"Cat Ladies" and "Mama's Boys": A Mixed-Methods Analysis of the Gendered Discrimination and Stereotypes of Single Women and Single Men.
Do single women and single men differ in their experiences of "singlism"? This mixed-methods research examined whether single women and single men report quantitative differences in amounts of singlehood-based discrimination and explored qualitative reports of stereotypic traits associated with single women and single men. We recruited Canadian and American single adults across two Prolific studies (total N = 286). The results demonstrated that single female and male participants did not differ in their personal discrimination, but female participants perceived single women to experience more discrimination than single men. Furthermore, qualitative analyses revealed four overlapping "archetypes" of single women and men including: Professional ("independent," "hard-working"), Carefree ("free," "fun"), Heartless ("selfish," "promiscuous"), and Loner ("lonely," "antisocial"). Overall, single women and men may experience similar stereotypes and discrimination, but there are also important nuances that highlight the need for more research at the intersection of gender and singlehood.


TRIM47 Promotes the Development of Glioma by Ubiquitination and Degradation of FOXO1.
To investigate the effect of TRIM47 on glioma cells and further explore its underlying molecular mechanisms. Mouse xenograft model was used in this study. The mRNA expression of TRIM47 was detected by qRT-PCR. The cell viability and proliferation activity was detected by MTT assay and colony formation assay. The migration and invasion of glioma cells were determined by Transwell assay. The protein levels of TRIM47, FOXO1, CyclinD1, C-myc, MMP-2 and TIMP-1 were assessed by Western-blotting. The interaction between TRIM47 and FOXO1 was measured by Co-immunoprecipitation (Co-IP) assay. In glioma tissues and cells, TRIM47 was significantly up-regulated. Silencing the expression of TRIM47 inhibited the cell viability and proliferation of cells A172 and U251, as well as their ability to invade and migrate. Among them, the expression levels of C-myc and CyclinD1 also decreased, and MMP-2 was down-regulated and TIMP-1 was up-regulated. Similarly, in vivo model, tumor volume and weight also decreased after TRIM47 knockout. Further research showed that TRIM47 inhibited FOXO1 expression by ubiquitination and degradation of FOXO1, thereby promoting glioma growth and progression. In our study, we confirmed functional role of the TRIM47-FOXO1 axis in the progression of gliomas and provided a potential target for glioma treatment.


Antibiotics from basidiomycetes. XVII. The effect of marasmic acid on nucleic acid metabolism.
From submerged cultures of Lachnella villosa, Lachnella sp. 541, and Peniophora laeta we isolated marasmic acid (1), a metabolite first described from surface cultures of Marasmius conigenus. The sesquiterpenoid exhibits potent antimicrobial and cytotoxic properties. In cells of the ascitic form of Ehrlich carcinoma RNA and DNA syntheses are preferentially inhibited. Marasmic acid inhibits RNA synthesis in isolated nuclei, but does not interfere with the transport of nucleoside precursors into the cells. RNA polymerase II and capping enzyme (mRNA guanylyltransferase), two enzymes of nucleic acid metabolism, are markedly affected after preincubation with marasmic acid. We assume that marasmic acid acts on nucleic acid syntheses by direct inhibition of some of the enzymes involved. This mode of action would also explain its mutagenic properties. The preparation and testing of two derivatives, 2 and 3, revealed that the alpha,beta-unsaturated aldehyde is essential for the antimicrobial and cytotoxic activity of marasmic acid.


CALHM1 controls the Ca²⁺-dependent MEK, ERK, RSK and MSK signaling cascade in neurons.
Calcium homeostasis modulator 1 (CALHM1) is a Ca(2+) channel controlling neuronal excitability and potentially involved in the pathogenesis of Alzheimer's disease (AD). Although strong evidence indicates that CALHM1 is required for neuronal electrical activity, its role in intracellular Ca(2+) signaling remains unknown. In the present study, we show that in hippocampal HT-22 cells, CALHM1 expression led to a robust and relatively selective activation of the Ca(2+)-sensing kinases ERK1/2. CALHM1 also triggered activation of MEK1/2, the upstream ERK1/2-activating kinases, and of RSK1/2/3 and MSK1, two downstream effectors of ERK1/2 signaling. CALHM1-mediated activation of ERK1/2 signaling was controlled by the small GTPase Ras. Pharmacological inhibition of CALHM1 permeability using Ruthenium Red, Zn(2+), and Gd(3+), or expression of the CALHM1 N140A and W114A mutants, which are deficient in mediating Ca(2+) influx, prevented the effect of CALHM1 on the MEK, ERK, RSK and MSK signaling cascade, demonstrating that CALHM1 controlled this pathway via its channel properties. Importantly, expression of CALHM1 bearing the natural P86L polymorphism, which leads to a partial loss of CALHM1 function and is associated with an earlier age at onset in AD patients, showed reduced activation of ERK1/2, RSK1/2/3, and MSK1. In line with these results obtained in transfected cells, primary cerebral neurons isolated from Calhm1 knockout mice showed significant impairments in the activation of MEK, ERK, RSK and MSK signaling. The present study identifies a previously uncharacterized mechanism of control of Ca(2+)-dependent ERK1/2 signaling in neurons, and further establishes CALHM1 as a critical ion channel for neuronal signaling and function.


Progression of occlusive atherosclerosis. Long-term administration of pyridinol carbamate.
The effects of pyridinol carbamate, a drug with demonstrated capacity to inhibit development of atherosclerotic plaques in the rabbit, were studied in humans with symptoms of arterial occlusive disease in the lower extremities. Microcirculation, perfusion, claudication distance, peripheral pulsations, and angiographic appearances were supplemented by clinical impressions over a two-year period. Although the drug was discontinued in several patients from a larger group because of gastrointestinal tract symptoms, and for other reasons, seven of eight patients receiving it showed no progression of their disease, whereas all 15 patients receiving identical-appearing placebos did. Although the number of patients is not sufficient to warrant statistical conclusions, the observations were totally objective and strongly encourage further control of studies.


Disrupted core-periphery structure of multimodal brain networks in Alzheimer's disease.
In Alzheimer's disease (AD), the progressive atrophy leads to aberrant network reconfigurations both at structural and functional levels. In such network reorganization, the core and peripheral nodes appear to be crucial for the prediction of clinical outcome because of their ability to influence large-scale functional integration. However, the role of the different types of brain connectivity in such prediction still remains unclear. Using a multiplex network approach we integrated information from DWI, fMRI, and MEG brain connectivity to extract an enriched description of the core-periphery structure in a group of AD patients and age-matched controls. Globally, the regional coreness-that is, the probability of a region to be in the multiplex core-significantly decreased in AD patients as result of a random disconnection process initiated by the neurodegeneration. Locally, the most impacted areas were in the core of the network-including temporal, parietal, and occipital areas-while we reported compensatory increments for the peripheral regions in the sensorimotor system. Furthermore, these network changes significantly predicted the cognitive and memory impairment of patients. Taken together these results indicate that a more accurate description of neurodegenerative diseases can be obtained from the multimodal integration of neuroimaging-derived network data.


Antenatal breast milk expression by women with diabetes for improving infant outcomes.
Some women with diabetes in pregnancy are encouraged to express and store colostrum prior to birthing. Following birth, the breastfed infant may be given the stored colostrum to minimise the use of artificial formula or intravenous dextrose administration if correction of hypoglycaemia is required. However, findings from observational studies suggest that antenatal breast milk expression may stimulate labour earlier than expected and increase admissions to special care nurseries for correction of neonatal hypoglycaemia. To evaluate the benefits and harms of the expression and storage of breast milk during late pregnancy by women with diabetes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2014). All published and unpublished randomised controlled trials comparing antenatal breast milk expressing with not expressing, by pregnant women with diabetes (pre-existing or gestational) and a singleton pregnancy. Two review authors independently evaluated reports identified by the search strategy. There were no published or unpublished randomised controlled trials comparing antenatal expressing with not expressing. One randomised trial is currently underway. There is no high level systematic evidence to inform the safety and efficacy of the practice of expressing and storing breast milk during pregnancy.


Primary retinal cultures as a tool for modeling diabetic retinopathy: an overview.
Experimental models of diabetic retinopathy (DR) have had a crucial role in the comprehension of the pathophysiology of the disease and the identification of new therapeutic strategies. Most of these studies have been conducted in vivo, in animal models. However, a significant contribution has also been provided by studies on retinal cultures, especially regarding the effects of the potentially toxic components of the diabetic milieu on retinal cell homeostasis, the characterization of the mechanisms on the basis of retinal damage, and the identification of potentially protective molecules. In this review, we highlight the contribution given by primary retinal cultures to the study of DR, focusing on early neuroglial impairment. We also speculate on possible themes into which studies based on retinal cell cultures could provide deeper insight.


Fight for survival: the life of a Hansen's disease sufferer through his correspondence with Adolpho Lutz.
This project presents the complete set of letters between the family of a Hansen's disease (leprosy) sufferer in the state of Maranhão, in the Northeast of Brazil, and the doctor and bacteriologist Adolpho Lutz. For more than twenty years Fabricio Caldas de Oliveira and Numa Pires de Oliveira, father and son, exchanged a steady flow of letters with the scientist in pursuit of a cure for the disease that had assailed Numa since childhood. The 24 letters compiled here paint a unique portrait of the medical and social drama confronted by this family, and the results of the use of chaulmoogra oil and other medications in their search for alternative treatments.


