Parathyroidectomy in Maryland: effects of an endocrine center.
Surgery for hyperparathyroidism is associated with high cure rates and low morbidity and mortality when performed by experienced surgeons. We wanted to determine whether referral of patients with hyperparathyroidism to an endocrine surgery center has an impact on patient outcomes and costs. Data from 901 patients who underwent parathyroidectomy recorded in the Maryland inpatient discharge database between 1990 and 1994 at 52 hospitals were compared with 169 consecutive patients who underwent surgical exploration by one surgeon (R.U.) at the Johns Hopkins Hospital. Although in 47 of 52 hospitals fewer than 10 parathyroidectomies were performed each year, in these hospitals four of five related deaths occurred before patient discharge. The percentage of parathyroidectomies in Maryland performed by one endocrine surgeon has increased from 8% in 1990 to 21% in 1994 and is associated with a 97% cure rate and no mortality. Moreover, while hospital length of stay (LOS) in the state has decreased from 7 to 3.1 days, LOS for the high-volume provider has declined to a mean of 1.3 days. Patients with hyperparathyroidism are increasingly referred to an endocrine surgery center, which results in a high cure rate, low morbidity, no mortality, and a shorter LOS. Improved surgical outcomes and lower costs depend on an experienced surgeon and argue for the referral of these patients to endocrine surgery centers.


Body Composition and Dietary Intake of Elite Cross-country Skiers Members of the Greek National Team.
To assess the anthropometric characteristics and dietary intake of the Greek national cross-country skiing team. Thirty-three athletes (10 females aged 20 ± 5 years; 23 males aged 20 ± 6 years old) participated in the study. All athletes were members of the Greek national ski team, and they had been selected to take part in the Winter Olympics, World Ski Championships, European Ski Championships or other international events, according to their performance. Body composition was estimated by bioelectrical impedance (BIA) and skinfold thickness. The athletes recorded their physical activity and dietary intake for 3 training days, and on a competition day. The female skiers had 14.2±1.9% body fat, the men 11.0±1.5% body fat. Female athletes consumed a diet of 1988±319 Kcal during training days and 2011±330 Kcal during competition days. Male athletes consumed 2255±790 Kcal and 2125±639 Kcal respectively. These values are below those recommended for highly active people. During the training period, carbohydrate, fat and protein contributed to 44.5±7.1%, 39.2±5.3% and 16.1±3.7% of the total energy intake (EI) respectively for the males, and to 52.8±5.6%, 33.0±3.7% and 14.3±2.5% of the EI of the women. Between training and competition days, men demonstrated an increased carbohydrate and reduced fat consumption when competing (P<0.001 for both). Women, on the other hand, consumed more carbohydrate and less protein during competition days (P<0.05 for both). Protein intake was within the recommended range for both males and females, but fat exceeded the recommended values and was consumed at the expense of carbohydrate. Vitamins B(12), D, E and K, biotin, folate, Ca, Mg, K, I were inadequately consumed (below the RDA) by both women and men, while the women also exhibited inadequate intakes of iron and the men of manganese. The inadequate energy and nutrient intake in the Greek national cross-country ski team could put the athletes at risk of nutritional deficiencies, and possibly compromise their athletic performance.


Lung function is related to salivary cytokines and hormones in healthy children. An exploratory cross-sectional study.
Pulmonary mechanics has been traditionally viewed as determined by lung size and physical factors such as frictional forces and tissue viscoelastic properties, but few information exists regarding potential influences of cytokines and hormones on lung function. Concentrations of 28 cytokines and hormones were measured in saliva from clinically healthy scholar children, purposely selected to include a wide range of body mass index (BMI). Lung function was assessed by impulse oscillometry, spirometry, and diffusing capacity for carbon monoxide, and expressed as z-score or percent predicted. Ninety-six scholar children (55.2% female) were enrolled. Bivariate analysis showed that almost all lung function variables correlated with one or more cytokine or hormone, mainly in boys, but only some of them remained statistically significant in the multiple regression analyses. Thus, after adjusting by height, age, and BMI, salivary concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) in boys were associated with zR5-R20 and reactance parameters (zX20, zFres, and zAX), while glucagon inversely correlated with resistances (zR5 and zR20). Thus, in physiological conditions, part of the mechanics of breathing might be influenced by some cytokines and hormones, including glucagon and GM-CSF. This endogenous influence is a novel concept that warrants in-depth characterization.


Acute migraine attack therapy: comparison of naproxen sodium and an ergotamine tartrate compound.
The efficacy of safety of naproxen sodium and ergotamine tartrate were compared for the treatment of acute migraine attack in a randomized, parallel trial with 114 participating patients. At the start of symptoms, patients took either three tablets of naproxen sodium (275 mg each) or one of an ergotamine combination (containing 2 mg ergotamine tartrate, 91.5 mg caffeine, and 50 mg cyclizine chlorhydrate). Patients were followed for three months or until six attacks were monitored, whichever came first. Both medications substantially shortened the duration of migraine attacks and reduced the severity of symptoms. When the test medications were taken within 2 h of onset of attack, naproxen sodium was statistically significantly more effective than the ergotamine combination in reducing the severity of headache pain, nausea, and lightheadedness. The ergotamine combination was associated with significantly more vomiting, need for rescue medication, and side effects than was naproxen sodium. Four patients required discontinuation of the ergotamine combination and one of naproxen sodium. Both patients and investigators rated tolerance for naproxen sodium as superior to tolerance for the ergotamine combination. Naproxen sodium seems to be an effective and safe treatment for migraine attacks.


Agreement Between Maternal Report and Medical Records During Pregnancy: Medications for Rheumatoid Arthritis and Asthma.
There are limited data regarding the comparability of medication exposure information during pregnancy from maternal report and medical records, including for rheumatoid arthritis and asthma-related medications. This study included pregnant women with rheumatoid arthritis (n = 216) and asthma (n = 172) enrolled in the MothertoBaby Pregnancy Studies (2009-2014). Women reported types and dates of medications used through semi-structured telephone interviews up to three times during pregnancy and once after delivery, and medical records were obtained. We calculated Cohen's kappa coefficients and 95% confidence intervals (CIs) and per cent agreement for agreement between report and records. For rheumatoid arthritis, prednisone was reported most frequently (53%). During pregnancy, kappa coefficients for rheumatoid arthritis medications ranged from 0.32 (95% CI 0.15, 0.50) for ibuprofen, with 84.3% agreement, to 0.90 (95% CI 0.84, 0.96) for etanercept with 95.4% agreement, and was 0.44 (95% CI 0.33, 0.55) for prednisone, with 71.3% agreement. For asthma, albuterol was reported most frequently (77.9%). During pregnancy, kappa coefficients for asthma medications ranged from 0.21 (95% CI 0.08, 0.35), with 64.5% agreement for albuterol to 0.84 (95% CI 0.71, 0.96) for budesonide/formoterol, with 96.5% agreement. Where kappas for any use during pregnancy were less than excellent (i.e. ≤0.80), medication use was more frequently captured by report than record. Agreement was higher for medications typically used continuously than sporadically. Information on medication use from medical records alone may not be adequate when studying the impact of intermittently used medications during pregnancy on perinatal outcomes.


Associations of exposure to multiple metals with blood pressure and hypertension: A cross-sectional study in Chinese preschool children.
Exposure to metals might be a risk factor for hypertension, which contributes largely to the global burden of disease and mortality. However, relevant epidemiological studies of associations between metals exposure with hypertension among preschoolers are limited. This study aimed to explore the associations of urine metals with blood pressure and hypertension among Chinese preschoolers. A total of 1220 eligible participants who had urine metals measurement, blood pressure measurements, and relevant covariates were included in this cross-sectional study. Urine concentrations of metals were measured by inductively coupled plasma mass spectrometer. The single and multiple metals regression models were used to investigate the associations of urine metal with blood pressure and the risk of hypertension after adjusting for potential confounders. We observed urine concentrations of chromium, iron, and barium were negatively associated with levels of systolic blood pressure, diastolic blood pressure and the risk of hypertension in the single metal model (all P-FDR adjustment <0.05). Significant associations of urine chromium concentrations with systolic blood pressure, diastolic blood pressure and the risk of hypertension were found in the multi-metal model (β or OR (95% confidence interval) was -3.07 (-5.12, -1.02), -2.25 (-4.29, -0.22), and 0.51 (0.26, 0.97) for 3rd quartile, compared with 1st quartile, respectively). The same association was found for barium concentrations in the multi-metal model, while none of the associations among iron quartiles was significant. In addition, urine chromium, iron and barium may have joint effects on systolic blood pressure, diastolic blood pressure and hypertension. Children's age and body mass index could modify the associations of chromium, iron, and barium concentrations with blood pressure. Our findings suggested that exposure to chromium, iron, and barium was inversely associated with blood pressure and hypertension among preschool children. These findings need further validation in prospective studies.


Enhanced immunological detection of epigenetic modifications of DNA in healthy and cancerous cells by fluorescence microscopy.
Epigenetic modifications of DNA, including methylation, hydroxymethylation, formylation, and carboxylation of cytosines, are proposed to function in gene regulation during reproduction and development. Changes in cytosine methylation are associated with a range of diseases, such as cancer. Immunofluorescence uses specific antibodies to quantitatively detect the global amount of cytosine modifications by fluorescence microscopy. The most critical stage of immunofluorescence is the antigen retrieval to remove the protein content around the DNA, allowing specific antibodies to bind to DNA epitopes. Acid treatments have commonly been used for antigen retrieval. Previously, trypsin was added after acid in the protocol, which increased the amount of detectable DNA methylation. In this study, the protocol was further enhanced by the addition of pepsin, which is able to target charged hydrophobic amino acids in proteins, unlike trypsin, which breaks positive hydrophilic amino acids. The global levels of cytosine modifications in CF-1, HeLa, and AR42J cells were compared using this protocol. In all cells, the sequential treatment of trypsin and pepsin increased the specificity of the staining. With the synergistic effect of the two enzymes, it is possible to target different protein groups packaging DNA molecules and removing them effectively. The findings suggest that this revised protocol can be conveniently used for each cytosine modification in the cells examined, and should be optimized for other cells. These new antigen retrieval conditions may more accurately detect the changes in cytosine modifications during development and in diseases.


