Relation between leaf senescence and stomatal closure: Senescence in light.
Senescence of isolated oat seedling leaves, floating on water or solutions in white light, has been followed by the disappearance of chlorophyll and the liberation of free amino nitrogen. In parallel, measurements of stomatal aperture were made with a diffusion resistance porometer, and borne out also by changes in fresh weight. The stomata open as expected in the light but slowly begin to close after the first day; correspondingly, in the dark they close at once but gradually begin to open on successive days. Abscisic acid causes closure and this is accompanied by senescence. Phenylmercuric nitrate also causes closure and again the reaction is closely paralleled by senescence. Kinetin maintains stomatal opening even more than does light alone, and this is accompanied by complete prevention of chlorophyll loss for at least 5 days. Covering the leaf surface with a film of Vaseline, especially when detergents are added, accelerates senescence. Merely floating the leaf segments on hypertonic solutions of sucrose or mannitol suffices to bring the rate of senescence in light up to the rate in darkness. It is concluded that the effect of light in delaying senescence is primarily due to its effect on the stomatal aperture, and, more generally, that stomatal aperture is the principal controlling agent in leaf senescence.


Balneotherapy with a psychoeducation program for the promotion of a balanced care in family caregivers of older adults.
This study aimed to analyze the efficacy of an intervention program for informal caregivers of elderly dependent that combined balneotherapy with group psychoeducation (BT-PE) based on the balanced care model. The BT-PE intervention (N = 124) was compared with a comparison group only exposed to balneotherapy (BT) (N = 76). The two modalities included both primary and secondary informal caregivers. A three-way mixed ANOVA was conducted to determine the effects of two between-subjects´ factors (intervention group and caregiver type) and one within-subjects´ factor (time) on burden, depression, anxiety, maladjustment and care satisfaction. Results showed less burden and more care satisfaction in both primary and secondary caregivers participating in the BT-PE program after the interventions. Primary caregivers also showed lower levels of maladjustment in the experimental group at post-intervention. Although depressive symptoms and anxiety decreased significantly in both intervention groups, BT-PE did not show lower scores compared with the application of sole BT. The relevance of caregivers´ psychoeducation on the balanced care model and its combination with balneotherapy is highlighted.


Replacement of corn in the diet of broiler chickens using foxtail millet produced by 2 different cultivation strategies.
Foxtail millet is well-suited to climatic conditions in semi-arid tropic regions where it is cultivated using both agro-ecologic and conventional cultivation practices. This study evaluated the nutritional value, digestibility, and physiological effects of agro-ecologic and conventionally cultivated foxtail millet in comparison with corn. Chemical and TME(n) analysis of foxtail millet cultivated conventionally and agro-ecologically indicated similar nutritional value. In total, 432 eight-day-old Ross 308 broiler chicks, using a 2 × 3 factorial arrangement, were randomly assigned to 4 replicate pens for each of 6 isonitrogenous and isoenergetic diets. Experimental diets were formulated by replacing corn with conventional or agro-ecologic millet at 3 levels (33, 66, or 100% of corn replacement). Body weight at 21 and 42 d of age was higher (P < 0.05) at 100% millet inclusion versus the lower inclusion levels. At 42 d of age, feed intake and feed conversion ratios were also improved (P < 0.05) at the 100% millet inclusion level. Similarly, the apparent ileal digestibility of CP increased (P < 0.05) for 100% millet diets. There were no differences in ileal digestibility of nutrients between millet growth conditions. Millet inclusion level significantly affected small intestinal morphology such that crypt depth was lowest (P < 0.05) in the 100% inclusion group for duodenum, jejunum, and ileum at 28 d of age, and for duodenum and ileum at 42 d of age. The villus crypt ratio was also highest (P < 0.05) in the 100% millet inclusion group for jejunum and ileum at 28 d of age, and duodenum, jejunum, and ileum at 42 d of age. Millet growth condition did not markedly affect small intestinal morphology. Serum antibody responses to Gumboro and Newcastle diseases were not affected by millet inclusion level or growth condition. In conclusion, foxtail millet could be considered as an alternate cereal for inclusion in the diet of broiler chickens. Broiler chicken performance and physiological responses to foxtail millet were similar whether grown conventionally or using agro-ecologic practices.


Hypoxic-ischaemic encephalopathy: early and late magnetic resonance imaging findings in relation to outcome.
Sixteen infants with hypoxic-ischaemic encephalopathy (HIE) were studied using serial magnetic resonance imaging (MRI) up to the age of 2 years. The infants had regular neurological and developmental assessments. An nuclear magnetic resonance (NMR) score was devised to quantify the early and late MRI findings and a neurological optimality score was used to quantify abnormal neurological signs at the time of the final examination. The follow up MRI score was compared with the neonatal MRI score and the outcome of the child. There was a strong positive correlation between the neonatal and follow up MRI scores and between MRI scores and optimality score. All infants with a normal outcome had patchy white matter abnormalities. All infants with an abnormal outcome had extensive white matter abnormalities. The outcome was most severe in those infants with additional basal ganglia atrophy with or without cyst formation. Infants with mild HIE who are developmentally normal at the age of 2 years do not have normal MRI scans and may be at risk of minor neurological problems by school age. Bilateral basal ganglia abnormalities are associated with severe developmental delay, but infants with mainly white matter and cortical abnormalities have less severe problems despite extensive tissue loss.


[The assessment of the state of the immune system in the patients presenting with bronchial asthma and concomitant diseases of the nasal cavity and paranasal sinuses].
The objective of the present investigation was to study the influence of diseases of the nasal cavity (NC) and paranasal sinuses (PNS) concomitant with bronchial asthma (BA) on the development of peculiar features of the patients' immune status. Phenotypic characteristics of the main lymphocyte subpopulations from peripheral blood of 101 patients were obtained by means of flow cytometry with the use of fluorescein isocyanate- or phycoerythrin-labeled monoclonal antibodies. Special emphasis was laid on the elucidation of characteristics of humoral and cell-mediated immunity in the patients presenting with BA and concomitant NC and PNS diseases and their comparison with the respective parameters in the patients with isolated lesions in the upper respiratory tract (allergic rhinitis and polypous rhinosinusitis) and lower respiratory tract (bronchial asthma). It was shown that the patients with concurrent lesions of the upper and lower respiratory tracts experience marked intensification of the immune reactions in the form of the elevated number of activated B-lymphocytes (CD23+), serum IgE level, and peripheral eosinophil count.


High Growth Potential of Long-Term Starved Deep Ocean Opportunistic Heterotrophic Bacteria.
Experiments with bacteria in culture have shown that they often display "feast and famine" strategies that allow them to respond with fast growth upon pulses in resource availability, and enter a growth-arrest state when resources are limiting. Although feast responses have been observed in natural communities upon enrichment, it is unknown whether this blooming ability is maintained after long periods of starvation, particularly in systems that are energy limited like the bathypelagic ocean. Here we combined bulk and single-cell activity measurements with 16S rRNA gene amplicon sequencing to explore the response of a bathypelagic community, that had been starved for 1.6 years, to a sudden organic carbon supply. We observed a dramatic change in activity within 30 h, with leucine incorporation rates increasing over two orders of magnitude and the number of translationally active cells (mostly Gammaproteobacteria) increasing 4-fold. The feast response was driven by a single operational taxonomic unit (OTU) affiliated with the Marinobacter genus, which had remained rare during 7 months of starvation. Our work suggests that bathypelagic communities harbor a seed bank of highly persistent and resourceful "feast and famine" strategists that might disproportionally contribute to carbon fluxes through fast responses to occasional pulses of organic matter.


Accurate determination of complex materials coefficients of piezoelectric resonators.
This paper presents a method of accurately determining the complex piezoelectric and elastic coefficients of piezoelectric ceramic resonators from the measurement of the normalized electric admittance, Y, which is electric admittance Y of piezoelectric resonator normalized by the angular frequency omega. The coefficients are derived from the measurements near three special frequency points that correspond to the maximum and the minimum normalized susceptance (B) and the maximum normalized conductance (G). The complex elastic coefficient is determined from the frequencies at these points, and the real and imaginary parts of the piezoelectric coefficient are related to the derivative of the susceptance with respect to the frequency and the asymmetry of the conductance, respectively, near the maximum conductance point. The measurements for some lead zirconate titanate (PZT) based ceramics are used as examples to demonstrate the calculation and experimental procedures and the comparisons with the standard methods.


Call for fellowship programs in stem cell-based regenerative and cellular medicine: new stem cell training is essential for physicians.
Stem cell-based regenerative and cellular medicine is an exciting, emerging area of medical practice. While bone marrow transplantation, a stem cell-based therapy, has been a part of medicine for decades, in recent years newer and more diverse forms of stem cell-based therapies are being used to treat a rapidly growing population of patients in the USA as well as worldwide. Nonetheless, to this author's knowledge, there is currently not a single academic medical fellowship training program in the USA that specifically prepares physicians for treating patients with stem cell-based therapies other than bone marrow or hematopoietic stem cell transplantation. An increasing number of physicians untrained in stem cell-based regenerative and cellular medicine are nonetheless transplanting stem cells into hundreds if not thousands of patients for a striking diversity of conditions. Furthermore, as stem cell technology advances, a growing number of physicians with academic affiliations may look to legitimately practice regenerative and cellular medicine. What little training that physicians can currently obtain must be found on an ad hoc basis. This article should act as a call for the development of formal academic medical fellowship programs to train physicians in the practice of cellular and regenerative medicine. The USA is used here as an example of a medical sphere in which it can be argued that such training would be helpful, however such programs would be quite helpful globally.


Effect of anticonvulsant drugs on plasma total cholesterol, high-density lipoprotein cholesterol, and apolipoproteins A and B in children with epilepsy.
The effect of long-term anticonvulsant drug therapy with phenobarbital, phenytoin, carbamazepine, primidone, and valproic acid in epileptic children on plasma total cholesterol and high-density lipoprotein cholesterol (HDLC) was studied. Except valproic acid, all the drugs significantly increased the total cholesterol and HDLC, but the effect was more pronounced with HDLC. Among the subfractions of HDLC, almost all the increase due to drug therapy were in the HDLC-2 fraction. Treatment with antiepileptic drugs had no effect on HDLC-3. Apolipoprotein-A levels were significantly higher with drug therapy, but no effect was seen in the apolipoprotein-B levels. Plasma concentration of total cholesterol, HDLC, or its components was unaffected with valproic acid therapy.


