ice crystals, was identified. Hydrolysis of lactose also improved the sweetness and brightness of frozen yogurt. The improved textural properties of lactose-free product results from the fact that monosaccharides produced during lactose hydrolysis depress the freezing point of the mix, which enables product with softer structure and bigger resistance to ice recrystallization to be obtained. The study showed that lactose-free frozen yogurt may be used successfully for production of novel lactose-free frozen desserts. Lactose hydrolysis improves the texture and viscosity of the product,     as well as enhancing its sensory quality.


Permeability enhancement for transdermal delivery of large molecule using low-frequency sonophoresis combined with microneedles.
Transdermal drug delivery is limited by the high resistance of skin towards diffusion of high-molecular-weight drugs. This is mainly because of the fact that the outer layer of the skin, that is the stratum corneum, can prevent diffusion of molecules whose molecular weight is greater than 500 Da. Sonophoresis can be used to enhance the permeability of the skin. However, in the delivery of large molecules, ultrasound alone cannot provide sufficient permeability enhancement. In addressing this issue, we propose optimised ultrasound combined with microneedles to further increase the permeation rates. In this paper, we use porcine ear skin to simulate human skin and treat the skin samples with both ultrasound and microneedles. Further, bovine serum albumin (BSA) is used as a model of larger molecular weight molecule. Our results show that the permeability of BSA is increased to 1 μm/s with the combination of 1.5 mm microneedles patch and 15-W ultrasound output which is about 10 times higher than the permeability obtained in passive diffusion. Diffusion with only microneedles or ultrasound pre-treatment is also tested. The maximum permeability from microneedles and ultrasound treatment reached 0.43 and 0.4 μm/s, respectively.


Early retirees under Social Security: health status and economic resources.
Some proposals to change the Social Security program to ensure long-run solvency would reduce or eliminate benefits for early retirees. This article documents the health and financial resources of Old-Age and Survivors Insurance (OASI) beneficiaries aged 62-64. It identifies a substantial minority of early retirees who might be economically vulnerable if either the early eligibility age or normal retirement age was raised. Attention is directed at the extent to which poor health limits work in this age group and the extent to which curtailment of early OASI benefits might lead to increases in the Disability Insurance (DI) program rolls. Using a set of comprehensive health measures, we estimate that over 20 percent of OASI beneficiaries aged 62-64 have health problems that substantially impair their ability to work. This finding implies that in this age range, as many severely disabled persons receive OASI benefits as disability benefits. In fact, 12 percent of early beneficiaries would meet a more stringent criterion for being classified "disabled"--SSA's medical standard for disability benefits. The evidence therefore indicates that OASI functions as a substantial, albeit unofficial, disability program for early retirees. Compared with those who have no health problems or are less severely impaired, early OASI beneficiaries who meet the medical criteria for disability benefits are more likely to be living alone and more likely to be poor or "near poor." The great majority of the group--almost 80 percent--are women. Analysis of their earnings histories suggests that most of these beneficiaries do not satisfy the insured-status requirements for Disability Insurance benefits. The article considers the different roles of the OASI program and the DI program for health-impaired individuals aged 62-64. Disability modelers sometimes overlook an important aspect of program administration. Under customary screening procedures implemented in Social Security field offices, applicants for early OASI benefits who appear to be severely impaired simultaneously apply for DI benefits if they are disability insured. If they are found eligible for DI benefits, those applicants become DI beneficiaries. The implication is that raising the earliest entitlement age would have little impact on the DI rolls. Unless there are changes in eligibility criteria, the DI program would not serve as a safety net for many of the most severely disabled early retirees.


[What is Men's Health? A definition].
Target of the study: Men's Health is increasingly coming into focus of health research, epidemiology, health care organization, and health policy. Over the past 10-15 years have been published by some countries and the EU Men's Health reports where problems of health noted in men. Starting point for a scientific study of men's health is the definition of "Men's Health". A group of German experts in the field of men's health has taken on this task. A literature review in international and national databases was performed for the years 1990-2014 by selected MeSH terms and for "experts for men's health". Another research concerned "gray literature" in Germany, especially health reports and web pages. This was followed by a conference of experts to define "Men's Health" using a modified Delphi method according to W. Zinn. From the expert group minimum criteria for a definition "Men's Health" were created and discussed, which must comply with the new definition of men's health. This definition was created in the third round of the Delphi method. The international literature review yielded 7 definitions of "Men's Health" in the English-speaking and 5 definitions in the German inkl. in the "gray" literature. Due to the developed by the Expert Group 7 minimum criteria 15 relevant topics were listed, of which by weighting 8 subject areas were considered relevant for a new definition. In comparison with the previous definitions none could fulfill these 8 criteria. Therefore, in the next step of the expert group a new definition "Men's Health" was elaborated. The definition has reference to the WHO concept of "health" and includes dimensions of health and disease, risk and protective factors that require special prevention and care services for all phases of life. All participants in the expert group agreed on the definition developed. The definition of Men's Health is a basis for further scientific work and practice to improve men's health in Germany and other countries.