Biomarker and Genomic Risk Factors for Liver Function Test Abnormality in Hazardous Drinkers.
Alcohol dependence and long-term excessive alcohol use may cause liver damage, but only some patients develop cirrhosis. Similarly, high alcohol intake without evident liver disease often but not always produces abnormal enzymatic liver function tests (LFTs), particularly gamma-glutamyl transferase (GGT). We postulate that the factors predisposing to cirrhosis in alcoholics and to liver enzyme abnormality in drinkers are similar, and that biochemical LFTs could therefore be useful as markers of risk of alcoholic liver disease in excessive drinkers. Data from participants in twin and twin-family studies on alcohol use and dependence were used to identify 1,003 people who had reported excessive alcohol intake (28 drinks or more per week). A total of 962 of these provided blood for biochemical tests at the same time. Body mass index (BMI) and biomarkers of metabolic syndrome, inflammation, and iron stores were used in logistic regression with abnormality in serum GGT, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) as outcomes. We conducted genome-wide association analyses for GGT, ALT, and AST separately in the group reporting excessive alcohol intake (N = 951) and a low-intake group reporting 14 drinks or fewer per week (N = 8,716), and compared results. Abnormal GGT and ALT among excessive drinkers were associated with higher BMI, triglycerides, insulin, uric acid, C-reactive protein, ferritin, and transferrin saturation; and with lower high-density-lipoprotein cholesterol. Abnormal AST was associated with triglycerides, ferritin, and transferrin saturation. ALT was significantly associated with variants at reported genetic loci for alcoholic liver disease (PNPLA3, rs738409, p = 0.0076; TM6SF2, rs10401969, p = 0.0076; HSD17B13, rs10433879, p = 0.0024). Known risk factors for alcoholic cirrhosis including obesity and markers of metabolic syndrome, iron overload and inflammation are associated with liver enzyme abnormality in excessive drinkers.


The temporal factor of change in stressor-strain relationships: a growth curve model on a longitudinal study in east Germany.
Several theoretical models describing how stressor-strain relationships unfold in time (e.g., M. Frese & D. Zapf, 1988) were tested with a longitudinal study, with 6 measurement waves, using multivariate latent growth curve models. The latent growth curve model made it possible to decompose trait and state components of strains and to show that both trait and state components are affected by work stressors. Because East Germany constitutes a high-change environment, it is an appropriate setting in which to study the relationship between work stressors and strains. The results showed that both the state and trait components of strains were affected by stressors. For example, individual trends in uncertainty (stressor) and worrying (strain) were related, whereas worrying also showed a short-term relationship with time pressure (another stressor). In particular, the decomposition into trait and state components was only possible with the growth curve method that was used.


[Substituted sydnonimines: hemodynamic effects and distribution of coronary blood flow in normal and ischemic myocardium].
Some aspects of hemodynamic effects and distribution of coronary flow of molsidomine were evaluated in anesthetized dogs with open chest. Three experimental groups were performed: In groups I and II 100 micrograms/kg and 200 micrograms/kg of molsidomine were administered respectively. Cardiac output (CO), end diastolic pressure (EDP), mean arterial pressure (MAP), heart rate (HR), systolic left ventricular pressure (SLVP), their maximal rates of development and fall (+P and -P, respectively), developed tension (DT), their maximal contraction (+T) and relaxation (-T) rates, were measured. Peripheral resistance (PR) and the ratios +P/-P and +T/-T were calculated. In group III 100 micrograms/kg of molsidomine were administered after the ligature of the anterior descendent artery (AD) was performed. In this group the distribution of coronary flow was measured through radioactive microspheres injection in the circumflex area (CX) (normal area) and in the AD area (ischemic area). After injecting the microspheres and following its effects for one hour, the maximum effect was determined in 30 minutes. Heart rate did not show any statistically significant variation at any of the doses used. MAP fell from 92 +/- 3 mmHg to 77 +/- 5 mmHg (P less than 0.05) in group I and from 87 +/- 3 mmHg to 69 +/- 4 mmHg in group II. Cardiac output fell from 1.63 +/- 0.13 1/min to 1.22 +/- 0.12 1/min (P less than 0.05) in group I and from 1.60 +/- 0.19 1/min to 1.13 +/- 0.18 1/min (P less than 0.05) in group II. PR did not show any significant change in any of the groups. +P decreased 13 +/- 6% (P less than 0.05) in group I and 13 +/- 5% (P less than 0.05) in group II. The decrease of -P was of 17 +/- 5% (P less than 0.05) in both groups. EDP decreased from 6.0 +/- 1.0 mmHg to 3.9 +/- 0.9 mmHg (P less than 0.05) and from 5.5 +/- 0.5 mmHg to 2.9 +/- 0.8 mmHg (P less than 0.05) in groups I and II, respectively. DT, +T, -T, +T/-T and +P/-P did not show any significant change. EDP fell from 8 +/- 1 mmHg to 4.1 +/- 1.3 mmHg (P less than 0.05); MAP fell from 82 +/- 4 mmHg to 62 +/- 6 mmHg (P less than 0.05) and CO fell from 2.05 +/- 0.27 1/min to 1.30 +/- 0.14 1/min in group III. HR and PR did not show any significant change in group III.(ABSTRACT TRUNCATED AT 400 WORDS)


Transport Phenomena in Nano/Molecular Confinements.
The transport of fluid and ions in nano/molecular confinements is the governing physics of a myriad of embodiments in nature and technology including human physiology, plants, energy modules, water collection and treatment systems, chemical processes, materials synthesis, and medicine. At nano/molecular scales, the confinement dimension approaches the molecular size and the transport characteristics deviates significantly from that at macro/micro scales. A thorough understanding of physics of transport at these scales and associated fluid properties is undoubtedly critical for future technologies. This compressive review provides an elaborate picture on the promising future applications of nano/molecular transport, highlights experimental and simulation metrologies to probe and comprehend this transport phenomenon, discusses the physics of fluid transport, tunable flow by orders of magnitude, and gating mechanisms at these scales, and lists the advancement in the fabrication methodologies to turn these transport concepts into reality. Properties such as chain-like liquid transport, confined gas transport, surface charge-driven ion transport, physical/chemical ion gates, and ion diodes will provide avenues to devise technologies with enhanced performance inaccessible through macro/micro systems. This review aims to provide a consolidated body of knowledge to accelerate innovation and breakthrough in the above fields.


Evaluation of Lens Culinaris Agglutinin-Reactive α-Fetoprotein in Diagnosis of Malignant Tumors.
To assess the potential of AFP-L3% for the utility to diagnose malignant tumors. AFP-L3 was concentrated from clinically-collected serum samples via the Hotgen Biotech glycosyl capture spin columns and then measured through the protein microarrays. The levels of AFP and AFP-L3 were detected by electrochemiluminescence immunoassay. In this retrospective study, 266 patients with the level of serum AFP-L3 over 1 ng/mL were recruited from December 2014 through April 2019. Among them, 155 patients were clinically diagnosed/confirmed with malignant tumors, including 101 hepatocellular carcinomas, 47 stomach malignant tumors, and 7 other malignant tumors; and the rest of 111 patients were nonmalignant tumors. Patients with serum AFP-L3 level of greater than 1 ng/mL were mainly detected in hepatic diseases, including hepatocellular carcinoma, cirrhosis and chronic hepatitis. In patients with no tumors, the levels of serum AFP-L3 over 1 ng/mL were only observed in liver disease. The levels of AFP-L3 in blood were substantially greater in patients with HCC. Among the malignant tumor patients with the level of serum AFP-L3 over 1 ng/mL, HCC accounted for 60%, gastric cancer for nearly 40%. The AFP, AFP-L3, and AFP-L3% in blood were increased significantly in patients with liver malignancy, chronic liver disease, and cirrhosis. However, the elevation of AFP-L3 and AFP-L3% in the malignant cohort was more evident than that in the nonmalignant counterpart. AFP-L3 is likely to contribute to the differential diagnosis of HCC as well as other hepatic diseases. AFP-L3% is a reliable indicator for diagnosing benign and malignant tumors.


[The constitution and attribution of government research agencies. A matter of need for science-generated policy knowledge?].
Government research agencies are a form of extra-university research institutions. In contrast to other extra-university research facilities they are subordinate to and financed by respective German governmental departments. As their mission they provide science-generated information, services, and monitoring to support the governmental departments. In science studies researchers proclaim a rigid association between the installation, attribution, and development of government research agencies and the increasing need for science-generated policy knowledge. The article examines this assumed association based on the personal, institutional, financial, and mission specific development of government research agencies between the years 1965 and 2005. According to the results the expansion of government research agencies stagnates--like science in general.


Mucorales fungi suppress nitric oxide production by macrophages.
In October 2022, Mucorales fungi were listed in the "High Priority Group" on the first-ever list of fungal priority pathogens by the World Health Organization. As the causative agent of mucormycosis, Mucorales have become of great clinical and public health importance with growing mucormycosis numbers, notably with the exponential rise of COVID-19-associated mucormycosis cases. Despite the dire need, there are limited therapeutic options to treat mucormycosis. Our research fills in critical gaps of knowledge about how Mucorales fungi evade the host immune system. Specifically, we offer evidence that Mucorales block nitric oxide production, which is a key mediator and signaling molecule of the mammalian innate immune response to microbial pathogens. Our work offers new insight into immune evasion mechanisms by Mucorales fungi.


Development of a PointNet for Detecting Morphologies of Self-Assembled Block Oligomers in Atomistic Simulations.
Molecular simulations with atomistic or coarse-grained force fields are a powerful approach for understanding and predicting the self-assembly phase behavior of complex molecules. Amphiphiles, block oligomers, and block polymers can form mesophases with different ordered morphologies describing the spatial distribution of the blocks, but entirely amorphous nature for local packing and chain conformation. Screening block oligomer chemistry and architecture through molecular simulations to find promising candidates for functional materials is aided by effective and straightforward morphology identification techniques. Capturing 3-dimensional periodic structures, such as ordered network morphologies, is hampered by the requirement that the number of molecules in the simulated system and the shape of the periodic simulation box need to be commensurate with those of the resulting network phase. Common strategies for structure identification include structure factors and order parameters, but these fail to identify imperfect structures in simulations with incorrect system sizes. Building upon pioneering work by DeFever et al. [Chem. Sci. 2019, 10, 7503-7515] who implemented a PointNet (i.e., a neural network designed for computer vision applications using point clouds) to detect local structure in simulations of single-bead particles and water molecules, we present a PointNet for detection of nonlocal ordered morphologies of complex block oligomers. Our PointNet was trained using atomic coordinates from molecular dynamics simulation trajectories and synthetic point clouds for ordered network morphologies that were absent from previous simulations. In contrast to prior work on simple molecules, we observe that large point clouds with 1000 or more points are needed for the more complex block oligomers. The trained PointNet model achieves an accuracy as high as 0.99 for globally ordered morphologies formed by linear diblock, linear triblock, and 3-arm and 4-arm star-block oligomers, and it also allows for the discovery of emerging ordered patterns from nonequilibrium systems.