[A new therapy concept in esthesioneuroblastoma].
We introduce a new concept in treatment of esthesioneuroblastomas, developed in the University Medical School of Graz, Austria. Six patients suffering from esthesioneuroblastoma have been treated in the years 1993-1999; five of them with a curative aspect, one with a palliative one. Three tumours were classified according to Kadish as stage B, three as stage C. The selection criteria included tumours without deep infiltration into the orbit nor into the pterygopalatine fossa and without any involvement of the posterior wall of the frontal sinus. The treatment consists of endoscopic nasal and paranasal sinus surgery and consecutive stereotactic radiosurgery by means of the Gamma-Knife unit. Over an average follow-up period of 38 months all patients remained free of disease. Because of the minimally invasive character of our concept the complications and side effects are minimised and the patients are less traumatised in comparison to conventional treatment such as craniofacial resection or irradiation. Due to the excellent outcome of our six patients we recommend this new treatment concept, in selected cases, as an alternative to the usual therapeutic modalities for esthesioneuroblastoma.


Photoreaction between benzoylthiophenes and N-BOC-tryptophan methyl ester.
Drug-induced photoallergy requires as the first step formation of covalent drug-protein photoadducts. One of the key amino acids involved in this process is tryptophan (Trp). In this context, several diaryl ketones, including 2-benzoylthiophene (BT), [2-(5-benzoyl-5-thienyl)]-2-methylpropanoic methyl ester (TPA methyl ester) and 4-(2-thienylcarbonyl)phenyl]-2-methylpropanoic methyl ester (SUP methyl ester) have been irradiated in the presence of N-BOC-(L)-tryptophan methyl ester. Laser flash photolysis has allowed to detect three neutral radicals (ketyl, indolyl and skatolyl radicals) resulting from formal hydrogen-atom abstraction. This correlates well with the isolation of homodimers, as well as with cross-coupling products, in the preparative irradiation. The main cross-coupling products were in all cases lactones arising from the reaction of the Trp-derived skatolyl radicals with the corresponding ketyl radicals. These lactones were obtained as the (4R) stereoisomers with remarkable diasteroselectivity. No coupling products through the phenyl p-position of BT or TPA methyl ester were found. By contrast, ketone homodimers and cross-coupling products arising from reaction through the thienyl 5-position were obtained when using BT and SUP methyl ester; this is very interesting, because stable LAT-derived products are difficult to isolate.


Double SCN5A mutation underlying asymptomatic Brugada syndrome.
The purpose of this study was to identify risk markers in patients with Brugada syndrome. Patients with Brugada syndrome who experience syncope or aborted sudden death are at high risk for recurrent lethal arrhythmias. The prognosis and therapeutic approaches in asymptomatic individuals with a Brugada-type ECG (asymptomatic Brugada syndrome) are controversial. We genetically screened 30 asymptomatic probands (29 men and 1 woman; mean age 47.1 years) exhibiting a spontaneous Brugada-type ECG. Family members of patients with Brugada syndrome were excluded from the study. Twenty-nine of 30 patients (96.7%) remained symptom-free for at least 3 years. One patient (case 1) with a family history of sudden death died suddenly during sleep. Ventricular fibrillation was induced by programmed electrical stimulation in 14 of 18 subjects (78%), but none of these 18 subjects developed spontaneous ventricular arrhythmias. Genetic screening failed to identify SCN5A mutations in most cases but demonstrated a novel double missense mutation (K1527R and A1569P) located on the same allele in another asymptomatic subject (case 2). Heterologously expressed mutant Na channels exhibited a negative shift of steady-state inactivation (9.2 mV) and enhanced slow inactivation, suggesting this individual harbors a subclinical channel dysfunction compatible with symptomatic Brugada syndrome. Asymptomatic individuals with a Brugada-type ECG generally have a better prognosis than their symptomatic counterparts, but a subgroup of these individuals may have a poor prognosis. Severe Na channel dysfunction as a result of SCN5A mutations may not be sufficient to cause symptoms or arrhythmias in patients with Brugada syndrome, suggesting unknown factors or modifier genes influence arrhythmogenesis.


Lung injury and repair: DNA synthesis following 1,1-dichloroethylene.
Injury and cellular proliferation in the lung were examined following administration of 1,1-dichloroethylene (1,1-DCE) or vinylidene chloride. C57BL/6 male mice were treated orally with 200 mg/kg of 1,1-DCE prior to a single pulse of tritiated thymidine [( 3H]TdR). Necrosis and exfoliation of Clara cells of bronchiolar epithelium were evident by 1 day after chemical administration, and increased in severity by 2 days. A regenerative response was observed at 3 days after 1,1-DCE administration, and by 7 days the epithelium was substantially restored. At 30 days after 1,1-DCE, re-epithelization was achieved and areas devoid of epithelium were not observed. Changes in cellular proliferation were calculated from measurements of [3H]TdR incorporation into total pulmonary DNA. Activity of [3H]TdR was significantly inhibited at 1 day after chemical administration and thereafter increased: a peak of synthesis occurred between 3 and 5 days. At 7 days after 1,1-DCE administration, incorporation of [3H]TdR decreased to levels that were not significantly different from those of control animals. Autoradiographic examination of 0.5 micron thick plastic-embedded lung sections showed that [3H]TdR was incorporated into the DNA of bronchiolar epithelial cells, macrophages, interstitial, endothelial and Type II alveolar cells. However, the majority of the label was taken up by the nonciliated bronchiolar epithelial cells. The increased [3H]TdR incorporation into whole lung correlated with repopulation of bronchioles which was observed following injury. The results demonstrated that 1,1-DCE-induced damage to Clara cells of the bronchiolar epithelium was severe and rapid; re-epithelization was achieved in a relatively short time whereas differentiation was a prolonged process.


Circulating interleukin-6, soluble CD14, and other inflammation biomarker levels differ between obese and nonobese HIV-infected adults on antiretroviral therapy.
Obesity and chronic, treated HIV infection are both associated with persistent systemic inflammation and a similar constellation of metabolic and cardiovascular diseases, but the combined effects of excess adiposity and HIV on circulating proinflammatory cytokines and other biomarkers previously shown to predict disease risk is not well described. We measured inflammation biomarker levels in 158 predominantly virologically suppressed adults on long-term antiretroviral therapy (ART) with a range of body mass index (BMI) values from normal to morbidly obese. We assessed the relationship between BMI and each biomarker using multivariable linear regression adjusted for age, sex, race, CD4(+) count, tobacco use, data source, protease inhibitor use, and routine nonsteroidal antiinflammatory drug (NSAID) or aspirin use. Among normal-weight (n=48) and overweight participants (n=41; BMI <30 kg/m(2)), incremental BMI increases were associated with significantly higher serum highly sensitive C-reactive protein (hsCRP; β=2.47, p=0.02) and tumor necrosis factor (TNF)-α receptor 1 levels (β=1.53, p=0.03), and significantly lower CD14 levels (β=0.84, p=0.01), but similar associations were not observed in the obese participants. Among the obese (n=69; BMI ≥30 kg/m(2)), however, higher serum levels of interleukin-6 (IL-6; β=1.30, p=0.02) and macrophage inflammatory protein-1α (β=1.77, p<0.01) were associated with higher BMI, a finding not observed among the nonobese. Among all participants, IL-6 and TNF-α receptor 1 levels were most closely associated with hsCRP (p<0.01). Further studies are needed to determine whether higher serum inflammation biomarker levels found in obese HIV-infected individuals on ART reflect an increased likelihood of adverse health outcomes, or if novel markers to estimate mortality and disease risk are needed in this population.


A Bayesian evaluation of three diagnostic assays for the detection of Giardia duodenalis in symptomatic and asymptomatic dogs.
A Bayesian approach was used to evaluate three commonly used diagnostic assays for the detection of Giardia duodenalis in dogs: microscopical examination (ME), a commercial immunofluorescence assay (IFA: MerifluorGiardia test) and a commercial immunochromatographic assay (SNAP: Idexx SNAPGiardia test). These assays were evaluated for use in two different settings: in a cross-sectional epidemiological survey in household dogs and in a clinical survey, both conducted in the northern part of Belgium. A total of 272 faecal samples from household dogs and 141 faecal samples from clinically affected dogs were examined using these three diagnostic assays. The Bayesian analysis indicated that all tests were highly specific (specificity above 90%), and that the IFA is more sensitive than SNAP and ME, both in an epidemiological and in a clinical setting. For all three tests, the estimated sensitivity values were higher in the clinical compared to the epidemiological survey, whereas the specificity values were comparable in both studies. The results of the present study indicate that IFA is a highly specific and sensitive technique for the detection of G. duodenalis cysts, both for use in an epidemiological or clinical survey. The SNAP is a specific and fairly sensitive technique for the diagnosis of Giardia in clinically affected dogs. Overall, the ME was found to be a specific diagnostic technique, although lacking sensitivity.


Pulmonary Function Test and Obstructive Sleep Apnea Hypopnea Syndrome in Obese Adults: A Retrospective Study.
We explore risk factors related to severe obstructive sleep apnea (OSA) in obese patients, including pulmonary ventilation function, diffusion function, and impulse oscillometry (IOS) data. The medical records of 207 obese patients who were prepared to undergo bariatric surgery in a hospital from May 2020 to September 2021 were retrospectively reviewed. Polysomnography (PSG), pulmonary ventilation function, diffusion function, and IOS parameters were collected according to the ethical standards of the institutional research committee (registration number: KYLL-202008-144). Logistic regression analysis was used to analyze the related independent risk factors. There were significantly statistical difference in a number of pulmonary ventilation and diffusion function parameters among the non-OSAHS group, the mild-to-moderate OSA group, and the severe OSA group. However, only airway resistance parameters R5%, R10%, R15%, R20%, R25%, and R35% increased with increasing OSA severity and were positively correlated with apnea hypopnea index (AHI). Age (P = 0.012, 1.104 (1.022, 1.192)), body mass index (P< 0.0001, 1.12 (1.057, 1.187)), gender (P = 0.003, 4.129 (1.625, 10.49)), and R25% (P = 0.007, 1.018 (1.005, 1.031)) were independent risk factors for severe OSA. In patients aged 35 to 60, RV/TLC (P = 0.029, 1.272 (1.025, 1.577)) is an independent risk factor for severe OSA. R25% was an independent risk factor for severe OSA in obese individuals, while RV/TLC was also an independent risk factor in those aged 35 to 60. Pulmonary function tests (PFTs), particularly IOS levels, are recommended to assess severe OSA in obese patients.


