Trimethoprim as adjuvant treatment in schizophrenia: a double-blind, randomized, placebo-controlled clinical trial.
Various infectious agents, such as Toxoplasma gondii, have been hypothesized to be potentially relevant etiological factors in the onset of some cases of schizophrenia. We conducted a randomized, double-blind, placebo-controlled treatment trial in an attempt to explore the hypothesis that the symptoms of schizophrenia may be related to infection of the central nervous system with toxoplasma gondii. Systematically selected patients with ongoing and at least moderately severe schizophrenia from Butajira, in rural Ethiopia, were randomly allocated to trimethoprim or placebo, which were added on to participants' regular antipsychotic treatments. Trial treatments were given for 6 months. The Positive and Negative Syndrome Scale (PANSS) was used to assess outcome. Ninety-one patients were included in the study, with 80 cases (87.9%) positive for T. gondii immunoglobulin G antibody. Seventy-nine subjects (87.0%) completed the trial. The mean age of subjects was 35.3 (SD = 8.0) years, with a mean duration of illness of 13.2 (SD = 6.7) years. Both treatment groups showed significant reduction in the overall PANSS score with no significant between-group difference. In this sample of patients with chronic schizophrenia, trimethoprim used as adjuvant treatment is not superior to placebo. However, it is not possible to draw firm conclusion regarding the etiological role of toxoplasmosis on schizophrenia based on this study because the timing and the postulated mechanisms through which toxoplasmosis produces schizophrenia are variable.


Is outpatient brain tumor surgery feasible in India?
The current trend in all fields of surgery is towards less invasive procedures with shorter hospital stays. The reasons for this change include convenience to patients, optimal resource utilization, and cost saving. Technological advances in neurosurgery, aided by improvements in anesthesia, have resulted in surgery that is faster, simpler, and safer with excellent perioperative recovery. As a result of improved outcomes, some centers are performing brain tumor surgery on an outpatient basis, wherein patients arrive at the hospital the morning of their procedure and leave the hospital the same evening, thus avoiding an overnight stay in the hospital. In addition to the medical benefits of the outpatient procedure, its impact on patient satisfaction is substantial. The economic benefits are extremely favorable for the patient, physician, as well as the hospital. In high volume centers, a day surgery program can exist alongside those for elective and emergency surgeries, providing another pathway for patient care. However, due to skepticism surrounding the medicolegal aspects, and how radical the concept at first sounds, these procedures have not gained widespread popularity. We provide an overview of outpatient brain tumor surgery in the western world, discussing the socioeconomic, medicolegal, and ethical issues related to its adaptability in a developing nation.


Immunohistochemical localization of dopamine-beta-hydroxylase in human and monkey eyes.
To investigate the pattern of dopamine-beta-hydroxylase (DBH)-containing fibers in human and monkey eyes. DBH-containing fibers were detected by immunohistochemistry. The primary antibody used recognized DBH, the key enzyme in the conversion of dopamine to noradrenaline. In the anterior segment, DBH immunoreaction product was found in the peripheral corneal endothelium layer, in both the dilator and sphincter muscles of the iris, as well as in the anterior border layer of the iris. The ciliary muscle and the stroma of the ciliary processes were also zones of concentration. In the posterior segment, staining was seen around blood vessels in the choroid, in the vascular walls of the short posterior ciliary arteries and in the ciliary nerves. The retina was also immunopositive, with specific labeling in cones and rods of photoreceptors, inner and outer plexiform layers and ganglion cell layer. There was no significant difference in the distribution of DBH-related immunoreactivity in human and monkey eyes. The localization of DBH-related immunoreactivity is generally consistent with the known physiological roles of noradrenaline. However, an apparently high concentration of the enzyme in the anterior border layer of the iris and in retinal photoreceptors raises questions about the possible role of DBH-containing fibers in these structures.


Comparison of Epidural Bupivacaine, Levobupivacaine and Dexmedetomidine in Patients Undergoing Vascular Surgery.
Levobupivacaine is the s-isomer of racemic Bupivacaine. It is less cardio, neurotoxic and equally potent local anaesthetic compared to its racemate. It is known to cause less Depression of myocardial contractility. Dexmeditomidine when used via epidural route has synergistic effect with local anaesthetics. Majority of patients presenting for vascular surgery are elderly and have associated co-morbidities like diabetes, hypertension, and coronary artery disease. We intend to study safety and efficacy of epidural Levoupivacaine and Dexmedetomidine in this group of patients. Sixty adult patients undergoing lower limb vascular surgery under lumbar epidural anaesthesia were randomly allocated to three groups. All groups were preloaded with 10ml/kg of crystalloid solution. B group was scheduled to receive 15 ml of racemic Bupivacaine, L-group was scheduled to receive 15ml of Levobupivacaine and LD-group received 15ml of Levobupivacaine with 0.5 mics/kg Dexmeditomedine. Time to onset of sensory block to T-10, maximum sensory level achieved, Bromage scale, time to two segment regression, time to total regression, sedation level achieved and patients assessment of quality of anaesthesia were assessed. Haemodynamic parameters were monitored throughout study period. Adverse effects were noted and treated appropriately. Baseline parameters were comparable among all the groups. Time to onset of sensory block to T-10 and maximum level of block achieved, was comparable among the groups. Time to two segment regression and time to total regression was significantly prolonged in LD group compared to other two groups. There was significant bradycardia noted in LD group which required treatment. Levobupivacaine can be safely used in elderly high risk patients undergoing vascular surgery. Addition of dexmedetomidine prolongs the duration of anaesthesia and postoperative analgesia.


Contemporary Formulations for Drug Delivery of Anticancer Bioactive Compounds.
The immense development in the field of anticancer research has led to an increase in the research of bioactive compounds with anticancer potential. It has been known that many bioactive natural compounds have low solubility (and low bioavailability) as their main drawback when it comes to the formulation and drug delivery to specific sites. As many attempts have been made to overcome this issue, this review gives a summary of the current accomplishments regarding the development of new Drug Delivery Systems (DDSs) represented by nanoparticles (NPs) and exosomes. We analyzed the published data concerning selected compounds that present the most prominent plant secondary metabolites with anticancer potential, specifically flavone (quercetin), isoflavone (genistein and curcumin) and stilbene (resveratrol) groups that have been formulated as NPs and exosomes. In addition, we summarized the patent literature published from 2015-2018 that address these formulations. Although the exact mechanism of action for the selected natural compounds still remains unclear, the anticancer effect is evident and the main research efforts are directed to finding the most suitable delivery systems. Recent patents in this field serve as evidence that these newly designed natural compound delivery systems could be powerful new anticancer agents in the very near future if the noted difficulties are overcome. The focus of recent research is not only to clarify the exact mechanisms of action and therapeutic effects, but also to answer the issue of suitable delivery systems that can transport sufficient doses of bioactive compounds to the desired target.


Intrauterine Exposure to Diabetic Milieu Does Not Induce Diabetes and Obesity in Male Adulthood in a Novel Rat Model.
Several studies show an association of maternal diabetes during pregnancy with adverse offspring metabolic health. Other studies, however, suggest that this effect might be biased by obesity, which is independently associated with offspring metabolic disease and often coexistent to maternal diabetes. We performed a prospective study in a rat model to test the hypothesis that the burden of a diabetic pregnancy without obesity deteriorates metabolic health in male offspring. We generated maternal type 2 diabetes before conception that persisted during pregnancy by knockdown of the insulin receptor in small hairpin RNA-expressing transgenic rats. Male WT (wild type) offspring were followed up until adulthood and metabolically challenged by high-fat diet. Blood glucose was measured continuously via a telemetry device. Glucose and insulin tolerance tests were performed, and body composition was analyzed. Weight gain and glucose levels during adolescence and adulthood were similar in male offspring of diabetic and control pregnancies. Body weight and fat mass after high-fat diet, as well as glucose and insulin tolerance tests, were unaltered between male adult offspring of both groups. Glycemic control consisting of up to 49 000 individual glucose measures was comparable between both groups. Intrauterine exposure to maternal hyperglycemia and hyperinsulinemia without obesity had no impact on male offspring metabolic health in our model. We conclude that the intrauterine exposure itself does not represent a mechanism for fetal programming of diabetes and obesity in our model. Other maternal metabolic parameters during pregnancy, such as obesity, might impact long-term offspring metabolic health.


Sympathy for the devil: the role of thromboxane in the regulation of vascular tone and blood pressure.
Historically, the vasodilatory prostanoids, especially prostacyclin and prostaglandin E(2), are believed to contribute significantly to the regulation of normal vascular tone and blood pressure (BP), primarily by counteracting the prevailing effects of the systemic vasoconstrictor systems, including angiotensin II, the catecholamines, and vasopressin. In contrast, the primary vasoconstrictor prostanoid thromboxane A(2) (TxA(2)) is produced in far smaller quantities in the normal state. While TxA(2) is believed to play a significant role in a variety of cardiovascular diseases, such as myocardial infarction, cerebral vasospasm, hypertension, preeclampsia, and various thrombotic disorders, its role in the regulation of vascular tone and BP in the normal physiological state is, at best, uncertain. Numerous studies have firmly established the dogma that TxA(2), while important in pathophysiological states in males, plays little or no role in the regulation of vascular tone or BP in females, except in the pulmonary vasculature. However, this concept is largely based on the predominant and preferential use of males in animal and human studies. Recent studies from our laboratory and others challenge this dogma and reveal that the TxA(2) pathway in the systemic vascular wall is an estrogen-dependent mechanism that appears to play an important role in the regulation of vascular tone and BP in females, in both normal and pathophysiological states. It is proposed that the potent vasoconstrictor action of TxA(2) is beneficial in the female in the normal state by acting as a local counterregulatory mechanism to increase vascular tone and BP and defend against hypotension that could result from the multiple estrogen-sensitive local vasodilator mechanisms present in the female vascular wall. Validation of this proposal must await further studies at the systemic, tissue, and molecular levels.