Variants of DNA repair genes and the risk of biliary tract cancers and stones: a population-based study in China.
Biliary tract cancers, which encompass tumors of the gallbladder, extrahepatic ducts, and ampulla of Vater, are relatively rare tumors with a high fatality rate. Other than a close link with gallstones, the etiology of biliary tract cancers is poorly understood. We conducted a population-based case-control study in Shanghai, China, to examine whether genetic variants in several DNA repair genes are associated with biliary tract cancers or biliary stones. Genomic DNA from 410 patients with biliary tract cancers (236 gallbladder, 127 bile duct, and 47 ampulla of Vater), 891 patients with biliary stones, and 786 healthy subjects randomly selected from the Shanghai population were genotyped for putative functional single nucleotide polymorphisms in four DNA repair genes (MGMT, RAD23B, CCNH, and XRCC3). Of the five single nucleotide polymorphisms examined, only one (MGMT EX5-25C>T, rs12917) was associated with biliary tract cancer. Independent of gallstones, subjects carrying the CT genotype of the MGMT EX5-25C>T marker had a significantly reduced risk of gallbladder cancer [odds ratio (OR), 0.63; 95% confidence interval (95% CI), 0.41-0.97; P = 0.02] and nonsignificant reduced risks of bile duct (OR, 0.61; 95% CI, 0.35-1.06) and ampulla of Vater (OR, 0.85; 95% CI, 0.39-1.87) cancers. However, this marker was not associated with biliary stones, and the other markers examined were not significantly associated with either biliary tract cancers or stones. Findings from this population-based study in Shanghai suggest that MGMT gene variants may alter susceptibility to biliary tract cancer, particularly gallbladder cancer. Confirmation in future studies, however, is required.


Infrared spectroscopy of a Wilkinson catalyst in a room-temperature ionic liquid.
Homogeneous catalysis in room-temperature ionic liquids (ILs) constitutes a most interesting field of research with high potential in technical applications. As concerns the hydrogenation of unsaturated hydrocarbons, Wilkinson's compound RhCl(PPh(3))(3) represents a catalyst that provides high selectivity and activity. Herein, we demonstrate the application of infrared spectroscopy to the quantitative analysis of the Wilkinson catalyst in the IL 1-ethyl-3-methylimidazolium acetate ([EMIM][OAc]). Our study demonstrates for the first time the quantitative, accurate and reproducible determination of the concentration of a rhodium catalyst by means of IR spectroscopy and, moreover, allows the investigation of intermolecular interactions. Spectral features, located mainly in the fingerprint region of the IR spectrum, are identified revealing the influence of the dissolved catalyst on the IL's vibrational structure. In particular, the ring-bending mode of the imidazolium ring shows a frequency shift as a function of catalyst concentration, probably due to hydrogen-bond formation between the IL cation and the Rh complex. The results show the potential of IR spectroscopy both for application as a quick process control technology in catalytic processes and as a tool for better understanding of IL-catalyst interactions.


Surgeon Agreement on the Presence of Pathologic Anterior Instability on Shoulder Imaging Studies.
In the setting of anterior shoulder instability, it is important to assess the reliability of orthopaedic surgeons to diagnose pathologic characteristics on the 2 most common imaging modalities used in clinical practice: standard plain radiographs and magnetic resonance imaging (MRI). To assess the intra- and interrater reliability of diagnosing pathologic characteristics associated with anterior shoulder instability using standard plain radiographs and MRI. Cohort study (diagnosis); Level of evidence, 3. Patient charts at a single academic institution were reviewed for anterior shoulder instability injuries. The study included 40 sets of images (20 radiograph sets, 20 MRI series). The images, along with standardized evaluation forms, were distributed to 22 shoulder/sports medicine fellowship-trained orthopaedic surgeons over 2 points in time. Kappa values for inter- and intrarater reliability were calculated. The overall response rate was 91%. For shoulder radiographs, interrater agreement was fair to moderate for the presence of glenoid lesions (κ = 0.49), estimate of glenoid lesion surface area (κ = 0.59), presence of a Hill-Sachs lesion (κ = 0.35), and estimate of Hill-Sachs surface area (κ = 0.50). Intrarater agreement was moderate for radiographs (κ = 0.48-0.57). For shoulder MRI, interrater agreement was fair to moderate for the presence of glenoid lesions (κ = 0.44), glenoid lesion surface area (κ = 0.35), Hill-Sachs lesion (κ = 0.33), Hill-Sachs surface area (κ = 0.28), humeral head edema (κ = 0.41), and presence of a capsulolabral injury (κ = 0.36). Fair agreement was found for specific type of capsulolabral injury (κ = 0.21). Intrarater agreement for shoulder MRI was moderate for the presence of glenoid lesion (κ = 0.59), presence of a Hill-Sachs lesion (κ = 0.52), estimate of Hill-Sachs surface area (κ = 0.50), humeral head edema (κ = 0.51), and presence of a capsulolabral injury (κ = 0.53), and agreement was substantial for glenoid lesion surface area (κ = 0.63). Intrarater agreement was fair for determining the specific type of capsulolabral injury (κ = 0.38). Fair to moderate agreement by surgeons was found when evaluating imaging studies for anterior shoulder instability. Agreement was similar for identifying pathologic characteristics on radiographs and MRI. There was a trend toward better agreement for the presence of glenoid-sided injury. The lowest agreement was observed for specific capsulolabral injuries.


Fruit Development in Ficus carica L.: Morphological and Genetic Approaches to Fig Buds for an Evolution From Monoecy Toward Dioecy.
The mechanism behind the bud evolution towards breba or main crop in Ficus carica L. is uncertain. Anatomical and genetic studies may put a light on the possible similarities/differences between the two types of fruits. For this reason, we collected complimentary data from anatomical, X-ray imaging, and genetic techniques. The RNA seq together with structural genome annotation allowed the prediction of 34,629 known genes and 938 novel protein-coding genes. Transcriptome analysis of genes during bud differentiation revealed differentially expressed genes in two fig varieties (Dottato and Petrelli) and in breba and main crop. We chose Dottato and Petrelli because the first variety does not require pollination to set main crop and the latter does; moreover, Petrelli yields many brebas whereas Dottato few. Of the 1,615 and 1,904 loci expressed in Dottato and Petrelli, specifically in breba or main crop, respectively, only 256 genes appeared to be transcripts in both varieties. The buds of the two fig varieties were observed under optical microscope and using 3D X-ray tomography, highlighting differences mainly related to the stage of development. The X-ray images of buds showed a great structural similarity between breba and main crop during the initial stages of development. Analysis at the microscope indicated that inflorescence differentiation of breba was split in two seasons whereas that of main crop started at the end of winter of season 2 and was completed within 2 to 3 months. The higher expression of floral homeotic protein AGAMOUS in breba with respect to main crop, since this protein is required for normal development of stamens and carpels in the flower, may indicate an original role of these fruits for staminate flowers production for pollination of the main crop, as profichi in the caprifig. Several genes related to auxin (auxin efflux carrier, auxin response factor, auxin binding protein, auxin responsive protein) and to GA synthesis (GA20ox) were highly expressed in brebas with respect to main crop for the development of this parthenocarpic fruit.


Sequential radiation of unrelated organisms: the gall fly Eurosta solidaginis and the tumbling flower beetle Mordellistena convicta.
Host shifts and the formation of insect-host races are likely common processes in the speciation of herbivorous insects. The interactions of goldenrods Solidago (Compositae), the gall fly Eurosta solidaginis (Diptera: Tephritidae) and the beetle Mordellistena convicta (Coleoptera: Mordellidae) provide behavioural, ecological and genetic evidence of host races that may represent incipient species forming via sympatric speciation. We summarize evidence for Eurosta host races and show that M. convicta has radiated from goldenrod stems to Eurosta galls to form host-part races and, having exploited the galler's host shift, has begun to differentiate into host races within galls. Thus, host-race formation has occurred in two interacting, but unrelated organisms representing two trophic levels, resulting in 'sequential radiation' (escalation of biodiversity up the trophic system). Distributions of host races and their behavioural isolating mechanisms suggest sympatric differentiation. Such differentiation suggests host-race formation and subsequent speciation may be an important source of biodiversity.


One-dimensional lead iodide hybrid stabilized by inorganic hexarhenium cluster cations as a new broad-band emitter.
A novel one-dimensional (1D) hybrid {[Re6S8(PzH)6][Pb3I8(DMF)2]}·6(DMF) with hexarhenium cluster cations has been synthesized and characterized by means of single-crystal X-ray diffraction. Two DMF oxygen atoms bridge three lead iodides to form a set of lead iodides, {[PbI4/2I(ODMF)1/2][PbI4/2(ODMF)2/2][PbI4/2I(ODMF)1/2]}2-, and these sets of lead iodide share edges to form a 1D lead iodide chain, [Pb3I8(DMF)2]2- which has never been reported before and is different from the typical edge sharing of octahedral PbI6 units. 1D lead iodide chains are stacked along the a axis, and [Re6S8(PzH)6]2+ cations with H-bonded DMF molecules to pyrazole N-H reside between 1D lead iodide chains. This 1D lead iodide hybrid shows strong broad-band emission with a peak at 634 nm. The excellent photoluminescent properties of the new lead iodide hybrid exhibit great potential for optoelectronic applications in photonic devices with broad-band emission and stability. This study introduces a new class of lead iodide hybrid compounds having new inorganic cluster cations rather than the organic amine cations that have been used in numerous studies to date. This work opens a promising path to overcome the instability of perovskites including of organic amine cations.


[Human immunodeficiency virus infection - treatment beyond medication].
Human Immunodeficiency Virus (HIV) infection is presently considered a chronic disorder. Infected people need a thorough medical surveillance and chronic therapy, which affects families and other caregivers. Infected children are also affected by their parents' infection and by the stigma that is still associated with this particular illness. Regular meetings were organized for HIV infected children, their families and the health team with recreational and formative purposes. These meetings were evaluated in a strongly positive manner by all the intervenients. The goal to maintain these activities is proposed as a way of improving the follow-up and the prognosis of these children.