DISTREE: a tool for estimating genetic distances between aligned DNA sequences.
Substitution rates estimated from aligned DNA data can be used as genetic distances to investigate the phylogenetic relationship of those sequences. For this purpose, a Markov model of nucleotide substitution has to be assumed that describes this process most adequately. A program is presented that estimates substitution rates and their standard errors for a variety of Markov models. The model introduced by Hasegawa et al. (J. Mol. Evol., 22, 160-174, 1985) is the only one for which distances and standard deviations need to be calculated numerically, since analytical formulae cannot be derived. Each model is implemented in two different variants: (i) assuming rate homogeneity or (ii) starting from Gamma-distributed substitution rates across sequence sites. The estimation of heterogeneous substitution rates is based on a method suggested by Tamura and Nei (Mol. Biol. Evol., 10, 512-526, 1993). All required parameters are estimated from sequence data, hence the user is not asked to supply any additional input. One goal of the program is to support the user when choosing a particular model that describes most adequately the evolution of the given data set. For this purpose, a more detailed analysis of this model fit is provided. Phylogenetic trees reconstructed from the inferred distances using the neighbor-joining algorithm are also available.


Transcriptomic fingerprinting of Pseudomonas putida under alternative physiological regimes.
Pseudomonas putida KT2440 is a metabolically versatile soil bacterium useful both as a model biodegradative organism and as a host of catalytic activities of biotechnological interest. In this report, we present the high-resolution transcriptome of P. putida cultured on different carbon sources as revealed by deep sequencing of the corresponding RNA pools. Examination of the data from growth on substrates that are processed through distinct pathways (glucose, fructose, succinate and glycerol) revealed that ≥ 20% of the P. putida genome is differentially expressed depending on the ensuing physiological regime. Changes affected not only metabolic genes but also a suite of global regulators, e.g. the rpoS sigma subunit of RNA polymerase, various cold-shock proteins and the three HU histone-like proteins. Specifically, the genes encoding HU subunit variants hupA, hupB and hupN drastically altered their expression levels (and thus their ability to form heterodimeric combinations) under the diverse growth conditions. Furthermore, we found that two small RNAs, crcZ and crcY, known to inhibit the Crc protein that mediates catabolite repression in P. putida, were both down-regulated by glucose. The raw transcriptomic data generated in this work is made available to the community through the Gene Expression Omnibus database.


[Treatment of unstable coronary disease].
The clinical presentations of ischemic heart disease comprises the term of acute ischaemia syndromes, that include unstable angina pectoris, non-Q-wave myocardial infarction, Q-wave-myocardial infarction and sudden death. Among the different presentations of acute ischemic syndromes, the unstable angina and non-Q-wave myocardial infarction can be regarded together. In both pathologic entity, the plaque rupture, or erosion signifies the primary event, which is the source of the highly thrombogenic substances coming out from the core of the atherosclerotic plaque and entering to the coronary and systemic circulation. They cause a thrombocyte-rich "white" intracoronary thrombus, that is not fully obstructive, or there is adequate collateral circulation, being the pathogenetic substrate that prevents the development of transmural necrosis. The nosologically-bound two clinical entity can be called as "unstable coronary artery disease" (UCAD), since they have uniform etiologic, risk stratification and therapeutic backgrounds and also therapeutic targets that are basically distinct, they are admitted for transmural "ST-elevation" infarction. The review is discussing the therapy and the questions of follow-up of the disease according to the guidelines of the European Society of Cardiology and to the multicenter evidence based studies.


A comparison of a moderate with moderate-high intensity oral anticoagulant treatment in patients with mechanical heart valve prostheses.
The long-term administration of oral anticoagulants to patients with mechanical heart valve prostheses is generally accepted. However, the appropriate intensity of oral anticoagulant treatment in these patients is still controversial. From March 1991 to March 1994, patients referred to the Padova Thrombosis Center who had undergone mechanical heart valve substitution at least 6 months earlier were randomly assigned to receive oral anticoagulants at moderate intensity (target INR = 3) or moderate-high intensity (target INR = 4). Principal end points were major bleeding, thromboembolism and vascular death. Minor bleeding was a secondary end-point. A total of 104 patients were assigned to the target 3 group and 101 to the target 4 group; they were followed for from 1.5 years to up 4.5 years (mean, 3 years). Principal end-points occurred in 13 patients in the target 3 group (4 per 100 patient-years) and in 20 patients in the target 4 group (6.9 per 100 patient-years). Major hemorrhagic events occurred in 15 patients, 4 in the target 3 group (1.2 per 100 patient-years) and 11 in the target 4 group (3.8 per 100 patient-years) (p = 0.019). The 12 recorded episodes of thromboembolism, 4 of which consisted of a visual deficit, were all transient ischemic attacks, 6 in the target 3 group (1.8 per 100 patient-years) and 6 in the target 4 group (2.1 per 100 patient-years). There were 3 vascular deaths in each group (0.9 and 1 per 100 patient-years for target 3 and target 4 groups, respectively). Minor bleeding episodes occurred 85 times (26 per 100 patient-years) in the target 3 group and 123 times (43 per 100 patient-years) in the target 4 group (p = 0.001). Mechanical heart valve patients on anticoagulant treatment who had been operated on at least 6 months earlier experienced fewer bleeding complications when maintained on a moderate intensity regimen (target INR = 3) than those on a moderate-high intensity regimen (target INR = 4). The number of thromboembolic events and vascular deaths did not differ between the two groups.


The application of serological techniques to the taxonomy of Arthrobacter and related organisms.
Antisera were raised against rods of 17 named Arthrobacter and Aureobacterium strains. Antigenic relationships between these strains, other soil bacteria and new Arthrobacter isolates from several soils were studied, using agglutination, immunodiffusion, immunofluorescence and ELISA techniques. Many of the named Arthrobacter species had common antigens, and there were also common antigens amongst named Arthrobacter strains and many fresh Arthrobacter isolates. Agglutination, ELISA and immunofluorescence tests revealed greater antigenic differences between the named strains than did immunodiffusion tests. Serological similarities between the 17 named strains and the fresh Arthrobacter isolates were calculated using SJ coefficients. The occurrence of named strains in serogroups based on immunodiffusion data supported the taxonomic scheme for arthrobacters in Bergey's Manual of Systematic Bacteriology. The distribution of soil isolates in serogroups resembled that in groups based on numerical analysis of diverse characters. This makes it possible to use serological tests to locate particular species in soil samples. Arthrobacter atrocyaneus was serologically distinct from other members of the Ar. globiformis/Ar. citreus group and did not cluster with them phenetically. Serological data suggest that Ar. aurescens, Ar. ureafaciens and Ar. histidinolovorans constitute a single species. Although A. simplex and A. tumescens have been placed in the genus Pimelobacter, they are serologically distinct from one another and more closely resemble Ar. globiformis. Aureobacterium strains were serologically distinct from arthrobacters. Micrococcus roseus showed many cross-reactions with several antisera, supporting the placement of micrococci in the same family as arthrobacters.


Training low vision patients.
The importance of training low vision-patients to use low vision aids is discussed. The team approach is emphasized and the advantages of the additional expertise considered. Specific procedures and techniques are are recommended to enhance the chances for success of the training program and it is concluded that training is an important aspect of follow-up care which should be made an intergral part of low vision care.


Natural course of LGI1 encephalitis: 3-5 years of follow-up without immunotherapy.
Antibodies against LGI1 (leucin-rich glioma-inactivated 1 protein) are associated with limbic encephalitis (LE), which is characterized by a favorable outcome following immunotherapy. Here, we present two cases, where antibodies against LGI1 were detected in the sera 36 and 53 months after acute LE, respectively, and none of the patients received immunotherapy. LE showed characteristics of LGI1 encephalitis in both cases, including low sodium content in the sera; disorientation, hallucination, short-term memory loss; and epileptic seizures. One patient had faciobrachial tonic seizures. MRI indicated bilateral inflammation of the hippocampus in one case. We reviewed longitudinal clinical and MRI data covering 53 and 36 months after LE without immunotherapy, respectively. Both patients became seizure-free and spontaneously recovered with mild/moderate cognitive impairment. No relapses have been observed. Follow-up brain MRI indicated early hippocampal sclerosis and global brain atrophy in one case characterized by more pronounced cognitive deficit. Memory and verbal fluency were affected most during the natural course of LGI1 encephalitis. LGI1 encephalitis had a monophasic course and spontaneously improved, suggesting that a relatively benign natural course may contribute to the favorable outcome observed after immunotherapy. Our data also indicate that LGI1 antibodies can be present in the sera without clinical disease activity.


Maternal and paternal lineages of the Samaritan isolate: mutation rates and time to most recent common male ancestor.
The Samaritan community is a small, isolated, and highly endogamous group numbering some 650 members who have maintained extensive genealogical records for the past 13-15 generations. We performed mutation detection experiments on mitochondrial DNAs and Y chromosomes from confirmed maternal and paternal lineages to estimate mutation rates in these two haploid compartments of the genome. One hundred and twenty four DNA samples from different pedigrees (representing 200 generation links) were analyzed for the mtDNA hypervariable I and II regions, and 74 male samples (comprising 139 links) were typed for 12 Y-STRs mapping to the non-recombining portion of the Y chromosome (NRY). Excluding two somatic heteroplasmic substitutions and several length variants in the homopolymeric C run in the HVII region, no mutations were found in the Samaritans' maternal lineages. Based on mutations found in Samaritan paternal lineages, an estimate of a mutation rate of 0.42% (95% confidence interval of 0.22%-0.71%) across 12 Y-STRs was obtained. This estimate is slightly higher than those obtained in previous pedigree studies in other populations. The haplotypes identified in Samaritan paternal lineages that belong to the same haplogroup were used to estimate the number of generations elapsed since their most recent common ancestor (MRCA). The estimate of 80 generations corresponds with accepted traditions of the origin of this sect.


Regulation of the cellular heat shock response in Caenorhabditis elegans by thermosensory neurons.
Temperature pervasively affects all cellular processes. In response to a rapid increase in temperature, all cells undergo a heat shock response, an ancient and highly conserved program of stress-inducible gene expression, to reestablish cellular homeostasis. In isolated cells, the heat shock response is initiated by the presence of misfolded proteins and therefore thought to be cell-autonomous. In contrast, we show that within the metazoan Caenorhabditis elegans, the heat shock response of somatic cells is not cell-autonomous but rather depends on the thermosensory neuron, AFD, which senses ambient temperature and regulates temperature-dependent behavior. We propose a model whereby this loss of cell autonomy serves to integrate behavioral, metabolic, and stress-related responses to establish an organismal response to environmental change.