Anticipatory guidance: a modest intervention in the nursery.
Although the importance of anticipatory guidance in the care of children is well recognized, pediatricians devote only about 10% of the average well child visit to parent education. The reluctance to engage more extensively in preventive interventions may relate to the paucity of evidence that such efforts are effective. This study was designed to test whether a modest anticipatory intervention, easily adaptable to other settings, could favorably influence maternal behavior. Mothers of newborn infants in a municipal hospital were assigned in alternate 2-week periods to an intervention program (n = 49) or a control group (n = 54). The intervention in the nursery consisted of a short group meeting, reinforced by a handout, advocating delayed introduction of solid foods and juices, and the use only of safe pacifiers. The mothers were interviewed at all visits to the general pediatric clinic using a standard format questionnaire. The two groups of mothers were demographically comparable but differed significantly in both the foods they introduced and the pacifiers they used for their babies. As an unexpected benefit, intervention mothers tended to view their babies as healthier than did control mothers. The implications of these findings are discussed.


IGF-1 receptor inhibition by picropodophyllin in medulloblastoma.
The insulin-like growth factor-1 receptor (Igf1r) is a multifunctional membrane-associated tyrosine kinase associated with regulation of transformation, proliferation, differentiation and apoptosis. Increased IGF pathway activity has been reported in human and murine medulloblastoma. Tumors from our genetically-engineered medulloblastoma mouse model over-express Igf1r, and thus this mouse model is a good platform with which to study the role of Igf1r in tumor progression. We hypothesize that inhibition of IGF pathway in medulloblastoma can slow or inhibit tumor growth and metastasis. To test our hypothesis, we tested the role of IGF in tumor growth in vitro by treatment with the tyrosine kinase small molecule inhibitor, picropodophyllin (PPP), which strongly inhibits the IGF pathway. Our results demonstrate that PPP-mediated downregulation of the IGF pathway inhibits mouse tumor cell growth and induces apoptotic cell death in vitro in primary medulloblastoma cultures that are most reflective of tumor cell behavior in vivo.


Differential impact of diverse anticancer chemotherapeutics on the Cdc25A-degradation checkpoint pathway.
When exposed to DNA-damaging insults such as ionizing radiation (IR) or ultraviolet light (UV), mammalian cells activate checkpoint pathways to halt cell cycle progression or induce cell death. Here we examined the ability of five commonly used anticancer drugs with different mechanisms of action to activate the Chk1/Chk2-Cdc25A-CDK2/cyclin E cell cycle checkpoint pathway, previously shown to be induced by IR or UV. Whereas exposure of human cells to topoisomerase inhibitors camptothecin, etoposide, or adriamycin resulted in rapid (within 1 h) activation of the pathway including degradation of the Cdc25A phosphatase and inhibition of cyclin E/CDK2 kinase activity, taxol failed to activate this checkpoint even after a prolonged treatment. Unexpectedly, although the alkylating agent cisplatin also induced degradation of Cdc25A (albeit delayed, after 8-12 h), cyclin E/CDK2 activity was elevated and DNA synthesis continued, a phenomena that correlated with increased E2F1 protein levels and consequently enhanced expression of cyclin E. These results reveal a differential impact of various classes of anticancer chemotherapeutics on the Cdc25A-degradation pathway, and indicate that the kinetics of checkpoint induction, and the relative balance of key components within the DNA damage response network may dictate whether the treated cells arrest their cell cycle progression.


High prevalence of antimicrobial resistance among common bacterial isolates in a tertiary healthcare facility in Rwanda.
Antimicrobial resistance (AMR) is a serious public health threat in both developed and developing countries. Many developing countries, including Rwanda, lack adequate surveillance systems, and therefore, the prevalence of AMR is not well-known. We conducted a prospective observational study to assess the prevalence of AMR among common bacterial isolates from clinical specimens obtained from patients on the medical wards of Kigali University Teaching Hospital (KUTH). We evaluated the antibiotic sensitivity patterns of bacterial pathogens cultured from urine, blood, sputum, and wound swab specimens obtained over a 6-month period (July 1 to December 30, 2013). There were 154 positive cultures from specimens obtained from 141 unique patients over the study period. Urine, blood, wound swab, and sputum cultures comprised 55.2%, 25.3%, 16.2%, and 3.3% of the total specimens evaluated; 31.4% and 58.7% of Escherichia coli and Klebsiella isolates, respectively, were resistant to at least one of the third generation cephalosporins. Eight percent of E. coli isolates were resistant to imipenem; 82% and 6% of Staphylococcus aureus strains were oxacillin- and vancomycin-resistant respectively. Antimicrobial resistance rates are high in Rwanda and pose a serious therapeutic challenge to the management of common infections.


Linguistic and auditory temporal processing in children with specific language impairment.
Several studies suggest the association of specific language impairment (SLI) to deficits in auditory processing. It has been evidenced that children with SLI present deficit in brief stimuli discrimination. Such deficit would lead to difficulties in developing phonological abilities necessary to map phonemes and to effectively and automatically code and decode words and sentences. However, the correlation between temporal processing (TP) and specific deficits in language disorders--such as syntactic comprehension abilities--has received little or no attention. To analyze the correlation between: TP (through the Frequency Pattern Test--FPT) and Syntactic Complexity Comprehension (through a Sentence Comprehension Task). Sixteen children with typical language development (8;9 +/- 1;1 years) and seven children with SLI (8;1 +/- 1;2 years) participated on the study. Accuracy of both groups decreased with the increase on syntactic complexity (both p < 0.01). On the between groups comparison, performance difference on the Test of Syntactic Complexity Comprehension (TSCC) was statistically significant (p = 0.02).As expected, children with SLI presented FPT performance outside reference values. On the SLI group, correlations between TSCC and FPT were positive and higher for high syntactic complexity (r = 0.97) than for low syntactic complexity (r = 0.51). Results suggest that FPT is positively correlated to syntactic complexity comprehension abilities.The low performance on FPT could serve as an additional indicator of deficits in complex linguistic processing. Future studies should consider, besides the increase of the sample, longitudinal studies that investigate the effect of frequency pattern auditory training on performance in high syntactic complexity comprehension tasks.


Structural equation models for evaluating dynamic concepts within longitudinal twin analyses.
A great deal of prior research using structural equation models has focused on longitudinal analyses and biometric analyses. Some of this research has even considered the simultaneous analysis of both kinds of analytic problems. The key benefits of these kinds of analyses come from the estimation of novel parameters, such as the heritability of changes. This paper discusses some recent extensions of longitudinal multivariate models that can be informative within biometric designs. In the methods section we review a previous latent growth structural equation analysis of the New York Twin (NYT) longitudinal data (from McArdle et al., 1998). In the models section we recast this growth model in terms of latent difference scores, add several new dynamic components, including coupling parameters, and consider biometric components and examine model stability. In the results section we present new univariate and bivariate dynamic estimates and tests of various dynamic hypotheses for the NYT data, and we consider a few ways to interpret the age-related biometric components of these models. In the discussion we consider our limitations and present suggestions for future dynamic-genetic research.


[Diagnosis and treatment of expiratory stenosis of the trachea and main bronchi in children].
The results of examination and the course of expiratory stenosis were studied in 15 children, 3 of them suffered from bronchomalacia of the left main bronchus. Bronchoscopy and poly-positional radioscopy with contrast study of the trachea and the large bronchi are the principal diagnostic methods in this disease. Sclerosing therapy was carried out in III degree expiratory stenosis. Two patients with bronchomalacia of the main bronchus and cystic lung hypoplasia underwent pulmonectomy with treatment of the main bronchus at the site of its branching off from the tracheal bifurcation. The results of sclerosing therapy and operations were good.


Predicting the sensitivity of butterfly phenology to temperature over the past century.
Studies to date have documented substantial variation among species in the degree to which phenology responds to temperature and shifts over time, but we have a limited understanding of the causes of such variation. Here, we use a spatially and temporally extensive data set (ca. 48 000 observations from across Canada) to evaluate the utility of museum collection records in detecting broad-scale phenology-temperature relationships and to test for systematic differences in the sensitivity of phenology to temperature (days °C(-1) ) of Canadian butterfly species according to relevant ecological traits. We showed that the timing of flight season predictably responded to temperature both across space (variation in average temperature from site to site in Canada) and across time (variation from year to year within each individual site). This reveals that collection records, a vastly underexploited resource, can be applied to the quantification of broad-scale relationships between species' phenology and temperature. The timing of the flight season of earlier fliers and less mobile species was more sensitive to temperature than later fliers and more mobile species, demonstrating that ecological traits can account for some of the interspecific variation in species' phenological sensitivity to temperature. Finally, we found that phenological sensitivity to temperature differed across time and space implying that both dimensions of temperature will be needed to translate species' phenological sensitivity to temperature into accurate predictions of species' future phenological shifts. Given the widespread temperature sensitivity of flight season timing, we can expect long-term temporal shifts with increased warming [ca. 2.4 days °C(-1) (0.18 SE)] for many if not most butterfly species.


[Perioperative care in subthalamic stimulation surgery].
Bilateral stimulation of the subthalamic nucleus (STN) seems to be one of the most effective treatments for advanced forms of Parkinson's disease. Success of the postoperative clinical outcome depends on the quality of the inclusion of patients and the optimal targeting and stimulation of the cerebral nucleus.<p> We describe the case of a 68 years old male with intracerebral hemorrhage, cognitive deterioration and generalized convulsions in the early postoperative period of a bilateral deep brain stimulation (DBS) of STN. Although this kind of surgery is included in the concept of "minimal invasive" surgery, there are risks and side effects, some of them very serious, as in the case report we present. Perioperative management is complex because of the nature of the surgery and the type of patient, so that some of the aspects are still under debate for both the anesthesiologist and the rest of specialists involved.


Massive Vector Fields in Rotating Black-Hole Spacetimes: Separability and Quasinormal Modes.
We demonstrate the separability of the massive vector (Proca) field equation in general Kerr-NUT-AdS black-hole spacetimes in any number of dimensions, filling a long-standing gap in the literature. The obtained separated equations are studied in more detail for the four-dimensional Kerr geometry and the corresponding quasinormal modes are calculated. Two of the three independent polarizations of the Proca field are shown to emerge from the separation ansatz and the results are found in an excellent agreement with those of the recent numerical study where the full coupled partial differential equations were tackled without using the separability property.