Primate translational vestibuloocular reflexes. IV. Changes after unilateral labyrinthectomy.
The effects of unilateral labyrinthectomy on the properties of the translational vestibuloocular reflexes (trVORs) were investigated in rhesus monkeys trained to fixate near targets. Translational motion stimuli consisted of either steady-state lateral and fore-aft sinusoidal oscillations or short-lasting transient displacements. During small-amplitude, steady-state sinusoidal lateral oscillations, a small decrease in the horizontal trVOR sensitivity and its dependence on viewing distance was observed during the first week after labyrinthectomy. These deficits gradually recovered over time. In addition, the vertical response component increased, causing a tilt of the eye velocity vector toward the lesioned side. During large, transient lateral displacements, the deficits were larger and longer lasting. Responses after labyrinthectomy were asymmetric, with eye velocity during movements toward the side of the lesion being more compromised. The most profound effect of the lesions was observed during fore-aft motion. Whereas responses were kinematically appropriate for fixation away from the side of the lesion (e.g., to the left after right labyrinthectomy), horizontal responses were anticompensatory during fixation at targets located ipsilateral to the side of the lesion (e.g., for targets to the right after right labyrinthectomy). This deficit showed little recovery during the 3-mo post-labyrinthectomy testing period. These results suggest that inputs from both labyrinths are important for the proper function of the trVORs, although the details of how bilateral signals are processed and integrated remain unknown.


SCH772984 ameliorates lipopolysaccharide-induced hypoglycemia in mice through reversing MEK/ERK/Foxo1-mediated gluconeogenesis suppression.
Lipopolysaccharide (LPS) results in a lethal hypoglycemic response. However, the main molecular mechanism involved in LPS-induced glucose metabolism disorder is poorly understood. This study intends to investigate the signaling pathways involved in LPS-induced hypoglycemia and potential efficacy of extracellular signal-regulated kinase (ERK) inhibitor SCH772984. The effects of LPS and SCH772984 on gluconeogenesis, glucose absorption, and glycogenolysis were evaluated by pyruvate tolerance test, oral glucose tolerance test, and glucagon test, respectively. After a single intraperitoneal injection of 0.5 mg/kg LPS, the mice's blood glucose levels and gluconeogenesis ability were significantly lower than that of control group. Besides, mRNA and protein expression of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) decreased significantly after LPS treatment. LPS induced the phosphorylation of ERK1/2, MEK1/2 (mitogen-activated protein kinase), and Foxo1 while inhibited Foxo1 expression in the nucleus, indicating an important role of the MEK/ERK/Foxo1 signaling in the inhibition of gluconeogenesis by LPS. Furthermore, SCH772984 elevated blood glucose, increased the G6Pase and PEPCK expression, and inhibited pERK1/2 and pFoxo1 expression in LPS-induced mice. In summary, LPS inhibited gluconeogenesis and induced hypoglycemia through the MEK/ERK/Foxo1 signal pathway, and ERK inhibitor could effectively reverse decreased blood glucose in mice with LPS treatment. These findings provide a novel therapeutic target for LPS-induced hypoglycemia.


Autologous Osteochondral Graft for Early Posttraumatic Arthritis of Tibiotalar Joints After Comminuted Pilon Fractures in Young Patients.
Posttraumatic arthritis of tibiotalar joints after AO/OTA type C3 pilon fractures, especially in young patients with a significant osteochondral defect in the tibial plafond joint surface, is a challenging situation. We report a joint-preserving technique using autologous osteochondral graft in combination with ankle distraction and supramalleolar osteotomy (SMOT), if necessary, to improve its outcome. Seventeen patients with an average age of 32.1 years with Takakura grade 1 to 3A posttraumatic arthritis of the tibiotalar joint after AO/OTA type C3 pilon fractures received osteochondral autograft transplantation, ankle distraction, and SMOT, when supramalleolar malalignment was present, between February 2010 and November 2015. The visual analog scale (VAS), Short-Form 36 (SF-36) score, American Orthopaedic Foot & Ankle Society (AOFAS) score, and ankle range of motion were used for outcome analysis. Radiographic assessment of any SMOT and the apparent joint space was performed. Fourteen patients were followed for an average of 18 months. The VAS, SF-36, and AOFAS scores as well as the ankle range of motion all improved significantly at the last follow-up after the surgery (P < .01). No deep surgical site infection, donor site complication, nonunion, osteochondral block loosening, or resorption was noted. No secondary arthrodesis was needed at the end of follow-up. Autologous osteochondral graft transplantation in combination with ankle distraction and SMOT was a promising joint-preserving technique for early posttraumatic arthritis of tibiotalar joint after severe pilon fractures in young patients. Level IV, case series.


Diagnosis of Chlamydia pneumoniae infection in patients with chronic obstructive pulmonary disease by micro-immunofluorescence and ELISA.
The incidence of Chlamydia pneumoniae infection was determined in patients with chronic obstructive pulmonary diseases (COPD) by prospective serial serology. Chlamydia-specific IgG, IgM and IgA antibodies were detected with a recombinant DNA lipopolysaccharide (LPS) ELISA as well as with a micro-immunofluorescence (MIF) assay with C. pneumoniae elementary bodies. From 271 consecutive COPD patients who visited the outpatient clinic of the department of pulmonary diseases (211 males, 60 females, age range 34-88 years, mean age 66 SD 10 years), blood samples (n = 1058) were taken every 2-7 months; the observation period ranged from 3 to 19 months (mean 15 SD 4). The prevalence of chlamydial IgG was 72% with the MIF and 53% with the rDNA LPS ELISA. More than 90% of the COPD patients had no significant changes in their chlamydia-specific IgG, IgA and IgM titres in either test during the observation period. Seven (3%) patients had MIF results indicating acute C. pneumoniae infection during their surveillance period, of whom five were confirmed by rDNA LPS ELISA. Eleven (4%) additional patients were infected during observation, as determined by rDNA LPS ELISA only. These patients had significantly elevated C. pneumoniae-specific IgG and IgA MIF titres, as compared with the patients without infection. All 18 patients with serological evidence of acute infection during their surveillance period were re-tested in a commercial MIF test that can distinguish between C. pneumoniae, C. trachomatis and C. psittaci LPS-specific antibodies, but no evidence of C. trachomatis or C. psittaci infection was found. The incidence of chlamydial infection was 2.2 and 5.3/100 person-years, when diagnosed by MIF and rDNA LPS ELISA, respectively. It is concluded that the rDNA LPS chlamydia assay may currently be the most sensitive serological tool for diagnosing recent respiratory chlamydia infections and that C. pneumoniae infection occurs frequently in COPD patients.


[Patient rehabilitation after gastric resection for peptic ulcer].
The authors evaluated the results of gastric resection in the Hofmeister-Finsterer modification in 262 patients with ulcer disease. Treatment considered of drugs, balneotherapy and electric stimulation with consideration of the functional state of the resected stomach. The used rehabilitation complex allowed to improve the results of surgical treatment, to reduce time of temporary loss of working capacity by 2-3 weeks.


The language profile of formal thought disorder.
Formal thought disorder (FTD) is clinically manifested as disorganized speech, but there have been only few investigations of its linguistic properties. We examined how disturbance of thought may relate to the referential function of language as expressed in the use of noun phrases (NPs) and the complexity of sentence structures. We used a comic strip description task to elicit language samples from 30 participants with schizophrenia (SZ), 15 with moderate or severe FTD (SZ + FTD), and 15 minimal or no FTD (SZ-FTD), as well as 15 first-degree relatives of people with SZ (FDRs) and 15 neurotypical controls (NC). We predicted that anomalies in the normal referential use of NPs, sub-divided into definite and indefinite NPs, would identify FTD; and also that FTD would also be linked to reduced linguistic complexity as specifically measured by the number of embedded clauses and of grammatical dependents. Participants with SZ + FTD produced more referential anomalies than NC and produced the fewest definite NPs, while FDRs produced the most and thus also differed from NC. When referential anomalies were classed according to the NP type in which they occurred, the SZ + FTD group produced more anomalies in definite NPs than NC. Syntactic errors did not distinguish groups, but the SZ + FTD group exhibited significantly less syntactic complexity than non-SZ groups. Exploratory regression analyses suggested that production of definite NPs distinguished the two SZ groups. These results demonstrate that FTD can be identified in specific grammatical patterns which provide new targets for detection, intervention, and neurobiological studies.


Self-assembly of octadecyltrichlorosilane: Surface structures formed using different protocols of particle lithography.
Particle lithography offers generic capabilities for the high-throughput fabrication of nanopatterns from organosilane self-assembled monolayers, which offers the opportunity to study surface-based chemical reactions at the molecular level. Nanopatterns of octadecyltrichlorosilane (OTS) were prepared on surfaces of Si(111) using designed protocols of particle lithography combined with either vapor deposition, immersion, or contact printing. Changing the physical approaches for applying molecules to masked surfaces produced OTS nanostructures with different shapes and heights. Ring nanostructures, nanodots and uncovered pores of OTS were prepared using three protocols, with OTS surface coverage ranging from 10% to 85%. Thickness measurements from AFM cursor profiles were used to evaluate the orientation and density of the OTS nanostructures. Differences in the thickness and morphology of the OTS nanostructures are disclosed based on atomic force microscopy (AFM) images. Images of OTS nanostructures prepared on Si(111) that were generated by the different approaches provide insight into the self-assembly mechanism of OTS, and particularly into the role of water and solvents in hydrolysis and silanation.