Evaluation framework for facilitating the technology transfers of universities: Focusing on the perspective of technology donors.
Technological innovation and preoccupation with new markets through technological innovation have become critical factors in achieving success in the global market. Currently, companies cannot develop and commercialize all technologies. Therefore, the importance of technology transfers is rapidly increasing. Technology transfer is a crucial strategy adopted by organizations to remain innovative and competitive. However, Korea's technology transfer rate is only 37.9%. In particular, the technology transfer rate from universities to companies is lower than that from government-funded research institutes in Korea. Although the fundamental approach for resolving barriers to technology transfer have been studied, previous research has been conducted from a narrow definition of technology transfer. Furthermore, previous research has focused on analyzing the success factors of technology transfer, presenting technology transfer processes, or conducting case studies. Therefore, it is necessary to develop a technology donor diagnosis framework based on CSFs (Critical Success Factors) to eliminate obstacles to technology transfers. To lower the barriers to technology transfers, it is necessary to develop a strategy for a successful technology transfer based on the diagnosis of technology donors. This study develops a diagnosis framework for universities from the perspective of technology donors, implements and tests the framework using case studies, and proposes strategies for each stage of technology transfer growth. The framework is able to assess multidimensional perspectives, because CSFs and PMs were extracted based on BSC. Furthermore, by comparing the perspectives score of technology donors in different universities, technology donors can identify the areas in which each university is lacking in its current situation. Multidimensional diagnosis and aggregation score of technology donors offer to extract optimal CSFs for technology transfer activation for each growth stage.


[Simultaneous treatment of carotid paraganglioma and stenosis of the carotid arteries].
The article deals with a rare clinical case of a combination of two pathological processes in the area of the bifurcation of carotid arteries, i. e. carotid paraganglioma and critical atherosclerotic stenosis of the internal carotid artery. The first clinical manifestation of atherosclerotic stenosis was cerebral infarction. The additional examination was followed by surgical treatment - removal of the carotid paraganglioma and simultaneous eversion carotid endarterectomy. The postoperative period was uneventful. In the available literature similar combinations are mentioned only sporadically.


Are There 3D Changes in Spine and Rod Shape in the 2 Years After Adolescent Idiopathic Scoliosis Instrumentation?
Retrospective analysis of spine and rods 3D shape in the 2 years after adolescent idiopathic scoliosis (AIS) posterior surgical instrumentation. To evaluate spine and rod shape 3D changes in the 2 years after AIS instrumentation with different rod materials. Postoperative loss of correction has been reported with modern segmental instrumentation. The postoperative 3D rod shape changes of different rod materials and their implication in postoperative loss of correction have never been studied. A total of 42 Lenke 1 AIS cases who underwent surgery all with pedicle screws and 5.5 mm rods of three different materials were retrospectively reviewed (14 cases for each of the three rod material subgroups: titanium, cobalt-chromium, stainless steel). 3D reconstructions of the spine were performed using biplanar radiographs preoperatively, 1-week postoperatively (1WPO), and 2 years follow-up (2YFU). Rods 3D shape also was reconstructed at 1WPO and 2YFU. The spine and rods shapes were analyzed and compared between time points. An average of 1.93 implant per vertebra was used. The main thoracic curve (61° ± 9°) was corrected on average by 75% (15° ± 6°, P < 0.01) with no change at 2YFU (17° ± 7°, P = 0.14). The apical vertebral rotation (23° ± 7°) was corrected by 44% (13° ± 9°, P < 0.01) with no change at 2YFU (14° ± 9°, P = 0.64). The thoracic kyphosis (24° ± 12°) remained unchanged (P = 0.78). The orientation of the planes of maximal curvature with respect to the sagittal plane of the main thoracic curve (39° ± 15°) and of the rods (concave: 28° ± 23°, convex: 12° ± 10°) at 1WPO was unchanged at 2YFU (all P > 0.05). Rod curvature and deflection also remained unchanged (all P > 0.05). 3D curve correction was maintained in the 2YFU for all rod materials subgroups (all P > 0.05). The lumbar lordosis changed from 1WPO (47° ± 8°) to 2YFU (56° ± 9°, P < 0.01). At preoperatively, 57% of the cases had a balanced posture (sacral vertical axis/sacral femoral distance ≤0.5 and sacral vertical axis ≤0), 33% at 1WPO and 79% at 2YFU. There was no significant 3D shape change of the instrumented thoracic spine or of the rods postoperatively for any of the segmental pedicle screw constructs with titanium, stainless steel, and cobalt-chromium rods. Patients overall unbalanced sagittal posture documented immediately after surgery came back to balanced 2 years after surgery. 3.


Dynamic changes in optic disc morphology, choroidal thickness, anterior chamber parameters, and intraocular pressure during Valsalva maneuver.
To investigate the effects of the Valsalva maneuver (VM) on optic disc morphology, choroidal thickness, and anterior chamber parameters. This prospective observational study included 60 eyes of 60 healthy subjects. The anterior chamber parameters, including central corneal thickness (CCT), anterior chamber depth (ACD), anterior chamber angle (ACA), anterior chamber volume (ACV), pupil diameter (PD), axial length (AL), subfoveal and peripapillary choroidal thickness, optic disc parameters, and intraocular pressure (IOP), were measured at rest and during VM. VM did not have any significant influence on AL, subfoveal and peripapillary choroidal thickness, optic disc area, rim area, cup area, cup-to-disc area ratio, vertical cup-to-disc ratio, rim volume, cup volume, and nerve head volume measurements (for all; p >0.05). IOP and PD significantly increased during VM (for both; p <0.001). VM significantly decreased CCT, ACD, ACA, and ACV values (for all; p <0.001). Moreover, the optic nerve cup volume decreased and the horizontal cup-to-disc ratio significantly increased during VM (for both; p <0.05). VM may cause transient changes in IOP, optic disc morphology, and anterior chamber parameters.


Carbonic anhydrase inhibition and the management of glaucoma: a literature and patent review 2013-2019.
Introduction: Glaucoma affects more than 70 million people worldwide. One of the major therapeutic options for its management is based on the inhibition of the metalloenzyme carbonic anhydrases (CAs, EC 18.104.22.168). CA inhibitors (CAIs) diminish ocular hypertension in glaucomatous patients by reducing the rate of bicarbonate formation and thus, the secretion of the aqueous humor. Areas covered: This review is intended to cover the major contributions in terms of patent literature reports for the treatment of ophthalmic diseases by means of CAIs in a time frame spanning from 2013 to date. Expert opinion: The patent literature is dominated by innovative pharmaceutical formulations including a CAI alone or in combination with other therapeutic agents. Very few novelties within drug discovery are currently present and they mainly account for new CAI moieties and classical CAIs merged into scaffolds bearing additional chemical functionalities beneficial for the pharmacological treatment of the disease. It is reasonable to expect that in the near future the so-called 'old drugs' will achieve pharmacological performances in the management of ocular hypertension beyond any expectations and thus open a new era of drug repurposing merely based on material science advancements.


Revealing inhomogeneous Si incorporation into GaN at the nanometer scale by electrochemical etching.
Typical methods of doping quantification are based on spectroscopy or conductivity measurements. The spatial dopant distribution assessment with nanometer-scale precision is limited usually to one or two dimensions. Here we demonstrate an approach to detect three-dimensional dopant homogeneity in GaN:Si layers using electrochemical etching (ECE). GaN:Si layers are grown by plasma-assisted molecular beam epitaxy. Dopant incorporation is uniform when the growth front morphology is atomically flat. Non-uniform Si incorporation into GaN is observed when step-bunches are present on the surface during epitaxy. In this study we show that local Si concentration in the area of step-bunch is about three times higher than in the area between step-bunches. ECE spatial resolution in our experiment is estimated to be about 50 nm. This makes ECE a simple and quantitative probing tool for local three-dimensional conductivity homogeneity assessment. Our study proves that ECE could be important both for fundamental studies of crystal growth physics and impurity incorporation and for ion-implanted structures and post-processing device control.


Tin oxide microspheres with exposed {101} facets for dye-sensitized solar cells: enhanced photocurrent and photovoltage.
Hierarchical SnO2 microspheres with exposed {101} facets are synthesized by a one-pot solvothermal reaction and explored as a scattering layer on top of a SnO2 nanoparticle film for dye-sensitized solar cells (DSCs). The microspheres not only enhance photon harvesting by effective light scattering/reflecting but also improve the energy level of the conduction band edge of the SnO2 photoanode, which leads to a simultaneous increase of the short-circuit photocurrent by 17% and open-circuit photovoltage by 20%. An improved overall conversion efficiency of 3.46% is achieved for DSCs using the SnO2 microspheres, which is the highest value reported so far for pure-SnO2 DSCs. Moreover, the SnO2 -microsphere DSCs exhibit a better photostability than the conventional TiO2 DSCs under simulated full sunlight.


Allogeneic Stem Cell Transplantation for Relapsed/Refractory B Cell Lymphomas: Results of a Multicenter Phase II Prospective Trial including Rituximab in the Reduced-Intensity Conditioning Regimen.
The treatment of patients with refractory/relapsed B cell non-Hodgkin lymphoma (NHL) is evolving because of the availability of novel drugs. Allogeneic stem cell transplantation (alloSCT) can be curative, but its morbidity and mortality remain a matter of concern. We conducted a multicenter prospective phase II trial to evaluate the benefit of including only 1 dose of rituximab in the conditioning regimen before alloSCT. The primary endpoint was progression-free survival. The study enrolled 121 patients with relapsed/refractory B cell lymphomas. The conditioning regimen consisted of thiotepa, cyclophosphamide, fludarabine, and rituximab (500 mg/m2). Rabbit antithymocyte globulin was administered only in case of unrelated donors. Sixty-seven (55%) and 54 (45%) patients received grafts from related and unrelated donors, respectively. The crude cumulative incidence (CCI) of nonrelapse mortality (NRM) was 21% at 3 years. The CCIs of chronic graft-verus-host disease (GVHD) at 3 years were 54% and 31% in recipients of matched sibling and unrelated grafts, respectively. At a median follow-up of 41 months, the estimated 3-year progression-free and overall survival were 50% and 61%, respectively. Long-term outcome was also evaluated with the composite endpoint of GVHD-free and relapse-free survival (GRFS). This is the first work evaluating the GRFS in a prospective trial of lymphoma patients: the 1-year and 3-year GRFS were 40% and 34%, respectively. AlloSCT can cure a fraction of patients with rather low NRM and an encouraging PFS and GRFS.