The combination of follicle-stimulating hormone and human menopausal gonadotropin for the induction of multiple follicular maturation for in vitro fertilization.
One hundred fifty-one cycles in 134 consecutive patients were stimulated with 150 IU of human urinary follicle-stimulating hormone (FSH) and 150 IU of human menopausal gonadotropin (hMG) on cycle days 3 and 4 and then with 150 IU of hMG daily for the purpose of multiple follicular development for in vitro fertilization (IVF). Seventy-three patients did not have a prior IVF attempt, and 61 patients in 78 cycles had prior IVF attempts at least once with their previous cycles stimulated with the same method and/or hMG and/or FSH. There was an average of three preovulatory oocytes retrieved per laparoscopy and a pregnancy rate of 27% per transfer cycle. The results were equally favorable in "new" and "old" patient cycles. The pregnancy rate increased with the transfer of two or more conceptuses of preovulatory origin. The multiple pregnancy rate, but not the abortion rate, increased with increased numbers of conceptuses transferred.


Fat absorption in germ-free and conventional rats artificially deprived of bile secretion.
Bile duct ligation was performed in germ-free and conventional rats in order to study the effects of bile deprivation on the absorption of dietary lipids and the excretion of faecal lipids in the presence or the absence of gastrointestinal flora. The main consequence of bile duct ligation in conventional rats was decrease of about 50% in the apparent absorption of dietary lipids (peanut oil). In germ-free rats, absorption decreased by only about 25%. In conventional as well as in germ-free controls, faecal lipids were mainly excreted as compounds directly soluble in organic solvents that is, free fatty acids, triglycerides, partial glycerides, cholesterol, cholesterol esters. Deprivation of bile secretion significantly increased the faecal excretion of 'insoluble' compounds-that is, calcium soaps-both in germ-free and conventional rats. Free fatty acids and sterol esters were the two main class of soluble faecal lipids both in germ-free and conventional rats deprived of bile secretion. Faecal excretion of triglycerides remained low in germ-free as well as in conventional animals. No significant difference of fatty acid absorption was observed between germ-free and conventional controls. Deprivation of bile secretion resulted in a significant decrease in the absorption of all fatty acids in germ-free as well as in conventional animals. However, the decrease was larger for saturated fatty acids-that is, 16:0 or 18:0- than for unsaturated fatty acids-that is, 18:1 or 18:2. The absorption of all fatty acids, except linoleic acid (18:2), was significantly lower in conventional rats artificially deprived of bile secretion than in their germ-free counterparts. Evidence was given for a negative digestive balance of stearic acid (18:0) in bile deprived conventional animals. This observation was correlated with a very efficient biohydrogenation of dietary unsaturated fatty acids as revealed by radio gas chromatography of faecal acids in bile deprived conventional rats fed a diet containing 1-14C oleic acid (18:1) as homogeneous triglycerides. Nevertheless, biohydrogenation of unsaturated dietary fatty acids by the gastrointestinal flora was not considered to be the only factor involved in the origin of the difference of fat absorption between bile deprived germ-free and conventional animals.


[Biological notes and behavior of Liogenys suturalis Blanchard (Coleoptera: Melolonthidae) in Mato Grosso do Sul State, Brazil].
Liogenys suturalis Blanchard is one of the main soil pests associated to corn, wheat and oat crops in the Southern Mato Grosso do Sul State. This work aimed to investigate the bioecological and behavioral aspects of this pest. The study was carried out in several municipalities of Mato Grosso do Sul State under field and laboratory conditions from August 2004 to December 2006. In the laboratory, we studied the incubation period and egg viability, the number of instars, and pupal and adult sex-related traits. The insect distribution was determined yearly, as well as the period of insect flying and some behavioral aspects during mating. Egg viability averaged 81.7%, with an incubation period of 22.8 + or - 4.32 days. Liogenys suturalis took the whole year to complete its life cycle, developing through three different instars. The highest larval feeding activity and development occurred in February and June, and adult flight activities were between the second fortnight of September and December. Sex dimorphism was observed in both pupae and adults. Flights were concentrated from 7:00 to 8:00 PM. The average time for mating was 9.82 min. The observed adult sex ratio was 0.63.


Early sign language acquisition and the development of hand preference in young children.
Hand preference for signing and for nonsign actions was examined longitudinally in 24 young children (3 deaf, 21 hearing) with deaf parents. Most of these children showed a strong preference for their right hands in their sign production. This preference emerged early in their development, was relatively consistent over time, and predicted mature hand preference. Although most of the children also preferred to use their right hands in nonsign actions, their right-hand preference for signing was much stronger. Hand preference scores for two types of nonsign actions, communicative gestures and object actions, were significantly correlated with those for signing. Hand preference also was linked to rate of motor development but not to sign language acquisition. These findings are discussed with regard to current conceptualizations about the interrelationships among language, motor processes, and laterality.


Development of the nervous system in Phoronopsis harmeri (Lophotrochozoa, Phoronida) reveals both deuterostome- and trochozoan-like features.
Inferences concerning the evolution of invertebrate nervous systems are often hampered by the lack of a solid data base for little known but phylogenetically crucial taxa. In order to contribute to the discussion concerning the ancestral neural pattern of the Lophotrochozoa (a major clade that includes a number of phyla that exhibit a ciliated larva in their life cycle), we investigated neurogenesis in Phoronopsis harmeri, a member of the poorly studied Phoronida, by using antibody staining against serotonin and FMRFamide in combination with confocal microscopy and 3D reconstruction software. The larva of Phoronopsis harmeri exhibits a highly complex nervous system, including an apical organ that consists of four different neural cell types, such as numerous serotonin-like immunoreactive flask-shaped cells. In addition, serotonin- and FMRFamide-like immunoreactive bi- or multipolar perikarya that give rise to a tentacular neurite bundle which innervates the postoral ciliated band are found. The preoral ciliated band is innervated by marginal serotonin-like as well as FMRFamide-like immunoreactive neurite bundles. The telotroch is innervated by two neurite bundles. The oral field is the most densely innervated area and contains ventral and ventro-lateral neurite bundles as well as several groups of perikarya. The digestive system is innervated by both serotonin- and FMRFamide-like immunoreactive neurites and perikarya. Importantly, older larvae of P. harmeri show a paired ventral neurite bundle with serial commissures and perikarya. Serotonin-like flask-shaped cells such as the ones described herein for Phoronopsis harmeri are found in the majority of lophotrochozoan larvae and therefore most likely belong to the ground pattern of the last common lophotrochozoan ancestor. The finding of a transitory paired ventral neurite bundle with serially repeated commissures that disappears during metamorphosis suggests that such a structure was part of the "ur-phoronid" nervous system, but was lost in the adult stage, probably due to its acquired sessile benthic lifestyle.


Invasion of epithelial mammalian cells by Paracoccidioides brasiliensis leads to cytoskeletal rearrangement and apoptosis of the host cell.
Paracoccidioides brasiliensis (Pb) yeast cells can enter mammalian cells and probably manipulate the host cell environment to favor their own growth and survival. We studied the uptake of strain Pb 18 into A549 lung and Vero epithelial cells, with an emphasis on the repercussions in the cytoskeleton and the apoptosis of host cells. Cytoskeleton components of the host cells, such as actin and tubulin, were involved in the P. brasiliensis invasion process. Cytochalasin D and colchicine treatment substantially reduced invasion, indicating the functional participation of microfilaments (MFs) and microtubules (MTs) in this mechanism. Cytokeratin could also play a role in the P. brasiliensis interaction with the host. Gp43 was recognized by anti-actin and anti-cytokeratin antibodies, but not by anti-tubulin. The apoptosis induced by this fungus in infected epithelial cells was demonstrated by various techniques: TUNEL, DNA fragmentation and Bak and Bcl-2 immunocytochemical expression. DNA fragmentation was observed in infected cells but not in uninfected ones, by both TUNEL and gel electrophoresis methods. Moreover, Bcl-2 and Bak did not show any differences until 24 h after infection of cells, suggesting a competitive mechanism that allows persistence of infection. Overexpression of Bak was observed after 48 h, indicating the loss of competition between death and survival signals. In conclusion, the mechanisms of invasion of host cells, persistence within them, and the subsequent induction of apoptosis of such cells may explain the efficient dissemination of P. brasiliensis.


Pharmacist-led group medical appointment model in type 2 diabetes.
The purpose of this study was to assess whether the VA-MEDIC (Veterans Affairs Multi-disciplinary Education and Diabetes Intervention for Cardiac risk reduction), a pharmacist-led group medical visit program, could improve achievement of target goals in hypertension, hyperglycemia, hyperlipidemia, and tobacco use in patients with type 2 diabetes compared to usual care. This was a randomized controlled trial of VA-MEDIC intervention in addition to usual care versus usual care alone in diabetic patients to reduce cardiac risk factors. VA-MEDIC consisted of a 40- to 60-minute educational component by nurse, nutritionist, physical therapist, or pharmacist followed by pharmacist-led behavioral and pharmacological interventions over 4 weekly sessions. Measures The attainment of target goals in hemoglobin A1C (A1C), blood pressure, fasting lipids, and tobacco use recommended by the American Diabetes Association. Of 118 participants, 109 completed the study. VA-MEDIC (n = 58) participants were younger and had greater tobacco use at baseline than usual care but were similar in other cardiovascular risk factors. After 4 months, a greater proportion of VA-MEDIC participants versus controls achieved an A1C of less than 7% and a systolic blood pressure less than 130 mm Hg. No significant change was found in lipid control or tobacco use between the 2 study arms. Pharmacist-led group medical visits are feasible and efficacious for improving cardiac risk factors.


Feasibility, enablers and challenges of using timeliness metrics for household contact tracing and TB preventive therapy in Pakistan.
Screening household contacts of TB patients and providing TB preventive therapy (TPT) is a key intervention to end the TB epidemic. Global and timely implementation of TPT in household contacts, however, is dismal. We adapted the 7-1-7 timeliness metric designed to evaluate and respond to infectious disease outbreaks or pandemics, and assessed the feasibility, enablers and challenges of implementing this metric for screening and management of household contacts of index patients with bacteriologically-confirmed pulmonary TB in Karachi city, Pakistan. We conducted an explanatory mixed methods study with a quantitative component (cohort design) followed by a qualitative component (descriptive design with focus group discussions). From January-June 2023, 92% of 450 index patients had their household contacts line-listed within seven days of initiating anti-TB treatment ("first 7"). In 84% of 1342 household contacts, screening outcomes were ascertained within one day of line-listing ("next 1"). In 35% of 256 household contacts eligible for further evaluation by a medical officer (aged ≤5 years or with chest symptoms), anti-tuberculosis treatment, TPT or a decision for no drugs was made within seven days of symptom screening ("second 7"). The principal reason for not starting anti-tuberculosis treatment or TPT was failure to consult a medical officer: only 129(50%) of 256 contacts consulted a medical officer. Reasons for poor performance in the "second 7" component included travel costs to see a medical officer, loss of daily earnings and fear of a TB diagnosis. Field staff reported that timeliness metrics motivated them to take prompt action in household contact screening and TPT provision and they suggested these be included in national guidelines. Field staff found "7-1-7" timeliness metrics to be feasible and useful. Integration of these metrics into national guidelines could improve timeliness of diagnosis, treatment and prevention of TB within households of index patients.