Lesion border detection in dermoscopy images using ensembles of thresholding methods.
Dermoscopy is one of the major imaging modalities used in the diagnosis of melanoma and other pigmented skin lesions. Due to the difficulty and subjectivity of human interpretation, automated analysis of dermoscopy images has become an important research area. Border detection is often the first step in this analysis. In many cases, the lesion can be roughly separated from the background skin using a thresholding method applied to the blue channel. However, no single thresholding method appears to be robust enough to successfully handle the wide variety of dermoscopy images encountered in clinical practice. In this article, we present an automated method for detecting lesion borders in dermoscopy images using ensembles of thres holding methods. Experiments on a difficult set of 90 images demonstrate that the proposed method is robust, fast, and accurate when compared to nine state-of-the-art methods.


Identifying potential biomarkers for non-obstructive azoospermia using WGCNA and machine learning algorithms.
The cause and mechanism of non-obstructive azoospermia (NOA) is complicated; therefore, an effective therapy strategy is yet to be developed. This study aimed to analyse the pathogenesis of NOA at the molecular biological level and to identify the core regulatory genes, which could be utilised as potential biomarkers. Three NOA microarray datasets (GSE45885, GSE108886, and GSE145467) were collected from the GEO database and merged into training sets; a further dataset (GSE45887) was then defined as the validation set. Differential gene analysis, consensus cluster analysis, and WGCNA were used to identify preliminary signature genes; then, enrichment analysis was applied to these previously screened signature genes. Next, 4 machine learning algorithms (RF, SVM, GLM, and XGB) were used to detect potential biomarkers that are most closely associated with NOA. Finally, a diagnostic model was constructed from these potential biomarkers and visualised as a nomogram. The differential expression and predictive reliability of the biomarkers were confirmed using the validation set. Furthermore, the competing endogenous RNA network was constructed to identify the regulatory mechanisms of potential biomarkers; further, the CIBERSORT algorithm was used to calculate immune infiltration status among the samples. A total of 215 differentially expressed genes (DEGs) were identified between NOA and control groups (27 upregulated and 188 downregulated genes). The WGCNA results identified 1123 genes in the MEblue module as target genes that are highly correlated with NOA positivity. The NOA samples were divided into 2 clusters using consensus clustering; further, 1027 genes in the MEblue module, which were screened by WGCNA, were considered to be target genes that are highly correlated with NOA classification. The 129 overlapping genes were then established as signature genes. The XGB algorithm that had the maximum AUC value (AUC=0.946) and the minimum residual value was used to further screen the signature genes. IL20RB, C9orf117, HILS1, PAOX, and DZIP1 were identified as potential NOA biomarkers. This 5 biomarker model had the highest AUC value, of up to 0.982, compared to other single biomarker models; additionally, the results of this biomarker model were verified in the validation set. As IL20RB, C9orf117, HILS1, PAOX, and DZIP1 have been determined to possess the strongest association with NOA, these five genes could be used as potential therapeutic targets for NOA patients. Furthermore, the model constructed using these five genes, which possessed the highest diagnostic accuracy, may be an effective biomarker model that warrants further experimental validation.


[Not Available].
This report deals with the situation of the state of military veterinary medicine in the Austro-Hungarian Monarchy shortly before the outbreak of the First World War and in the years immediately afterwards (1920). Specifically we will follow the career of a student in the Military Veterinary Academy and his practice as Military Veterinarian through the end of the Austro-Hungarian Monarchy. We will examine the role of Farrier-Veterinarians as predecessors of University trained Veterinarians, as well as the details surrounding the entrance into service, the course of study, and the official duties of the veterinary students. Finally we will consider the representative organisation of the Military Veterinarians and their duties in the field.


Synergistic degradation of arabinoxylan with alpha-L-arabinofuranosidase, xylanase and beta-xylosidase from soy sauce koji mold, Aspergillus oryzae, in high salt condition.
This study addresses induction and some properties of alpha-L-arabinofuranosidase from a soy sauce koji mold, Aspergillus oryzae HL15, cultured on solid and liquid media. Alpha-L-arabinofuranosidase was induced by soybean polysaccharide and secreted into media on solid cultivation; the enzyme was associated with mycelium as a cell-wall-bound form in liquid cultivation. A major alpha-L-arabinofuranosidase, which was purified homogeneously on SDS-PAGE, showed highest activity in the presence of 10% of NaCl; also, somewhat higher activity was observed even in 25% NaCl than in the absence of NaCl. Arabinoxylan was synergistically degraded by xylanase, beta-xylosidase, and alpha-L-arabinofuranosidase from A. oryzae HL15 in the condition of imitative pH 5.0 and 15% NaCl concentration of the soy sauce moromi mash. These results suggest that arabinose and xylose, which are closely related to melanoidin formation, can be released by synergistic action of these enzymes in soy sauce moromi mash.