End-of-Life Care Transition Patterns of Medicare Beneficiaries.
To characterize the patterns of transitions in care and factors associated with multiple transitions in the last 6 months of life of U.S. decedents (N = 660,132). Retrospective study. United States. Medicare beneficiaries aged 66 and older who died from July to December 2011. Transitions between healthcare settings (e.g., hospital, skilled nursing facility, inpatient hospice, home hospice, home without hospice) in the last 6 months of life. A count variable for number of transitions was summarized, and Sankey diagrams were produced to illustrate the sequences of healthcare transitions. Multivariable analyses were used to identify factors associated with likelihood of having four or more transitions. More than 80% decedents (n = 556,437) had at least one transition within the last 6 months of life; 218,731 had four or more transitions within the last 6 months of life. The most-frequent transition pattern (19.3% of all decedents; n = 127,435) was home to hospital, back to home or skilled nursing facility, to hospital again, and then to settings other than hospital, ending with four or more transitions. The average number of transitions in the last 6 months of life varied substantially across states, ranging from 1.8 in Alaska to 3.1 in New Jersey. Transitions became more intensive for decedents approaching death. In multivariable analyses, women, blacks, individuals younger than 85, and individuals without dementia were more likely to have four or more transitions (all P < .05). Approximately one-third of the Medicare beneficiaries who died in 2011 had four or more transitions within their last 6 months of life. Identifying interventions that can facilitate care transitions consistent with beneficiaries' preferences is warranted.


Hybrid total hip arthroplasty: state-of-the-art in the new millennium?
Clinical results from the past 30 years have proven total hip arthroplasty (THA) to be an effective technique for treating arthritic and degenerative conditions of the hip. Though there is little question concerning the effectiveness THA in general, significant debate exists concerning the best technique for performing the procedure. Sir John Chamley's concept of low-friction arthroplasty (LFA), considered to be the gold standard for THA, employs a cemented fixation technique for both the femoral and acetabular components. Over time, the merits of cemented fixation have been called into question as significant percentages of LFA implants failed and required revision surgery. Hybrid total hip arthroplasty is a variation of LFA that employs cemented fixation of the femoral component with cementless fixation of the acetabular component. Intermediate-term clinical results of hybrid THA have shown it to be a promising technique, with revision rates of both the femoral and acetabular components superior to Chanley LFA studies at similar lengths of follow-up. Though these results are encouraging, long-term data from the hybrid THA studies are required before a conclusion can be made as to whether the hybrid method is in fact superior to the LFA technique for performing THA.


Advances and gaps in the knowledge of thermodynamics and crystallography of acid mine drainage sulfate minerals.
Acidic and metal-rich waters produced by sulfide decomposition at mining sites are termed acid mine drainage (AMD). They precipitate a number of minerals, very often sulfates. The recent advances in thermodynamic properties and crystallography of these sulfates are reviewed here. There is a reasonable amount of data for the divalent (Mg, Ni, Co, Fe(2+), Cu, Zn) sulfates and these data may be combined with and optimized by temperature-relative humidity brackets available in the literature. For the sulfates with Fe(3+), most data exist for jarosite; for other minerals and phases in this system, a few calorimetric studies were reported. No data whatsoever are available for the Fe(2+)-Fe(3+) sulfates. A significant advance is the development of the Pitzer model for Fe(3+)sulfate solutions and its confrontation with the available thermodynamic and solubility data. In summary, our knowledge about the thermodynamic properties of the AMD sulfates is unsatisfactory and fragmented.


Surgical options after Fontan failure.
The objective of this European multicenter study was to report surgical outcomes of Fontan takedown, Fontan conversion and heart transplantation (HTX) for failing Fontan patients in terms of all-cause mortality and (re-)HTX. A retrospective international study was conducted by the European Congenital Heart Surgeons Association among 22 member centres. Outcome of surgery to address failing Fontan was collected in 225 patients among which were patients with Fontan takedown (n=38; 17%), Fontan conversion (n=137; 61%) or HTX (n=50; 22%). The most prevalent indication for failing Fontan surgery was arrhythmia (43.6%), but indications differed across the surgical groups (p<0.001). Fontan takedown was mostly performed in the early postoperative phase after Fontan completion, while Fontan conversion and HTX were mainly treatment options for late failure. Early (30 days) mortality was high for Fontan takedown (ie, 26%). Median follow-up was 5.9 years (range 0-23.7 years). The combined end point mortality/HTX was reached in 44.7% of the Fontan takedown patients, in 26.3% of the Fontan conversion patients and in 34.0% of the HTX patients, respectively (log rank p=0.08). Survival analysis showed no difference between Fontan conversion and HTX (p=0.13), but their ventricular function differed significantly. In patients who underwent Fontan conversion or HTX ventricular systolic dysfunction appeared to be the strongest predictor of mortality or (re-)HTX. Patients with valveless atriopulmonary connection (APC) take more advantage of Fontan conversion than patients with a valve-containing APC (p=0.04). Takedown surgery for failing Fontan is mostly performed in the early postoperative phase, with a high risk of mortality. There is no difference in survival after Fontan conversion or HTX.


A novel screening tool for the health risk in recreational waters near estuary: The Carrying Capacity indicator.
The present study aims to provide a conceptual framework to help practitioners to improve the quality of recreational waters near estuary, which may be affected by untreated wastewater from Combined Sewer Overflows (CSOs). When CSOs are activated, the concentration of bacteria (e.g., Enterococci and E. coli) in estuary increases, thereby resulting in a potential health threat to swimmers. Here, the bacterial exposure is evaluated using physically-based stochastic model for contaminant transport, while human health risk is determined by Quantitative Microbial Risk Assessment (QMRA). Based on human health risk framework, we quantify the Carrying Capacity (CC) of the recreational water body. Such an indicator is defined as the number of swimming individuals that can be sustained in a beach resort with an acceptable risk threshold. The CC increases by dilution processes and by reduction of the source concentration, which in turn depends on the improvements in the sewage system. The presented approach can be a useful screening tool for policy-makers and other stakeholders, thereby providing a potential solution to the trade-off between economic development and the sustainable ecosystem in coastal areas.


Allosteric equilibrium model explains steady-state coupling of beta-adrenergic receptors to adenylate cyclase in turkey erythrocyte membranes.
We used a simple experimental approach to clarify some contradictory predictions of the collision coupling and equilibrium models (e.g. ternary complex, two-state ternary complex or quinternary complex), which describe G-protein-mediated beta-adrenergic receptor signalling in essentially different manners. Analysis of the steady-state coupling of beta-adrenoceptors to adenylate cyclase in turkey erythrocyte membranes showed that: (1) in the absence of an agonist, Gpp(NH)p (a hydrolysis-resistant analogue of GTP) can activate adenylate cyclase very slowly; (2) this activity reaches a steady state in approx. 5 h, the extent of activity depending on the concentration of the nucleotide; (3) isoprenaline-activated steady-state adenylate cyclase can be inactivated by propranolol (a competitive antagonist that relaxes the receptor activation), in the presence of Gpp(NH)p (which provides a virtual absence of GTPase) and millimolar concentrations of Mg2+ (the rate of this inactivation is relatively fast); (4) increasing the concentration of Gpp(NH)p can saturate the steady-state activity of adenylate cyclase. The saturated enzyme activity was lower than that induced by isoprenaline under the same conditions. This additional agonist-induced activation was reversible. In the light of these results, we conclude that agonist can also activate the guanine nucleotide-saturated system in the absence of GTPase by a mechanism other than guanine nucleotide exchange. We explain these phenomena in the framework of a quinternary complex model as an agonist-induced and receptor-mediated dissociation of guanine nucleotide-saturated residual heterotrimer, the equilibrium concentration of which is not necessarily zero. These results, which suggest a continuous interaction between receptor and G-protein, can hardly be accommodated by the collision coupling model that was originally suggested for the present experimental system and then applied to many other G-protein systems. Therefore we attempt to unify the equilibrium and collision coupling approaches to provide a consistent theoretical basis for the G-protein-mediated beta-adrenergic receptor signalling in turkey erythrocyte membranes.


The incudopetrosal joint of the human middle ear: a transient morphology in fetuses.
In spite of the amount of research on fetal development of the human middle ear and ear ossicles, there has been no report showing a joint between the short limb of incus and the otic capsule or petrous part of the temporal bone. According to observations of serial histological sections from 65 embryos and fetuses at 7-17 weeks of development, the incudopetrosal joint exhibited a developmental sequence similar to the other joints of ossicles, with an appearance of an interzone followed by a trilaminar configuration at 7-12 weeks, a joint cavitation at 13-15 weeks and development of intraarticular and capsular ligaments at 16-17 weeks. These processes occurred at the same time or slightly later than any other joint. Thus, the joint development might coordinate with vibrating ossicles in utero. The growing short limb of incus appeared to accelerate an expansion of the epitympanic recess of the tympanic cavity. Additional observations of five late-stage fetuses demonstrated the incudopetrosal joint located in the fossa incudis joint changing to syndesmosis. Consequently, a real joint with a cavity existed transiently between the human neurocranium and the first pharyngeal arch derivative (i.e. incus) in contrast to the tympanostapedial joint or syndesmosis between the neurocranium and the second arch derivative. The newly described joint might have an effect on the widely accepted primary jaw concept: the mammalian jaw should thus have been created within the first pharyngeal arch, although the connection with neurocranium by the stapes is of a different origin.


Associations of growth from birth to puberty with blood pressure and lipid profile at ~17.5 years: evidence from Hong Kong's "Children of 1997" birth cohort.
The role of early growth in later health is controversial. We examined the associations of growth at different phases from birth to puberty with blood pressure and lipid profile at ~17.5 years. In the population-representative "Children of 1997" birth cohort, growth was measured as (i) weight-for-age z score (WAZ) at birth and WAZ gains from 0 to 2 and 2 to 8 years and (ii) body-mass-index-for-age z score (BAZ) and length/height-for-age z score (LAZ) at 3 months and BAZ and LAZ gains from 3 months to 3 years, 3 to 8 years and 8 to 14 years, based on the World Health Organization growth standards/references. Adjusted partial least squares regression was used to assess simultaneously the associations of growth with height-, age- and sex-specific systolic (SBPZ) and diastolic blood pressure z scores (DBPZ), low- (LDL) and high-density lipoprotein (HDL) and triglycerides (TG) at ~17.5 years. Among 3410 children, higher WAZ, BAZ and LAZ gains from initial size to 8 years were associated with higher SBPZ. Higher gains in WAZ and BAZ from 2 to 8 years were consistently associated with higher DBPZ, LDL and TG and lower HDL. Lower LAZ at 3 months and higher LAZ gain from 3 months to 3 years were associated with lower HDL and higher TG. Greater growth in weight, body mass index and length/height had negative associations with blood pressure and lipid profile at ~17.5 years, but the differences by growth measure, phase and outcome suggest a complex underlying process.