Operative laparoscopy for the management of tubal pregnancy.
Laparoscopic management of selected cases of tubal pregnancy may be an alternative to the conventional approach, laparotomy. Twenty-seven patients were managed with this technique; each had a readily accessible unruptured ampullary pregnancy less than 4 cm in diameter. All but one went home by the second hospital day. One suffered an immediate postoperative hemorrhage that required laparotomy to control. Six of eight patients tested from three to ten months after the operation had tubal patency. Five of eight patients attempting conception have become pregnant, with one repeat ipsilateral tubal pregnancy. In five patients, serum beta-human chorionic gonadotropin remained elevated for more than 30 days after laparoscopy with no untoward effect. Although insufficient data exist to compare reproductive outcome after this technique with that after laparotomy, in properly selected cases operative laparoscopy seems to be safe and effective conservative therapy, decreasing the need for laparotomy and the duration of hospitalization.


Synthesis and Antimycobacterial Activity of 2-(Phenylthio) benzoylarylhydrazone Derivatives.
A series of new 2-(phenylthio) benzoylarylhydrazones were synthesized by acid-catalyzed condensation of hydrazide 3 with corresponding aldehydes. The chemical structures of the compounds were elucidated by FT-IR, (1)H-NMR and Mass spectra. All newly synthesized compounds were evaluated for their antimycobacterial activities against Mycobacterium tuberculosis H37Rv using the microplatealamar blue assay (MABA). Compounds 4f (5-Nitro-2-furyl analogue) and 4g (5-Nitro-2-thienyl analogue) showed antimycobacterial activity with IC90, 7.57 and 2.96 μg/mL, respectively.


Gut microbiota mediates diurnal variation of acetaminophen induced acute liver injury in mice.
Acetaminophen (APAP) induced hepatotoxicity is a leading cause of acute liver failure worldwide. It is well established that the liver damage induced by acetaminophen exhibits diurnal variation. However, the detailed mechanism for the hepatotoxic variation is not clear. Herein, we aimed to determine the relative contributions of gut microbiota in modulating the diurnal variation of hepatotoxicity induced by APAP. Male Balb/C mice were treated with or without antibiotics and a single dose of orally administered APAP (300 mg/kg) at ZT0 (when the light is on-start of resting period) and ZT12 (when the light is off-start of active period). In agreement with previous findings, hepatic injury was markedly enhanced at ZT12 compared with ZT0. Interestingly, upon antibiotic treatment, ZT12 displayed a protective effect against APAP hepatotoxicity similar to ZT0. Moreover, mice that received the cecal content from ZT12 showed more severe liver damage than mice that received the cecal content from ZT0. 16S sequencing data revealed significant differences in the cecal content between ZT0 and ZT12 in the compositional level. Furthermore, metabolomic analysis showed that the gut microbial metabolites were also different between ZT0 and ZT12. Specifically, the level of 1-phenyl-1,2-propanedione (PPD) was significantly higher at ZT12 than ZT0. Treatment with PPD alone did not cause obvious liver damage. However, PPD synergistically enhanced APAP-induced hepatic injury in vivo and in vitro. Finally, we found Saccharomyces cerevisiae, which could reduce intestinal PPD levels, was able to markedly alleviate APAP-induced liver damage at ZT12. The gut microbial metabolite PPD was responsible, at least in part, for the diurnal variation of hepatotoxicity induced by APAP by decreasing glutathione levels. Acetaminophen (APAP) induced acute liver failure because of over dose is a leading public health problem. APAP-induced liver injury exhibits diurnal variation, specifically APAP causes more severe liver damage when taken at night compared with in the morning. Herein, we showed that gut microbial metabolite, 1-phenyl-1,2-propanedione is involved in the rhythmic hepatotoxicity induced by APAP, by depleting hepatic glutathione (an important antioxidant) levels. Our data suggest gut microbiota may be a potential target for reducing APAP-induced acute liver injury.


Conformational Sampling and Binding Site Assessment of Suppression of Tumorigenicity 2 Ectodomain.
Suppression of Tumorigenicity 2 (ST2), a member of the interleukin-1 receptor (IL-1R) family, activates type 2 immune responses to pathogens and tissue damage via binding to IL-33. Dysregulated responses contribute to asthma, graft-versus-host and autoinflammatory diseases and disorders. To study ST2 structure for inhibitor development, we performed the principal component (PC) analysis on the crystal structures of IL1-1R1, IL1-1R2, ST2 and the refined ST2 ectodomain (ST2ECD) models, constructed from previously reported small-angle X-ray scattering data. The analysis facilitates mapping of the ST2ECD conformations to PC subspace for characterizing structural changes. Extensive coverage of ST2ECD conformations was then obtained using the accelerated molecular dynamics simulations started with the IL-33 bound ST2ECD structure as instructed by their projected locations on the PC subspace. Cluster analysis of all conformations further determined representative conformations of ST2ECD ensemble in solution. Alignment of the representative conformations with the ST2/IL-33 structure showed that the D3 domain of ST2ECD (containing D1-D3 domains) in most conformations exhibits no clashes with IL-33 in the crystal structure. Our experimental binding data informed that the D1-D2 domain of ST2ECD contributes predominantly to the interaction between ST2ECD and IL-33 underscoring the importance of the D1-D2 domain in binding. Computational binding site assessment revealed one third of the total detected binding sites in the representative conformations may be suitable for binding to potent small molecules. Locations of these sites include the D1-D2 domain ST2ECD and modulation sites conformed to ST2ECD conformations. Our study provides structural models and analyses of ST2ECD that could be useful for inhibitor discovery.


Longitudinal patterns in physical activity and sedentary behaviour from mid-life to early old age: a substudy of the Whitehall II cohort.
There are few longitudinal data on physical activity patterns from mid-life into older age. The authors examined associations of self-reported physical activity, adiposity and socio-demographic factors in mid-life with objectively assessed measures of activity in older age. Participants were 394 healthy men and women drawn from the Whitehall II population-based cohort study. At the baseline assessment in 1997 (mean age 54 years), physical activity was assessed through self-report and quantified as metabolic equivalent of task hours/week. At the follow-up in 2010 (mean age 66 years), physical activity was objectively measured using accelerometers worn during waking hours for seven consecutive days (average daily wear time 891 ± 68 min/day). Self-reported physical activity at baseline was associated with objectively assessed activity at follow-up in various activity categories, including light-, moderate- and vigorous-intensity activity (all ps<0.04). Participants in the highest compared with lowest quartile of self-reported activity level at baseline recorded on average 64.1 (95% CI 26.2 to 102.1) counts per minute more accelerometer-assessed activity at follow-up and 9.0 (2.0-16.0) min/day more moderate-to-vigorous daily activity, after adjusting for baseline covariates. Lower education, obesity and self-perceived health status were also related to physical activity at follow-up. Only age and education were associated with objectively measured sedentary time at follow-up. Physical activity behaviour in middle age was associated with objectively measured physical activity in later life after 13 years of follow-up, suggesting that the habits in adulthood are partly tracked into older age.


Purified outer membranes of Serpulina hyodysenteriae contain cholesterol.
We have isolated outer and inner membranes of Serpulina hyodysenteriae by using discontinuous sucrose density gradients. The outer and inner membrane fractions contained less than 1 and 2%, respectively, of the total NADH oxidase activity (soluble marker) in the cell lysate. Various membrane markers including lipooligosaccharide (LOS), the 16-kDa outer membrane lipoprotein (SmpA), and the C subunit of the F1F0 ATPase indicated that the lowest-density membrane fraction contained outer membranes while the high-density membrane fraction contained inner membranes and that both are essentially free of contamination by the periplasmic flagella, a major contaminant of membranes isolated by other techniques. The outer membrane fractions (rho = 1.10 g/cm3) contained 0.25 mg of protein/mg (dry weight), while the inner membrane samples (rho = 1.16 g/cm3) contained significantly more protein (0.55 mg of protein/mg [dry weight]). Lipid analysis revealed that the purified outer membranes contained cholesterol as a major component of the membrane lipids. Treatment of intact S. hyodysenteriae with different concentrations of digitonin, a steroid glycoside that interacts with cholesterol, indicated that the outer membrane could be selectively removed at concentrations as low as 0.125%.


Activation of AMP-activated protein kinase regulates hippocampal neuronal pH by recruiting Na(+)/H(+) exchanger NHE5 to the cell surface.
Strict regulation of intra- and extracellular pH is an important determinant of nervous system function as many voltage-, ligand-, and H(+)-gated cationic channels are exquisitely sensitive to transient fluctuations in pH elicited by neural activity and pathophysiologic events such as hypoxia-ischemia and seizures. Multiple Na(+)/H(+) exchangers (NHEs) are implicated in maintenance of neural pH homeostasis. However, aside from the ubiquitous NHE1 isoform, their relative contributions are poorly understood. NHE5 is of particular interest as it is preferentially expressed in brain relative to other tissues. In hippocampal neurons, NHE5 regulates steady-state cytoplasmic pH, but intriguingly the bulk of the transporter is stored in intracellular vesicles. Here, we show that NHE5 is a direct target for phosphorylation by the AMP-activated protein kinase (AMPK), a key sensor and regulator of cellular energy homeostasis in response to metabolic stresses. In NHE5-transfected non-neuronal cells, activation of AMPK by the AMP mimetic AICAR or by antimycin A, which blocks aerobic respiration and causes acidification, increased cell surface accumulation and activity of NHE5, and elevated intracellular pH. These effects were effectively blocked by the AMPK antagonist compound C, the NHE inhibitor HOE694, and mutation of a predicted AMPK recognition motif in the NHE5 C terminus. This regulatory pathway was also functional in primary hippocampal neurons, where AMPK activation of NHE5 protected the cells from sustained antimycin A-induced acidification. These data reveal a unique role for AMPK and NHE5 in regulating the pH homeostasis of hippocampal neurons during metabolic stress.