Neural correlates of letter reversal in children and adults.
Children often make letter reversal errors when first learning to read and write, even for letters whose reversed forms do not appear in normal print. However, the brain basis of such letter reversal in children learning to read is unknown. The present study compared the neuroanatomical correlates (via functional magnetic resonance imaging) and the electrophysiological correlates (via event-related potentials or ERPs) of this phenomenon in children, ages 5-12, relative to young adults. When viewing reversed letters relative to typically oriented letters, adults exhibited widespread occipital, parietal, and temporal lobe activations, including activation in the functionally localized visual word form area (VWFA) in left occipito-temporal cortex. Adults exhibited significantly greater activation than children in all of these regions; children only exhibited such activation in a limited frontal region. Similarly, on the P1 and N170 ERP components, adults exhibited significantly greater differences between typical and reversed letters than children, who failed to exhibit significant differences between typical and reversed letters. These findings indicate that adults distinguish typical and reversed letters in the early stages of specialized brain processing of print, but that children do not recognize this distinction during the early stages of processing. Specialized brain processes responsible for early stages of letter perception that distinguish between typical and reversed letters may develop slowly and remain immature even in older children who no longer produce letter reversals in their writing.


GFP Plasmid and Chemoreagent Conjugated with Graphene Quantum Dots as a Novel Gene Delivery Platform for Colon Cancer Inhibition In Vitro and In Vivo.
Scientists have studied intensively the gene delivery carriers for treating genetic diseases. However, there are challenges that impede the application of naked gene-based therapy at the clinical level, such as quick elimination of the circulation, lack of membrane penetrability, and poor endosome trapping. Herein, we develop graphene quantum dots (GQDs)-derivative nanocarriers and introduce polyethylenimine (PEI) to equip the system with enhanced biocompatibility and abundant functional groups for modification. In addition to carrying green fluorescent protein (GFP) as an example of gene delivery, this system covalently binds colon cancer cells targeted antibody and epidermal growth factor receptor (EGFR) to enhance cell membrane penetrability and cell uptake of nanocarriers. To achieve multistrategy cancer therapy, the anticancer drug doxorubicin (Dox) is noncovalently encapsulated to achieve pH-induced drug release at tumor sites and leaves space for further functional gene modification. This nanoparticle serves as a multifunctional gene delivery system, which facilitates improved cytotoxicity and longer-sustained inhibition capacity compared to free Dox treatments in colon cancer cells. Moreover, our GQD composites display compatible tumor suppression ability compared with the free Dox treatment group in xenograft mice experiment with significantly less toxicity. This GQD nanoplatform was demonstrated as a multifunctional gene delivery system that could contribute to treating other genetic diseases in the future.


Parental substance use consequences and adolescent psychopathology.
This study examines the relationship between parental substance use consequences and adolescent psychological problems by gender of the adolescent and gender of the parent. The data in this study were collected between 1989 and 1994 from 173 (116 proband and 57 control) families participating in the Collaborative Study on the Genetics of Alcoholism (COGA) project. All 173 adolescents (89 [51%] boys) completed the Structured Assessment Record of Alcoholic Homes (SARAH) to assess parental substance use consequences. In addition, the Semi-Structured Assessment for the Genetics of Alcoholism for Adolescents (C-SSAGA-A) was administered to all adolescents to obtain clinical psychiatric diagnoses. Concern about mother's substance use was significantly associated with adolescent alcohol dependence and major depressive disorder. In addition, concern about father's substance use was significantly related to adolescent alcohol dependence. Avoidance of mother when she was drinking or using drugs and maternal anger when drinking or using drugs also was significantly associated with adolescent alcohol dependence, conduct disorder and major depressive disorder. In contrast, avoidance of father and paternal anger when drinking or using drugs was not related to any of the adolescent diagnoses. These results suggest that maternal substance use consequences may be more closely linked to adolescent psychological adjustment than are paternal substance use consequences.


Obtainment of pellets using the standardized liquid extract of Brosimum gaudichaudii Trécul (Moraceae).
The standardized liquid extract of Brosimum gaudichaudii Trécul is an alternative for the treatment of vitiligo. There is a shortage of solid oral dosage forms developed from standardized extracts of this plant specie. This study is aimed to obtain pellets with a standardized liquid extract of B. gaudichaudii. The standardized liquid extract of B. gaudichaudii was obtained through maceration and percolation with a 55% ethanol-water solution (v/v). Pellets were obtained through a mixture of extract of 500 g of B. gaudichaudii standardized extract, 500 g of microcrystalline cellulose PH101 and 10 g of hydroxypropyl methylcellulose K100. The pellets obtained presented a homogeneity yield of 92%, aspect ratio of 1.16 ± 0.65, shape fator e R of 0.35 ± 0.09 and Feret diammeter of 0.87 ± 0.27. These pellets were coated with a suspension composed of titanium dioxide, aluminum red lacquer, ethyl cellulose, talc and magnesium stearate. Before the photostability test, the uncoated pellets showed psoralen content equal to 0.13 ± 0.01% and to the 5-MOP was 1.40 ± 0.27%. After exposure to one level (3 J.cm(-2)) of UVB irradiation the uncoated pellets presented a degradation of 2.16% of psoralen and 8.1% of 5-MOP. After exposure to three levels (10, 20 and 30 J.cm(-2)) of UVA irradiation the uncoated pellets exhibited photodegradation of 9.78, 17.64, 24.21% of psoralen and 18.95, 23.68, 28.48% for 5-MOP. The coated pellets where unaffected after photostability test. Pellets were obtained with the standardized liquid extract of B. gaudichaudii and coating is a technological alternative to ensure the stability of the formula.


Replication of colicin E1 plasmid DNA in cell extracts.
Cell extracts were prepared from Escherichia coli carrying colicin E1 plasmid. The DNA in extracts was almost exclusively closed-circular DNA of the plasmid. Labeled deoxyribonucleotides were incorporated into DNA in extracts. DNA of colicin E1 plasmid was the sole DNA product, and was composed of completely replicated molecules and a class of replicative intermediates. The intermediates carried an average of approximately two pieces of DNA fragments that had a sedimentation coefficient of approximately 6 S and were not covalently attached to the parental DNA strands. The replication was initiated on closed-circular molecules and the complete molecules were synthesized semiconservatively. The DNA synthesis depended on the four ribonucleoside triphosphates and was sensitive to rifampicin. A round of DNA replication, once initiated, was completed in the presence of rifampicin, indicating that RNA synthesis is involved in the initiation of replication of the plasmid DNA. Most of the replicated molecules were isolated in super-coiled structures. These results indicate that this soluble system is capable of carrying out a complete round of replication of colicin E1 plasmid DNA.


Advancing human rights in patient care through strategic litigation: challenging medical confidentiality issues in countries in transition.
The concept of human rights in patient care offers a framework, relevant to both patients and providers, for identifying and addressing human rights violations within a state's health system. While a range of legal and non-legal mechanisms are available to advance this concept (and, indeed, are generally used to best effect in combination as part of a wider advocacy strategy), this paper considers the use of strategic litigation to hold states to account and encourage broader systemic change. As an illustration of such an approach, this article focuses on the issue of breaches of medical confidentiality-a pervasive problem in certain countries in Eastern Europe and Central Asia, with serious implications for vulnerable or marginalized individuals. This paper presents an overview of the European Court of Human Rights' approach to this topic and discusses the potential for further strategic litigation in Eastern Europe and Central Asia.


Timing and completeness of trial results posted at ClinicalTrials.gov and published in journals.
The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration-approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001). The main study limitation was that we considered only the publication describing the results for the primary outcomes. Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article.


Effect of Oxidation and Protonation States on [2Fe-2S] Cluster Nitrosylation Giving {Fe(NO)2}9 Dinitrosyl Iron Complexes (DNICs).
The nitrosylation of biological Fe/S clusters to give protein-bound dinitrosyl iron complexes (DNICs) is physiologically important. Biomimetic studies on the reaction of synthetic [2Fe-2S] clusters with NO have so far been limited to diferric model complexes. This work now compares the nitrosylation of [2Fe-2S] clusters with SN- or NN-chelating benzimidazolate/thiophenolate or bis(benzimidazolate) capping ligands in their diferric (12- and 22-) and mixed-valent (FeIIFeIII, 13-, and 23-) forms. Furthermore, the effect of protonation of the imidazole part of the SN ligand has been probed on both the nitrosylation reaction and properties of the resulting DNIC. The reaction of 12- and 22- with 4 equiv NO yields the new anionic {Fe(NO)2}9 DNICs 3- and 4-, respectively, which have been comprehensively characterized, including X-ray crystallography of their PPN+ salts. Nitrosylation of mixed-valent [2Fe-2S] clusters 13- and 23- first leads to slow oxidation to the corresponding diferric congeners, followed by core degradation and DNIC formation. In the case of 23-, a second diferric intermediate very similar to 22- is detected by UV-vis spectroscopy, but could not be further identified. Nitrosylation of 1H2 gives the neutral, N-protonated DNIC 3H, and acid/base titrations show that interconversion between 3- and 3H is reversible. Peripheral ligand protonation leads to a blue shift of the NO stretching vibrations by about 23 cm-1 and a significant shift of the reduction potential to less negative values (Δ E1/2 = 0.26 V), but no effect on 57Fe Mössbauer parameters is observed. Density functional theory calculations based on the structure of 3- indicate that the electronic ground-state properties of 3- and 3H are similar, although the NO(π*) → Fe 3d π-donation is slightly increased and π-backbonding is slightly decreased upon protonation. As a result, protonation has a significant effect on the NO stretching frequencies, but only minor effects on the Fe-(NO)2 modes. This is confirmed by nuclear inelastic scattering of 3- and 3H, which shows no clear influence of protonation on the energy of the Fe-(NO)2 bending and stretching modes occurring in the range 400-600 cm-1, but characteristic changes below 350 cm-1 that reflect perturbation of free rotary motion of the thiophenolate and benzimidazole ring systems of the capping ligand after N-protonation. These findings add to the understanding of [2Fe-2S] cluster nitrosylation and will help to identify DNICs resulting from the reaction of NO with Fe/S cofactors featuring alternative, proton-responsive histidine ligands such as the Rieske and mitoNEET [2Fe-2S] clusters.