Studies of natural allele effects in mice can be used to identify genes causing common human obesity.
Although genes causing rare Mendelian forms of human obesity have provided much useful information about underlying causes of obesity, these genes do not explain significant proportions of common obesity. This review presents evidence that animal models can be used to uncover subtle genetic effects on obesity and can provide a powerful rigorous compliment to human association studies. We discuss the advantages of animal models of obesity, various approaches to discovering obesity genes, and the future of mapping and isolating naturally occurring alleles of obesity genes. We review evidence that it is important to map naturally occurring obesity genes using quantitative trait locus (QTL) mapping, instead of mutagenesis and knockout models because the latter do not allow study of interactions and because naturally occurring obesity alleles can interfere with cloning from mutagenesis projects. Because a substantial percentage of human obesity results from complex interactions, the underlying genes can only be identified by direct studies in humans, which are still very difficult, or by studies in mice that begin with QTL mapping. Finally, we emphasize that animal model studies can be used to prove that a specific gene, only associated with obesity in humans, can indeed be the underlying cause of obesity in mammals.


The correlation between IgM and IgG antibodies with blood profile in patients infected with severe acute respiratory syndrome coronavirus.
This study aimed to determine the levels of IgM and IgG antibody response to the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 in coronavirus disease 2019 (COVID-19) patients with different disease severity. IgM and IgG antibody levels were evaluated via enzyme-linked immunosorbent assay (ELISA). In total, 100 patients with confirmed SARS-CoV-2 infection were enrolled in this study and viral RNA was detected by using Real-time PCR technique. Clinical and laboratory data were collected and analyzed after hospital admission for COVID-19 and two months post-admission. The level of anti-SARS-CoV-2 antibody IgG was significantly higher in the severe patients than those in moderate and mild groups, 2 months after admission. Also, level of IgG was positively associated with increased WBC, NUT and LYM counts in sever than mild or moderate groups after admission to hospital. Our findings suggested that patients with severe illness might experience longer virus exposure times and have a stronger antibody response against viral infection. Thus, they have longer time immunity compared with other groups.


Applications of Click Chemistry in the Development of HIV Protease Inhibitors.
Acquired Immunodeficiency Syndrome (AIDS) has been devastating for millions of people around the world. Inhibition of the human immunodeficiency virus (HIV) protease is among the most important approaches for the therapeutic intervention in HIV infection. Since the discovery of the HIV-1 protease, this enzyme has been considered as a key target for the inhibition of viral replication. A large body of research has been done to develop an effective HIV-1 protease inhibitor. There are to date 10 HIV-1 protease inhibitor drugs approved by the Food and Drug Administration (FDA) that have improved the survival and quality of life of HIV infected people. These drugs are prescribed in combination with the reverse transcriptase inhibitors, which is referred to as highly active antiretroviral therapy (HAART). The HIV-1 protease inhibitors play a vital role in HAART. The applications of click chemistry are dispersing in the field of drug discovery. Recently, click chemistry has captured a lot of attention and has become a powerful tool for the synthesis of medicinal skeletons in the discovery of anti-HIV drugs. Click reaction is a well-known method for making carbon-heteroatom-carbon bonds. Click reactions are popular because they are wide in scope, of high yielding, quick to perform, and easy to purify. In this review, we outlined current approaches towards the development of HIV-1 protease inhibitors employing click chemistry.


Coevolution with bacteriophages drives genome-wide host evolution and constrains the acquisition of abiotic-beneficial mutations.
Studies of antagonistic coevolution between hosts and parasites typically focus on resistance and infectivity traits. However, coevolution could also have genome-wide effects on the hosts due to pleiotropy, epistasis, or selection for evolvability. Here, we investigate these effects in the bacterium Pseudomonas fluorescens SBW25 during approximately 400 generations of evolution in the presence or absence of bacteriophage (coevolution or evolution treatments, respectively). Coevolution resulted in variable phage resistance, lower competitive fitness in the absence of phages, and greater genome-wide divergence both from the ancestor and between replicates, in part due to the evolution of increased mutation rates. Hosts from coevolution and evolution treatments had different suites of mutations. A high proportion of mutations observed in coevolved hosts were associated with a known phage target binding site, the lipopolysaccharide (LPS), and correlated with altered LPS length and phage resistance. Mutations in evolved bacteria were correlated with higher fitness in the absence of phages. However, the benefits of these growth-promoting mutations were completely lost when these bacteria were subsequently coevolved with phages, indicating that they were not beneficial in the presence of resistance mutations (consistent with negative epistasis). Our results show that in addition to affecting genome-wide evolution in loci not obviously linked to parasite resistance, coevolution can also constrain the acquisition of mutations beneficial for growth in the abiotic environment.


Impact of magnetic nanoparticles in biomedical applications.
In the recent years, there has been a growing interest in the development of nanoparticles based targeting agents for the tumor diagnostics and therapeutics. This is because of their potential to detect the tumor and treat the diseased tissue at the cellular and molecular level. In this respect nanoscale magnetic materials have shown a very promising therapeutic concept and offer a new perspective for the diagnostic and target drug delivery approach. The magnetic nanocarriers have the ability to accumulate at any desired pharmacological site just by the guidance of external magnetic field. But, the interactions of these magnetic nanocarriers with the biological environment are rare and depend largely upon their surface chemistry and size. To increase the interactions and achieve the desired pharmaceutically acceptable delivery system, the surface of magnetic nanocarriers is modified in various ways by coating with organic polymers and inorganic metals or oxides. On the basis of surface characteristics, a number of effective magnetically driven therapies have been proposed by many researchers and protected through patents time to time.


Report from the Society of Thoracic Surgeons National Database Workforce: clarifying the definition of operative mortality.
Several distinct definitions of postoperative death have been used in various quality reporting programs. Some have defined postoperative mortality as the occurrence of death after a surgical procedure when the patient dies while still in the hospital, while others have considered all deaths occurring within a predetermined, standardized time interval after surgery to be postoperative mortality. While mortality data are still collected and reported using both these individual definitions, the Society of Thoracic Surgeons (STS) believes that either approach alone may be inadequate. Accordingly, the STS prefers a more encompassing metric, Operative Mortality. Operative Mortality is defined in all STS databases as (1) all deaths, regardless of cause, occurring during the hospitalization in which the operation was performed, even if after 30 days (including patients transferred to other acute care facilities); and (2) all deaths, regardless of cause, occurring after discharge from the hospital, but before the end of the 30th postoperative day. This article provides clarification for some uncommon but important scenarios in which the correct application of this definition may be challenging.


Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions.
The chemokine CXCL1/MGSA plays a pivotal role in the host immune response by recruiting and activating neutrophils for microbial killing at the tissue site. CXCL1 exists reversibly as monomers and dimers, and mediates its function by binding glycosaminoglycans (GAG) and CXCR2 receptor. We recently showed that both monomers and dimers are potent CXCR2 agonists, the dimer is the high-affinity GAG ligand, lysine and arginine residues located in two non-overlapping domains mediate GAG interactions, and there is extensive overlap between GAG and receptor-binding domains. To understand how these structural properties influence in vivo function, we characterized peritoneal neutrophil recruitment of a trapped monomer and trapped dimer and a panel of WT lysine/arginine to alanine mutants. Monomers and dimers were active, but WT was more active indicating synergistic interactions promote recruitment. Mutants from both domains showed reduced GAG heparin binding affinities and reduced neutrophil recruitment, providing compelling evidence that both GAG-binding domains mediate in vivo trafficking. Further, mutant of a residue that is involved in both GAG binding and receptor signaling showed the highest reduction in recruitment. We conclude that GAG interactions and receptor activity of CXCL1 monomers and dimers are fine-tuned to regulate neutrophil trafficking for successful resolution of tissue injury.


Quorum sensing and biofilm formation in Streptococcal infections.
Members of the bacterial genus Streptococcus are responsible for causing a wide variety of infections in humans. Many Streptococci use quorum-sensing systems to regulate several physiological properties, including the ability to incorporate foreign DNA, tolerate acid, form biofilms, and become virulent. These quorum-sensing systems are primarily made of small soluble signal peptides that are detected by neighboring cells via a histidine kinase/response regulator pair.


Carbogen breathing significantly enhances the penetration of red light in murine tumours in vivo.
We report results of experiments that evaluated the influence of oxygenation on the penetration of red light in tissue, with particular emphasis on 630 and 650 nm laser wavelengths commonly used in photodynamic therapy (PDT) of solid tumours. Direct measurements in tissue-simulating phantoms comprised of intact human erythrocytes suspended in a scattering emulsion demonstrated significant enhancements in fluence rate at depths of 0.5-2 cm from the irradiated surface when the cells were fully oxygenated versus fully deoxygenated. The 630 and 650 nm fluence rates at depth in the homogeneous phantoms continued to increase when examined over a continuous range of oxygen partial pressures from 0 to 160 Torr. When considered as a function of haemoglobin oxygen saturation, the largest increases in fluence rate were observed as the saturation increased beyond 70%. Dramatic increases in optical fluence rate were measured at the base of 1-cm-thick subcutaneous EMT6 mammary carcinomas in vivo when the tumour-bearing mouse was subjected to carbogen through a nose cone. These results indicate that improved tumour oxygenation is important in PDT not only for the maintenance of the oxygen-dependent photochemistry but, through the effects reported here, may also enable more efficient treatment of thicker lesions.


Age of diagnosis among Medicaid-enrolled children with autism, 2001-2004.
This study examined child- and county-level factors associated with age of diagnosis of autism among Medicaid-enrolled children and the change in age of diagnosis over time. National Medicaid claims from 2002 to 2004 were used to identify age of diagnosis and characteristics of children younger than ten years old with a diagnosis of autism (ICD-9 codes 299, 299.0x, or 299.8x). These data were linked to county-level education and health care variables. Linear regression with random effects for state and county was used to examine associations between these variables and age of diagnosis. A total of 28,722 Medicaid-enrolled children newly diagnosed with an autism spectrum disorder were identified. Their average age of diagnosis was 64.9 months. Adjusted average age of diagnosis dropped 5.0 months for autistic disorder and 1.8 months for other spectrum disorders during the study period. Asian children were diagnosed earlier than children in other racial or ethnic groups, although these differences were much more pronounced for other spectrum disorders than for autistic disorder. Children eligible for Medicaid through the poverty category were diagnosed earlier, on average, than children who were eligible through disability, foster care, or other reasons, although this difference decreased over time. Children in large urban or rural counties were diagnosed later than children in small urban or suburban counties. Findings showed that diagnosis of autism occurs much later than it should among Medicaid-enrolled children, although timeliness is improving over time. Analyses suggest that most of the observed variation is accounted for by child-level variables, rather than county-level resources or state policies.