[Triple-negative breast carcinoma--rewiev of current literature].
Breast cancer is one of the most common malignancies in women. Approximately 15% of cases belong to the triple-negative breast cancer (TNBC) group, in which no estrogen/progesterone receptors, or HER2 expression is detected. The unfavorable prognosis of this group of patients, as well as the lack of effective targeted therapy makes TNBC the subject of intensive research. In the present study, we searched PubMed for publications from January 2007 to June 2009 with the following key-words in addition to "breast cancer" and "triple negative": "epidemiology" or "gene-profile" or "predictive" or "prognostic" or "therapy" or "review". A total of 513 publications were identified. Relevant references were also reviewed. Beyond the well-known facts that TNBC affects younger patients, and is more common among Afro- or Hispano-Americans with lower socioeconomic status, hormonal environment and obesity emerged as potential etiologic factors. TNBC is not a homogenous disease. It can be further sub-classified based on histomorphologic features and immunohistochemistry. Hereditary BRCA1 mutations as well as acquired BRCA1 disfunction are described to be common in TNBC. Previously, many investigators considered TNBC to be identical to a subgroup called basal-like breast cancer defined by gene expression micro-array technology, but in the light of more recent findings, this view is no longer accepted by most investigators. Several large studies provide evidence that triple negativity, per se, is an independent adverse prognostic factor, in spite of the fact that approximately 10% of TNBC patients have a good prognosis. The therapy of choice for TNBC is systemic chemotherapy. Promising novel targeted chemotherapeutic agents include PARP1 inhibitors, a new group of compounds exploiting the defective DNA repair machinery. Rubovszky G, Udvarhelyi N, Horváth Z, Láng I, Kásler M. Triple negative breast carcinoma - rewiev of current literature.


Lattice parameter determination of a strained area of an InAs layer on a GaAs substrate using CBED.
All the six lattice parameters (a, b, c, alpha, beta and gamma) of a strained area of an InAs layer grown on a GaAs substrate were determined without any assumption of the crystal lattice symmetry from the higher-order Laue zone (HOLZ) lines appearing in one convergent-beam electron diffraction (CBED) pattern. The analysis was performed with three steps. Firstly, the parameters alpha and beta were determined from the deviations of the HOLZ lines from the mirror symmetry perpendicular to the [001] direction. Secondly, the parameter c was determined from the distance between the intersections of the HOLZ lines, which have the same h and k indices but different l indices. Finally, the parameters a, b and gamma were determined simultaneously from several distances between the intersections of the HOLZ lines. The lattice parameters determined for the strained area were a = 0.611(2) nm, b = 0.615(1) nm, c = 0.6119(7) nm, alpha = 89.5(1) degrees, beta = 89.0(2) degrees and gamma = 89.1(2) degrees. This result implies that the cubic lattice of InAs is elongated approximately in the [111] direction and the exact lattice symmetry is triclinic. The same analysis procedure was applied to another two specimen areas. It was found that the areas have orthorhombic distortions with lattice parameters a = 0.607(2) nm, b = 0.604(1) nm and c = 0.6085(7) nm for one area, and with a = 0.607(2) nm, b = 0.605(1) nm and c = 0.6065(7) nm for the other area. It is should be emphasized that the present analysis of lattice distortions is immediately applicable to the other semiconductors, such as Si, SiGe or GaAs layers, without assuming any crystal system.


Cytokine profiles in various graft-versus-host disease target organs following hematopoietic stem cell transplantation.
Previous studies using genetic-deficient murine models suggest that different T-helper subsets may contribute to different types of tissue damages in graft-versus-host disease (GvHD). However, there is limited information available on the distribution of T-helper cytokines in the various GvHD target tissues. In the current study, an acute GvHD murine model was set up to directly assess the in situ cytokine profiles in various GvHD tissue lesions; in addition, we also studied GvHD tissues from patients who had undergone bone marrow transplantation procedures. We observed that interferon-γ (IFN-γ was dominant in murine liver and gastrointestinal tissue lesions, whereas IFN-γ and interleukin 17 (IL-17) were abundant in murine skin lesions. Furthermore, in human GvHD tissues, interleukin 4 (IL-4) and IFN-γ were predominant in liver lesions and colon lesions, respectively, while no specific cytokine was prevalent in human GvHD skin lesions. In addition, a low ratio of CD4(+) T helper (Th) versus CD8(+) T cytotoxic (Tc) cells in human GvHD tissue lesions, especially in the liver, was detected, and this contrasts with the situation in murine GvHD tissues where CD4(+) Th cells were predominant. Dual staining for CD markers and cytokine expression showed that IFN-γ-secreting T cells were enriched in all murine GvHD target tissue lesions, and Tc1 and Tc2 cells were predominant in human GvHD colon and liver sections, respectively. However, IFN-γ(+) Th1, IL-17(+) Th17, IFN-γ(+) Tc1, and IL-17(+) Tc17 cells were slightly more frequent in human skin lesions compared to IL-4(+) Th2 and IL-4(+) Tc2 cells. To sum up, these results suggest that differences in cytokine imbalances may significantly contribute to tissue-specific pathogenesis in GvHD target organs, and CD8(+) Tc cells may play an important role in human GvHD induction.


The origin of amnitoic fluid lecithin.
Lecithin has been measured in amniotic fluid, pharyngeal aspirate, fetal and maternal plasma and fetal membranes from the same pregnancy. In the amniotic fluid from a term pregnancy 79 per cent of the lecithin is found in the reconstituted precipitate of centrifuged fluid. It is suggested that the lecithin of amniotic fluid may originate from sources other than fetal lung and that lecithin concentration is therefore a measure of overall fetal maturity.


Hemolytic uremic syndrome in small-bowel transplant recipients: the first two case reports.
Post-transplant hemolytic uremic syndrome (HUS) is an uncommon but well-described complication in solid organ transplant recipients. Believed to be secondary to immunosuppressive therapy, it has been reported after kidney, liver, pancreas, heart, and lung transplants. In all reported cases, the primary organ affected was the kidney (transplant or native). But until now, no cases after small-bowel transplants and no cases in which the kidney was not the primary organ affected have been reported. We report two cases of HUS in small-bowel transplant recipients. In our first case, clinical presentation was with renal failure; biopsy of the native kidney demonstrated the typical histological changes seen with HUS, namely occlusion of the microcirculation by thrombi and platelet aggregation. Immunosuppression was changed from tacrolimus to cyclosporin, but with no improvement in renal function. In our second case, the transplanted bowel was the primary organ affected. This recipient presented with ulcers in the bowel mucosa, which were believed to be ischemic in origin, secondary to occlusive vascular lesions affecting the small vessels in the transplanted bowel. Her tacrolimus dose was decreased with resolution of ulcers and no evidence of rejection. These two cases represent the first reports of HUS after small-bowel transplants; in addition, our second case represents the first report of an extrarenal graft as the primary organ affected. When caring for small-bowel transplant recipients, physicians must be alert to the possibility of HUS and its various presentations.


Genetics in pulmonary fibrosis--familial cases provide clues to the pathogenesis of idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is the most common form of the idiopathic interstitial pneumonias and remains a disease with a poor prognosis. Familial interstitial pneumonia (FIP) occurs when 2 or more individuals from a given family have an idiopathic interstitial pneumonia. FIP cases have been linked to mutations in surfactant protein C, surfactant protein A2, telomerase reverse transcriptase and telomerase RNA component. Together, mutations in these 4 genes likely explain only 15% to 20% of FIP cases and are even less frequent in sporadic IPF. However, dysfunctional aspects of the pathways that are involved with these genes are present in sporadic forms of IPF even in the absence of mutations, suggesting common underlying disease mechanisms. By serving as a resource for identifying the current and future genetic links to disease, FIP families hold great promise in defining IPF pathogenesis, potentially suggesting targets for the development of future therapies.


Controlling health costs: physician responses to patient expectations for medical care.
Physicians have dual responsibilities to make medical decisions that serve their patients' best interests but also utilize health care resources wisely. Their ability to practice cost-consciously is particularly challenged when faced with patient expectations or requests for medical services that may be unnecessary. To understand how physicians consider health care resources and the strategies they use to exercise cost-consciousness in response to patient expectations and requests for medical care. Exploratory, qualitative focus groups of practicing physicians were conducted. Participants were encouraged to discuss their perceptions of resource constraints, and experiences with redundant, unnecessary and marginally beneficial services, and were asked about patient requests or expectations for particular services. Sixty-two physicians representing a variety of specialties and practice types participated in nine focus groups in Michigan, Ohio, and Minnesota in 2012 MEASUREMENTS: Iterative thematic content analysis of focus group transcripts Physicians reported making trade-offs between a variety of financial and nonfinancial resources, considering not only the relative cost of medical decisions and alternative services, but the time and convenience of patients, their own time constraints, as well as the logistics of maintaining a successful practice. They described strategies and techniques to educate patients, build trust, or substitute less costly alternatives when appropriate, often adapting their management to the individual patient and clinical environment. Physicians often make nuanced trade-offs in clinical practice aimed at efficient resource use within a complex flow of clinical work and patient expectations. Understanding the challenges faced by physicians and the strategies they use to exercise cost-consciousness provides insight into policy measures that will address physician's roles in health care resource use.


How Food Choices Impact on Male Fertility.
Increasing evidence on the significance of nutrition in reproduction is emerging from both animal and human studies, suggesting an association between nutrition and male fertility. Here, we have highlighted the impact of the various food groups on reproductive hormones and on spermatogenesis, and the effects of classical and latest dietary patterns such as Mediterranean diet, Western diet, intermittent fasting, ketogenic diet, and vegan/vegetarian diet on male fertility. Nutrients are the precursors of molecules involved in various body's reactions; therefore, their balance is essential to ensure the correct regulation of different systems including the endocrine system. Hormones are strongly influenced by the nutritional status of the individual, and their alteration can lead to dysfunctions or diseases like infertility. In addition, nutrients affect sperm production and spermatogenesis, controlling sexual development, and maintaining secondary sexual characteristics and behaviors. The consumption of fruit, vegetables, fish, processed meats, dairy products, sugars, alcohol, and caffeine importantly impact on male fertility. Among dietary patterns, the Mediterranean diet and the Western diet are most strongly associated with the quality of semen. Nutrients, dietary patterns, and hormonal levels have an impact on male infertility. Therefore, understanding how these factors interact with each other is important for strategies to improve male fertility.