Lysines in the RNA Polymerase II C-Terminal Domain Contribute to TAF15 Fibril Recruitment.
Many cancer-causing chromosomal translocations result in transactivating protein products encoding FET family (FUS, EWSR1, TAF15) low-complexity (LC) domains fused to a DNA binding domain from one of several transcription factors. Recent work demonstrates that higher-order assemblies of FET LC domains bind the carboxy-terminal domain of the large subunit of RNA polymerase II (RNA pol II CTD), suggesting FET oncoproteins may mediate aberrant transcriptional activation by recruiting RNA polymerase II to promoters of target genes. Here we use nuclear magnetic resonance (NMR) spectroscopy and hydrogel fluorescence microscopy localization and fluorescence recovery after photobleaching to visualize atomic details of a model of this process, interactions of RNA pol II CTD with high-molecular weight TAF15 LC assemblies. We report NMR resonance assignments of the intact degenerate repeat half of human RNA pol II CTD alone and verify its predominant intrinsic disorder by molecular simulation. By measuring NMR spin relaxation and dark-state exchange saturation transfer, we characterize the interaction of RNA pol II CTD with amyloid-like hydrogel fibrils of TAF15 and hnRNP A2 LC domains and observe that heptads far from the acidic C-terminal tail of RNA pol II CTD bind TAF15 fibrils most avidly. Mutation of CTD lysines in heptad position 7 to consensus serines reduced the overall level of TAF15 fibril binding, suggesting that electrostatic interactions contribute to complex formation. Conversely, mutations of position 7 asparagine residues and truncation of the acidic tail had little effect. Thus, weak, multivalent interactions between TAF15 fibrils and heptads throughout RNA pol II CTD collectively mediate complex formation.


Specific gene expression in pancreatic beta-cells: cloning and characterization of differentially expressed genes.
Identification and characterization of genes expressed preferentially in pancreatic beta-cells will clarify the mechanisms involved in the specialized properties of these cells, as well as providing new markers of the development of type 1 diabetes. Despite major efforts, relatively few beta-cell-specific genes have been characterized. We applied representational difference analysis to identify genes expressed selectively in the pancreatic beta-cell line betaTC1 compared with the pancreatic alpha-cell line alphaTC1 and isolated 26 clones expressed at higher levels in the beta-cells than in the alpha-cells. DNA sequencing revealed that 14 corresponded to known genes (that is, present in GenBank). Only four of those genes had been shown previously to be expressed at higher levels in beta-cells (insulin, islet amyloid polypeptide, neuronatin, and protein kinase A regulatory subunit [RIalpha]). The known genes include transcription factors (STAT6) and mediators of signal transduction (guanylate cyclase). The remaining 12 genes are absent from the GenBank database or are present as expressed sequence tag (EST) sequences (4 clones). Some of the genes are expressed in a highly specific pattern-expression in betaTC1 and islet cells and in relatively few of the non-beta-cell types examined; others are expressed in most cell types tested. The identification of these differentially expressed genes may aid in attaining a clearer understanding of the mechanisms involved in beta-cell function and of the possible immunogens involved in development of type 1 diabetes.


The first decade of the Malawi College of Medicine: a critical appraisal.
The College of Medicine of the University of Malawi was opened in April 1991. Over almost a decade it has flourished in the face of economic and political constraints, as well as a change in the philosophy of donor support. We review the past, assess the present and look to the future.


Trapezium Tunnel Syndrome.
The trapezium tunnel is situated on the lateral side of the carpal tunnel, lined with synovial tissue, and accommodates the flexor carpi radialis tendon. Trapezium tunnel syndrome is characterized by flexor carpi radialis tendinitis/peritendinitis and may lead to complicated clinical scenarios, such as flexor carpi radialis tendon rupture and the formation of primary or recurrent ganglion cysts on the volar radial side of the wrist and thenar area. Notably, the simultaneous presence of trapezium tunnel syndrome might contribute to unsuccessful outcomes in carpal tunnel surgeries. Trapezium tunnel syndrome may arise from either intrinsic or extrinsic factors. The entity of trapezium tunnel syndrome has attracted a low index of clinical suspicion because the other causes of radial side wrist pain that are more prevalent and frequent. We present a narrative review of this condition in an endeavor to heighten awareness and clinical suspicion of trapezium tunnel syndrome.


A regulatory locus for mouse beta-glucuronidase induction, Gur, controls messenger RNA activity.
A regulatory locus in a higher organism has been shown to control a specific messenger RNA activity. The Gur locus in mice regulates the production of kidney beta-glucuronidase messenger RNA activity after induction of the beta-glucuronidase structural gene, Gus, by testosterone. beta-Glucuronidase messenger RNA was assayed by its ability to direct the synthesis of catalytically active murine beta-glucuronidase in Xenopus oocytes.


Carbon - the first frontier of information processing.
Information is often encoded as an aperiodic chain of building blocks. Modern digital computers use bits as the building blocks, but in general the choice of building blocks depends on the nature of the information to be encoded. What are the optimal building blocks to encode structural information? This can be analysed by substituting the operations of addition and multiplication of conventional arithmetic with translation and rotation. It is argued that at the molecular level, the best component for encoding discretized structural information is carbon. Living organisms discovered this billions of years ago, and used carbon as the back-bone for constructing proteins that function according to their structure. Structural analysis of polypeptide chains shows that an efficient and versatile structural language of 20 building blocks is needed to implement all the tasks carried out by proteins. Properties of amino acids indicate that the present triplet genetic code was preceded by a more primitive one, coding for 10 amino acids using two nucleotide bases.


Network meta-analysis of Chinese herbal injections combined with the chemotherapy for the treatment of pancreatic cancer.
This study sought to use a network meta-analysis to assess the effectiveness and safety of Chinese herbal injections (CHIs) combined with the chemotherapy for the treatment of pancreatic cancer. Randomized controlled trials (RCTs) regarding CHIs to treat pancreatic cancer were searched in PubMed, the Cochrane library, Embase, the China National Knowledge Infrastructure Database (CNKI), the Wan-Fang Database, the Chinese Scientific Journals Full-text Database (VIP), and the Chinese Biomedical Literature Database (SinoMed) up to November 2016. The quality assessment was conducted by the Cochrane risk of bias tool and network meta-analysis was performed to compare the effectiveness and safety of different CHIs combined with the chemotherapy. Data were analyzed using STATA 12.0 and Win-BUGS 1.4 software. A total of 278 records were searched, and 22 eligible RCTs involving 1329 patients and 9 CHIs were included. The results of the network meta-analysis demonstrated that compared with the chemotherapy alone, Compound Kushen, Kangai or Kanglaite injection combined with chemotherapy yielded significantly higher probability of improving performance status. Aidi injection combined with chemotherapy was more effective in relieving leucopenia than using chemotherapy single. And these between-group differences were statistically significant. However, CHIs combined with chemotherapy could not achieve a better effect in the total clinical effect, nausea and vomiting. As for the cluster analysis for the adverse reactions (ADRs), the chemotherapy alone and Huachansu injection combined with the chemotherapy were inferior to relieve ADRs than the other CHIs plus chemotherapy for patients with pancreatic cancer. The current evidence showed that using CHIs on the basis of the chemotherapy could be beneficial for patients with pancreatic cancer in improving performance status and reducing the ADRs.


Vagal afferent neurons in high fat diet-induced obesity; intestinal microflora, gut inflammation and cholecystokinin.
The vagal afferent pathway is the major neural pathway by which information about ingested nutrients reaches the CNS and influences both GI function and feeding behavior. Vagal afferent neurons (VAN) express receptors for many of the regulatory peptides and molecules released from the intestinal wall, pancreas, and adipocytes that influence GI function, glucose homeostasis, and regulate food intake and body weight. As such, they play a critical role in both physiology and pathophysiology, such as obesity, where there is evidence that vagal afferent function is altered. This review will summarize recent findings on changes in vagal afferent function in response to ingestion of high fat diets and explore the hypothesis that changes in gut microbiota and integrity of the epithelium may not only be important in inducing these changes but may be the initial events that lead to dysregulation of food intake and body weight in response to high fat, high energy diets.


DUX-family transcription factors regulate zygotic genome activation in placental mammals.
In animal embryos, transcription is mostly silent for several cell divisions, until the release of the first major wave of embryonic transcripts through so-called zygotic genome activation (ZGA). Maternally provided ZGA-triggering factors have been identified in Drosophila melanogaster and Danio rerio, but their mammalian homologs are still undefined. Here, we provide evidence that the DUX family of transcription factors is essential to this process in mice and potentially in humans. First, human DUX4 and mouse Dux are both expressed before ZGA in their respective species. Second, both orthologous proteins bind the promoters of ZGA-associated genes and activate their transcription. Third, Dux knockout in mouse embryonic stem cells (mESCs) prevents the cells from cycling through a 2-cell-like state. Finally, zygotic depletion of Dux leads to impaired early embryonic development and defective ZGA. We conclude that DUX-family proteins are key inducers of zygotic genome activation in placental mammals.


Parallel organization of contralateral and ipsilateral prefrontal cortical projections in the rhesus monkey.
The neocortical commissures have a fundamental role in functional integration across the cerebral hemispheres. We investigated whether commissural projections in prefrontal cortices are organized according to the same or different rules as those within the same hemisphere, by quantitatively comparing density, topography, and laminar origin of contralateral and ipsilateral projections, labeled after unilateral injection of retrograde tracers in prefrontal areas. Commissural projection neurons constituted less than one third of the ipsilateral. Nevertheless, projections from the two hemispheres were strongly correlated in topography and relative density. We investigated to what extent the distribution of contralateral projections depended on: (a) geographic proximity of projection areas to the area homotopic to the injection site; (b) the structural type of the linked areas, based on the number and neuronal density of their layers. Although both measures were good predictors, structural type was a comparatively stronger determinant of the relative distribution and density of projections. Ipsilateral projection neurons were distributed in the superficial (II-III) and deep (V-VI) layers, in proportions that varied across areas. In contrast, contralateral projection neurons were found mostly in the superficial layers, but still showed a gradient in their distribution within cortical layers that correlated significantly with cortical type, but not with geographic proximity to the homotopic area. The organization of ipsilateral and contralateral prefrontal projections is similar in topography and relative density, differing only by higher overall density and more widespread laminar origin of ipsilateral than contralateral projections. The projections on both sides are highly correlated with the structural architecture of the linked areas, and their remarkable organization is likely established by punctuated development of distinct cortical types. The preponderance of contralateral projections from layer III may be traced to the late development of the callosal system, whose function may be compromised in diseases that have their root late in ontogeny.