Absorption, metabolism, and excretion of green tea flavan-3-ols in humans with an ileostomy.
Green tea containing 634 micromol of flavan-3-ols was ingested by human subjects with an ileostomy. Ileal fluid, plasma, and urine collected 0-24 h after ingestion were analysed by HPLC-MS. The ileal fluid contained 70% of the ingested flavan-3-ols in the form of parent compounds (33%) and 23 metabolites (37%). The main metabolites effluxed back into the lumen of the small intestine were O-linked sulphates and methyl-sulphates of (epi)catechin and (epi)gallocatechin. Thus, in subjects with a functioning colon substantial quantities of flavan-3-ols would pass from the small to the large intestine. Plasma contained 16 metabolites, principally methylated, sulphated, and glucuronidated conjugates of (epi)catechin and (epi)gallocatechin, exhibiting 101-256 nM peak plasma concentration and the time to reach peak plasma concentration ranging from 0.8 to 2.2 h. Plasma pharmacokinetic profiles were similar to those obtained with healthy subjects, indicating that flavan-3-ol absorption occurs in the small intestine. Ileostomists had earlier plasma time to reach peak plasma concentration values than subjects with an intact colon, indicating the absence of an ileal brake. Urine contained 18 metabolites of (epi)catechin and (epi)gallocatechin in amounts corresponding to 6.8+/-0.6% of total flavan-3-ol intake. However, excretion of (epi)catechin metabolites was equivalent to 27% of the ingested (-)-epicatechin and (+)-catechin.


Sound response mediated by the TRP channels NOMPC, NANCHUNG, and INACTIVE in chordotonal organs of Drosophila larvae.
Mechanical stimuli, including tactile and sound signals, convey a variety of information important for animals to navigate the environment and avoid predators. Recent studies have revealed that Drosophila larvae can sense harsh or gentle touch with dendritic arborization (da) neurons in the body wall and can detect vibration with chordotonal organs (Cho). Whether they can also detect and respond to vibration or sound from their predators remains an open question. Here we report that larvae respond to sound of wasps and yellow jackets, as well as to pure tones of frequencies that are represented in such natural sounds, with startle and burrowing behaviors. The larval response to sound/vibration requires Cho neurons and, to a lesser extent, class IV da neurons. Our calcium imaging and electrophysiological experiments reveal that Cho neurons, but not class IV da neurons, are excited by natural sounds or pure tones, with tuning curves and intensity dependence appropriate for the behavioral responses. Furthermore, our study implicates the transient receptor potential (TRP) channels NOMPC, NANCHUNG, and INACTIVE, but not the dmPIEZO channel, in the mechanotransduction and/or signal amplification for the detection of sound by the larval Cho neurons. These findings indicate that larval Cho, like their counterparts in the adult fly, use some of the same mechanotransduction channels to detect sound waves and mediate the sensation akin to hearing in Drosophila larvae, allowing them to respond to the appearance of predators or other environmental cues at a distance with behaviors crucial for survival.


Polyploidy associated with altered and broader ecological niches in the Claytonia perfoliata (Portulacaceae) species complex.
Polyploids are often hypothesized to have distinct and broader niches than their diploid progenitors. Differences in geographic distributions between diploid and polyploids are frequently used to infer niche differentiation and increased breadth, but they are seldom used to test these hypotheses explicitly. Niche overlap and breadth were compared for diploids, tetraploids, and hexaploids of three taxa in the Claytonia perfoliata complex (C. parviflora, C. perfoliata, and C. rubra) with the use of species distribution models. Resampling and randomization approaches were used to test hypotheses of niche differentiation, breadth, and conservatism. Niche differentiation was detected between polyploid and diploid cytotypes assigned to the same taxon (e.g., C. parviflora 2× vs. 4×) but not between hexaploids and tetraploids within a taxon (e.g., C. parviflora 4× vs. 6×). Individual hexaploid cytotypes had broader ecological niches than individual diploid cytotypes. However, as a group the three hexaploid taxa did not exceed the combined niche breadth of the three diploids, suggesting that polyploidy does not result in transgressive niche breadth for this group. Niche overlap was lowest among diploids and was highest among the three hexaploid cytotypes, consistent with introgression associated with polyploidy resulting in greater ecological similarity. Although cytotypes possessed nonidentical niches, after accounting for environmental differences among ranges, cytotypes were more similar than expected, suggesting niche conservatism and similar responses to environmental characteristics. These results suggest that polyploids occupy distinct and broader niches relative to diploids but that cytotypes also share fundamentally similar responses to environmental variation across ploidy levels.


Results of MyPlan 2.0 on Physical Activity in Older Belgian Adults: Randomized Controlled Trial.
The beneficial effects of physical activity (PA) for older adults are well known. However, few older adults reach the health guideline of 150 min per week of moderate-to-vigorous PA (MVPA). Electronic health (eHealth) interventions are effective in increasing PA levels in older adults in the short term but, rarely, intermediate-term effects after a period without the support of a website or an app have been examined. Furthermore, current theory-based interventions focus mainly on preintentional determinants, although postintentional determinants should also be included to increase the likelihood of successful behavior change. This study aimed to investigate the effect of the theory-based eHealth intervention, MyPlan 2.0, focusing on pre- and postintentional determinants on both accelerometer-based and self-reported PA levels in older Belgian adults in the short and intermediate term. This study was a randomized controlled trial with three data collection points: baseline (N=72), post (five weeks after baseline; N=65), and follow-up (three months after baseline; N=65). The study took place in Ghent, and older adults (aged ≥65 years) were recruited through a combination of random and convenience sampling. At all the time points, participants were visited by the research team. Self-reported domain-specific PA was assessed using the International Physical Activity Questionnaire, and accelerometers were used to objectively assess PA. Participants in the intervention group got access to the eHealth intervention, MyPlan 2.0, and used it independently for five consecutive weeks after baseline. MyPlan 2.0 was based on the self-regulatory theory and focused on both pre- and postintentional processes to increase PA. Multilevel mixed-models repeated measures analyses were performed in R (R Foundation for Statistical Computing). Significant (borderline) positive intervention effects were found for accelerometer-based MVPA (baseline-follow-up: intervention group +5 min per day and control group -5 min per day; P=.07) and for accelerometer-based total PA (baseline-post: intervention group +20 min per day and control group -24 min per day; P=.05). MyPlan 2.0 was also effective in increasing self-reported PA, mainly in the intermediate term. A positive intermediate-term intervention effect was found for leisure-time vigorous PA (P=.02), moderate household-related PA (P=.01), and moderate PA in the garden (P=.04). Negative intermediate-term intervention effects were found for leisure-time moderate PA (P=.01) and cycling for transport (P=.07). The findings suggest that theory-based eHealth interventions focusing on pre- and postintentional determinants have the potential for behavior change in older adults. If future studies including larger samples and long-term follow-up can confirm and clarify these findings, researchers and practitioners should be encouraged to use a self-regulation perspective for eHealth intervention development. Clinicaltrials.gov NCT03194334; https://clinicaltrials.gov/ct2/show/NCT03783611.


Regulation of skeletal muscle peroxisome proliferator-activated receptor gamma expression by exercise and angiotensin-converting enzyme inhibition in fructose-fed hypertensive rats.
The purpose of this study was to examine the effects of chronic exercise training and angiotensin-converting enzyme (ACE) inhibition on peroxisome proliferator-activated receptor gamma (PPAR gamma) expression in fat and skeletal muscle in fructose-fed spontaneously hypertensive rats (SHR). SHR were fed a fructose-rich diet over 16 weeks of either exercise training (Ex group: 20 m/min, 0% grade, 60 min/day, 5 days/week), ACE inhibitor administration (TM group: temocapril, 10 mg/kg/day), or a combination of both treatments (TM+Ex group). The systolic blood pressure was reduced exclusively in the temocapril-treated groups. Serum leptin level was positively correlated with the ratio of epididymal fat weight to body weight (p<0.001). Exercise training significantly upregulated the PPARgamma expression in all tissues, which was attenuated by temocapril. PPARgamma expression was significantly upregulated in skeletal muscles in the Ex group, and temocapril administration attenuated this effect in the Ex+TM group. The level of PPARgamma protein was significantly higher in the extensor digitorum longus muscle than in the soleus muscle. Both TM and Ex prevented the fructose diet-induced transitions of fiber type. These data suggested that PPARgamma expression is tissue-specific, and that alterations in PPARgamma expression in the skeletal muscle induced by either or both treatments may have contributed to reducing the fat mass via the regulation of metabolic homeostasis. Changes in muscle morphology were independent of PPARgamma expression, and the higher proportion of type I fiber might also explain some of the beneficial impact of exercise and ACE inhibition on energy metabolism.


[Biochemical characteristics of membrane fractions from different types of cerebral cortex synaptosomes].
The activity of acetylcholinesterase (ACE) and Na, K-ATPase is distributed among three subfractions of synaptic membranes isolated from light (C) and heavy (D) synaptosomes of the optic area of the rabbit cerebral cortex. The levels of specific activity of both enzymes in C subfractions are similar to those in D subfractions. At the same time the specific activity of ACE and Na, K-ATPase in membrane fractions from both light and heavy synaptosomes is different. Such a biochemistry of subsynaptic components from certain brain structures favors studying a fine morphochemical organization of an isolated nerve terminal and its relationship with the activity of CNS in different functional states.