[Schizophrenia among urban and rural patients. Comparative clinico-demographic characteristics (according to the results of an epidemiologic study)].
Results of a comparative clinico-epidemiological study carried out on a representative group of schizophrenic patients living in towns and rural districts of the Vinnitsa Region (the Ukraine) are presented. The comparison of the urban and rural patients made with regard to many clinical and demographic characteristics showed that the groups being analyzed did not differ substantially in the age at the disease onset, and were analogous in the distribution of the disease onset age as regards the patients' sex and the disease pattern *earlier onset of the disease in males, prevalence of the early onset of the sluggish and malignant forms). In the patient populations being examined certain differences in the prevalence of some particular forms of the disease were revealed. This can be explained by some peculiarities of the population's tolerance and the level of the work of the psychiatric services in town and country.


Proteomics of microparticles with SILAC Quantification (PROMIS-Quan): a novel proteomic method for plasma biomarker quantification.
Unbiased proteomic analysis of plasma samples holds the promise to reveal clinically invaluable disease biomarkers. However, the tremendous dynamic range of the plasma proteome has so far hampered the identification of such low abundant markers. To overcome this challenge we analyzed the plasma microparticle proteome, and reached an unprecedented depth of over 3000 plasma proteins in single runs. To add a quantitative dimension, we developed PROMIS-Quan-PROteomics of MIcroparticles with Super-Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC) Quantification, a novel mass spectrometry-based technology for plasma microparticle proteome quantification. PROMIS-Quan enables a two-step relative and absolute SILAC quantification. First, plasma microparticle proteomes are quantified relative to a super-SILAC mix composed of cell lines from distinct origins. Next, the absolute amounts of selected proteins of interest are quantified relative to the super-SILAC mix. We applied PROMIS-Quan to prostate cancer and compared plasma microparticle samples of healthy individuals and prostate cancer patients. We identified in total 5374 plasma-microparticle proteins, and revealed a predictive signature of three proteins that were elevated in the patient-derived plasma microparticles. Finally, PROMIS-Quan enabled determination of the absolute quantitative changes in prostate specific antigen (PSA) upon treatment. We propose PROMIS-Quan as an innovative platform for biomarker discovery, validation, and quantification in both the biomedical research and in the clinical worlds.


Oocyte quality in women with infertility associated endometriosis.
The mechanisms of endometriosis-related infertility remain still unknown. Endometriosis and clinical markers of oocyte quality are a very important problem of reproduction. The purpose of the study is to assess the quality of oocytes in women with infertility associated with endometriosis. The study included infertile reproductive aged women, between 29 and 40 years who underwent IVF and ICSI procedures. The patients were divided into three groups: group I involved 50 (n = 50) patients with recurrent unilateral endometriomas, group II included 50 patients (n = 50) unilateral endometriomas after surgical treatment and control group with 30 (n = 30) patients with tubal factor infertility. Clinical and morphological assessment of oocyte quality was performed in all IVF/ICSI cycles. The results of the study demonstrate a statistically significant increase in the number of immature oocytes of metaphase MI and immature oocytes at the GV germinal vesicle stage in patients with infertility associated with endometriosis, compared with the control group (p<.005). There is deterioration in the quality of the obtained oocytes in patients with the presence of endometrioma more than 3 cm in diameter. The results of this study allow to conclude that endometriomas negatively affect quality of oocyte and ovarian reserve, whereas endometriomas after cystectomy, have a deleterious and sustained effect on ovarian reserve.


Being community-responsive physicians. Doing the right thing.
To explore how primary care physicians respond to a community's needs and challenges. Qualitative study using focus groups. Fee-for-service practices or community health centres in downtown Toronto, Ont. Purposive sample of 21 community family physicians (10 women and 11 men). Participants were invited to join focus groups of four to six physicians. Themes were derived from qualitative analysis of the data using grounded theory. Three major themes were identified by these community-responsive physicians: they carry out specific roles (collaborator, health educator, advocate, resource, and tailor of care); they face several challenges, including lack of funding and a dysfunctional health care system; and they share common beliefs about practising medicine. Whether current health care structures support physicians to actually carry out these roles in practice, however, is unclear. This study increased understanding of how primary care physicians respond to community needs and what they experience in the process.


Higher neuronal discharge rate in the motor area of the subthalamic nucleus of Parkinsonian patients.
In Parkinson's disease, pathological synchronous oscillations divide the subthalamic nucleus (STN) of patients into a dorsolateral oscillatory region and ventromedial nonoscillatory region. This bipartite division reflects the motor vs. the nonmotor (associative/limbic) subthalamic areas, respectively. However, significant topographic differences in the neuronal discharge rate between these two STN subregions in Parkinsonian patients is still controversial. In this study, 119 STN microelectrode trajectories (STN length > 2 mm, mean = 5.32 mm) with discernible oscillatory and nonoscillatory regions were carried on 60 patients undergoing deep brain stimulation surgery for Parkinson's disease. 2,137 and 2,152 multiunit stable signals were recorded (recording duration > 10 s, mean = 21.25 s) within the oscillatory and nonoscillatory STN regions, respectively. Spike detection and sorting were applied offline on every multiunit stable signal using an automatic method with systematic quantification of the isolation quality (range = 0-1) of the identified units. In all, 3,094 and 3,130 units were identified in the oscillatory and nonoscillatory regions, respectively. On average, the discharge rate of better-isolated neurons (isolation score > 0.70) was higher in the oscillatory region than the nonoscillatory region (44.55 ± 0.87 vs. 39.97 ± 0.77 spikes/s, N = 665 and 761, respectively). The discharge rate of the STN neurons was positively correlated to the strength of their own and their surrounding 13- to 30-Hz beta oscillatory activity. Therefore, in the Parkinsonian STN, beta oscillations and higher neuronal discharge rate are correlated and coexist in the motor area of the STN compared with its associative/limbic area.


Frictional behavior of micro-patterned silicon surface.
A micro-patterned silicon surface, consisting of depressions with walls having a tilt angle of 30°, was created by photolithography followed by etching. The friction forces in single asperity contact acting between such a surface and an AFM tip was measured in air. This allowed elucidation of the validity of some common friction rules for this particular situation where a small tip traces a surface having roughness features that are significantly larger than the tip itself. The rules that was compared with our data were Amontons' first rule of friction stating that the friction force should be proportional to the load; Amontons' third rule stating that the friction force should be independent of sliding speed, and Euler's rule providing a relation between slope angle and friction coefficient. We found that both nanoscale surface heterogeneities and the μm-sized depressions affect friction forces, and considerable reproducible variations were found along a particular scan line. Nevertheless Amontons' first rule described average friction forces well. Amontons' third rule and Euler's rule were found to be less applicable to our system.


Retinal Findings in Young Children With Increased Intracranial Pressure From Nontraumatic Causes.
Increased intracranial pressure (ICP) has been suggested in legal settings as an alternative cause of retinal hemorrhages (RHs) in young children who may have sustained abusive head trauma. We assessed the prevalence and characteristics of RHs in children with increased ICP. We conducted a prospective, multicenter study of children <4 years old with newly diagnosed increased ICP as determined by using direct measurement and/or clinical criteria. Infants who were premature, neonates, and suspected survivors of abusive head trauma were excluded on the basis of nonocular findings. Fundus examinations were performed; extent, number, and type of RH in each of 4 distinct retinal zones were recorded. Fifty-six children (27 boys) were studied (mean age 15.4 months; range 1-43 months). All of the children had elevated ICP that required intervention. One child had papilledema. No child (0%; 95% confidence interval: 0%-6.4%) or eye (0%; 95% confidence interval: 0%-3.3%) was found to have an RH. Causes of increased ICP included hydrocephalus, intraventricular hemorrhage, congenital malformations, malfunctioning shunts, and the presence of intracranial space-occupying lesions. Although acute increased ICP can present in children with a pattern of peripapillary superficial RHs in the presence of papilledema, our study supports the conclusion that RHs rarely occur in the absence of optic disc swelling and do not present beyond the peripapillary area in the entities we have studied.


Community prescribing and resistant Streptococcus pneumoniae.
We investigated the association between prescribing antimicrobial agents and antimicrobial resistance of Streptococcus pneumoniae among children with acute otitis media in southern Israel. During a 6-year period, all prescriptions of a sample of approximately 20% of Jewish and Bedouin children <5 years of age were recorded and all pneumococcal isolates from middle ear fluid were collected. Although antimicrobial drug use was significantly higher in Bedouin children, the proportion of S. pneumoniae isolates with penicillin MIC = or > 1.0 microg/mL was significantly higher in Jewish children. In both populations, antimicrobial prescriptions were markedly reduced over time, especially for penicillins and erythromycin. In contrast, azithromycin prescriptions increased from 1998 to 2001 with a parallel increase in macrolide and multidrug resistance. Penicillin resistance was associated with macrolide resistance. These findings strongly suggest that azithromycin affects increased antimicrobial resistance, including multidrug resistance, in S. pneumoniae.


Mycotoxins in Zea mays, their quantification and HPLC analysis of physico-biological detoxification.
Present research delves in the isolation, extraction and identification of mycotoxins from ten corn samples collected from the northern province of Pakistan. Average concentration of aflatoxin B1 and B2 by HP-TLC found in all corn samples was 27.87 and 1.35 μg/kg, respectively. Following HP-TLC, detoxification of the identified and isolated mycotoxin was performed, which was analyzed by HPLC. Screening of mycoflora exhibited Aspergillus niger and Fusarium as the most dominant fungal strains. Aflatoxin B1 was physically detoxified under UV-Lamp and direct sunlight displaying detoxification percentage of 48% and 99%, respectively. Biological detoxification involved the use of botanicals such as neem leaves, garlic and ginger powder, which portrayed an approximate detoxification of 70% from corn samples. Current research concludes that the tested physical and biological methods can be easily adopted at field and storage rooms after the harvesting of crops to avoid fungal contamination and subsequent food spoilage.