Detecting recurrence domains of dynamical systems by symbolic dynamics.
We propose an algorithm for the detection of recurrence domains of complex dynamical systems from time series. Our approach exploits the characteristic checkerboard texture of recurrence domains exhibited in recurrence plots. In phase space, recurrence plots yield intersecting balls around sampling points that could be merged into cells of a phase space partition. We construct this partition by a rewriting grammar applied to the symbolic dynamics of time indices. A maximum entropy principle defines the optimal size of intersecting balls. The final application to high-dimensional brain signals yields an optimal symbolic recurrence plot revealing functional components of the signal.


Disruption of eye movements by ethanol intoxication affects perception of depth from motion parallax.
Motion parallax, the ability to recover depth from retinal motion generated by observer translation, is important for visual depth perception. Recent work indicates that the perception of depth from motion parallax relies on the slow eye movement system. It is well known that ethanol intoxication reduces the gain of this system, and this produces the horizontal gaze nystagmus that law enforcement's field sobriety test is intended to reveal. The current study demonstrates that because of its influence on the slow eye movement system, ethanol intoxication impairs the perception of depth from motion parallax. Thresholds in a motion parallax task were significantly increased by acute ethanol intoxication, whereas thresholds for an identical test relying on binocular disparity were unaffected. Perhaps a failure of motion parallax plays a role in alcohol-related driving accidents; because of the effects of alcohol on eye movements, intoxicated drivers may have inaccurate or inadequate information for judging the relative depth of obstacles from motion parallax.


Eicosapentaenoic acid for the prevention of recurrent atrial fibrillation.
n-3 polyunsaturated fatty acids, primarily eicosapentaenoic acid (EPA), has been reported to have antiarrhythmic and antiinflammatory effects. The aim of the present study was to examine whether the combination of antiarrhythmic drugs and EPA reduced the frequency of atrial fibrillation (AF) in patients with paroxysmal AF. We studied 50 patients with paroxysmal AF (age, 54 ± 9 years) after excluding the clinical conditions associated with an increased risk of AF. Patients were initially treated with antiarrhythmic drugs for 6 months (the observation period), and thereafter, EPA was added at a dose of 1.8 g/day for 6 months (the intervention period). During a one-year period, patients obtained an ECG recording using a portable device each morning and when arrhythmia-related symptom occurred. The end point was the difference of the AF burden (defined by the days of AF per month) between observation period and intervention period. Plasma EPA and C-reactive protein (CRP) levels were also determined. There was no significant difference in the AF burden before and after intervention (2.6 ± 2.2 days/months vs. 2.5 ± 2.2 days/months, P = 0.45). Although EPA level was significantly increased (42 ± 15 μg/mL to 120 ± 47 μg/mL, P < 0.001), CRP level was unchanged (1.04 ± 0.69 mg/L to 0.96 ± 0.56 mg/L, P = 0.24) following EPA treatment. Treatment of EPA in combination with antiarrhythmic drugs did not reduce the AF burden or the CRP levels in paroxysmal AF patients who had no evidence of substantial structural heart disease.


Antihypertensive drugs: a perspective on pharmaceutical price erosion and its impact on cost-effectiveness.
When comparators' prices decrease due to market competition and loss of exclusivity, the incremental clinical effectiveness required for a new technology to be cost-effective is expected to increase; and/or the minimum price at which it will be funded will tend to decrease. This may be, however, either unattainable physiologically or financially unviable for drug development. The objective of this study is to provide an empirical basis for this discussion by estimating the potential for price decreases to impact on the cost-effectiveness of new therapies in hypertension. Cost-effectiveness at launch was estimated for all antihypertensive drugs launched between 1998 and 2008 in the United Kingdom using hypothetical degrees of incremental clinical effectiveness within the methodologic framework applied by the UK National Institute for Health and Clinical Excellence. Incremental cost-effectiveness ratios were computed and compared with funding thresholds. In addition, the levels of incremental clinical effectiveness required to achieve specific cost-effectiveness thresholds at given prices were estimated. Significant price decreases were observed for existing drugs. This was shown to markedly affect cost-effectiveness of technologies entering the market. The required incremental clinical effectiveness was in many cases greater than physiologically possible so, as a consequence, a number of products might not be available today if current methods of economic appraisal had been applied. We conclude that the definition of cost-effectiveness thresholds is fundamental in promoting efficient innovation. Our findings demonstrate that comparator price attrition has the potential to put pressure in the pharmaceutical research model and presents a challenge to new therapies being accepted for funding.


Fourier-domain multichannel autofocus for synthetic aperture radar.
Synthetic aperture radar (SAR) imaging suffers from image focus degradation in the presence of phase errors in the received signal due to unknown platform motion or signal propagation delays. We present a new autofocus algorithm, termed Fourier-domain multichannel autofocus (FMCA), that is derived under a linear algebraic framework, allowing the SAR image to be focused in a noniterative fashion. Motivated by the mutichannel autofocus (MCA) approach, the proposed autofocus algorithm invokes the assumption of a low-return region, which generally is provided within the antenna sidelobes. Unlike MCA, FMCA works with the collected polar Fourier data directly and is capable of accommodating wide-angle monostatic SAR and bistatic SAR scenarios. Most previous SAR autofocus algorithms rely on the prior assumption that radar's range of look angles is small so that the phase errors can be modeled as varying along only one dimension in the collected Fourier data. And, in some cases, implicit assumptions are made regarding the SAR scene. Performance of such autofocus algorithms degrades if the assumptions are not satisfied. The proposed algorithm has the advantage that it does not require prior assumptions about the range of look angles, nor characteristics of the scene.


Transcriptional activation of HIF-1 by a ROS-ERK axis underlies the resistance to photodynamic therapy.
Photodynamic therapy (PDT), a promising treatment option for cancer, involves the activation of a photosensitizer (PS) by local irradiation with visible light. Excitation of the PS leads to a series of photochemical reactions and consequently the local generation of harmful reactive oxygen species (ROS) causing limited or none systemic defects. However, the development of resistance to this promising therapy has slowed down its translation into the clinical practice. Thus, there is an increase need in understanding of the molecular mechanism underlying resistance to PDT. Here, we aimed to examine whether a relationship exists between PDT outcome and ROS-involvement in the resistance mechanism in photosensitized cancer cells. In order to recapitulate tumor architecture of the respective original tumor, we developed a multicellular three-dimensional spheroid system comprising a normoxic periphery, surrounding a hypoxic core. Using Me-ALA, a prodrug of the PS PpIX, in human colorectal spheroids we demonstrate that HIF-1 transcriptional activity was strongly up-regulated and mediates PDT resistant phenotype. RNAi knockdown of HIF-1 impairs resistance to PDT. Oxidative stress-mediated activation of ERK1/2 followed PDT was involved on positive modulation of HIF-1 transcriptional activity after photodynamic treatment. ROS scavenging and MEK/ERK pathway inhibition abrogated the PDT-mediated HIF-1 upregulation. Together our data demonstrate that resistance to PDT is in part mediated by the activation of a ROS-ERK1/2-HIF-1 axis, thus, identifying novel therapeutic targets that could be used in combination with PDT.


Rat exocrine pancreatic secretion by vagal stimulation occurs via multiple mediators.
The vagus is a mixed nerve containing cholinerrgic and non-cholinergic neurons. Vagal fibers interact with peptidergic neurons of the enteric nervous system which stain immunohistochemically for cholecystokinin, vasoactive intestinal polypeptide, and gastrin releasing peptide. The contribution of these peptidergic neurons in the pancreatic response to vagal stimulation is unknown. We tested the effect of specific inhibitor of these stimulants against vagally mediated exocrine secretion in rats. The response to vagal stimulation was blocked significantly by each of the following: the ganglionic blocker hexamethonium (100% inhibition); the muscarinic, cholinergic blocker atropine (85% inhibition); the specific cholecystokinin-A receptor blocker (91% inhibition); and a vasoactive intestinal polypeptide polyclonal antibody (89% inhibition). This observation is consistent with the hypothesis that potentiating interactions among several agonists mediate the vagal response. Our study, however, dose not exclude acetylcholine as the final common mediator.


A primer of complementary and alternative medicine commonly used by cancer patients.
Complementary and alternative medicine (CAM) is frequently used by cancer patients, and many oncologists have limited knowledge of CAM. This article provides a brief, evidence-based introduction to several CAM treatments relevant in the context of cancer. "Alternative" diets, chiropractic, coffee enemas, ozone therapy, and shark cartilage seem to have little to offer cancer patients. The evidence for or against homoeopathy and spiritual healing is at present inconclusive. Acupuncture, aromatherapy, and meditation may be useful for nausea/vomiting, for mild relaxation, and for pain/anxiety, respectively. Herbal treatments offer no reasonable prospect of a cure (mistletoe), but could be useful as palliative treatments (eg, for depression [St John's wort] or anxiety [kava]). Our knowledge regarding the potential benefit and harm of CAM is insufficient.


Selective binding of the scavenger receptor C-type lectin to Lewisx trisaccharide and related glycan ligands.
The scavenger receptor C-type lectin (SRCL) is an endothelial receptor that is similar in organization to type A scavenger receptors for modified low density lipoproteins but contains a C-type carbohydrate-recognition domain (CRD). Fragments of the receptor consisting of the entire extracellular domain and the CRD have been expressed and characterized. The extracellular domain is a trimer held together by collagen-like and coiled-coil domains adjacent to the CRD. The amino acid sequence of the CRD is very similar to the CRD of the asialoglycoprotein receptor and other galactose-specific receptors, but SRCL binds selectively to asialo-orosomucoid rather than generally to asialoglycoproteins. Screening of a glycan array and further quantitative binding studies indicate that this selectivity results from high affinity binding to glycans bearing the Lewis(x) trisaccharide. Thus, SRCL shares with the dendritic cell receptor DC-SIGN the ability to bind the Lewis(x) epitope. However, it does so in a fundamentally different way, making a primary binding interaction with the galactose moiety of the glycan rather than the fucose residue. SRCL shares with the asialoglycoprotein receptor the ability to mediate endocytosis and degradation of glycoprotein ligands. These studies suggest that SRCL might be involved in selective clearance of specific desialylated glycoproteins from circulation and/or interaction of cells bearing Lewis(x)-type structures with the vascular endothelium.