Effect of ofatumumab versus placebo in relapsing multiple sclerosis patients from Japan and Russia: Phase 2 APOLITOS study.
Ofatumumab, the first fully human anti-CD20 monoclonal antibody, has been developed as a treatment for relapsing multiple sclerosis (RMS) which can be self-administered at home. To investigate the efficacy and safety of ofatumumab in RMS patients from Japan and Russia. APOLITOS included a 24-week, double-blind, placebo-controlled core-part followed by an open-label extension-part. Patients were randomized (2:1) to subcutaneous ofatumumab 20 mg or placebo. Primary outcome was the number of gadolinium-enhancing (Gd+) T1 lesions per scan over 24 weeks. Sixty-four patients were randomized (ofatumumab, n = 43; placebo, n = 21). Primary endpoint was met; ofatumumab reduced Gd + T1 lesions versus placebo by 93.6% (p < 0.001) and the results were consistent across regions (Japan/Russia). Ofatumumab reduced annualized T2 lesion and relapse rate versus placebo by week 24. Both groups showed benefit from ofatumumab in the extension-part. Incidence of adverse events was lower with ofatumumab versus placebo (69.8% vs 81.0%); injection-related reactions were most common. No deaths, opportunistic infections, or malignancies were reported. Ofatumumab demonstrated superior efficacy versus placebo, with sustained effect through 48 weeks in RMS patients from Japan/Russia. Switching to ofatumumab after 24 weeks led to rapid radiological and clinical benefits. Safety findings were consistent with pivotal trials.


[Virtual screening for components in Chicory combined with CNT2 target based on molecular docking].
To virtual screen the compound of Chicory combined with the concentrative nucleoside transporter 2 (CNT2) in molecular docking technology.The homology model of hCNT2 was produced, and then the Vina software was employed to virtual screen the Chicory compound combined with CNT2. Compared with 7,8,3'-trihydroxyflavone, a CNT2 inhibitors, 23 score higher chicory compounds were hit.Meanwhile, the ten top compounds have been revealed that play important role in decrease the uric level. The bioactivity to CNT2 needs to be investigatedin experiment. CNT2 may be a potential target of chicory, which decreases the absorption of purine nucleoside in intestinal tract.


Differences in reporting of violence and deliberate self harm related injuries to health and police authorities, Rawalpindi, Pakistan.
The aim of study was to assess differences in reporting of violence and deliberate self harm (DSH) related injuries to police and emergency department (ED) in an urban town of Pakistan. Study setting was Rawalpindi city of 1.6 million inhabitants. Incidences of violence and DSH related injuries and deaths were estimated from record linkage of police and ED data. These were then compared to reported figures in both datasets. All persons reporting violence and DSH related injury to the police station, the public hospital's ED, or both in Rawalpindi city from July 1, 2007 to June 30, 2008 were included. In Rawalpindi city, 1016 intentional injury victims reported to police whereas 3012 reported to ED. Comparing violence related fatality estimates (N = 56, 95% CI: 46-64), police reported 75.0% and ED reported 42.8% of them. Comparing violence related injury estimates (N = 7990, 95% CI: 7322-8565), police reported 12.1% and ED reported 33.2% of them. Comparing DSH related fatality estimates (N = 17, 95% CI: 4-30), police reported 17.7% and ED reported 47.1% of them. Comparing DSH related injury estimates (N = 809, 95% CI: 101-1516), police reported 0.5% and ED reported 39.9% of them. In Rawalpindi city, police records were more likely to be complete for violence related deaths as compared to injuries due to same mechanism. As compared to ED, police reported DSH related injuries and deaths far less than those due to other types of violence.


Amorphous sub-nanometre Tb-doped SiO(x)N(y)/SiO2 superlattices for optoelectronics.
Amorphous sub-nanometre Tb-doped SiOxNy/SiO2 superlattices were fabricated by means of alternating deposition of 0.7 nm thick Tb-doped SiOxNy layers and of 0.9 nm thick SiO2 barrier layers in an electron-cyclotron-resonance plasma enhanced chemical vapour deposition system with in situ Tb-doping capability. High resolution transmission electron microscopy images showed a well-preserved superlattice morphology after annealing at a high temperature of 1000 °C. In addition, transparent indium tin oxide (ITO) electrodes were deposited by electron beam evaporation using a shadow mask approach to allow for the optoelectronic characterization of superlattices. Tb(3+) luminescent spectral features were obtained using three different excitation sources: UV laser excitation (photoluminescence (PL)), under a bias voltage (electroluminescence (EL)) and under a highly energetic electron beam (cathodoluminescence (CL)). All techniques displayed Tb(3+) inner transitions belonging to (5)D4 levels except for the CL spectrum, in which (5)D3 transition levels were also observed. Two competing mechanisms were proposed to explain the spectral differences observed between PL (or EL) and CL excitation: the population rate of the (5)D3 state and the non-radiative relaxation rate of the (5)D3-(5)D4 transition due to a resonant OH-mode. Moreover, the large number of interfaces (trapping sites) that electrons have to get through was identified as the main reason for observing a bulk-limited charge transport mechanism governed by Poole-Frenkel conduction in the J-V characteristic. Finally, a linear EL-J dependence was measured, with independent spectral shape and an EL onset voltage as low as 6.7 V. These amorphous sub-nanometre superlattices are meant to provide low-cost solutions in different areas including sensing, photovoltaics or photonics.


Determinants of utilisation of intrapartum obstetric care services in Cambodia, and gaps in coverage.
Facility delivery and skilled birth attendance are two of the most effective strategies for decreasing maternal mortality. The objectives of this study were to further define utilisation of these services in Cambodia and to uncover socio-economic or location-specific coverage gaps that may exist. We performed a cross-sectional analysis of the 2005 Cambodia Demographic Health Survey (CDHS) to determine prevalence, and determinants, of service utilisation. Out of 6069 women aged 15-49 years, 77% delivered at home, three-fourths without a skilled birth attendant. Poverty, lower education and rural residence were associated with the highest likelihood of poor utilisation of services. Discussion. While there has been an overall increase in facility deliveries and skilled birth attendance since 2000, improvements have been spread unevenly across the population, benefiting mostly urban, wealthier and better educated women. While recent financing initiatives and health system developments appear to have further increased service utilisation since 2005, the extent of their reach to the most vulnerable populations, and their ultimate impact on maternal mortality reduction, remain to be elucidated. Further expanding successful initiatives, particularly among vulnerable populations, is essential. Longitudinal evaluation of ongoing strategies and their impact remains critical.


Some rare Indo-Pacific coral species are probable hybrids.
Coral reefs worldwide face a variety of threats and many coral species are increasingly endangered. It is often assumed that rare coral species face higher risks of extinction because they have very small effective population sizes, a predicted consequence of which is decreased genetic diversity and adaptive potential. Here we show that some Indo-Pacific members of the coral genus Acropora have very small global population sizes and are likely to be unidirectional hybrids. Whether this reflects hybrid origins or secondary hybridization following speciation is unclear. The interspecific gene flow demonstrated here implies increased genetic diversity and adaptive potential in these coral species. Rare Acropora species may therefore be less vulnerable to extinction than has often been assumed because of their propensity for hybridization and introgression, which may increase their adaptive potential.


Characterization of the Escherichia coli Antifungal Protein PPEBL21.
An antifungal protein isolated from Escherichia coli BL21 (PPEBL21) and predicted to be alcohol dehydrogenase (ADH) was subjected to biological characterization. The PPEBL21, indeed, demonstrated propionaldehyde-specific ADH activity. The Km and Vmax of PPEBL21 were found to be 644.8 muM and 1.2 U/mg, respectively. In-gel activity assay also showed that PPEBL21 was a propionaldehyde-specific ADH. The pI of PPEBL21 was observed to be 7.8. PPEBL21 was found to be stable up to a temperature of 40 degrees C with optimum activity at pH 7.5. The decrease in pH decreased the activity of PPEBL21. These results suggested that PPEBL21 having alcohol dehydrogenase activity and stability at significantly high temperature might be an important lead antifungal molecule. Experiments were performed to identify the possible target of PPEBL21 in the pathogen A. fumigatus. Results revealed that PPEBL21 inhibited completely the expression of a 16 kDa protein in A. fumigatus. The 16 kDa protein of A. fumigatus targeted by PPEBL21 was identified as a hypothetical protein by peptide mass fingerprinting. It is thus hypothesized that a 16 kDa factor is essentially required by A. fumigatus for survival and its impaired synthesis due to treatment with PPEBL21 may lead to the death of pathogen.


Newly diagnosed chronic granulomatous disease in a 53-year-old woman with Crohn disease.
Chronic granulomatous disease (CGD) is characterized by defective bactericidal activity of white blood cells, specifically, a defect in superoxide production. Patients experience infections, predominantly caused by catalase-positive bacteria and fungal organisms, that may be severe and life-threatening. Most cases of CGD are diagnosed in children; however, it may rarely go undiagnosed until adulthood in individuals with unexplained infections and granulomatous inflammation. To describe an adult with Crohn disease and recurrent infections who was newly diagnosed as having CGD. A 53-year-old woman with a history of liver abscesses and Crohn disease presented with Burkholderia cepacia pneumonia and required a right middle lobe resection. Nitroblue tetrazolium test results confirmed the diagnosis of CGD, and Western blot analysis revealed the absence of the 47-phagocyte oxidase protein. Levels of Crohn-associated specific antibodies to Saccharomyces cerevisiae and Escherichia coli outer membrane porin C were elevated. The patient, newly diagnosed as having CGD, was given intravenous trimethoprim-sulfamethoxazole, after which she improved clinically and was discharged from the hospital in stable condition to receive daily oral trimethoprim-sulfamethoxazole treatment. The concomitant occurrence of Crohn disease and CGD, both characterized by granulomatous inflammation, is noteworthy. This case study demonstrates that CGD should be considered in adults with recurrent infections, especially those caused by catalase-positive organisms, such as B cepacia.