Human mammary epithelial cells express CYP27B1 and are growth inhibited by 25-hydroxyvitamin D-3, the major circulating form of vitamin D-3.
1alpha,25-dihydroxycholecalciferol [1alpha,25(OH)2D3], the active form of cholecalciferol, is a negative growth regulator of breast cancer cells. CYP27B1 is a cytochrome P450-containing hydroxylase expressed in kidney and other tissues that generates 1alpha,25(OH)2D3 from an inactive vitamin D precursor 25-hydroxycholecalciferol [25(OH)D3]. In these studies, we tested the hypothesis that mammary cells express CYP27B1 and locally produce 1alpha,25(OH)2D3, which acts in an autocrine manner to regulate cell turnover. Using Western blot and quantitative real-time PCR, CYP27B1 mRNA and protein were detected in immortalized, nontumorigenic human mammary epithelial cell (HMEC) cultures. Furthermore, HMEC cultures were dose dependently growth inhibited by physiological concentrations of 25(OH)D3, suggesting that CYP27B1 converts this precursor cholecalciferol metabolite to 1alpha,25(OH)2D3, the ligand for the vitamin D receptor (VDR). In support of this suggestion, both 1alpha,25(OH)2D3 and 25(OH)D3 transactivated VDR in HMEC cultures, as measured by induction of a vitamin D responsive reporter gene and upregulation of CYP24, an endogenous VDR target gene. No induction of CYP24 by 25(OH)D3 was observed in mammary cells derived from CYP27B1 null mice. Similar results were observed in 2 independently derived immortalized HMEC lines as well as in primary cultures derived from human breast epithelium. These are the first studies to demonstrate that nontransformed human mammary cells express CYP27B1, that they are growth inhibited by physiologically relevant concentrations of 25(OH)D3, and that they provide a biological mechanism linking vitamin D status to breast cancer risk.


Calcified renal artery aneurism in the right kidney causing hypertension.
The renal artery aneurysm (RAA) is defined as a renal artery segment that is twofold dilated than normally. It is very rare in children and often asymptomatic. However, it can cause severe hypertension (HTN) and kidney failure. Herein, we report a 14-year-old boy who with RAA which was presented with back pain. His medical history was remarkable for essential HTN that was refractory to antihypertensive medications. Plain abdominal radiography revealed calcification at the right flank area. On computed tomography images, calcification surrounding the right renal artery was detected. Selective renal angiography showed totally occluded right renal artery segment. Calcified RAA was detected on the operation and removed. Two months after, blood pressure was under control, but there was no functioning right kidney on DMSA. We think that clinicians should keep in mind RAA in the differential diagnosis of treatment-resistant HTN and use other radiologic methods even if Doppler is normal.


The Potential for Rapid Evolution under Anthropogenic Climate Change.
Understanding how natural populations will respond to rapid anthropogenic climate change is one of the greatest challenges for ecologists and evolutionary biologists. Much research has focussed on whether physiological traits can evolve quickly enough under rapidly increasing temperatures. While the simple Breeder's equation helps to understand how extreme temperatures and genetic variation might drive within-population evolution under climate change, it does not consider two key areas: how different forms of phenotypic plasticity interact and variation among populations. Plasticity can modify the exposure to climatic extremes and the strength of selection from those extremes, while differences among populations provide adaptive diversity not apparent within them. Here, we focus on terrestrial vertebrates and, with a case study on a tropical lizard, demonstrate the complex interplay between spatial, genetic and plastic contributions to variation in climate-relevant physiological traits. We identify several problems that need to be better understood: which traits are under selection in a changing climate; the different forms of plasticity relevant to population persistence and rapid evolution; plastic versus genetic contributions to geographic variation in climate-associated traits and whether plasticity can be harnessed to promote persistence of species. Given ongoing uncertainties around whether natural populations can evolve rapidly enough to persist, we advocate the use of field trials aimed at increasing rates of adaptation, especially in systems known to be strongly impacted by human-driven changes in climate.


Inosine pranobex enhances human NK cell cytotoxicity by inducing metabolic activation and NKG2D ligand expression.
Inosine pranobex (IP) is a synthetic immunomodulating compound, indicated for use in the treatment of human papillomavirus-associated warts and subacute sclerosing panencephalitis. Previous studies demonstrate that the immunomodulatory activity of IP is characterized by enhanced lymphocyte proliferation, cytokine production, and NK cell cytotoxicity. The activation of NKG2D signaling on NK cells, CD8+ T cells, and γδ T cells also produces these outcomes. We hypothesized that IP alters cellular immunity through the induction of NKG2D ligand expression on target cells, thereby enhancing immune cell activation through the NKG2D receptor. We tested this hypothesis and show that exposure of target cells to IP leads to increased expression of multiple NKG2D ligands. Using both targeted metabolic interventions and unbiased metabolomic studies, we found that IP causes an increase in intracellular concentration of purine nucleotides and tricarboxylic acid (TCA) cycle intermediates and NKG2D ligand induction. The degree of NKG2D ligand induction was functionally significant, leading to increased NKG2D-dependent target cell immunogenicity. These findings demonstrate that the immunomodulatory properties of IP are due to metabolic activation with NKG2D ligand induction.


Glycoprotein C of herpes simplex virus 1 is an inhibitor of the complement cascade.
Mammalian cells in culture express membrane receptors for C3b when infected with HSV-1. C3b binding is mediated by glycoprotein C (gC), a virus-specified membrane glycoprotein. In view of the inhibitory functions of other C3b-binding proteins, we studied the capacity of gC to modulate complement activation. Glycoprotein C was purified from HSV-1-infected cells by immunoaffinity chromatography. Glycoprotein C, but not a control viral glycoprotein, demonstrated dose-dependent acceleration of decay of C3bBb sites. In addition, gC produced a dose-dependent, time-independent depression of the overall hemolytic efficiency of C3bBb sites. Inhibition of C5b6-initiated reactive lysis of cells bearing C3b, but not cells bearing antibody alone, by gC suggests that the second effect represents interference with the C3b-C5/5b interaction. This hypothesis is supported by the failure of gC to inhibit reactive lysis when added after C5b67 insertion into target cells. Glycoprotein C does not accelerate C14b2a decay, nor does it impair classical pathway hemolytic efficiency when excess C5 is present. By limiting available C5/5b, some gC inhibition of C3b-C5/5b interactions can be unmasked in the classical pathway system. Glycoprotein C is devoid of factor I co-factor activity. HSV-1 gC is a modulator of complement activation, especially via the alternative pathway, and may represent a novel viral mechanism for evading host defense processes.


The effect of meteorological factors on the daily variation of airborne fungal spores in Granada (southern Spain).
A study was made of the link between climatic factors and the daily content of certain fungal spores in the atmosphere of the city of Granada in 1994. Sampling was carried out with a Burkard 7-day-recording spore trap. The spores analysed corresponded to the taxa Alternaria, Ustilago and Cladosporium, with two morphologically different spore types in the latter genus, cladosporioides and herbarum. These spores were selected both for their allergenic capacity and for the high level of their presence in the atmosphere, particularly during the spring and autumn. The spores of Cladosporium were the most abundant (93.82% of the total spores identified). The Spearman correlation coefficients between the spore concentrations studied and the meteorological parameters show different indices depending on the taxon being analysed. Alternaria and Cladosporium are significantly correlated with temperature and hours of sunlight, while Ustilago shows positive correlation indices with relative humidity and negative indices with wind speed.


Calcitonin expression of high endothelial venules during lymphocyte migration in human pharyngeal tonsil.
The migration routes of lymphocytes through high endothelial venules (HEVs) of control and hypertrophic pharyngeal tonsil (HPT) tissue sections were investigated by immunohistochemistry using the expression of a hormone [calcitonin (CT)] and two calcium-dependent endothelial adhesion molecules (E-selectin and P-selectin), as well as electron microscopy. A marked increase in CT-specific staining was observed in the endothelial cells of HEV in the HPT group compared to the control group. Expressions of E-selectin and P-selectin on HEVs of control group were faint, when compared to the strong expression of these selectins on HEVs of HPT. Electron microscopically, we demonstrated that lymphocytes transmigrated through HEV and observed the close membranous contact between endothelial cells and lymphocytes during this process. We speculate that increasing CT during inflammation may be important for lymphocyte migration through the HEVs via controlling the expression of E-selectin and P-selectin.


Cerebellar degeneration correlates with motor symptoms in Huntington disease.
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterized by variable motor and behavioral symptoms attributed to major neuropathology of mainly the basal ganglia and cerebral cortex. The role of the cerebellum, a brain region involved in the coordination of movements, in HD neuropathology has been controversial. This study utilizes postmortem human brain tissue to investigate whether Purkinje cell degeneration in the neocerebellum is present in HD, and how this relates to disease symptom profiles. Unbiased stereological counting methods were used to quantify the total number of Purkinje cells in 15 HD cases and 8 neurologically normal control cases. Based on their predominant symptoms, the HD cases were categorized into 2 groups: "motor" or "mood." The results demonstrated a significant 43% loss of Purkinje cells in HD cases with predominantly motor symptoms, and no cell loss in cases showing a major mood phenotype. There was no significant correlation between Purkinje cell loss and striatal neuropathological grade, postmortem delay, CAG repeat in the IT15 gene, or age at death. This study shows a compelling relationship between Purkinje cell loss in the HD neocerebellum and the HD motor symptom phenotype, which, together with our previous human brain studies on the same HD cases, provides novel perspectives interrelating and correlating the variable cerebellar, basal ganglia, and neocortical neuropathology with the variability of motor/mood symptom profiles in the human HD brain. ANN NEUROL 2019;85:396-405.