Evaluation and management of apparent life-threatening events in infants.
Apparent life-threatening events (ALTEs) are frightening to caregivers and clinicians alike. This article provides a comprehensive review of the causes, management, and consequences of ALTEs. The information provided was collected from an extensive literature review using the search terms ALTE, sudden infant death syndrome, and apnea. There is a wide array of contributing factors to ALTE syndrome and sequalae for both infants and caregivers of infants experiencing an ALTE.


Childhood brain tumour risk and its association with wireless phones: a commentary.
Case-control studies on adults point to an increased risk of brain tumours (glioma and acoustic neuroma) associated with the long-term use of mobile phones. Recently, the first study on mobile phone use and the risk of brain tumours in children and adolescents, CEFALO, was published. It has been claimed that this relatively small study yielded reassuring results of no increased risk. We do not agree. We consider that the data contain several indications of increased risk, despite low exposure, short latency period, and limitations in the study design, analyses and interpretation. The information certainly cannot be used as reassuring evidence against an association, for reasons that we discuss in this commentary.


Creating a state minority health policy report card.
A state minority health policy report card may provide an important tool for evaluating and promoting state policies to reduce health disparities. This study develops criteria that can form the basis of such a state report card and assesses the performance of all fifty states on these measures. The results indicate wide variation among states, with geographic region being a significant predictor of performance on all four measures. Future research should be conducted on other predictors of state variation in minority health policy and connections between state policy and health outcomes for minorities.


Maintenance anlotinib improves the survival prognosis of extensive-stage small cell lung cancer: a single-arm, prospective, phase II study.
The extent to which anlotinib provides survival benefits in the maintenance therapy of extensive-stage small cell lung cancer (ES-SCLC) remains unclear. Thus, this study aimed to assess the efficacy and safety of anlotinib monotherapy as maintenance therapy following induction chemotherapy in ES-SCLC patients. 27 ES-SCLC patients registered at the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine were screened from February 2022 to October 2022, of which 3 were not eligible. Eligible patients in stable status after first-line chemotherapy would subsequently accept oral anlotinib (12 mg, p.o., qd. on d1-d14, every 21 days). The maintenance method was continued until disease progression or unmanageable toxicity occurred. The primary endpoint is median progression-free survival (mPFS). The second endpoints include median duration of response (mDOR), median overall survival (mOS) and safety. The mPFS and mDOR have been determined (mPFS: 252 days, 95% CI: 217.782-286.218 days; mDOR: 126 days, 95% CI: 98.899-153.101 days). The mOS was not reached; only 7 patients were reached while 20 patients survived. The primary treatment-related adverse events included hypertension (n=7, 25.9%), fatigue (n=5, 18.5%), poor appetite (n=5, 18.5%), and others. Notably, no patients required a dose reduction due to the severity of adverse events. Patients were generally able to tolerate treatment with anlotinib and exhibited a favorable prognosis. Anlotinib achieved prospective efficacy and manageable safety in the maintenance treatment of ES-SCLC.


Cytogenetic analysis in peripheral lymphocytes of cancer patients treated with cytostatic drugs: results from an EC Collaborative Study.
Many of the cytostatic drugs commonly used in cancer chemotherapy treatments have been shown to be genotoxic in vivo and in vitro. We present a cytogenetic collaborative study on 13 cancer patients treated with different antitumor agents. For comparison we also carried out a cytogenetic analysis on 14 healthy untreated controls. The frequency of sister chromatid exchanges and structural chromosome aberrations in peripheral blood lymphocytes of the cancer patients was determined prior to the treatment, just after it and 3-7 weeks later. The results obtained show clear differences between the basal levels of cytogenetic alterations in cancer patients, even though the mean value is higher in this group than the basal levels of the group of healthy individuals. Treatment with cytostatics increases the frequency of both cytogenetic biomarkers analyzed, which declined to values similar to those initially observed several weeks after the treatment. Our data are in qualitative and quantitative agreement with other results previously found by other authors.


Determination of a Predictive Cleavage Motif for Eluted Major Histocompatibility Complex Class II Ligands.
CD4+ T cells have a major role in regulating immune responses. They are activated by recognition of peptides mostly generated from exogenous antigens through the major histocompatibility complex (MHC) class II pathway. Identification of epitopes is important and computational prediction of epitopes is used widely to save time and resources. Although there are algorithms to predict binding affinity of peptides to MHC II molecules, no accurate methods exist to predict which ligands are generated as a result of natural antigen processing. We utilized a dataset of around 14,000 naturally processed ligands identified by mass spectrometry of peptides eluted from MHC class II expressing cells to investigate the existence of sequence signatures potentially related to the cleavage mechanisms that liberate the presented peptides from their source antigens. This analysis revealed preferred amino acids surrounding both N- and C-terminuses of ligands, indicating sequence-specific cleavage preferences. We used these cleavage motifs to develop a method for predicting naturally processed MHC II ligands, and validated that it had predictive power to identify ligands from independent studies. We further confirmed that prediction of ligands based on cleavage motifs could be combined with predictions of MHC binding, and that the combined prediction had superior performance. However, when attempting to predict CD4+ T cell epitopes, either alone or in combination with MHC binding predictions, predictions based on the cleavage motifs did not show predictive power. Given that peptides identified as epitopes based on CD4+ T cell reactivity typically do not have well-defined termini, it is possible that motifs are present but outside of the mapped epitope. Our attempts to take that into account computationally did not show any sign of an increased presence of cleavage motifs around well-characterized CD4+ T cell epitopes. While it is possible that our attempts to translate the cleavage motifs in MHC II ligand elution data into T cell epitope predictions were suboptimal, other possible explanations are that the cleavage signal is too diluted to be detected, or that elution data are enriched for ligands generated through an antigen processing and presentation pathway that is less frequently utilized for T cell epitopes.


Revisiting the operational RNA code for amino acids: Ensemble attributes and their implications.
It has been suggested that tRNA acceptor stems specify an operational RNA code for amino acids. In the last 20 years several attributes of the putative code have been elucidated for a small number of model organisms. To gain insight about the ensemble attributes of the code, we analyzed 4925 tRNA sequences from 102 bacterial and 21 archaeal species. Here, we used a classification and regression tree (CART) methodology, and we found that the degrees of degeneracy or specificity of the RNA codes in both Archaea and Bacteria differ from those of the genetic code. We found instances of taxon-specific alternative codes, i.e., identical acceptor stem determinants encrypting different amino acids in different species, as well as instances of ambiguity, i.e., identical acceptor stem determinants encrypting two or more amino acids in the same species. When partitioning the data by class of synthetase, the degree of code ambiguity was significantly reduced. In cryptographic terms, a plausible interpretation of this result is that the class distinction in synthetases is an essential part of the decryption rules for resolving the subset of RNA code ambiguities enciphered by identical acceptor stem determinants of tRNAs acylated by enzymes belonging to the two classes. In evolutionary terms, our findings lend support to the notion that in the pre-DNA world, interactions between tRNA acceptor stems and synthetases formed the basis for the distinction between the two classes; hence, ambiguities in the ancient RNA code were pivotal for the fixation of these enzymes in the genomes of ancestral prokaryotes.


Enhancing the quasi-theoretical photocurrent density of ZnO nanorods via a lukewarm hydrothermal method.
A ∼10-μm-long one-dimensional (1D) ZnO nanorod array (NRA) vertically oriented on a fluorine-doped tin oxide (FTO) coated glass substrate is successfully fabricated via a lukewarm hydrothermal method. The reflection of light from the rough surface of this ultralong ZnO NRA, resulting from the variation in the characteristic length of individual ZnO NRs in a tapered geometry, is largely suppressed. This in turn favors the ZnO NRA as a photoelectrode effectively harnessing UV-light for solar water splitting, as evidently manifested in the quasi-theoretical photocurrent density that reached ∼0.9 mA cm-2 at 1VAg/AgCl. A further contribution to such an outstanding performance stems from additional photocurrent generation by the ZnO NRA upon visible light illumination. This is attributed to a variety of native defects and the surface hydroxyl groups present in the ZnO NRA, giving rise to the mid-gap states that mediate the associated electronic transitions. Moreover, those lattice imperfections further boost the carrier concentration of the ZnO NRA to facilitate the carrier transport which in turn enhances the photoelectrochemical activity.


Red cell distribution width identifies cerebral venous sinus thrombosis in patients with headache.
Diagnosing cerebral venous sinus thrombosis (CVST) in patients referring to emergency service or neurology outpatient unit with complaints of headache is a challenging task. Magnetic resonance (MR) venography is the gold standard, but there are limitations regarding its use. To evaluate the validity of red cell distribution width (RDW) in CVST diagnosis in patients presenting with headache. A total of 138 patients comprising 37 patients with CVST and 101 control primer headache cases were included in this retrospective cross-sectional study. Control group consists of hospitalized patients with primary headache. Venous blood hemoglobin (Hb), platelet, mean corpuscular volume (MCV), RDW, fibrinogen, and vitamin B12 levels of the patients were recorded at the first referral. Diagnosis of CVST was established by MR venography. The RDW ratio of patients with a diagnosis of CVST was significantly higher than that in patients with primary headache (15.3 ± 1.4 vs 13.3 ± 0.5; P <.0001). Fibrinogen and vitamin B12 levels were not significantly different between the 2 groups. In a total of 11 patients, there was more than 1 thrombosis. In 21 of the patients with CVST, gene mutation was detected. There was no significant difference between the patients with and without mutations regarding RDW values. Diagnostic validity of RDW was found to be excellent in differentiating patients with CVST and primary headache (area under the curve = 0.996; 95% CI: 0.990-1.000). Optimum RDW cutoff value was determined as 14.1% (sensitivity: 91.9%, specificity: 99%, positive predictive value: 92.8, negative predictive value: 0.082). We suppose that among patients presenting with the complaint of headache, RDW value may lead to diagnose CVST.