Pregnancy and other risk behaviors among adolescent girls in Ohio.
The purpose of this study was to determine whether teenage girls who had been pregnant were more likely to engage in other risk or problem behaviors than girls who had had sexual intercourse without becoming pregnant. The 1993 Ohio Youth Risk Behavior Survey was administered to a random sample of 2461 high school students. A subset of 592 girls (mean age 16.1 +/- 1.1 years, 69.2% Caucasian, 24.1% African-American, 2.4% Hispanic, 4.3% other) reported sexual activity (SA) on the anonymous survey. Demographic factors plus risk and problem behaviors were compared between 98 girls who had been pregnant and 494 girls who had never been pregnant using Chi-square analysis. Risk and problem behaviors were classified into four distinct groups: recent risk behaviors, age of onset of behavior, lifetime behavior, and general behavior. Variables which were univariately significant at p < 0.15 were considered in one of four stepwise multiple logistic regression models based on behavior type, with demographic factors considered in all four models. The final logistic regression model was developed using variables which were significant at p < 0.01. Variables which were significantly associated with pregnancy were summarized as odds ratios (OR) and 99% confidence intervals (CI); these ORs were adjusted for the effects of the other variables in the model. Pregnancy was more common in girls of color than in Caucasian girls (OR 99% and CI, 2.09, 1.06-4.11) and in older girls than in younger girls (1.52, 1.12-2.08). Among SA girls, weapon carrying in the past 30 days (4.06, 1.75-9.42) was significantly associated with pregnancy, whereas alcohol use in the past 30 days (0.37, 0.18-0.76) was less likely to be associated with pregnancy. The risk of pregnancy increased 1.75 times (1.26-2.43) for each additional sexual partner. Girls who had tried cocaine were 4.88 times (1.40-16.95) more likely to have been pregnant, and the risk of having been pregnant increased 1.43 times (1.14-1.80) for each additional year of SA. Past history of sexually transmitted disease (3.50, 1.28-9.55) was associated with increased pregnancy risk. Girls who had been pregnant also had engaged in other risk behaviors, including recent weapon carrying and cocaine use. A history of previous sexually transmitted diseases plus increasing numbers of partners add to the risk of pregnancy. Counseling and educational efforts should continue to identify teens at risk both to prevent pregnancy and to decrease associated risks.


Focus measure based on the energy of high-frequency components in the S transform.
Focus measure plays a fundamental role in the shape from focus technique. In this Letter, we suggest a focus measure in the S-transform domain that is based on the energy of high-frequency components. A localized spectrum by using variable window size provides a more accurate method of measuring image sharpness as compared to other focus measures proposed in spectral domains. An optimal focus measure is obtained by selecting an appropriate frequency-dependent window width. The performance of the proposed focus measure is compared with those of existing focus measures in terms of three-dimensional shape recovery. Experimental results demonstrate the effectiveness of the proposed focus measure.


Developmental perspectives on nutrition and obesity from gestation to adolescence.
Obesity results from a complex combination of factors that act at many stages throughout a person's life. Therefore, examining childhood nutrition and obesity from a developmental perspective is warranted. A developmental perspective recognizes the cumulative effects of factors that contribute to eating behavior and obesity, including biological and socioenvironmental factors that are relevant at different stages of development. A developmental perspective considers family, school, and community context. During gestation, risk factors for obesity include maternal diet, overweight, and smoking. In early childhood, feeding practices, taste acquisition, and eating in the absence of hunger must be considered. As children become more independent during middle childhood and adolescence, school nutrition, food marketing, and social networks become focal points for obesity prevention or intervention. Combining a multilevel approach with a developmental perspective can inform more effective and sustainable strategies for obesity prevention.


Increasing influenza vaccination rates: the need to vaccinate throughout the entire influenza season.
The burden of influenza on affected individuals and the healthcare system, as well as on society, is substantial. Although the supply of an effective and safe influenza vaccine was limited in previous years, advances in manufacture and distribution have alleviated such shortages. In most seasons, millions of doses go unused, and large numbers of unvaccinated, at-risk persons are left vulnerable to infection and its complications. According to insurance claims data, high-risk patients are seen by their healthcare providers on average 2.2 times between the peaks in vaccination (November) and in disease activity (February), yet they remain unvaccinated. The current 2- to 3-month time frame over which patients are traditionally immunized is too short to fully implement immunization recommendations and inconsistent with the duration of influenza activity. Both healthcare providers and patients should reevaluate their approach to influenza vaccination and recognize the need to extend the immunization time period into January and beyond. To increase influenza immunization rates, the Centers for Disease Control and Prevention (CDC) and other professional societies recommend an expanded immunization season, with vaccination offered at every opportunity between October and May.


A case of mandibuloacral dysplasia presenting with features of scleroderma.
Juvenile scleroderma, a relatively rare condition, may be confused with a number of progeroid syndromes like Hutchinson-Gilford syndrome, Werner syndrome and Rothmund-Thomson syndrome. In this case report, we describe a 9-year-old boy who presented with sclerodactyly, acroosteolysis and scleroderma-like involvement of the skin over hands and feet, which suggested a diagnosis of juvenile scleroderma initially. However, absence of Raynaud's phenomenon, sparing of the skin other than hands and feet and negative serological studies did not support this diagnosis. On the basis of additional findings (micrognathia, dental malformation, a 'beaked nose', open cranial sutures and sparse hair), the patient was diagnosed as mandibuloacral dysplasia, a rare autosomal recessive disease. This case demonstrates that mandibuloacral dysplasia should be considered in the differential diagnosis of juvenile scleroderma in the presence of atypical features such as negative serological studies, absence of Raynaud's phenomenon, sparse hair and micrognathia.


The effect of exercise on circulating immunoreactive calcitonin in men.
Moderate-duration exercise increases serum catecholamine and serum calcium levels and might as a result be also expected to increase the levels of circulating serum immunoreactive human calcitonin (HCT). To explore this possibility, HCT was studied during and after moderate duration symptom-limited dynamic exercise in 13 healthy males, mean age 28 +/- 6.9 (SD) years. The mean duration of exercise using the Bruce treadmill protocol was 14.1 +/- 2.2 (SD) minutes. The mean heart rate (HR) peaked at 185 +/- 6 (SD) bpm which was 96.1% of the predicted maximal HR for age. Values for HCT, uncorrected for changes in plasma volume, showed a minimal decrease in the recovery phase, whilst HCT corrected for changes in plasma volume did not alter during exercise or recovery. The serum parathyroid hormone (PTH) also did not change. At peak exercise, uncorrected but not corrected values for plasma noradrenaline, adrenaline and dopamine had increased significantly. Corrected plasma total calcium increased during recovery. In summary, dynamic weight-bearing moderate-duration exercise did not elevate HCT in healthy males.


Hepatitis B virus infection. Current concepts of chronicity and immunity.
Among the three types of viral hepatitis agents-A, B and non-A, non-B-the hepatitis B virus (HBV) has been best characterized by immunologic and recombinant DNA technologies. The indefinite persistence of hepatitis B virus infection in 85% to 90% of perinatally infected infants and in about 10% of those infected later in life accounts for a worldwide epidemiologic reservoir of more than 200 million carriers who are at a high risk for the development of delta-infection, chronic liver disease and hepatocellular carcinoma. Active immunization with a safe and effective vaccine, derived from the plasma of carriers of hepatitis B surface antigen (HBsAg), is envisaged to avoid viral hepatitis type B and its chronic sequelae. In addition to serologic and immunohistochemical markers of hepatitis B virus infection, hybridization assays using cloned HBV DNA have provided new insight into the biology of this virus, its persistence and its oncogenic potential in humans and in animal models. Genetic similarities have been recognized between HBV and the antigenically distinct non-A, non-B agents implicated in some cases of transfusion-associated chronic hepatitis. Structurally this unique group of HBV and HBV-like agents are DNA viruses with functional attributes of integration and replication analogous to the retroviruses.


Sulfur-oxidizing symbionts have not co-evolved with their hydrothermal vent tube worm hosts: an RFLP analysis.
A fine-scale phylogenetic comparison was made among the symbionts of different genera of hydrothermal vent tube worms. These included Riftia pachyptila and Tevnia jerichonona, which inhabit sites along the east Pacific Rise, and Ridgeia piscesae from the Juan de Fuca Ridge. An analysis of restriction fragment length polymorphism (RFLP) was employed using three symbiont-specific gene probes: eubacterial 16S rRNA, RuBPC/O Form II, and ATP sulfurylase (recently cloned from the Riftia symbiont). Results indicated that all of the symbionts from the three different hosts were conspecific and the Riftia and Tevnia symbionts were indistinguishable over and 1800-km range. Significantly, this indicates that the symbionts have not co-evolved with their respective hosts, which are known to belong to separate families. This study strongly supports the conclusion that the symbionts are acquired de novo by each generation of juvenile tube worms from a common source in the surrounding sea water.


Prospective clinical evaluation of the accuracy of 16S rRNA real-time PCR assay for the diagnosis of melioidosis.
The accuracy of a Burkholderia pseudomallei 16s rRNA real-time PCR assay was evaluated against culture for the diagnosis of melioidosis in Thailand. A total of 846 samples were obtained from 383 patients with suspected melioidosis. One or more specimens were PCR positive for 47 of 77 patients with culture-proven melioidosis (sensitivity 61.0%, 95% CI: 49.2-72.0%). PCR was negative for all 306 patients who were culture negative for B. pseudomallei (specificity 100%, 95% CI: 98.8-100%). Diagnostic sensitivity of PCR was 22.7% for patients who were culture positive for blood only, compared with 79.4% for patients who were culture positive for samples other than blood. The median (interquartile range) B. pseudomallei colony count in blood for 44 of 77 patients with positive blood cultures was 2.4 CFU/ml (0.2-13.5 CFU/ml); this may explain the low sensitivity of PCR for this specimen. The PCR assay described here is not sufficiently sensitive to replace culture in our clinical setting.


Assessment of medical technology students' perceptions of clinical site rotations and job choice criteria.
This study reflects an assessment conducted at the University of Utah to determine medical laboratory science students' perceptions and influence of clinical rotations on job choice criteria. A mixed method design was used, incorporating semistructured interviews and mailed questionnaires. This study identified both favorable as well as unfavorable factors that influence students' employment choices. Clinical managers should: 1) foster a positive organizational climate; 2) encourage constructive employee-student interaction and respect; 3) promote the clinical facilities' reputation of excellence in health care; and 4) continue to offer competitive wages and employee benefits. Clinical managers should avoid: 1) a lack of positive attitudes toward students; and 2) a lack of respect for the student's knowledge. This study provides crucial information for laboratory directors, managers, and supervisors who are interested in creating an ideal climate in which to recruit graduating medical laboratory science (MLS) students.