Automatic Feature Learning to Grade Nuclear Cataracts Based on Deep Learning.
Cataracts are a clouding of the lens and the leading cause of blindness worldwide. Assessing the presence and severity of cataracts is essential for diagnosis and progression monitoring, as well as to facilitate clinical research and management of the disease. Existing automatic methods for cataract grading utilize a predefined set of image features that may provide an incomplete, redundant, or even noisy representation. In this study, we propose a system to automatically learn features for grading the severity of nuclear cataracts from slit-lamp images. Local filters are first acquired through clustering of image patches from lenses within the same grading class. The learned filters are fed into a convolutional neural network, followed by a set of recursive neural networks, to further extract higher order features. With these features, support vector regression is applied to determine the cataract grade. The proposed system is validated on a large population-based dataset of [Formula: see text] images, where it outperforms the state of the art by yielding with respect to clinical grading a mean absolute error ( ε) of 0.304, a 70.7% exact integral agreement ratio ( R0), an 88.4% decimal grading error ≤ 0.5 ( Re0.5 ), and a 99.0% decimal grading error ≤ 1.0 ( Re1.0 ). The proposed method is useful for assisting and improving clinical management of the disease in the context of large-population screening and has the potential to be applied to other eye diseases.


Gaze following: A socio-cognitive skill rooted in deep time.
Social gaze has received much attention in social cognition research in both human and non-human animals. Gaze following appears to be a central skill for acquiring social information, such as the location of food and predators, but can also draw attention to important social interactions, which in turn promotes the evolution of more complex socio-cognitive processes such as theory of mind and social learning. In the past decades, a large number of studies has been conducted in this field introducing differing methodologies. Thereby, various factors influencing the results of gaze following experiments have been identified. This review provides an overview of the advances in the study of gaze following, but also highlights some limitations within the research area. The majority of gaze following studies on animals have focused on primates and canids, which limits evolutionary interpretations to only a few and closely related evolutionary lineages. This review incorporates new insights gained from previously understudied taxa, such as fishes, reptiles, and birds, but it will also provide a brief outline of mammal studies. We propose that the foundations of gaze following emerged early in evolutionary history. Basic, reflexive co-orienting responses might have already evolved in fishes, which would explain the ubiquity of gaze following seen in the amniotes. More complex skills, such as geometrical gaze following and the ability to form social predictions based on gaze, seem to have evolved separately at least two times and appear to be correlated with growing complexity in brain anatomy such as increased numbers of brain neurons. However, more studies on different taxa in key phylogenetic positions are needed to better understand the evolutionary history of this fundamental socio-cognitive skill.


Carcinoma of the vulva.
A series of 127 patients presenting at two London hospitals with carcinoma of the vulva during the period 1948-70 is reviewed. Patients with intraepithelial carcinoma or rodent ulcer are excluded, but the series includes two cases of malignant melanoma, one of adenocarcinoma of Bartholin's gland, and two of basal cell carcinoma. In the remainder the pathological diagnosis was squamous cell carcinoma.Leucoplakia was present in only 30 cases (24%) and it is therefore concluded that this condition is probably not so dangerous as a precursor of cancer as has been stated in the past, though an association with cancer of the vulva is undeniable.In only three cases was no form of treatment practicable. Of the remaining 124, two were treated by radiotherapy, 37 by simple vulvectomy, 12 by vulvectomy followed by separate inguinal lymphadenectomy, and 73 by radical vulvectomy combined with bilateral lymphadenectomy en bloc, pelvic lymphadenectomy being included whenever the superficial lymph nodes appeared to be involved or when Cloquet's node was shown by frozen-section examination to be invaded. Excellent results, with an absolute five-year survival rate of 66%, were obtained with this last procedure, especially when primary skin cover was provided by the delayed technique (five-year survival 73%). The results of simple vulvectomy were also surprisingly good, with an absolute five-year survival rate of 65%, and this operation may be a wise choice for the very old or infirm patient.


How Do Adults With Down Syndrome Perceive Physical Activity?
Adults with Down syndrome (DS) tend to have low physical activity levels, which may relate to how they perceive participation in physical activities. The current study entailed interviews with 30 adults with DS (age 18-71 yr, 18 women) to examine how they perceived physical activity, exercise, and sport. Through qualitative analysis informed by grounded theory, the investigators found that adults with DS have positive perceptions of physical activity that center on enjoyment. Three facets of enjoyment were identified: interaction, achievement, and process. Interaction reflected enjoyment of social contact with others including relatives, peers, caregivers, and animals. Achievement involved enjoyment of achieving particular ends including accomplishment of tasks, material rewards, formation of athletic identities, and improvement of health. Process represented enjoyment from performing a particular activity itself. This multifaceted enjoyment expressed by adults with DS may facilitate physical activity and should be considered when developing programs to improve their well-being.


Parallel genetic and phenotypic evolution of DNA superhelicity in experimental populations of Escherichia coli.
DNA supercoiling is the master function that interconnects chromosome structure and global gene transcription. This function has recently been shown to be under strong selection in Escherichia coli. During the evolution of 12 initially identical populations propagated in a defined environment for 20,000 generations, parallel increases in DNA supercoiling were observed in ten populations. The genetic changes associated with the increased supercoiling were examined in one population, and beneficial mutations in the genes topA (encoding topoisomerase I) and fis (encoding a histone-like protein) were identified. To elucidate the molecular basis and impact of these changes, we quantified the level of genetic, phenotypic, and molecular parallelism linked to DNA supercoiling in all 12 evolving populations. First, sequence determination of DNA topology-related loci revealed strong genetic parallelism, with mutations concentrated in three genes (topA, fis, and dusB), although the populations had different alleles at each locus. Statistical analyses of these polymorphisms implied the action of positive selection and, moreover, suggested that fis and dusB, which belong to the same operon, have related functions. Indeed, we demonstrated that DusB regulates the expression of fis by both experimental and phylogenetic analyses. Second, molecular analyses of five mutations in fis and dusB affecting the transcription, translation, and protein activity of Fis also revealed strong parallelism in the resulting phenotypic effects. Third, artificially increasing DNA supercoiling in one of the two populations that lacked DNA topology changes led to a significant fitness increase. The high levels of molecular and genetic parallelism, targeting a small subset of the many genes involved in DNA supercoiling, indicate that changes in DNA superhelicity have been important in the evolution of these populations. Surprisingly, however, most of the evolved alleles we tested had either no detectable or slightly deleterious effects on fitness, despite these signatures of positive selection.


Metabolic flux analysis of wild-type Escherichia coli and mutants deficient in pyruvate-dissimilating enzymes during the fermentative metabolism of glucuronate.
The fermentative metabolism of d-glucuronic acid (glucuronate) in Escherichia coli was investigated with emphasis on the dissimilation of pyruvate via pyruvate formate-lyase (PFL) and pyruvate dehydrogenase (PDH). In silico and in vivo metabolic flux analysis (MFA) revealed that PFL and PDH share the dissimilation of pyruvate in wild-type MG1655. Surprisingly, it was found that PDH supports fermentative growth on glucuronate in the absence of PFL. The PDH-deficient strain (Pdh-) exhibited a slower transition into the exponential phase and a decrease in specific rates of growth and glucuronate utilization. Moreover, a significant redistribution of metabolic fluxes was found in PDH- and PFL-deficient strains. Since no role had been proposed for PDH in the fermentative metabolism of E. coli, the metabolic differences between MG1655 and Pdh- were further investigated. An increase in the oxidative pentose phosphate pathway (ox-PPP) flux was observed in response to PDH deficiency. A comparison of the ox-PPP and PDH pathways led to the hypothesis that the role of PDH is the supply of reducing equivalents. The finding that a PDH deficiency lowers the NADH : NAD(+) ratio supported the proposed role of PDH. Moreover, the NADH : NAD(+) ratio in a strain deficient in both PDH and the ox-PPP (Pdh-Zwf-) was even lower than that observed for Pdh-. Strain Pdh-Zwf- also exhibited a slower transition into the exponential phase and a lower growth rate than Pdh-. Finally, a transhydrogenase-deficient strain grew more slowly than wild-type but did not show the slower transition into the exponential phase characteristic of Pdh- mutants. It is proposed that PDH fulfils two metabolic functions. First, by creating the appropriate internal redox state (i.e. appropriate NADH : NAD(+) ratio), PDH ensures the functioning of the glucuronate utilization pathway. Secondly, the NADH generated by PDH can be converted to NADPH by the action of transhydrogenases, thus serving as biosynthetic reducing power in the synthesis of building blocks and macromolecules.


Biosourced Multiphase Systems Based on Poly(Lactic Acid) and Polyamide 11 from Blends to Multi-Micro/Nanolayer Polymers Fabricated with Forced-Assembly Multilayer Coextrusion.
The objective of the present study was to investigate multiphase systems based on polylactic acid (PLA) and polyamide 11 (PA11) from blends to multilayers. Firstly, PLA/PA11 blends compatibilized with a multifunctionalized epoxide, Joncryl, were obtained through reactive extrusion, and the thermal, morphological, rheological, and mechanical behaviors of these materials were investigated. The role of Joncryl as a compatibilizer for the PLA/PA11 system was demonstrated by the significant decrease in particle size and interfacial tension as well as by the tensile properties exhibiting a ductile behavior. Based on these findings, we were able to further clarify the effects of interdiffusion and diffuse interphase formation on the structure, rheology, and mechanics of compatible multilayered systems fabricated with forced-assembly multilayer coextrusion. The results presented herein aim to provide a deeper understanding of the interfacial properties, including the rheological, mechanical, and morphological behaviors, towards the control of the interface and confinement in multilayer polymers resulting from coextrusion, and also to permit their use in advanced applications.


Pet dogs (Canis lupus familiaris) release their trapped and distressed owners: Individual variation and evidence of emotional contagion.
Domestic dogs have assisted humans for millennia. However, the extent to which these helpful behaviors are prosocially motivated remains unclear. To assess the propensity of pet dogs to actively rescue distressed humans without explicit training, this study tested whether sixty pet dogs would release their seemingly trapped owners from a large box. To examine the causal mechanisms that shaped this behavior, the readiness of each dog to open the box was tested in three conditions: 1) the owner sat in the box and called for help (distress test), 2) an experimenter placed high-value food rewards in the box (food test), and 3) the owner sat in the box and calmly read aloud (reading test). Dogs were as likely to release their distressed owner as to retrieve treats from inside the box, indicating that rescuing an owner may be a highly rewarding action for dogs. After accounting for opening ability, dogs released the owner more often when the owner called for help than when the owner read aloud calmly. In addition, opening latencies decreased with test number in the distress test but not the reading test. Thus, rescuing the owner could not be attributed solely to social facilitation, stimulus enhancement, or social contact-seeking behavior. Dogs displayed more stress behaviors in the distress test than in the reading test, and stress scores decreased with test number in the reading test but not in the distress test. This evidence of emotional contagion supports the hypothesis that rescuing the distressed owner was an empathetically-motivated prosocial behavior. Success in the food task and previous (in-home) experience opening objects were both strong predictors of releasing the owner. Thus, prosocial behavior tests for dogs should control for physical ability and previous experience.