CELLULAR LIPIDS OF A NOCARDIA GROWN ON PROPANE AND N-BUTANE.
Lipid fractions of propane- and n-butane-grown nocardial cells each contain a chloroform-soluble, ether-insoluble polymer not observed previously in liquid n-alkane-grown cells. The polymer in propane-grown cells is poly-beta-hydroxybutyrate. The polymer in n-butane-grown cells apparently contains unsaturation in the molecule, and is identified tentatively as a co-polymer of beta-hydroxybutyric and beta-hydroxybutenoic (specifically 3-hydroxy 2-butenoic) acids. The other major component of the lipid fraction consists of triglycerides containing principally palmitic and stearic acids. There seems to be little qualitative distinction in the glycerides of propane- or n-butane-grown cells. Oxidative assimilation of n-butane is described.


Resveratrol mobilizes endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: a putative mechanism for chemoprevention of cancer.
Plant polyphenols are important components of human diet, and a number of them are considered to possess chemopreventive and therapeutic properties against cancer. They are recognized as naturally occurring anti-oxidants but also act as pro-oxidants catalyzing DNA degradation in the presence of metal ions such as copper. The plant polyphenol resveratrol confers resistance to plants against fungal agents and has been implicated as a cancer chemopreventive agent. Of particular interest is the observation that resveratrol has been found to induce apoptosis in cancer cell lines but not in normal cells. Over the last few years, we have shown that resveratrol is capable of causing DNA breakage in cells such as human lymphocytes. Such cellular DNA breakage is inhibited by copper specific chelators but not by iron and zinc chelating agents. Similar results are obtained by using permeabilized cells or with isolated nuclei, indicating that chromatin-bound copper is mobilized in this reaction. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and resveratrol to generate reactive oxygen species responsible for DNA cleavage. The results are in support of our hypothesis that anti-cancer mechanism of plant polyphenols involves mobilization of endogenous copper and the consequent pro-oxidant action. Such a mechanism better explains the anti-cancer effects of resveratrol, as it accounts for the preferential cytotoxicity towards cancer cells.


Beta-galactosidase enzymatic activity as a molecular probe to detect specific antibodies.
The main antigenic region of foot-and-mouth disease virus serotype C1, also called site A, has been inserted in zones of the beta-galactosidase important for the stabilization of the active site, causing important changes in the Km and the specific activity of the resulting enzymes. The peptide is displayed at the surface of the recombinant proteins and, in all the cases, presents a good antigenicity. Among the recombinant proteins constructed, in proteins M278VP1 and M275SVP1 the peptide is inserted in a large loop of the beta-galactosidase (amino acids 272-288) involved in the formation of the activating interface. In these constructs, the binding of the specific antibodies directed to the foreign peptide causes an increase of the beta-galactosidase activity up to about 200%. This phenomenon has been proved using monoclonal antibodies and also using polyclonal sera generated against the peptide. Different hypothesis of the mechanism of modulation upon antibody binding are discussed. This insertion site seems to be sensitive enough to enzymatic modulation mediated by antibody binding. We propose further exploring this insertion site as a tool for a rapid detection of specific antibodies in a quick and simple homogeneous assay based on the colorimetric determination of beta-galactosidase activity.


How much confidence should we place in efficiency estimates?
Ordinary least squares (OLS) and stochastic frontier (SF) analyses are commonly used to estimate industry-level and firm-specific efficiency. Using cross-sectional data for English public hospitals, a total cost function based on a specification developed by the English Department of Health is estimated. Confidence intervals are calculated around the OLS residuals and around the inefficiency component of the SF residuals. Sensitivity analysis is conducted to assess whether conclusions about relative performance are robust to choices of error distribution, functional form and model specification. It is concluded that estimates of relative hospital efficiency are sensitive to estimation decisions and that little confidence can be placed in the point estimates for individual hospitals. The use of these techniques to set annual performance targets should be avoided.


Dorsal cortex lesions impair habituation in turtles (Chrysemys picta).
Two experiments investigated habituation in painted turtles (Chrysemys picta). In the first, turtles were given lesions of the dorsal cortex or sham lesions and then trained on a restraint. Although the sham-lesioned turtles learned to tolerate the restraint, the lesioned animals continued to struggle against it. Thus dorsal cortex lesions disrupted habituation to restraint. In order to test habituation to a looming stimulus in a second experiment, all animals were habituated to the restraint before surgery. Postoperatively they continued to be habituated to the restraint. The looming stimulus was a circular shadow that enlarged suddenly on a screen in front of the turtle. It was presented 5 times per day for 15 days. Between-day or long-term habituation was impaired by dorsal cortex lesions.


Brainstem projections of sensory and motor components of the vagus nerve in the rat.
The sensory and motor connections of the cervical vagus nerves and of its inferior ganglion (nodose ganglion) have been traced in the medulla and upper cervical spinal cord of 16 male Wistar rats by using horseradish peroxidase (HRP) neurohistochemistry. The use of tetramethyl benzidine (TMB) as the substrate for HRP permitted the visualization of transganglionic and retrograde transport in sensory nerve terminals and perikarya, respectively. The vagus nerve in the rat enters the medulla in numerous fascicles with points of entry covering the entire lateral aspect of the medulla extending from level +4 to -6 mm rostrocaudal to the obex. Fascicles of vagal sensory fibers enter the dorsolateral aspect of the medulla and travel to the tractus solitarius (TS) which was labeled for over 8.8 mm in the medulla. The caudal extent of the TS receiving vagal projections was found in lamina V of the cervical spinal cord (C1 to C2). Sensory terminal fields could be visualized bilaterally in the nucleus of the tractus solitarius (nTS), area postrema (ap) and dorsal motor nucleus of the vagus nerve (dmnX). The ipsilateral projection to the nTS and the dmnX was heavier than that found on the contralateral side. The area postrema was intensely labeled on both sides. Motor fibers from HRP-labeled perikarya in the dmnX travel ventromedially in a distinct fascicle and subsequently subdivide into a number of small fiber bundles that traverse the medullary reticular formation in the form of a fine network of HRP-labeled fibers. As these fibers from the dmnX approach the ventrolateral aspect of the medulla they are joined by axons from the nucleus ambiguus (nA), nucleus retroambigualis (nRA) and the retrofacial nucleus (nRF). These latter fibers form hairpin loops in the middle of the reticular formation to accompany the axons from the dmnX exiting from the medulla in a ventrolateral location. HRP-labeled perikarya, in contrast to transganglionically transported HRP in sensory terminals in the nTS, were visualized on one side only, thus indicating that motor control via the vagus nerve is exerted only by motor neurons located ipsilaterally. Sensory information on the other hand, diverges to many nuclear subgroups located on both sides of the medulla.


Identification of regulated proteins by resveratrol in glutamate-induced cortical injury of newborn rats.
Glutamate induces neuronal damage by generating oxidative stress and neurotoxicities. The neurological damage caused by glutamate is more severe during brain development in newborns than in adults. Resveratrol is naturally present in a variety of fruits and medicinal plants and exerts a neuroprotective effect against brain damage. The goal of this study was to evaluate the neuroprotective effects of resveratrol and to identify changed proteins in response to resveratrol treatment during glutamate-induced neonatal cortical damage. Sprague-Dawley rat pups (7 days old) were randomly divided into vehicle, resveratrol, glutamate, and glutamate and resveratrol groups. The animals were intraperitoneally injected with glutamate (10 mg/kg) and/or resveratrol (20 mg/kg) and their brain tissue was collected 4 hr after drug administration. Glutamate exposure caused severe histopathological changes, while resveratrol attenuated this damage. We identified regulated proteins by resveratrol in glutamate-induced cortical damaged tissue using two-dimensional gel electrophoresis and mass spectrometry. Among identified proteins, we focused on eukaryotic initiation factor 4A2, γ-enolase, protein phosphatase 2A subunit B, and isocitrate dehydrogenase. These proteins decreased in the glutamate-treated group, whereas the combination treatment of glutamate and resveratrol attenuated these protein reductions. These proteins are anti-oxidant proteins and anti-apoptotic proteins. These results suggest that glutamate induces brain cortical damage in newborns; resveratrol exerts a neuroprotective effect by controlling expression of various proteins with anti-oxidant and anti-apoptotic functions.


Aromatic Gain in a Supramolecular Polymer.
The synergy of aromatic gain and hydrogen bonding in a supramolecular polymer is explored. Partially aromatic bis(squaramide) bolaamphiphiles were designed to self-assemble through a combination of hydrophobic, hydrogen-bonding, and aromatic effects into stiff, high-aspect-ratio fibers. UV and IR spectroscopy show electron delocalization and geometric changes within the squaramide ring indicative of strong hydrogen bonding and aromatic gain of the monomer units. The aromatic contribution to the interaction energy was further supported computationally by nucleus-independent chemical shift (NICS) and harmonic oscillator model of aromaticity (HOMA) indices, demonstrating greater aromatic character upon polymerization: at least 30% in a pentamer. The aromatic gain-hydrogen bonding synergy results in a significant increase in thermodynamic stability and a striking difference in aggregate morphology of the bis(squaramide) bolamphiphile compared to isosteres that cannot engage in this effect.


LeProT1, a transporter for proline, glycine betaine, and gamma-amino butyric acid in tomato pollen.
During maturation, pollen undergoes a period of dehydration accompanied by the accumulation of compatible solutes. Solute import across the pollen plasma membrane, which occurs via proteinaceous transporters, is required to support pollen development and also for subsequent germination and pollen tube growth. Analysis of the free amino acid composition of various tissues in tomato revealed that the proline content in flowers was 60 times higher than in any other organ analyzed. Within the floral organs, proline was confined predominantly to pollen, where it represented >70% of total free amino acids. Uptake experiments demonstrated that mature as well as germinated pollen rapidly take up proline. To identify proline transporters in tomato pollen, we isolated genes homologous to Arabidopsis proline transporters. LeProT1 was specifically expressed both in mature and germinating pollen, as demonstrated by RNA in situ hybridization. Expression in a yeast mutant demonstrated that LeProT1 transports proline and gamma-amino butyric acid with low affinity and glycine betaine with high affinity. Direct uptake and competition studies demonstrate that LeProT1 constitutes a general transporter for compatible solutes.