Tobacco Smoking, Substance Use, and Mental Health Symptoms in People with HIV in an Urban HIV Clinic.
The prevalence of tobacco smoking among people with HIV (PWH) ranges from 40% to 70%. Additionally, tobacco smoking is higher among low-income individuals, yet few studies have examined tobacco smoking in low socioeconomic status PWH. Using data from a cohort of PWH receiving care in an urban HIV clinic, we characterized factors associated with current and former smoking and with initiation/re-initiation and cessation of tobacco use. Among a study sample of 1,607 PWH, the prevalence of current smoking was 46.6% among men and 46.0% among women. Current smoking in men and women was associated with Medicaid insurance status, substance use, and panic symptoms. In women, but not men, hazardous alcohol use decreased the likelihood of quitting smoking and increased the risk of initiation/re-initiation. Smoking interventions for low-income, urban PWH may need to be tailored to address mental health and substance use comorbidities.


Organocatalytic enantioselective hydrophosphonylation of aldehydes.
We report our results concerning the first squaramide-catalysed hydrophosphonylation of aldehydes. In all cases, the reactions proceeded smoothly and cleanly under mild reaction conditions rendering final α-hydroxy phosphonates in very good yields and high enantioselectivities. It is one of the few organocatalytic examples of this reaction using aldehydes. It is the first time that diphenylphosphite (1e) has been successfully employed in a chiral Pudovik reaction with aldehydes, in contrast to the dialkylphosphites used in previously published procedures, extending the generality of this asymmetric methodology.


Imaging expression of the human somatostatin receptor subtype-2 reporter gene with 68Ga-DOTATOC.
The human somatostatin receptor subtype 2 (hSSTr2)-68Ga-DOTATOC reporter system has several attractive features for potential translation to human studies. These include a low expression of hSSTr2 in most organs, a rapid internalized accumulation of 68Ga-DOTATOC in the SSTr2-expressing cells, and a rapid excretion of unbound radioligand by the renal system. We performed a series of in vitro and in vivo validation studies of this reporter system. A retroviral vector containing a dual reporter, pQCXhSSTr2-IRES-GFP (IRES: internal ribosome entry site; GFP: green fluorescent protein), was constructed and transduced into Jurkat, C6, and U87 cells. Stably transduced reporter cells were characterized in vitro using optical and radiometric methods. Multiple tumor-bearing mice were evaluated with 68Ga-DOTATOC PET studies. The dual-reporter genes were incorporated into all tumor cell lines, and their expression levels were confirmed by fluorescence-activated cell sorting (FACS), GFP visualization, and reverse-transcriptase polymerase chain reaction (RT-PCR) analysis for hSSTr2. In vitro, hSSTr2 cell membrane expression was 36,000, 280,000, and 1,250,000 copies per cell for the SSTR2-transfected Jurkat, U87, and C6 cell lines. Small-animal PET of 68Ga-DOTATOC in tumor-bearing mice demonstrated that the in vivo uptake of this radioligand was directly proportional to the in vitro expression of hSSTr2. The in vivo uptake of 68Ga-DOTATOC, at 2 h after injection, was low in all organs except the kidneys (7.8 percentage of injected dose per gram [%ID/g]) and as high as 15.2 %ID/g in transduced C6 tumors. The corresponding transduced-to-nontransduced tumor uptake ratio was 64, and the tumor-to-muscle uptake ratio was around 500. 68Ga-DOTATOC is an excellent specific ligand for this hSSTr2 reporter system and for hSSTr2 reporter gene PET. Because DOTATOC has undergone extensive clinical testing, this human reporter system has the potential for translation to human studies.


Arterial abnormalities of the shoulder in athletes.
Vascular lesions of the shoulder may be misinterpreted as one of the more familiar shoulder abnormalities by a treating physician. We are reporting on 13 athletes who were found to have symptoms related to compression of the subclavian or axillary artery or their tributaries. Nine were amateur or professional baseball pitchers. Severe arm fatigue or finger ischemia, secondary to embolization, were presenting symptoms. Arm fatigue was noted in all pitchers. After complete history and physical examination, including auscultation for bruits in functional positions, all athletes were evaluated by noninvasive tests (Doppler and Duplex scanning). Arteriography was performed with positional testing, recreating overhead activity, and complete radiographic visualization of the dye to the digital arteries. Two patients were found to have subclavian artery aneurysm. The remaining athletes were found to have compression of the subclavian artery beneath the anterior scalene muscle (five patients), the axillary artery beneath the pectoralis minor (two patients), both arterial segments (two patients), and one was found to have arterial compromise at the level of the humeral head. Branch artery compression was also noted. One pitcher occluded the posterior circumflex humeral artery with embolization to the digit. The two patients with subclavian aneurysms underwent saphenous vein bypass with cervical rib resection. All of the other athletes except one underwent resection of a 2 to 3 cm segment of the anterior scalene muscle or pectoralis minor muscles. All returned to their previous level of activity except one patient who developed impingement type symptoms and required acromioplasty. He is currently undergoing rehabilitation. Proper recognition of vascular compromise in the upper extremity of athletes is essential to avoid the catastropic complications of arterial thrombosis.


The value of integrating policy people and space in research.
In this article, we address several tangible and intangible factors, which are difficult to quantify and often overlooked yet are crucial for research success. We discuss three dimensions which encompass: (1) policy, (2) people, and (3) space. Policies, such as rules and regulations, define the culture of any research program/initiative. Governing rules and regulations defined within these policies are dictated by cultural values. Individuals who exhibit strong leadership, promote innovation, and exercise strategic planning often determine the governing policies. People are the most valuable asset available to any institution. Ensuring the professional growth (personal and scientific) and creating an environment which supports collaborative and collegial research through teamwork are factors that are important for individuals. Space, the physical work environment, is the third dimension of our model and is often an underutilized resource. In addition to the physical layout and design of the space, creating a positive work atmosphere which supports research initiatives is equally important and can create valuable momentum to research efforts. Collectively, these three dimensions (policy, people, and space) have a significant impact on the success of any research initiative. The primary objective of this article is to create awareness and emphasize the importance of implementing these variables within research initiatives in academic settings.


Diallel analysis of androgenetic plant production in hexaploid Triticale (X. triticosecale, Wittmack).
Studies were made on the genetic determination of androgenetic plant yield and its two components: embryo production and green plant regeneration. This involved the analysis of a complete 7×7 diallel cross of 4 androgenetic lines and 3 lines obtained by pedigree selection, one of them having the Triticum timopheevi cytoplasm. The three traits analysed are both heritable and environmentally influenced (by season and culture medium composition). The analysis of embryo production shows a mainly nuclear inheritance, with predominantly additive gene action, but also a favourable effect of Triticum timopheevi cytoplasm. Green plant regeneration has a more complex genetic determination, with additive as well as non-additive gene action and cytoplasmic influences. Hybrids appear superior to inbred lines for embryogenesis and green plant yield, but not for green plant regeneration. Androgenetic lines used as parents did not show superiority over other parents either in their own value or in the transmission of androgenetic abilities. Genetic improvement seems to be possible by recombination in progenies of hybrids between lines having complementary abilities.


Fenfluramine and fluoxetine spare protein consumption while suppressing caloric intake by rats.
The effects of fenfluramine and other sanorectic drugs on the consumption of both protein and total calories by rats given simultaneous access to two isocaloric diets containing 5 or 45 percent casein were examined. Anorectic doses of fenfluramine failed to decrease protein intake but increased the proportion of total dietary calories represented by protein. In contrast, anorectic doses of d-amphetamine decreased protein and calorie consumption proportionately. Subanorectic doses of fenfluramine also increased the proportion of caloric intake represented by protein among animals given prior treatment with the serotonin precursor tryptophan. Fluoxetine, a drug that blocks reuptake of serotonin, similarly spared protein consumption while reducing caloric intake. These observations indicate that two distinct brain mechanisms, sensitive to different drugs, underlie the elective consumption of protein and calories.


Antecedents of cerebral palsy. I. Univariate analysis of risks.
A large prospective study investigated prenatal and perinatal antecedents of chronic motor dysfunction (cerebral palsy [CP]), evaluating approximately 400 characteristics of the mothers, pregnancies, or deliveries. In addition to confirming some, but not all, of the classic risk factors for CP, this study observed relatively large increases in the CP rate in association with maternal mental retardation, seizure disorders, hyperthyroidism, or with the administration of thyroid hormone and estrogen in pregnancy. Some risk factors were predictive of CP only insofar as they were associated with low birth weight or low Apgar scores. Among factors not significantly related to CP rate were maternal age, parity, socioeconomic status, smoking history, maternal diabetes, first trimester vaginal bleeding, kidney or bladder infection, moderate hypertension, long cord, use of anesthetic agents, or use of oxytoxics for initiation or augmentation of labor. Duration of labor, whether precipitate or prolonged, was not a risk factor for CP.


Development of immunocompetent lymphocytes in vivo from murine umbilical cord blood cells.
Reports concerning the immunological functions of lymphocytes derived from umbilical cord blood cell (UCBC) have been limited. In murine syngeneic transplantation system using green fluorescent protein transgenic donors, UCBC-derived lymphocytes were studied for their immunological competence. Hematopoietic stem cells (HSC) among UCBC differentiated in the recipients into phenotypically mature T and B lymphocytes. The T lymphocytes were capable of specific recognition of major histocompatibility complex/peptide complex and of the subsequent activation. The antigen-induced CD4(+) T cells produced lymphokine upon in vitro antigen stimulation. CD8(+) T cells simulated in the mixed lymphocyte culture could lyze specific target cells. Furthermore, RAG2(-/-) mice reconstituted with UCBC mounted specific antibody responses to T-dependent antigen comparable to those by bone marrow chimeras and also rejected allogeneic skin grafts. Collectively the data indicated that T and B lymphocytes derived from UCBC-HSC are fully competent in immunological terms.


Metal-binding proteins in bream (Abramis brama L.) caught in the River Elbe.
Metal-binding proteins were investigated in livers of bream caught in the River Elbe from Steti (Czech Republic) to Hamburg (Federal Republic of Germany). A major zinc and copper binding protein fraction with a low molecular weight of 10 000 to 12 000 Da and with properties similar to mammalian hepatic metallothionein was isolated from bream livers using gel filtration chromatography. Two protein isoforms could be separated by reversed phase-high performance liquid chromatography (RP-HPLC), however, mercury was associated with only one isoform. The possibility of different detoxification potentials of the isoforms is discussed. Maximal concentrations of metal-binding protein were detected in samples from Dresden. If metal-binding proteins are to be included in a biological monitoring study, further investigations are required.