Engineered Microgels-Their Manufacturing and Biomedical Applications.
Microgels are hydrogel particles with diameters in the micrometer scale that can be fabricated in different shapes and sizes. Microgels are increasingly used for biomedical applications and for biofabrication due to their interesting features, such as injectability, modularity, porosity and tunability in respect to size, shape and mechanical properties. Fabrication methods of microgels are divided into two categories, following a top-down or bottom-up approach. Each approach has its own advantages and disadvantages and requires certain sets of materials and equipments. In this review, we discuss fabrication methods of both top-down and bottom-up approaches and point to their advantages as well as their limitations, with more focus on the bottom-up approaches. In addition, the use of microgels for a variety of biomedical applications will be discussed, including microgels for the delivery of therapeutic agents and microgels as cell carriers for the fabrication of 3D bioprinted cell-laden constructs. Microgels made from well-defined synthetic materials with a focus on rationally designed ultrashort peptides are also discussed, because they have been demonstrated to serve as an attractive alternative to much less defined naturally derived materials. Here, we will emphasize the potential and properties of ultrashort self-assembling peptides related to microgels.


Intestinal injury and gut permeability in sickle cell disease.
Due to recurrent hypoxia-reperfusion injury induced by vaso-occlusive crises (VOC), patients with sickle cell disease (SCD) may have intestinal injury and increased permeability. These may explain the qualitative and quantitative neutrophil abnormalities observed in these patients. Serum intestinal fatty-acid binding protein (iFABP), lipopolysaccharides (LPS), and CD62L were measured by ELISA. Multicolor flow cytometry was used to measure circulating aged neutrophils. Compared to controls, SCD individuals had higher iFABP (median: 1.38 ng/ml vs 0.81 ng/ml; p = 0.04) and LPS (median: 2.15 μg/ml vs 0.69 μg/ml; p = 0.03), indicating intestinal injury and increased intestinal bacterial translocation into the systemic circulation. They also had higher soluble CD62L (median: 1.38 μg/ml vs 1.11 μg/ml; p = 0.04). Among SCD individuals, soluble CD62L correlated positively with circulating aged neutrophils (R = 0.7, p = 0.03) and LPS (R = 0.66, p = 0.027). Surprisingly, serum iFABP in SCD correlated negatively with both LPS (R = - 0.7, p = 0.02) and soluble CD62L (R = - 0.56, p = 0.08). Since LPS translocation across the intestinal barrier may be due to increases in the intestinal bacterial density, gut permeability, or both, the negative correlations between iFABP and LPS, and CD62L raise the possibility that any damage-associated molecular patterns induced by intestinal injury may modulate the degree of bacterial translocation. Our results provide the first evidence of the presence of intestinal injury and increased gut permeability in SCD.


3-Chloro-2,4,5-trifluoro-benzoic acid.
The title compound, C7H2ClF3O2, was prepared by the chlorination of 3-amino-2,4,5-trifluoro-benzoic acid. The carboxyl group is twisted relative to the benzene ring by 6.8 (1)°. In the crystal, pairs of O-H⋯O hydrogen bonds link mol-ecules into typical centrosymmetric carb-oxy-lic acid dimers. These dimers are arranged into sheets parallel to (-103).


Models of Affective Decision Making: How Do Feelings Predict Choice?
Intuitively, how you feel about potential outcomes will determine your decisions. Indeed, an implicit assumption in one of the most influential theories in psychology, prospect theory, is that feelings govern choice. Surprisingly, however, very little is known about the rules by which feelings are transformed into decisions. Here, we specified a computational model that used feelings to predict choices. We found that this model predicted choice better than existing value-based models, showing a unique contribution of feelings to decisions, over and above value. Similar to the value function in prospect theory, our feeling function showed diminished sensitivity to outcomes as value increased. However, loss aversion in choice was explained by an asymmetry in how feelings about losses and gains were weighted when making a decision, not by an asymmetry in the feelings themselves. The results provide new insights into how feelings are utilized to reach a decision.


Methods for monitoring the functional status of the circadian system in dietary surveys studies: application criteria and interpretation of results.
To evaluate the circadian system status of the subject may be of special interest in nutrition. Particularly for those studies related to the assessment of diseases related to malnutrition, as it is the case of most of the degenerative diseases such as obesity, cancer, or cardiovascular diseases. For this purpose, one of the approaches consists to measure a) the external synchronizers of the internal clock, such as light intensity, and changes from fasting to eating and from resting to activity. Indeed, "chronodisruptors" have been defined as "exogenous and endogenous exposures or effectors which are chronobiologically active and can thus disrupt the timing and order. Another approach to assess the circadian system health is to measure the b) outputs of the internal clock (circadian marker rhythms). Among such outputs, the rhythm of body temperature, motor activity, melatonin, cortisol and clock gene expression are the most commonly used. From the genetic perspective, we are now able to measure failures in the internal clock, in order to assess c) the genetics of the molecular clock. Indeed, new nutrigenetics techniques are giving us the opportunity to measure the association between different genetic variants of our clock genes and several illnesses such as obesity, cardiovascular diseases, diabetes or cancer. In addition to these techniques, self-reported questionnaires based in the morning-evening preferences have been developed as complementary procedures to assess human chronotypes.


Significant impact of sequence variations in the nucleoprotein on CD8 T cell-mediated cross-protection against influenza A virus infections.
Memory CD8 T cells to influenza A viruses are widely detectable in healthy human subjects and broadly cross-reactive for serologically distinct influenza A virus subtypes. However, it is not clear to what extent such pre-existing cellular immunity can provide cross-subtype protection against novel emerging influenza A viruses. We show in the mouse model that naturally occurring sequence variations of the conserved nucleoprotein of the virus significantly impact cross-protection against lethal disease in vivo. When priming and challenge viruses shared identical sequences of the immunodominant, protective NP(366)/D(b) epitope, strong cross-subtype protection was observed. However, when they did not share complete sequence identity in this epitope, cross-protection was considerably reduced. Contributions of virus-specific antibodies appeared to be minimal under these circumstances. Detailed analysis revealed that the magnitude of the memory CD8 T cell response triggered by the NP(366)/D(b) variants was significantly lower than those triggered by the homologous NP(366)/D(b) ligand. It appears that strict specificity of a dominant public TCR to the original NP(366)/D(b) ligand may limit the expansion of cross-reactive memory CD8 T cells to the NP(366)/D(b) variants. Pre-existing CD8 T cell immunity may provide substantial cross-protection against heterosubtypic influenza A viruses, provided that the priming and the subsequent challenge viruses share the identical sequences of the immunodominant, protective CTL epitopes.


Does a missed obstetric anal sphincter injury at time of delivery affect short-term functional outcome?
Introduction This study aimed to ascertain whether missed obstetric anal sphincter injury at delivery had worse functional and quality of life outcomes than primary repair immediately following delivery. Materials and methods Two to one propensity matching was undertaken of patients presenting to a tertiary pelvic floor unit with ultrasound evidence of missed obstetric anal sphincter injury within 24 months of delivery with patients who underwent primary repair at the time of delivery by parity, grade of injury and time to assessment. Outcomes compared included Birmingham Bowel, Bladder and Urinary Symptom Questionnaire (BBUSQ), Wexner Incontinence Score, Short Form-36, Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire and anorectal physiology results. Results Thirty-two missed anal sphincter injuries were matched two to one with sixty-two patients who underwent primary repair of an anal sphincter defect. Mean time to follow-up was 9.31 ± 6.79 months. Patients with a missed anal sphincter injury had suffered more incontinence, as seen in higher the Birmingham Bowel, Bladder and Urinary Symptom Questionnaire (BBUSQ; 30.56% ± 14.41% vs. 19.75% ± 15.65%, P = 0.002) and Wexner scores (6.00 ± 3.76 vs. 3.67 ± 4.06, P = 0.009). They also had a worse BBUSQ urinary domain score (28.25% ± 14.9% vs. 17.01 ± 13.87%, P = 0.001) and worse physical functioning as measured by the Short Form-36 questionnaire (P = 0.045). There were no differences in other outcomes compared, including anorectal physiology and sexual function. Discussion In the short-term, patients with a missed obstetric anal sphincter injury had significantly worse faecal incontinence and urinary function scores, however quality of life and sexual function were largely comparable between groups. Conclusions Longer-term follow-up is needed to assess the effects of missed obstetric anal sphincter injury over time.


Welfare indicators in laying hens in relation to nest exclusion.
Consumer concerns about the welfare of laying hens are increasing, leading to increased interest in identifying reliable ways to assess welfare. The present study evaluated invasive and non-invasive welfare indicators in relation to a stressful challenge. The study included 126 Lohmann Selected Leghorn hens housed in furnished cages. Welfare indicators were measured between 61 and 70 wk of age in birds excluded from their nests for 5 consecutive d and control birds that had continuous access to nests. Baseline recordings were carried out in both groups prior to and post exclusion period. The assessed indicators were: corticosterone metabolites in droppings (FCM), corticosterone concentration in yolk, corticosterone concentration in plasma, irregularities of eggshells, heterophil to lymphocyte (H:L) ratio, tonic immobility duration, and feather cover. Behavioral observations showed that the birds had a clear preference for using the secluded nest sites, confirming that they were likely to perceive nest exclusion as an undesirable experience. Further, elevated levels of FCM in droppings, yolk corticosterone concentrations, H:L ratios and irregular eggshells were detected in both nest deprived and control birds during the exclusion. This suggests that these indicators were able to detect an increased stress response arising from nest deprivation, and it is hypothesized that the stress spread to birds in adjacent cages with access to nests. There was a positive and consistent correlation between FCM in droppings and eggshell irregularities, also supporting the use of eggshell irregularities as a potential non-invasive welfare indicator. However, the pattern of the stress response varied between indicators and correlations were generally few and inconsistent, highlighting the complexity of the relationship among welfare indicators.