Monosynaptic inference via finely-timed spikes.
Observations of finely-timed spike relationships in population recordings have been used to support partial reconstruction of neural microcircuit diagrams. In this approach, fine-timescale components of paired spike train interactions are isolated and subsequently attributed to synaptic parameters. Recent perturbation studies strengthen the case for such an inference, yet the complete set of measurements needed to calibrate statistical models is unavailable. To address this gap, we study features of pairwise spiking in a large-scale in vivo dataset where presynaptic neurons were explicitly decoupled from network activity by juxtacellular stimulation. We then construct biophysical models of paired spike trains to reproduce the observed phenomenology of in vivo monosynaptic interactions, including both fine-timescale spike-spike correlations and firing irregularity. A key characteristic of these models is that the paired neurons are coupled by rapidly-fluctuating background inputs. We quantify a monosynapse's causal effect by comparing the postsynaptic train with its counterfactual, when the monosynapse is removed. Subsequently, we develop statistical techniques for estimating this causal effect from the pre- and post-synaptic spike trains. A particular focus is the justification and application of a nonparametric separation of timescale principle to implement synaptic inference. Using simulated data generated from the biophysical models, we characterize the regimes in which the estimators accurately identify the monosynaptic effect. A secondary goal is to initiate a critical exploration of neurostatistical assumptions in terms of biophysical mechanisms, particularly with regards to the challenging but arguably fundamental issue of fast, unobservable nonstationarities in background dynamics.


Amino acids indigenous to the murray meteorite.
Analysis of the Murray meteorite, a type II carbonaceous chondrite, has led to the identification of 17 amino acids. For seven of the amino acids nearly equal amounts of the D and L isomers are present, and 11 of the amino acids are not found in protein. These results suggest that these amino acids, like the amino acids of the Murchison meteorite, are extraterrestrial in origin.


A revised view of cardiac sodium channel "blockade" in the long-QT syndrome.
Mutations in SCN5A, encoding the cardiac sodium (Na) channel, are linked to a form of the congenital long-QT syndrome (LQT3) that provokes lethal ventricular arrhythmias. These autosomal dominant mutations disrupt Na channel function, inhibiting channel inactivation, thereby causing a sustained ionic current that delays cardiac repolarization. Sodium channel-blocking antiarrhythmics, such as lidocaine, potently inhibit this pathologic Na current (I(Na)) and are being evaluated in patients with LQT3. The mechanism underlying this effect is unknown, although high-affinity "block" of the open Na channel pore has been proposed. Here we report that a recently identified LQT3 mutation (R1623Q) imparts unusual lidocaine sensitivity to the Na channel that is attributable to its altered functional behavior. Studies of lidocaine on individual R1623Q single-channel openings indicate that the open-time distribution is not changed, indicating the drug does not block the open pore as proposed previously. Rather, the mutant channels have a propensity to inactivate without ever opening ("closed-state inactivation"), and lidocaine augments this gating behavior. An allosteric gating model incorporating closed-state inactivation recapitulates the effects of lidocaine on pathologic I(Na). These findings explain the unusual drug sensitivity of R1623Q and provide a general and unanticipated mechanism for understanding how Na channel-blocking agents may suppress the pathologic, sustained Na current induced by LQT3 mutations.


Affective temperaments show stronger association with infertility treatment success compared to somatic factors, highlighting the role of personality focused interventions.
Infertility has a multifactorial background, where, besides somatic factors, psychological contributors also play a role in development and outcome. While affective temperaments have been associated with development, course, and outcome as well as treatment success in various somatic conditions, their association with infertility and its treatment has not been investigated so far. The purpose of our retrospective cohort study was to evaluate the influence of affective temperaments on fertility treatment outcomes. Among 578 women who underwent infertility treatment in an Assisted Reproduction Centre in Budapest, Hungary, treatment success, detailed medical history, and demographic parameters were recorded, and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A) was administered. Possible predictors of assisted reproduction outcome were analyzed using multivariate logistic regression models, followed by a receiver operating curve (ROC) analysis in order to define ideal affective temperament cut-off values for clinical applicability. Aside from age, BMI, and previous miscarriage, cyclothymic scores > 4 (OR = 0.51 CI 0.35-0.74, p < 0.001), depressive scores > 9 (OR = 0.59 CI 0.4-0.87, p = 0.009) and anxious scores > 9 (OR = 0.45 CI 0.31-0.66, p < 0.001) significantly decreased the odds of clinical pregnancy by 49%, 41% and 55%, respectively. Irritable and hyperthymic temperaments, as well as other somatic and socio-economic factors had no effect on infertility treatment outcomes. The results suggest that affective temperaments may be related to the outcome of infertility treatments. Thus, screening for affective temperaments may help identify high-risk patient groups and offer patient-tailored treatment, which may increase the chances of a successful pregnancy and live birth for women undergoing IVF treatment.


Intra- and intermolecular cooperative binding of high-mobility-group protein I(Y) to the beta-interferon promoter.
The mammalian high-mobility-group protein I(Y) [HMG I(Y)], while not a typical transcriptional activator, is required for the expression of many eukaryotic genes. HMG I(Y) appears to recruit and stabilize complexes of transcriptional activators through protein-DNA and protein-protein interactions. The protein binds to the minor groove of DNA via three short basic repeats, preferring tracts of adenines and thymines arranged on the same face of the DNA helix. However, the mode by which these three basic repeats function together to recognize HMG I(Y) binding sites has remained unclear. Here, using deletion mutants of HMG I(Y), DNase I footprinting, methylation interference, and in vivo transcriptional assays, we have characterized the binding of HMG I(Y) to the model beta-interferon enhancer. We show that two molecules of HMG I(Y) bind to the enhancer in a highly cooperative fashion, each molecule using a distinct pair of basic repeats to recognize the tandem AT-rich regions of the binding sites. We have also characterized the function of each basic repeat, showing that only the central repeat accounts for specific DNA binding and that the presence of a second repeat bound to an adjacent AT-rich region results in intramolecular cooperativity in binding. Surprisingly, the carboxyl-terminal acidic tail of HMG I(Y) is also important for specific binding in the context of the full-length protein. Our results present a detailed examination of HMG I(Y) binding in an important biological context, which can be extended not only to HMG I(Y) binding in other systems but also to the binding mode of many other proteins containing homologous basic repeats, which have been conserved from bacteria to humans.


Effects of n-6 and n-3 polyunsaturated acid-rich soybean phosphatidylcholine on membrane lipid profile and cryotolerance of human sperm.
To study the effects of n-6 and n-3 polyunsaturated acid-rich soybean phosphatidylcholine (soy-PC) on sperm cryotolerance with regard to sperm membrane lipid profile, membrane surface integrity, and routine semen parameters. Experimental study. University-affiliated tertiary hospital. A total of 20 normospermic fertile men. Semen samples examined for differences in semen parameters, sperm membrane lipid profile, and plasma membrane surface both before and after cryopreservation using basic freezing medium with N-tris(hydroxymethyl)-methyl-2-aminoethane sulfonic acid (TES) and tris-(hydroxymethyl)-aminomethane (TRIS) supplemented with purified soy-PC (TEST-PC) or egg yolk (TEST-Y), both alone or in association (TEST-Y-PC). Conventional semen parameters and membrane lipid profile by matrix-assisted laser/desorption ionization mass spectrometry (MALDI-MS). Postthaw sperm cell motility, vitality, and morphology parameters were similar for soy-PC (TEST-PC) and egg yolk (TEST-Y) cryoprotectants. However, sperm exposed to TEST-Y-PC presented better kinetic parameters, which were similar to the original quality of the fresh semen. Human sperm MALDI-MS lipid profiles revealed that the relative abundance of glycerophospholipids of m/z 760.44 [PC (34:1)+H]+, 781.55 [SM (20:0) +Na]+, 784.55 [PC (36:3) +H]+, 806.64 [PC (38:6) +H]+, 807.64 [SM (22:1) +Na]+, and 809.64 [SM (22:0) +Na]+ increased in soy-PC samples (TEST-PC). Nonetheless, only one lipid (m/z 781.55, [SM (20:0) +Na]+) statistically significantly changed when sperm was cryopreserved in TEST-Y-PC. Sphingomyelin was defined as a prospective biomarker of soy-PC treatment, and it could be related to the positive cryoprotective effects of soy-PC in human sperm, opening new perspectives to design of a more efficient synthetic cryoprotectant medium containing purified egg yolk biomolecules combined with soy-PC.