FISH using a gag-like fragment probe reveals a common Ty3-gypsy-like retrotransposon in genome of Coffea species.
The genus Coffea possesses about 100 species, and the most economically important are Coffea canephora and Coffea arabica. The latter is predominantly self-compatible with 2n = 4x = 44, while the others of the genus are diploid with 2n = 2x = 22 and mostly self-incompatible. Studies using molecular markers have been useful to detect differences between genomes in Coffea; however, molecular and cytogenetic studies have produced only limited information on the karyotypes organization. We used DOP-PCR to isolate repetitive elements from genome of Coffea arabica var. typica. The pCa06 clone, containing a fragment of 775 bp length, was characterized by sequencing and used as a probe in chromosomes of C. arabica and six other species: C. canephora, Coffea eugenioides, Coffea kapakata, Coffea liberica var. dewevrei, Coffea racemosa, and Coffea stenophylla. This insert shows similarities with a gag protein of the Ty3-gypsy-like super-family. Dot blot and FISH analyses demonstrated that pCa06 is differentially accumulated between species and chromosomes. Signals appeared scattered and clustered on the chromosomes and were also associated with heterochromatic regions. While the literature shows that there is a high karyotype similarity between Coffea species, our results point out differences in the accumulation and dispersion of this Ty3-gypsy-like retrotransposon during karyotype differentiation of Coffea.


Using an index-based approach to assess the population-level appropriateness of empirical antibiotic therapy.
The population-level appropriateness of empirical antibiotic therapy can be conventionally measured by ascertainment of treatment coverage. This method involves a complex resource-intensive case-by-case assessment of the prescribed antibiotic treatment and the resistance of the causative microorganism. We aimed to develop an alternative approach based, instead, on the use of routinely available surveillance data. We calculated a drug effectiveness index by combining three simple aggregated metrics: relative frequency of aetiological agents, level of resistance and relative frequency of antibiotic use. To evaluate the applicability of our approach, we used this metric to estimate the population-level appropriateness of guideline-compliant and non-guideline-compliant empirical treatment regimens in the context of the Dutch national guidelines for complicated urinary tract infections. The drug effectiveness index agrees within 5% with results obtained with the conventional approach based on a case-by-case ascertainment of treatment coverage. Additionally, we estimated that the appropriateness of 2008 antibiotic prescribing regimens would have declined by up to 4% by year 2011 in the Netherlands due to the emergence and expansion of antibiotic resistance. The index-based framework can be an alternative approach to the estimation of point values and counterfactual trends in population-level empirical treatment appropriateness. In resource-constrained settings, where empirical prescribing is most prevalent and comprehensive studies to directly measure appropriateness may not be a practical proposition, an index-based approach could provide useful information to aid in the development and monitoring of antibiotic prescription guidelines.


Objectively measured physical activity correlates with indices of insulin resistance in Danish children. The European Youth Heart Study (EYHS).
To explore the association between measures of insulin resistance with objectively assessed physical activity. School-based, cross-sectional study. A randomly selected sample of 589 children (310 girls, 279 boys, mean (standard deviations, s.d.) age=9.7 (0.44) y, weight=33.6 (6.4) kg, height=1.39 (0.06) m) from Denmark. Fasting blood samples were analysed for serum insulin and glucose. Physical activity was measured with the uniaxial Computer Science and Applications (CSA) model 7164 accelerometer, worn for at least 3 days (>/=10 h day(-1)). Adiposity was assessed by the sum of four skinfolds. Multiple linear regression were performed to model insulin and glucose from average CSA output, adjusted for age, gender, puberty, ethnicity, birth weight, parental smoking, socioeconomic group, and CSA unit. In addition, we adjusted for skinfold thickness. Mean fasting serum glucose ranged from 4.1 to 6.5 mmol l(-1) with a mean (s.d.) of 5.1 (0.37) mmol l(-1). Fasting insulin was negatively correlated with CSA output on levels of adjustment. Fasting glucose was not significantly associated with physical activity. However, in girls both indices of insulin resistance were significantly related to activity, whereas in boys none of the associations were significant. Physical activity is inversely associated with fasting insulin in the nondiabetic range of fasting glucose. The relationship was stronger for insulin than for glucose, indicating compensatory action by the beta cells. Our data emphasise the importance of physical activity in children for the maintenance of metabolic control.


A broader training for medical receptionists.
A course for 40 medical receptionists working in general practice was arranged at a local postgraduate centre. The curriculum was divided into two sections. The first dealt with the traditional, factual side of medical reception work and the second was concerned with the human behaviour aspect of a receptionist's work. It seems that there was some benefit to the receptionists from their experience of both aspects of this course.


Functional characterization of a bidirectional plant promoter from cotton leaf curl Burewala virus using an Agrobacterium-mediated transient assay.
The C1 promoter expressing the AC1 gene, and V1 promoter expressing the AV1 gene are located in opposite orientations in the large intergenic region of the Cotton leaf curl Burewala virus (CLCuBuV) genome. Agro-infiltration was used to transiently express putative promoter constructs in Nicotiana tabacum and Gossypium hirsutum leaves, which was monitored by a GUS reporter gene, and revealed that the bidirectional promoter of CLCuBuV transcriptionally regulates both the AC1 and AV1 genes. The CLCuBuV C1 gene promoter showed a strong, consistent transient expression of the reporter gene (GUS) in N. tabacum and G. hirsutum leaves and exhibited GUS activity two- to three-fold higher than the CaMV 35S promoter. The CLCuBuV bidirectional gene promoter is a nearly constitutive promoter that contains basic conserved elements. Many cis-regulatory elements (CREs) were also analyzed within the bidirectional plant promoters of CLCuBuV and closely related geminiviruses, which may be helpful in understanding the transcriptional regulation of both the virus and host plant.


Risk factors for venous thromboembolism in nursing home residents.
To determine risk factors for venous thromboembolism (VTE) among nursing home (NH) residents. This population-based historical cohort study used Minnesota Case Mix Review Program (MCMRP) Public Research Files to identify all unique Olmsted County, Minnesota, residents in any local NH from January 1, 1988, through December 31, 1994. Cases were defined as residents with a VTE diagnosis at any NH assessment. For each case, we identified 2 age- and sex-matched controls, defined as NH residents who did not have VTE but were assessed in the year of the case's earliest VTE diagnosis (ie, index assessment). Cases and controls were compared for preindex assessment characteristics. Accuracy of MCMRP VTE ascertainment was explored by comparing MCMRP cases with members of the Rochester Epidemiology Project incident cohort who were objectively diagnosed with VTE from January 1, 1988, through December 31, 1994, while residing in an Olmsted County NH. At the preindex assessment, cases were more likely than controls to have returned from hospital; to require assistance with grooming, toileting, transferring, bed positioning, or wheelchair use; or to need physical therapy, rehabilitation, clinical monitoring, or wound care and were less likely to have neurologic disease. There were 53 MCMRP VTE cases vs 161 Rochester Epidemiology Project NH VTE cases; the proportion with pulmonary embolism was 21% vs 62%; 1-year mortality was 24% vs 55%. Administrative data from NHs reveal important VTE risk factors not routinely documented in hospital or ambulatory records. However, ascertainment of VTE from NH administrative data appears biased toward surviving cases, highlighting concerns about using such data to assess provider quality and pointing to the need for studies that track individuals through multiple data sources across institutional settings.


Rapid purification of mammalian 70,000-dalton stress proteins: affinity of the proteins for nucleotides.
A new and rapid purification procedure has been developed for the mammalian 70,000-dalton (70-kDa) heat-shock (or stress) proteins. Both the constitutive 73-kDa protein and the stress-induced 72-kDa protein have been purified by a two-step procedure employing DE52 ion-exchange chromatography followed by affinity chromatography on ATP-agarose. The two proteins, present in approximately equal amounts in either the 12,000 X g supernatant or pellet of hypotonically lysed heat-shock-treated HeLa cells, were found to copurify in relatively homogenous form. The purified proteins were covalently labeled with the fluorescent dye tetramethylrhodamine isothiocyanate, and the fluorescently labeled proteins were introduced back into living rat embryo fibroblasts via microinjection. The microinjected cells maintained at 37 degrees C showed only diffuse nuclear and cytoplasmic fluorescence. After heat-shock treatment of the cells, fluorescence was observed throughout the nucleus and more prominently within the nucleolus. This result is consistent with our earlier indirect immunofluorescence studies which showed a nuclear and nucleolar distribution of the endogenous 72-kDa stress protein in heat-shock-treated mammalian cells. The result also indicates that, for at least the 72-kDa protein, (i) the protein has been purified in apparently "native" form and (ii) its nucleolar distribution is stress dependent.


Factors affecting recurrence rate of ingrown toenail treated with marginal toenail ablation.
This retrospective study analyzed marginal toenail ablation for ingrowing toenails and the factors affecting recurrences. Recurrence was defined as a return of the previous symptoms, regrowth of the nail edge, or patient dissatisfaction with the clinical outcome. Based on these criteria, nine patients (10.7%) were considered to have had a failed operation. There were significant differences for recurrence rate (p <.05) in the patients operated on under local anesthesia and in previously treated patients. Full exposure and excision of the germinal matrix were essential to avoid recurrence.


Age, ability, and the role of prior knowledge on the acquisition of new domain knowledge: promising results in a real-world learning environment.
Prior knowledge, fluid intelligence (Gf), and crystallized intelligence (Gc) were investigated as predictors of learning new information about cardiovascular disease and xerography with a sample of 199 adults (19 to 68 years). The learning environment included a laboratory multimedia presentation (high-constraint-maximal effort), and a self-directed at-home study component (low-constraint-typical performance). Results indicated that prior knowledge and ability were important predictors of knowledge acquisition for learning. Gc was directly related to learning from the video for both domains. Because the trajectory of Gc stays relatively stable throughout the life span, these findings provide a more optimistic perspective on the relationship between aging and learning than that offered by theories that focus on the role of fluid abilities in learning.