Closing the quality gap: revisiting the state of the science (vol. 8: improving health care and palliative care for advanced and serious illness).
To systematically review the evidence on the effectiveness of health care and palliative care interventions to improve outcomes for patients with advanced and serious illness. We searched MEDLINE®, CINAHL, PsycINFO, Cochrane, and DARE from 2000 through 2011. We identified additional studies from reference lists of eligible articles and relevant reviews, as well as from technical experts. We developed questions in collaboration with technical experts. We excluded retrospective and uncontrolled studies. Two investigators independently screened search results and abstracted data from eligible studies. We adapted previous frameworks to categorize included studies (e.g., by improvement target, setting). Because many studies did not report effect sizes and almost all studies were small (lt 200 studies), in order to be able to quantitatively describe the literature, we calculated the percentage of studies with a significant improvement in outcomes with the intervention compared to control group for each category. We also checked that all other studies did not report significant results in the opposite direction and checked that there were not differences between larger and smaller studies. We included 90 studies described in 96 articles. Of the 23 studies targeting continuity, coordination, and transitions, 33 percent of studies that evaluated quality of life as an outcome, 67 percent that evaluated patient satisfaction, and 31 percent that evaluated health care utilization (admissions and length of stay) found a statistically significant improvement with the intervention. Of the 21 studies targeting pain, almost all focused on patient education and self-management; 48 percent of them found a statistically significant improvement with the intervention. Findings for larger (>100) and smaller (le 100) studies were similar. For distress, only 29 percent of the seven included studies found a statistically significant impact. Of the 20 studies in communication and decisionmaking, only 22 percent of studies addressing patient or family satisfaction found a statistically significant improvement for this outcome, compared to 73 percent for the outcome of health care utilization. We found only two studies within hospice programs, both of which found a statistically significant improvement in at least one outcome; nine studies were in nursing homes, 78 percent of which demonstrated a significant improvement with the intervention. In terms of types of quality improvement, for the target of continuity, studies including patient-centered quality improvement types, such as education and self-management, had the strongest evidence of effectiveness on patient- and family-centered domains such as satisfaction and quality of life. Studies of provider-focused interventions (e.g., education, reminders) were more likely to have an impact on health care utilization. Only one of five studies addressing multiple targets and focusing on facilitated relay of clinical data to providers demonstrated a statistically significant improvement in either quality of life or satisfaction. In terms of consultative and integrative interventions, for the target of communication and decisionmaking, three-quarters of consultative interventions showed a statistically significant improvement with the intervention, compared to half of integrative interventions. The literature was too heterogeneous and effect sizes were too infrequently reported for quantitative synthesis. There was moderate strength of evidence for the target of continuity, coordination, and transitions and the outcome of patient and caregiver satisfaction but low strength of evidence for other outcomes. For the target of pain, there was moderate strength of evidence for pain as an outcome. For the target of communication and decisionmaking, there was moderate strength of evidence for the outcome of health care utilization but low strength of evidence for other outcomes. We found that evidence was strongest (moderate strength of evidence) for interventions for pain, and for the targets of communication and decisionmaking and continuity for selected outcomes. While a few high- and medium-quality, well-designed health care and palliative care interventions have been conducted to improve outcomes for patients with advanced and serious illness, this report highlights the continued presence of variable findings, quality deficiencies, vaguely defined interventions, and variable outcome measurement tools and reporting in much of this intervention literature. The evidence has a number of gaps, including few studies in the hospice setting or pediatrics. Future research needs include techniques for improving recruitment and retention to assure adequate sample size, better development and description of interventions, and further development and standardization of outcome measures and tools.


PROFILE: Wildland Recreation and Human Waste: A Review of Problems, Practices, and Concerns.
/ Proper disposal of human waste is an important concern for the appropriate management of wildlands. This paper reviews the state of knowledge regarding pathogens and human waste disposal in dispersed backcountry recreation areas in the United States. Of concern is the impact of travelers, such as backpackers, backcountry skiers, and mountaineers, in areas where toilets are not provided. At this time, the magnitude of problems related to human waste disposal in wildlands is unclear. Aesthetics and water contamination with the resultant potential for disease transmission are the predominant issues. Few studies have analyzed the aesthetics of human waste disposal. In wildlands, contamination of water sources primarily originates from surface soil. The fate of enteric pathogens on or in soils is highly variable and dependent on the complex interactions of many factors, most importantly soil type, moisture, and temperature. It is difficult to make general recommendations that apply to all ecosystems. There is still a relative dearth of studies that allow the manager or visitor to come up with specific practices that are the best for their area. The preferred method of disposal remains to dig a small hole (cat hole) and bury the waste. Other site specific methods are also discussed. Treatment of drinking water has become standard practice for most backcountry travel. With such treatment, there is little evidence currently to suggest that the health hazard to humans is great enough to impose further regulation in areas currently using cat holes.


Women with Genitourinary Syndrome of Menopause Treated with Vaginal Estriol, Microablative Fractional CO2 Laser and Microablative Fractional Radiofrequency: A Randomized Pilot Study.
Objective: This pilot study intended to assess the feasibility of a large-scale randomized clinical trial designed to analyze the effectiveness of microablative fractional CO2 laser (CO2L) and microablative fractional radiofrequency (RF) compared with vaginal estriol (VE) as treatments for women with moderate-to-severe Genitourinary Syndrome of Menopause (GSM). Methods: Participants were randomized into VE, CO2L, or RF groups. In the VE group, women were required to use vaginal estriol cream for 14 days and then twice a week for 4 months. In the CO2L and RF groups, three energy therapies were administered at monthly intervals. Visual Analog Scale (VAS) for GSM symptoms, Female Sexual Function Index (FSF-I), Vaginal Health Index (VHI), and Nugent Score (NS) were analyzed before and 120 days after the beginning of the treatments. Pain scores were verified after each CO2L and RF session. Results: Thirty-four participants completed the study: 11 in the VE group, 11 in the CO2L group, and 12 in the RF group. No unexpected or serious adverse events were observed. We also verified that GSM symptoms, sexual function, and VHI significantly improved (p < 0.05) with no difference among the groups. NS did not show statistically significant difference before and after the treatments. Pain during RF application was associated with higher scores. Conclusions: The study is feasible and does not seem to have safety implications. Preliminary results suggest that CO2L and RF are good alternatives to VE for ameliorating clinical symptoms, FSF-I, and VHI in patients with GSM. Clinical Trial Registration number: NCT04045379.


A novel bioactive haemodialysis system using dissolved dihydrogen (H2) produced by water electrolysis: a clinical trial.
Chronic inflammation in haemodialysis (HD) patients indicates a poor prognosis. However, therapeutic approaches are limited. Hydrogen gas (H(2)) ameliorates oxidative and inflammatory injuries to organs in animal models. We developed an HD system using a dialysis solution with high levels of dissolved H(2) and examined the clinical effects. Dialysis solution with H(2) (average of 48 ppb) was produced by mixing dialysate concentrates and reverse osmosis water containing dissolved H(2) generated by a water electrolysis technique. Subjects comprised 21 stable patients on standard HD who were switched to the test HD for 6 months at three sessions a week. During the study period, no adverse clinical signs or symptoms were observed. A significant decrease in systolic blood pressure (SBP) before and after dialysis was observed during the study, and a significant number of patients achieved SBP <140 mmHg after HD (baseline, 21%; 6 months, 62%; P < 0.05). Changes in dialysis parameters were minimal, while significant decreases in levels of plasma monocyte chemoattractant protein 1 (P < 0.01) and myeloperoxidase (P < 0.05) were identified. Adding H(2) to haemodialysis solutions ameliorated inflammatory reactions and improved BP control. This system could offer a novel therapeutic option for control of uraemia.


[Gene technology in the prevention of cancer].
Cancer may develop in connection with rare, genetic diseases or after exceptional, environmental exposures. Most commonly, however, cancer results from an unhappy coincidence of normal, genetic factors and ordinary, environmental conditions. Oncogenes are normal growth genes. Anti-oncogenes are normal regulatory genes which control growth genes. Cancer may result from changes (mutations) in an oncogene (such as in the Philadelphia chromosome), or from the lack of control of normal oncogenes. The latter may be due to loss of function of a suppressor gene (mutation in an anti-oncogene, such as in retinoblastoma) or through a change in the position of an oncogene (such as in Burkitt's lymphoma and in certain leukemias).


Child sexual abuse in Turkey: an analysis of 1002 cases.
This study investigated the characteristics of abuse suffered by children, the dimensions of the psychiatric effects associated with abuse, and the factors affecting these. One thousand two cases aged under 18, exposed to sexual abuse, and referred over a 7-year period were assessed. Girls represented 80.8% of cases, and the numbers rose with age. The aggressors were all male, and 88.2% were known to their victim. Approximately half the children were exposed to sexual abuse involving penetration. Psychological pathology was identified in 62.1%. Female gender, the presence of penetration, physical violence, and incest significantly increased the development of psychological pathology. Levels of awareness in people close to and trusted by the child must be raised to minimize the adverse effects of trauma in the long term, preventive measures must be taken, and medical and social support units from which victims can receive assistance need to be established.


Cre levels limit packaging signal excision efficiency in the Cre/loxP helper-dependent adenoviral vector system.
Helper-dependent (HD) adenovirus vectors devoid of all viral coding sequences have a large cloning capacity and provide long-term transgene expression in vivo with negligible toxicity, making them attractive vectors for gene therapy. Currently, the most efficient means of producing HD vectors involves coinfecting 293 cells expressing Cre with the HD vector and a helper virus bearing a packaging signal flanked by loxP sites. Cre-mediated packaging signal excision renders the helper virus genome unpackageable but still able to replicate and provide helper functions for HD vector propagation. Typically, helper virus contamination is < or =1% pre- and < or =0.1% postpurification by CsCl banding. While these contamination levels are low, further reduction is desirable. However, this objective has not been realized since the Cre/loxP system was first developed. This lack of progress is due, at least in part, to our lack of understanding of the origins of the contaminating helper virus, thus rendering its reduction or elimination difficult to achieve. This study was designed to investigate the possible sources of contaminating helper virus persisting during HD vector amplification. The results revealed that Cre is limiting in helper virus-infected Cre-expressing 293 cells, thereby permitting helper viruses to escape packaging signal excision and propagate. The results of this study should provide a foundation for developing rational strategies to further reduce or possibly eliminate the contaminating helper virus.


"Youth friendly" clinics: considerations for linking and engaging HIV-infected adolescents into care.
Linkage and engagement in care are critical corollaries to the health of HIV-infected adolescents. The adolescent HIV epidemic and adolescents' unique barriers to care necessitates innovation in the provision of care, including the consideration of the clinical experience. Little research has addressed how "youth friendly" clinics may influence care retention for HIV-infected youth. We conducted 124 interviews with providers, outreach workers, and case managers, at 15 Adolescent Medicine Trials Network clinics. Photographs of each clinic documented the characteristics of the physical space. Constant comparison and content and visual narrative methods were utilized for data analysis. Three elements of youth friendliness were identified for clinics serving HIV-infected youth, including: (1) role of target population (e.g., pediatric, adolescent, HIV); (2) clinics' physical environment; and (3) clinics' social environment. Working to create 'youth friendly' clinics through changes in physical (e.g., space, entertainment, and educational materials) and social (e.g., staff training related to development, gender, sexual orientation) environments may help reduce HIV-infected adolescents' unique barriers to care engagement. The integration of clinic design and staff training within the organization of a clinical program is helpful in meeting the specialized needs of HIV-infected youth.